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1. Beyond the Global Brain Differences:Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

Author: Boen, Rune, Kaufmann, Tobias, van der Meer, Dennis, Frei, Oleksandr, Agartz, Ingrid, Ames, David, Andersson, Micael, Armstrong, Nicola J., Artiges, Eric, Atkins, Joshua R., Bauer, Jochen, Benedetti, Francesco, Boomsma, Dorret I., Brodaty, Henry, Brosch, Katharina, Buckner, Randy L., Cairns, Murray J., Calhoun, Vince, Caspers, Svenja, Cichon, Sven, Corvin, Aiden P., Crespo-Facorro, Benedicto, Dannlowski, Udo, David, Friederike S., de Geus, Eco J.C., de Zubicaray, Greig I., Desrivières, Sylvane, Doherty, Joanne L., Donohoe, Gary, Ehrlich, Stefan, Eising, Else, Espeseth, Thomas, Fisher, Simon E., Forstner, Andreas J., Fortaner-Uyà, Lidia, Frouin, Vincent, Fukunaga, Masaki, Ge, Tian, Glahn, David C., Goltermann, Janik, Grabe, Hans J., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Grøntvedt, Gøril Rolfseng, Hahn, Tim, Hashimoto, Ryota, Hehir-Kwa, Jayne Y., Henskens, Frans A., Holmes, Avram J., Håberg, Asta K., Haavik, Jan, Jacquemont, Sebastien, Jansen, Andreas, Jockwitz, Christiane, Jönsson, Erik G., Kikuchi, Masataka, Kircher, Tilo, Kumar, Kuldeep, Le Hellard, Stephanie, Leu, Costin, Linden, David E., Liu, Jingyu, Loughnan, Robert, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Medland, Sarah E., Meinert, Susanne, Moreau, Clara A., Morris, Derek W., Mowry, Bryan J., Mühleisen, Thomas W., Nenadić, Igor, Nöthen, Markus M., Nyberg, Lars, Ophoff, Roel A., Owen, Michael J., Pantelis, Christos, Paolini, Marco, Paus, Tomas, Pausova, Zdenka, Persson, Karin, Quidé, Yann, Marques, Tiago Reis, Sachdev, Perminder S., Sando, Sigrid B., Schall, Ulrich, Scott, Rodney J., Selbæk, Geir, Shumskaya, Elena, Silva, Ana I., Sisodiya, Sanjay M., Stein, Frederike, Stein, Dan J., Straube, Benjamin, Streit, Fabian, Strike, Lachlan T., Teumer, Alexander, Teutenberg, Lea, Thalamuthu, Anbupalam, Tooney, Paul A., Tordesillas-Gutierrez, Diana, Trollor, Julian N., van ’t Ent, Dennis, van den Bree, Marianne B.M., van Haren, Neeltje E.M., Vázquez-Bourgon, Javier, Völzke, Henry, Wen, Wei, Wittfeld, Katharina, Ching, Christopher R.K., Westlye, Lars T., Thompson, Paul M., Bearden, Carrie E., Selmer, Kaja K., Alnæs, Dag, Andreassen, Ole A., Sønderby, Ida E., Boen, Rune, Kaufmann, Tobias, van der Meer, Dennis, Frei, Oleksandr, Agartz, Ingrid, Ames, David, Andersson, Micael, Armstrong, Nicola J., Artiges, Eric, Atkins, Joshua R., Bauer, Jochen, Benedetti, Francesco, Boomsma, Dorret I., Brodaty, Henry, Brosch, Katharina, Buckner, Randy L., Cairns, Murray J., Calhoun, Vince, Caspers, Svenja, Cichon, Sven, Corvin, Aiden P., Crespo-Facorro, Benedicto, Dannlowski, Udo, David, Friederike S., de Geus, Eco J.C., de Zubicaray, Greig I., Desrivières, Sylvane, Doherty, Joanne L., Donohoe, Gary, Ehrlich, Stefan, Eising, Else, Espeseth, Thomas, Fisher, Simon E., Forstner, Andreas J., Fortaner-Uyà, Lidia, Frouin, Vincent, Fukunaga, Masaki, Ge, Tian, Glahn, David C., Goltermann, Janik, Grabe, Hans J., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Grøntvedt, Gøril Rolfseng, Hahn, Tim, Hashimoto, Ryota, Hehir-Kwa, Jayne Y., Henskens, Frans A., Holmes, Avram J., Håberg, Asta K., Haavik, Jan, Jacquemont, Sebastien, Jansen, Andreas, Jockwitz, Christiane, Jönsson, Erik G., Kikuchi, Masataka, Kircher, Tilo, Kumar, Kuldeep, Le Hellard, Stephanie, Leu, Costin, Linden, David E., Liu, Jingyu, Loughnan, Robert, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Medland, Sarah E., Meinert, Susanne, Moreau, Clara A., Morris, Derek W., Mowry, Bryan J., Mühleisen, Thomas W., Nenadić, Igor, Nöthen, Markus M., Nyberg, Lars, Ophoff, Roel A., Owen, Michael J., Pantelis, Christos, Paolini, Marco, Paus, Tomas, Pausova, Zdenka, Persson, Karin, Quidé, Yann, Marques, Tiago Reis, Sachdev, Perminder S., Sando, Sigrid B., Schall, Ulrich, Scott, Rodney J., Selbæk, Geir, Shumskaya, Elena, Silva, Ana I., Sisodiya, Sanjay M., Stein, Frederike, Stein, Dan J., Straube, Benjamin, Streit, Fabian, Strike, Lachlan T., Teumer, Alexander, Teutenberg, Lea, Thalamuthu, Anbupalam, Tooney, Paul A., Tordesillas-Gutierrez, Diana, Trollor, Julian N., van ’t Ent, Dennis, van den Bree, Marianne B.M., van Haren, Neeltje E.M., Vázquez-Bourgon, Javier, Völzke, Henry, Wen, Wei, Wittfeld, Katharina, Ching, Christopher R.K., Westlye, Lars T., Thompson, Paul M., Bearden, Carrie E., Selmer, Kaja K., Alnæs, Dag, Andreassen, Ole A., and Sønderby, Ida E.
Abstract: BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’s regional difference and global difference, were used to test for regional differences that diverge from the global difference. RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
Published: 2024

2. Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers

Author: Boen, Rune, Kaufmann, Tobias, van der Meer, Dennis, Frei, Oleksandr, Agartz, Ingrid, Ames, David, Andersson, Micael, Armstrong, Nicola J., Artiges, Eric, Atkins, Joshua R., Bauer, Jochen, Benedetti, Francesco, Boomsma, Dorret I., Brodaty, Henry, Brosch, Katharina, Buckner, Randy L., Cairns, Murray J., Calhoun, Vince, Caspers, Svenja, Cichon, Sven, Corvin, Aiden P., Crespo-Facorro, Benedicto, Dannlowski, Udo, David, Friederike S., de Geus, Eco J.C., de Zubicaray, Greig I., Desrivières, Sylvane, Doherty, Joanne L., Donohoe, Gary, Ehrlich, Stefan, Eising, Else, Espeseth, Thomas, Fisher, Simon E., Forstner, Andreas J., Fortaner-Uyà, Lidia, Frouin, Vincent, Fukunaga, Masaki, Ge, Tian, Glahn, David C., Goltermann, Janik, Grabe, Hans J., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Grøntvedt, Gøril Rolfseng, Hahn, Tim, Hashimoto, Ryota, Hehir-Kwa, Jayne Y., Henskens, Frans A., Holmes, Avram J., Håberg, Asta K., Haavik, Jan, Jacquemont, Sebastien, Jansen, Andreas, Jockwitz, Christiane, Jönsson, Erik G., Kikuchi, Masataka, Kircher, Tilo, Kumar, Kuldeep, Le Hellard, Stephanie, Leu, Costin, Linden, David E., Liu, Jingyu, Loughnan, Robert, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Medland, Sarah E., Meinert, Susanne, Moreau, Clara A., Morris, Derek W., Mowry, Bryan J., Mühleisen, Thomas W., Nenadić, Igor, Nöthen, Markus M., Nyberg, Lars, Ophoff, Roel A., Owen, Michael J., Pantelis, Christos, Paolini, Marco, Paus, Tomas, Pausova, Zdenka, Persson, Karin, Quidé, Yann, Marques, Tiago Reis, Sachdev, Perminder S., Sando, Sigrid B., Schall, Ulrich, Scott, Rodney J., Selbæk, Geir, Shumskaya, Elena, Silva, Ana I., Sisodiya, Sanjay M., Stein, Frederike, Stein, Dan J., Straube, Benjamin, Streit, Fabian, Strike, Lachlan T., Teumer, Alexander, Teutenberg, Lea, Thalamuthu, Anbupalam, Tooney, Paul A., Tordesillas-Gutierrez, Diana, Trollor, Julian N., van ’t Ent, Dennis, van den Bree, Marianne B.M., van Haren, Neeltje E.M., Vázquez-Bourgon, Javier, Völzke, Henry, Wen, Wei, Wittfeld, Katharina, Ching, Christopher R.K., Westlye, Lars T., Thompson, Paul M., Bearden, Carrie E., Selmer, Kaja K., Alnæs, Dag, Andreassen, Ole A., Sønderby, Ida E., Boen, Rune, Kaufmann, Tobias, van der Meer, Dennis, Frei, Oleksandr, Agartz, Ingrid, Ames, David, Andersson, Micael, Armstrong, Nicola J., Artiges, Eric, Atkins, Joshua R., Bauer, Jochen, Benedetti, Francesco, Boomsma, Dorret I., Brodaty, Henry, Brosch, Katharina, Buckner, Randy L., Cairns, Murray J., Calhoun, Vince, Caspers, Svenja, Cichon, Sven, Corvin, Aiden P., Crespo-Facorro, Benedicto, Dannlowski, Udo, David, Friederike S., de Geus, Eco J.C., de Zubicaray, Greig I., Desrivières, Sylvane, Doherty, Joanne L., Donohoe, Gary, Ehrlich, Stefan, Eising, Else, Espeseth, Thomas, Fisher, Simon E., Forstner, Andreas J., Fortaner-Uyà, Lidia, Frouin, Vincent, Fukunaga, Masaki, Ge, Tian, Glahn, David C., Goltermann, Janik, Grabe, Hans J., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Grøntvedt, Gøril Rolfseng, Hahn, Tim, Hashimoto, Ryota, Hehir-Kwa, Jayne Y., Henskens, Frans A., Holmes, Avram J., Håberg, Asta K., Haavik, Jan, Jacquemont, Sebastien, Jansen, Andreas, Jockwitz, Christiane, Jönsson, Erik G., Kikuchi, Masataka, Kircher, Tilo, Kumar, Kuldeep, Le Hellard, Stephanie, Leu, Costin, Linden, David E., Liu, Jingyu, Loughnan, Robert, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Medland, Sarah E., Meinert, Susanne, Moreau, Clara A., Morris, Derek W., Mowry, Bryan J., Mühleisen, Thomas W., Nenadić, Igor, Nöthen, Markus M., Nyberg, Lars, Ophoff, Roel A., Owen, Michael J., Pantelis, Christos, Paolini, Marco, Paus, Tomas, Pausova, Zdenka, Persson, Karin, Quidé, Yann, Marques, Tiago Reis, Sachdev, Perminder S., Sando, Sigrid B., Schall, Ulrich, Scott, Rodney J., Selbæk, Geir, Shumskaya, Elena, Silva, Ana I., Sisodiya, Sanjay M., Stein, Frederike, Stein, Dan J., Straube, Benjamin, Streit, Fabian, Strike, Lachlan T., Teumer, Alexander, Teutenberg, Lea, Thalamuthu, Anbupalam, Tooney, Paul A., Tordesillas-Gutierrez, Diana, Trollor, Julian N., van ’t Ent, Dennis, van den Bree, Marianne B.M., van Haren, Neeltje E.M., Vázquez-Bourgon, Javier, Völzke, Henry, Wen, Wei, Wittfeld, Katharina, Ching, Christopher R.K., Westlye, Lars T., Thompson, Paul M., Bearden, Carrie E., Selmer, Kaja K., Alnæs, Dag, Andreassen, Ole A., and Sønderby, Ida E.
Abstract: Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference. Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
Published: 2024
Full Text: View/download PDF

3. Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers

Author: Boen, Rune, Kaufmann, Tobias, van der Meer, Dennis, Frei, Oleksandr, Agartz, Ingrid, Ames, David, Andersson, Micael, Armstrong, Nicola J., Artiges, Eric, Atkins, Joshua R., Bauer, Jochen, Benedetti, Francesco, Boomsma, Dorret I., Brodaty, Henry, Brosch, Katharina, Buckner, Randy L., Cairns, Murray J., Calhoun, Vince, Caspers, Svenja, Cichon, Sven, Corvin, Aiden P., Crespo-Facorro, Benedicto, Dannlowski, Udo, David, Friederike S., de Geus, Eco J.C., de Zubicaray, Greig I., Desrivières, Sylvane, Doherty, Joanne L., Donohoe, Gary, Ehrlich, Stefan, Eising, Else, Espeseth, Thomas, Fisher, Simon E., Forstner, Andreas J., Fortaner-Uyà, Lidia, Frouin, Vincent, Fukunaga, Masaki, Ge, Tian, Glahn, David C., Goltermann, Janik, Grabe, Hans J., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Grøntvedt, Gøril Rolfseng, Hahn, Tim, Hashimoto, Ryota, Hehir-Kwa, Jayne Y., Henskens, Frans A., Holmes, Avram J., Håberg, Asta K., Haavik, Jan, Jacquemont, Sebastien, Jansen, Andreas, Jockwitz, Christiane, Jönsson, Erik G., Kikuchi, Masataka, Kircher, Tilo, Kumar, Kuldeep, Le Hellard, Stephanie, Leu, Costin, Linden, David E., Liu, Jingyu, Loughnan, Robert, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Medland, Sarah E., Meinert, Susanne, Moreau, Clara A., Morris, Derek W., Mowry, Bryan J., Mühleisen, Thomas W., Nenadić, Igor, Nöthen, Markus M., Nyberg, Lars, Ophoff, Roel A., Owen, Michael J., Pantelis, Christos, Paolini, Marco, Paus, Tomas, Pausova, Zdenka, Persson, Karin, Quidé, Yann, Marques, Tiago Reis, Sachdev, Perminder S., Sando, Sigrid B., Schall, Ulrich, Scott, Rodney J., Selbæk, Geir, Shumskaya, Elena, Silva, Ana I., Sisodiya, Sanjay M., Stein, Frederike, Stein, Dan J., Straube, Benjamin, Streit, Fabian, Strike, Lachlan T., Teumer, Alexander, Teutenberg, Lea, Thalamuthu, Anbupalam, Tooney, Paul A., Tordesillas-Gutierrez, Diana, Trollor, Julian N., van ’t Ent, Dennis, van den Bree, Marianne B.M., van Haren, Neeltje E.M., Vázquez-Bourgon, Javier, Völzke, Henry, Wen, Wei, Wittfeld, Katharina, Ching, Christopher R.K., Westlye, Lars T., Thompson, Paul M., Bearden, Carrie E., Selmer, Kaja K., Alnæs, Dag, Andreassen, Ole A., Sønderby, Ida E., Boen, Rune, Kaufmann, Tobias, van der Meer, Dennis, Frei, Oleksandr, Agartz, Ingrid, Ames, David, Andersson, Micael, Armstrong, Nicola J., Artiges, Eric, Atkins, Joshua R., Bauer, Jochen, Benedetti, Francesco, Boomsma, Dorret I., Brodaty, Henry, Brosch, Katharina, Buckner, Randy L., Cairns, Murray J., Calhoun, Vince, Caspers, Svenja, Cichon, Sven, Corvin, Aiden P., Crespo-Facorro, Benedicto, Dannlowski, Udo, David, Friederike S., de Geus, Eco J.C., de Zubicaray, Greig I., Desrivières, Sylvane, Doherty, Joanne L., Donohoe, Gary, Ehrlich, Stefan, Eising, Else, Espeseth, Thomas, Fisher, Simon E., Forstner, Andreas J., Fortaner-Uyà, Lidia, Frouin, Vincent, Fukunaga, Masaki, Ge, Tian, Glahn, David C., Goltermann, Janik, Grabe, Hans J., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Grøntvedt, Gøril Rolfseng, Hahn, Tim, Hashimoto, Ryota, Hehir-Kwa, Jayne Y., Henskens, Frans A., Holmes, Avram J., Håberg, Asta K., Haavik, Jan, Jacquemont, Sebastien, Jansen, Andreas, Jockwitz, Christiane, Jönsson, Erik G., Kikuchi, Masataka, Kircher, Tilo, Kumar, Kuldeep, Le Hellard, Stephanie, Leu, Costin, Linden, David E., Liu, Jingyu, Loughnan, Robert, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Medland, Sarah E., Meinert, Susanne, Moreau, Clara A., Morris, Derek W., Mowry, Bryan J., Mühleisen, Thomas W., Nenadić, Igor, Nöthen, Markus M., Nyberg, Lars, Ophoff, Roel A., Owen, Michael J., Pantelis, Christos, Paolini, Marco, Paus, Tomas, Pausova, Zdenka, Persson, Karin, Quidé, Yann, Marques, Tiago Reis, Sachdev, Perminder S., Sando, Sigrid B., Schall, Ulrich, Scott, Rodney J., Selbæk, Geir, Shumskaya, Elena, Silva, Ana I., Sisodiya, Sanjay M., Stein, Frederike, Stein, Dan J., Straube, Benjamin, Streit, Fabian, Strike, Lachlan T., Teumer, Alexander, Teutenberg, Lea, Thalamuthu, Anbupalam, Tooney, Paul A., Tordesillas-Gutierrez, Diana, Trollor, Julian N., van ’t Ent, Dennis, van den Bree, Marianne B.M., van Haren, Neeltje E.M., Vázquez-Bourgon, Javier, Völzke, Henry, Wen, Wei, Wittfeld, Katharina, Ching, Christopher R.K., Westlye, Lars T., Thompson, Paul M., Bearden, Carrie E., Selmer, Kaja K., Alnæs, Dag, Andreassen, Ole A., and Sønderby, Ida E.
Abstract: Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference. Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
Published: 2024
Full Text: View/download PDF

4. Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study

Author: Georgiadis, Foivos; https://orcid.org/0000-0001-8784-9653, Larivière, Sara, Glahn, David, Hong, L Elliot, Kochunov, Peter, Mowry, Bryan; https://orcid.org/0000-0002-4115-5645, Loughland, Carmel, Pantelis, Christos; https://orcid.org/0000-0002-9565-0238, Henskens, Frans A; https://orcid.org/0000-0003-2358-5630, Green, Melissa J; https://orcid.org/0000-0002-9361-4874, Cairns, Murray J; https://orcid.org/0000-0003-2490-2538, Michie, Patricia T; https://orcid.org/0000-0002-4169-8519, Rasser, Paul E, Catts, Stanley, Tooney, Paul; https://orcid.org/0000-0003-3745-4367, Scott, Rodney J; https://orcid.org/0000-0001-7724-3404, Schall, Ulrich, Carr, Vaughan; https://orcid.org/0000-0002-8907-5804, Quidé, Yann; https://orcid.org/0000-0002-8569-7139, Krug, Axel; https://orcid.org/0000-0002-0564-2497, Stein, Frederike, Nenadić, Igor; https://orcid.org/0000-0002-0749-7473, Brosch, Katharina; https://orcid.org/0000-0002-0526-8095, Ji, Ellen; https://orcid.org/0000-0003-1527-8868, Homan, Stephanie; https://orcid.org/0000-0003-1449-7508, Omlor, Wolfgang, Homan, Philipp; https://orcid.org/0000-0001-9034-148X, Seifritz, Erich; https://orcid.org/0000-0002-7311-4426, ENIGMA Schizophrenia Consortium, Kirschner, Matthias; https://orcid.org/0000-0002-9486-1439, et al, Georgiadis, Foivos; https://orcid.org/0000-0001-8784-9653, Larivière, Sara, Glahn, David, Hong, L Elliot, Kochunov, Peter, Mowry, Bryan; https://orcid.org/0000-0002-4115-5645, Loughland, Carmel, Pantelis, Christos; https://orcid.org/0000-0002-9565-0238, Henskens, Frans A; https://orcid.org/0000-0003-2358-5630, Green, Melissa J; https://orcid.org/0000-0002-9361-4874, Cairns, Murray J; https://orcid.org/0000-0003-2490-2538, Michie, Patricia T; https://orcid.org/0000-0002-4169-8519, Rasser, Paul E, Catts, Stanley, Tooney, Paul; https://orcid.org/0000-0003-3745-4367, Scott, Rodney J; https://orcid.org/0000-0001-7724-3404, Schall, Ulrich, Carr, Vaughan; https://orcid.org/0000-0002-8907-5804, Quidé, Yann; https://orcid.org/0000-0002-8569-7139, Krug, Axel; https://orcid.org/0000-0002-0564-2497, Stein, Frederike, Nenadić, Igor; https://orcid.org/0000-0002-0749-7473, Brosch, Katharina; https://orcid.org/0000-0002-0526-8095, Ji, Ellen; https://orcid.org/0000-0003-1527-8868, Homan, Stephanie; https://orcid.org/0000-0003-1449-7508, Omlor, Wolfgang, Homan, Philipp; https://orcid.org/0000-0001-9034-148X, Seifritz, Erich; https://orcid.org/0000-0002-7311-4426, ENIGMA Schizophrenia Consortium, Kirschner, Matthias; https://orcid.org/0000-0002-9486-1439, and et al
Abstract: Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia's alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network ar
Published: 2024

5. Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis

Author: Haas, Shalaila S., Ge, Ruiyang, Agartz, Ingrid, Amminger, G. Paul, Andreassen, Ole A., Bachman, Peter, Baeza, Inmaculada, Choi, Sunah, Colibazzi, Tiziano, Cropley, Vanessa L., De La Fuente-Sandoval, Camilo, Ebdrup, Bjørn H., Fortea, Adriana, Fusar-Poli, Paolo, Glenthøj, Birte Yding, Glenthøj, Louise Birkedal, Haut, Kristen M., Hayes, Rebecca A., Heekeren, Karsten, Hooker, Christine I., Hwang, Wu Jeong, Jahanshad, Neda, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Koike, Shinsuke, Kristensen, Tina D., Kwon, Jun Soo, Lawrie, Stephen M., Lebedeva, Irina, Lee, Jimmy, Lemmers-Jansen, Imke L.J., Lin, Ashleigh, Ma, Xiaoqian, Mathalon, Daniel H., McGuire, Philip, Michel, Chantal, Mizrahi, Romina, Mizuno, Masafumi, Møller, Paul, Mora-Durán, Ricardo, Nelson, Barnaby, Nemoto, Takahiro, Nordentoft, Merete, Nordholm, Dorte, Omelchenko, Maria A., Pantelis, Christos, Pariente, Jose C., Raghava, Jayachandra M., Reyes-Madrigal, Francisco, Røssberg, Jan I., Rössler, Wulf, Salisbury, Dean F., Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K., Theodoridou, Anastasia, Thomopoulos, Sophia I., Thompson, Paul M., Tomyshev, Alexander S., Uhlhaas, Peter J., Værnes, Tor G., Van Amelsvoort, Therese A.M.J., Van Erp, Theo G.M., Waltz, James A., Wenneberg, Christina, Westlye, Lars T., Wood, Stephen J., Zhou, Juan H., Hernaus, Dennis, Jalbrzikowski, Maria, Kahn, René S., Corcoran, Cheryl M., Frangou, Sophia, Haas, Shalaila S., Ge, Ruiyang, Agartz, Ingrid, Amminger, G. Paul, Andreassen, Ole A., Bachman, Peter, Baeza, Inmaculada, Choi, Sunah, Colibazzi, Tiziano, Cropley, Vanessa L., De La Fuente-Sandoval, Camilo, Ebdrup, Bjørn H., Fortea, Adriana, Fusar-Poli, Paolo, Glenthøj, Birte Yding, Glenthøj, Louise Birkedal, Haut, Kristen M., Hayes, Rebecca A., Heekeren, Karsten, Hooker, Christine I., Hwang, Wu Jeong, Jahanshad, Neda, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Koike, Shinsuke, Kristensen, Tina D., Kwon, Jun Soo, Lawrie, Stephen M., Lebedeva, Irina, Lee, Jimmy, Lemmers-Jansen, Imke L.J., Lin, Ashleigh, Ma, Xiaoqian, Mathalon, Daniel H., McGuire, Philip, Michel, Chantal, Mizrahi, Romina, Mizuno, Masafumi, Møller, Paul, Mora-Durán, Ricardo, Nelson, Barnaby, Nemoto, Takahiro, Nordentoft, Merete, Nordholm, Dorte, Omelchenko, Maria A., Pantelis, Christos, Pariente, Jose C., Raghava, Jayachandra M., Reyes-Madrigal, Francisco, Røssberg, Jan I., Rössler, Wulf, Salisbury, Dean F., Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K., Theodoridou, Anastasia, Thomopoulos, Sophia I., Thompson, Paul M., Tomyshev, Alexander S., Uhlhaas, Peter J., Værnes, Tor G., Van Amelsvoort, Therese A.M.J., Van Erp, Theo G.M., Waltz, James A., Wenneberg, Christina, Westlye, Lars T., Wood, Stephen J., Zhou, Juan H., Hernaus, Dennis, Jalbrzikowski, Maria, Kahn, René S., Corcoran, Cheryl M., and Frangou, Sophia
Abstract: Question Are brain morphometric changes that deviate significantly from healthy variation associated with the risk of psychosis? Findings In this case-control study of 1340 individuals at clinical high risk for psychosis and 1237 healthy participants, individual-level variation in macroscale neuromorphometric measures in the group at clinical high risk for psychosis was largely nested within healthy variation and was not associated with the severity of positive symptoms or conversion to a psychotic disorder. Meaning The findings suggest the macroscale neuromorphometric measures have limited utility as diagnostic biomarkers of psychosis risk. Abstract Importance The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)–derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures For each regional morphometric measure, Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the
Published: 2024

6. Maternal inflammation during pregnancy is associated with risk of ADHD in children at age 10

Author: Rosenberg, Julie B., Richardt Møllegaard Jepsen, Jens, Mohammadzadeh, Parisa, Sevelsted, Astrid, Vinding, Rebecca, Sørensen, Mikkel E., Horner, David, Aagaard, Kristina, Fagerlund, Birgitte, Brix, Susanne, Følsgaard, Nilofar, Schoos, Ann-marie M., Stokholm, Jakob, Chawes, Bo, Pantelis, Christos, Dalsgaard, Søren, Glenthøj, Birte Y., Bilenberg, Niels, Bønnelykke, Klaus, Ebdrup, Bjørn H., Rosenberg, Julie B., Richardt Møllegaard Jepsen, Jens, Mohammadzadeh, Parisa, Sevelsted, Astrid, Vinding, Rebecca, Sørensen, Mikkel E., Horner, David, Aagaard, Kristina, Fagerlund, Birgitte, Brix, Susanne, Følsgaard, Nilofar, Schoos, Ann-marie M., Stokholm, Jakob, Chawes, Bo, Pantelis, Christos, Dalsgaard, Søren, Glenthøj, Birte Y., Bilenberg, Niels, Bønnelykke, Klaus, and Ebdrup, Bjørn H.
Published: 2024

7. Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis

Author: Haas, Shalaila S., Ge, Ruiyang, Agartz, Ingrid, Amminger, G. Paul, Andreassen, Ole A., Bachman, Peter, Baeza, Inmaculada, Choi, Sunah, Colibazzi, Tiziano, Cropley, Vanessa L., De La Fuente-Sandoval, Camilo, Ebdrup, Bjørn H., Fortea, Adriana, Fusar-Poli, Paolo, Glenthøj, Birte Yding, Glenthøj, Louise Birkedal, Haut, Kristen M., Hayes, Rebecca A., Heekeren, Karsten, Hooker, Christine I., Hwang, Wu Jeong, Jahanshad, Neda, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Koike, Shinsuke, Kristensen, Tina D., Kwon, Jun Soo, Lawrie, Stephen M., Lebedeva, Irina, Lee, Jimmy, Lemmers-Jansen, Imke L.J., Lin, Ashleigh, Ma, Xiaoqian, Mathalon, Daniel H., McGuire, Philip, Michel, Chantal, Mizrahi, Romina, Mizuno, Masafumi, Møller, Paul, Mora-Durán, Ricardo, Nelson, Barnaby, Nemoto, Takahiro, Nordentoft, Merete, Nordholm, Dorte, Omelchenko, Maria A., Pantelis, Christos, Pariente, Jose C., Raghava, Jayachandra M., Reyes-Madrigal, Francisco, Røssberg, Jan I., Rössler, Wulf, Salisbury, Dean F., Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K., Theodoridou, Anastasia, Thomopoulos, Sophia I., Thompson, Paul M., Tomyshev, Alexander S., Uhlhaas, Peter J., Værnes, Tor G., Van Amelsvoort, Therese A.M.J., Van Erp, Theo G.M., Waltz, James A., Wenneberg, Christina, Westlye, Lars T., Wood, Stephen J., Zhou, Juan H., Hernaus, Dennis, Jalbrzikowski, Maria, Kahn, René S., Corcoran, Cheryl M., Frangou, Sophia, Haas, Shalaila S., Ge, Ruiyang, Agartz, Ingrid, Amminger, G. Paul, Andreassen, Ole A., Bachman, Peter, Baeza, Inmaculada, Choi, Sunah, Colibazzi, Tiziano, Cropley, Vanessa L., De La Fuente-Sandoval, Camilo, Ebdrup, Bjørn H., Fortea, Adriana, Fusar-Poli, Paolo, Glenthøj, Birte Yding, Glenthøj, Louise Birkedal, Haut, Kristen M., Hayes, Rebecca A., Heekeren, Karsten, Hooker, Christine I., Hwang, Wu Jeong, Jahanshad, Neda, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Koike, Shinsuke, Kristensen, Tina D., Kwon, Jun Soo, Lawrie, Stephen M., Lebedeva, Irina, Lee, Jimmy, Lemmers-Jansen, Imke L.J., Lin, Ashleigh, Ma, Xiaoqian, Mathalon, Daniel H., McGuire, Philip, Michel, Chantal, Mizrahi, Romina, Mizuno, Masafumi, Møller, Paul, Mora-Durán, Ricardo, Nelson, Barnaby, Nemoto, Takahiro, Nordentoft, Merete, Nordholm, Dorte, Omelchenko, Maria A., Pantelis, Christos, Pariente, Jose C., Raghava, Jayachandra M., Reyes-Madrigal, Francisco, Røssberg, Jan I., Rössler, Wulf, Salisbury, Dean F., Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K., Theodoridou, Anastasia, Thomopoulos, Sophia I., Thompson, Paul M., Tomyshev, Alexander S., Uhlhaas, Peter J., Værnes, Tor G., Van Amelsvoort, Therese A.M.J., Van Erp, Theo G.M., Waltz, James A., Wenneberg, Christina, Westlye, Lars T., Wood, Stephen J., Zhou, Juan H., Hernaus, Dennis, Jalbrzikowski, Maria, Kahn, René S., Corcoran, Cheryl M., and Frangou, Sophia
Abstract: Question Are brain morphometric changes that deviate significantly from healthy variation associated with the risk of psychosis? Findings In this case-control study of 1340 individuals at clinical high risk for psychosis and 1237 healthy participants, individual-level variation in macroscale neuromorphometric measures in the group at clinical high risk for psychosis was largely nested within healthy variation and was not associated with the severity of positive symptoms or conversion to a psychotic disorder. Meaning The findings suggest the macroscale neuromorphometric measures have limited utility as diagnostic biomarkers of psychosis risk. Abstract Importance The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)–derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures For each regional morphometric measure, Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the
Published: 2024

8. Fine-mapping genomic loci refines bipolar disorder risk genes

Author: Koromina, Maria, Ravi, Ashvin, Panagiotaropoulou, Georgia, Schilder, Brian M., Humphrey, Jack, Braun, Alice, Bidgeli, Tim, Chatzinakos, Chris, Coombes, Brandon, Kim, Jaeyoung, Liu, Xiaoxi, Terao, Chikashi, O'Connell, Kevin S., Adams, Mark, Adolfsson, Rolf, Alda, Martin, Alfredsson, Lars, Andlauer, Till, Andreassen, Ole A., Antoniou, Anastasia, Baune, Bernhard T., Bengesser, Susanne, Biernacka, Joanna, Boehnke, Michael, Bosch, Rosa, Cairns, Murray, Carr, Vaughan J., Casas Brugué, Miquel, Catts, Stanley, Cichon, Sven, Corvin, Aiden, Craddock, Nicholas, Dafnas, Konstantinos, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, Di Florio, Arianna, Dikeos, Dimitris, Fellendorf, Frederike Tabea, Ferentinos, Panagiotis, Forstner, Andreas Josef, Forty, Liz, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gizer, Ian R., Gordon-Smith, Katherine, Green, Melissa J., Grigoroiu-Serbanescu, Maria, Guzman-Parra, José, Hahn, Tim, Henskens, Frans, Hillert, Jan, Jablensky, Assen V., Jones, Lisa, Jones, Ian, Jonsson, Lina, Kelsoe, John R., Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Kogevinas, Manolis, Landén, Mikael, Leboyer, Marion, Lenger, Melanie, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, MacIntyre, Donald, Martin, Nicholas G., Maratou, Eirini, Mathews, Carol A., Mayoral, Fermı́n, McElroy, Susan L., McGregor, Nathaniel W., McIntosh, Andrew M., McQuillin, Andrew, Michie, Patricia, Milanova, Vihra, Mitchell, Philip B., Moutsatsou, Paraskevi, Mowry, Bryan, Müller-Myhsok, Bertram, Myers, Richard M., Nenadić, Igor, Nöthen, Markus Maria, O'Donovan, Claire, O'Donovan, Michael, Ophoff, Roel André, Owen, Michael J., Pantelis, Christos, Pato, Carlos, Pato, Michele T., Patrinos, George P., Pawlak, Joanna M., Perlis, Roy H., Porichi, Evgenia, Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rietschel, Marcella, Schall, Ulrich, Schulze, Thomas Gerd, Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Shannon Weickert, Cynthia, Smoller, Jordan W., Soler Artigas, Marı́a, Stein, Dan J., Streit, Fabian, Toma, Claudio, Tooney, Paul, Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas, Witt, Stephanie H., Hong, Kyung Sue, Ikeda, Masashi, Iwata, Nakao, Świątkowska, Beata, Won, Hong-Hee, Edenberg, Howard J., Ripke, Stephan, Raj, Towfique, Coleman, Jonathan R. I., Mullins, Niamh, Koromina, Maria, Ravi, Ashvin, Panagiotaropoulou, Georgia, Schilder, Brian M., Humphrey, Jack, Braun, Alice, Bidgeli, Tim, Chatzinakos, Chris, Coombes, Brandon, Kim, Jaeyoung, Liu, Xiaoxi, Terao, Chikashi, O'Connell, Kevin S., Adams, Mark, Adolfsson, Rolf, Alda, Martin, Alfredsson, Lars, Andlauer, Till, Andreassen, Ole A., Antoniou, Anastasia, Baune, Bernhard T., Bengesser, Susanne, Biernacka, Joanna, Boehnke, Michael, Bosch, Rosa, Cairns, Murray, Carr, Vaughan J., Casas Brugué, Miquel, Catts, Stanley, Cichon, Sven, Corvin, Aiden, Craddock, Nicholas, Dafnas, Konstantinos, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, Di Florio, Arianna, Dikeos, Dimitris, Fellendorf, Frederike Tabea, Ferentinos, Panagiotis, Forstner, Andreas Josef, Forty, Liz, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gizer, Ian R., Gordon-Smith, Katherine, Green, Melissa J., Grigoroiu-Serbanescu, Maria, Guzman-Parra, José, Hahn, Tim, Henskens, Frans, Hillert, Jan, Jablensky, Assen V., Jones, Lisa, Jones, Ian, Jonsson, Lina, Kelsoe, John R., Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Kogevinas, Manolis, Landén, Mikael, Leboyer, Marion, Lenger, Melanie, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, MacIntyre, Donald, Martin, Nicholas G., Maratou, Eirini, Mathews, Carol A., Mayoral, Fermı́n, McElroy, Susan L., McGregor, Nathaniel W., McIntosh, Andrew M., McQuillin, Andrew, Michie, Patricia, Milanova, Vihra, Mitchell, Philip B., Moutsatsou, Paraskevi, Mowry, Bryan, Müller-Myhsok, Bertram, Myers, Richard M., Nenadić, Igor, Nöthen, Markus Maria, O'Donovan, Claire, O'Donovan, Michael, Ophoff, Roel André, Owen, Michael J., Pantelis, Christos, Pato, Carlos, Pato, Michele T., Patrinos, George P., Pawlak, Joanna M., Perlis, Roy H., Porichi, Evgenia, Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rietschel, Marcella, Schall, Ulrich, Schulze, Thomas Gerd, Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Shannon Weickert, Cynthia, Smoller, Jordan W., Soler Artigas, Marı́a, Stein, Dan J., Streit, Fabian, Toma, Claudio, Tooney, Paul, Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas, Witt, Stephanie H., Hong, Kyung Sue, Ikeda, Masashi, Iwata, Nakao, Świątkowska, Beata, Won, Hong-Hee, Edenberg, Howard J., Ripke, Stephan, Raj, Towfique, Coleman, Jonathan R. I., and Mullins, Niamh
Abstract: Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).
Published: 2024

9. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author: Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., Francks, Clyde, Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., and Francks, Clyde
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023
Full Text: View/download PDF

10. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author: Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., Francks, Clyde, Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., and Francks, Clyde
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023
Full Text: View/download PDF

11. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author: Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., Francks, Clyde, Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., and Francks, Clyde
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023
Full Text: View/download PDF

12. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Author: Schijven, Dick, Schijven, Dick, Postema, Merel C, Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja MC, van Haren, Neeltje EM, Cahn, Wiepke, Hulshoff Pol, Hilleke E, Kahn, René S, Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T, Agartz, Ingrid, Andreassen, Ole A, Jönsson, Erik G, Kochunov, Peter, Bruggemann, Jason M, Catts, Stanley V, Michie, Patricia T, Mowry, Bryan J, Quidé, Yann, Rasser, Paul E, Schall, Ulrich, Scott, Rodney J, Carr, Vaughan J, Green, Melissa J, Henskens, Frans A, Loughland, Carmel M, Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W, de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G, Stein, Frederike, Jansen, Andreas, Kircher, Tilo TJ, Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D, Bustillo, Juan, Mathalon, Daniel H, Preda, Adrian, Calhoun, Vince D, Ford, Judith M, Potkin, Steven G, Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W, Voineskos, Aristotle N, Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M, Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M, Whalley, Heather C, Lawrie, Stephen M, du Plessis, Stefan, Luckhoff, Hilmar K, Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T, Rootes-Murdy, Kelly, Stephen, Julia M, Mayer, Andrew R, Antonucci, Linda A, Schijven, Dick, Schijven, Dick, Postema, Merel C, Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja MC, van Haren, Neeltje EM, Cahn, Wiepke, Hulshoff Pol, Hilleke E, Kahn, René S, Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T, Agartz, Ingrid, Andreassen, Ole A, Jönsson, Erik G, Kochunov, Peter, Bruggemann, Jason M, Catts, Stanley V, Michie, Patricia T, Mowry, Bryan J, Quidé, Yann, Rasser, Paul E, Schall, Ulrich, Scott, Rodney J, Carr, Vaughan J, Green, Melissa J, Henskens, Frans A, Loughland, Carmel M, Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W, de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G, Stein, Frederike, Jansen, Andreas, Kircher, Tilo TJ, Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D, Bustillo, Juan, Mathalon, Daniel H, Preda, Adrian, Calhoun, Vince D, Ford, Judith M, Potkin, Steven G, Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W, Voineskos, Aristotle N, Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M, Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M, Whalley, Heather C, Lawrie, Stephen M, du Plessis, Stefan, Luckhoff, Hilmar K, Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T, Rootes-Murdy, Kelly, Stephen, Julia M, Mayer, Andrew R, and Antonucci, Linda A
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023

13. Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.

Author: Constantinides, Constantinos, Constantinides, Constantinos, Han, Laura KM, Alloza, Clara, Antonucci, Linda Antonella, Arango, Celso, Ayesa-Arriola, Rosa, Banaj, Nerisa, Bertolino, Alessandro, Borgwardt, Stefan, Bruggemann, Jason, Bustillo, Juan, Bykhovski, Oleg, Calhoun, Vince, Carr, Vaughan, Catts, Stanley, Chung, Young-Chul, Crespo-Facorro, Benedicto, Díaz-Caneja, Covadonga M, Donohoe, Gary, Plessis, Stefan Du, Edmond, Jesse, Ehrlich, Stefan, Emsley, Robin, Eyler, Lisa T, Fuentes-Claramonte, Paola, Georgiadis, Foivos, Green, Melissa, Guerrero-Pedraza, Amalia, Ha, Minji, Hahn, Tim, Henskens, Frans A, Holleran, Laurena, Homan, Stephanie, Homan, Philipp, Jahanshad, Neda, Janssen, Joost, Ji, Ellen, Kaiser, Stefan, Kaleda, Vasily, Kim, Minah, Kim, Woo-Sung, Kirschner, Matthias, Kochunov, Peter, Kwak, Yoo Bin, Kwon, Jun Soo, Lebedeva, Irina, Liu, Jingyu, Mitchie, Patricia, Michielse, Stijn, Mothersill, David, Mowry, Bryan, de la Foz, Víctor Ortiz-García, Pantelis, Christos, Pergola, Giulio, Piras, Fabrizio, Pomarol-Clotet, Edith, Preda, Adrian, Quidé, Yann, Rasser, Paul E, Rootes-Murdy, Kelly, Salvador, Raymond, Sangiuliano, Marina, Sarró, Salvador, Schall, Ulrich, Schmidt, André, Scott, Rodney J, Selvaggi, Pierluigi, Sim, Kang, Skoch, Antonin, Spalletta, Gianfranco, Spaniel, Filip, Thomopoulos, Sophia I, Tomecek, David, Tomyshev, Alexander S, Tordesillas-Gutiérrez, Diana, van Amelsvoort, Therese, Vázquez-Bourgon, Javier, Vecchio, Daniela, Voineskos, Aristotle, Weickert, Cynthia S, Weickert, Thomas, Thompson, Paul M, Schmaal, Lianne, van Erp, Theo GM, Turner, Jessica, Cole, James H, ENIGMA Schizophrenia Consortium, Dima, Danai, Walton, Esther, Constantinides, Constantinos, Constantinides, Constantinos, Han, Laura KM, Alloza, Clara, Antonucci, Linda Antonella, Arango, Celso, Ayesa-Arriola, Rosa, Banaj, Nerisa, Bertolino, Alessandro, Borgwardt, Stefan, Bruggemann, Jason, Bustillo, Juan, Bykhovski, Oleg, Calhoun, Vince, Carr, Vaughan, Catts, Stanley, Chung, Young-Chul, Crespo-Facorro, Benedicto, Díaz-Caneja, Covadonga M, Donohoe, Gary, Plessis, Stefan Du, Edmond, Jesse, Ehrlich, Stefan, Emsley, Robin, Eyler, Lisa T, Fuentes-Claramonte, Paola, Georgiadis, Foivos, Green, Melissa, Guerrero-Pedraza, Amalia, Ha, Minji, Hahn, Tim, Henskens, Frans A, Holleran, Laurena, Homan, Stephanie, Homan, Philipp, Jahanshad, Neda, Janssen, Joost, Ji, Ellen, Kaiser, Stefan, Kaleda, Vasily, Kim, Minah, Kim, Woo-Sung, Kirschner, Matthias, Kochunov, Peter, Kwak, Yoo Bin, Kwon, Jun Soo, Lebedeva, Irina, Liu, Jingyu, Mitchie, Patricia, Michielse, Stijn, Mothersill, David, Mowry, Bryan, de la Foz, Víctor Ortiz-García, Pantelis, Christos, Pergola, Giulio, Piras, Fabrizio, Pomarol-Clotet, Edith, Preda, Adrian, Quidé, Yann, Rasser, Paul E, Rootes-Murdy, Kelly, Salvador, Raymond, Sangiuliano, Marina, Sarró, Salvador, Schall, Ulrich, Schmidt, André, Scott, Rodney J, Selvaggi, Pierluigi, Sim, Kang, Skoch, Antonin, Spalletta, Gianfranco, Spaniel, Filip, Thomopoulos, Sophia I, Tomecek, David, Tomyshev, Alexander S, Tordesillas-Gutiérrez, Diana, van Amelsvoort, Therese, Vázquez-Bourgon, Javier, Vecchio, Daniela, Voineskos, Aristotle, Weickert, Cynthia S, Weickert, Thomas, Thompson, Paul M, Schmaal, Lianne, van Erp, Theo GM, Turner, Jessica, Cole, James H, ENIGMA Schizophrenia Consortium, Dima, Danai, and Walton, Esther
Abstract: Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.
Published: 2023

14. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author: Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., Francks, Clyde, Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., and Francks, Clyde
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023
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15. The heterogeneity of attenuated and brief limited psychotic symptoms::association of contents with age, sex, country, religion, comorbidities, and functioning

Author: Theisen, Christian, Rosen, Marlene, Meisenzahl, Eva, Koutsouleris, Nikolaos, Lichtenstein, Theresa, Ruhrmann, Stephan, Kambeitz, Joseph, Kambeitz-Ilankovic, Lana, Riecher-Rössler, Anita, Chisholm, Katharine, Upthegrove, Rachel, Antonucci, Linda A., Bertolino, Alessandro, Pigoni, Alessandro, Salokangas, Raimo K. R., Pantelis, Christos, Wood, Stephen J., Lencer, Rebekka, Falkai, Peter, Hietala, Jarmo, Brambilla, Paolo, Schmidt, André, Andreou, Christina, Borgwardt, Stefan, Osman, Naweed, Schultze-Lutter, Frauke, Theisen, Christian, Rosen, Marlene, Meisenzahl, Eva, Koutsouleris, Nikolaos, Lichtenstein, Theresa, Ruhrmann, Stephan, Kambeitz, Joseph, Kambeitz-Ilankovic, Lana, Riecher-Rössler, Anita, Chisholm, Katharine, Upthegrove, Rachel, Antonucci, Linda A., Bertolino, Alessandro, Pigoni, Alessandro, Salokangas, Raimo K. R., Pantelis, Christos, Wood, Stephen J., Lencer, Rebekka, Falkai, Peter, Hietala, Jarmo, Brambilla, Paolo, Schmidt, André, Andreou, Christina, Borgwardt, Stefan, Osman, Naweed, and Schultze-Lutter, Frauke
Abstract: Introduction: The Attenuated Psychosis Symptoms (APS) syndrome mostly represents the ultra-high-risk state of psychosis but, as does the Brief Intermittent Psychotic Symptoms (BIPS) syndrome, shows a large variance in conversion rates. This may be due to the heterogeneity of APS/BIPS that may be related to the effects of culture, sex, age, and other psychiatric morbidities. Thus, we investigated the different thematic contents of APS and their association with sex, age, country, religion, comorbidity, and functioning to gain a better understanding of the psychosis-risk syndrome. Method: A sample of 232 clinical high-risk subjects according to the ultra-high risk and basic symptom criteria was recruited as part of a European study conducted in Germany, Italy, Switzerland, and Finland. Case vignettes, originally used for supervision of inclusion criteria, were investigated for APS/BIPS contents, which were compared for sex, age, country, religion, functioning, and comorbidities using chi-squared tests and regression analyses. Result: We extracted 109 different contents, mainly of APS (96.8%): 63 delusional, 29 hallucinatory, and 17 speech-disorganized contents. Only 20 contents (18.3%) were present in at least 5% of the sample, with paranoid and referential ideas being the most frequent. Thirty-one (28.5%) contents, in particular, bizarre ideas and perceptual abnormalities, demonstrated an association with age, country, comorbidity, or functioning, with regression models of country and obsessive-compulsive disorders explaining most of the variance: 55.8 and 38.3%, respectively. Contents did not differ between religious groups. Conclusion: Psychosis-risk patients report a wide range of different contents of APS/BIPS, underlining the psychopathological heterogeneity of this group but also revealing a potential core set of contents. Compared to earlier reports on North-American samples, our maximum prevalence rates of contents were considerably lower; this likely being r
Published: 2023

16. Midline brain structures in adult niemann-pick type c disease: A cross-sectional study

Author: Walterfang, Mark, Takahashi, Tsutomu, Di Biase, Maria A., Cropley, Vanessa L., Sasabayashi, Daiki, Suzuki, Michio, Velakoulis, Dennis, Pantelis, Christos, Walterfang, Mark, Takahashi, Tsutomu, Di Biase, Maria A., Cropley, Vanessa L., Sasabayashi, Daiki, Suzuki, Michio, Velakoulis, Dennis, and Pantelis, Christos
Abstract: Objective: A range of neuropathological changes occur in the brains of individuals with adult Niemann-Pick type C disease (NPC), a recessive disorder of cholesterol trafficking that results in accumulation of cholesterol and gangliosides in lysosomes, particularly in neurons. One of the most significant regions of grey matter loss occurs in the thalami, which abut the midline. What is not known is whether these are neurodevelopmental in origin well prior to symptomatic onset. We aimed to examine other markers of midline developmental anomalies in adults with NPC. Method: We examined the size of adhesio interthalamica (AI) and cavum septum pellucidum (CSP) (if present) in nine individuals diagnosed with NPC and nine healthy comparison subjects, matched for age and gender, using a 3T magnetic resonance volumetric sequence and measured the length of the AI and CSP in mm. Results: We found that 5/9 NPC patients and 0/9 controls had a missing AI. AI length was significantly shorter in the patient group. No subject in other group had a large CSP, and CSP length did not differ. Duration of illness showed a trend to a negative correlation with AI length in patients. Conclusions: Our findings suggest that adult NPC patients show some markers of early neurodevelopmental disturbance, matching findings seen in psychotic disorders. The differences in AI, but not CSP, suggest neurodevelopmental change may occur early in gestation rather than post-partum. The relationship with duration of illness suggests that there may be atrophy over time in these structures, consistent with prior analyses of grey matter regions in NPC.
Published: 2023

17. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author: Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., Francks, Clyde, Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., and Francks, Clyde
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023
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18. Structural and functional brain patterns predict formal thought disorder’s severity and its persistence in recent-onset psychosis:Results from the PRONIA Study

Author: Buciuman, Madalina-Octavia, Oeztuerk, Oemer Faruk, Popovic, David, Enrico, Paolo, Ruef, Anne, Bieler, Nadia, Sarisik, Elif, Weiske, Johanna, Dong, Mark Sen, Dwyer, Dominic B., Kambeitz-Ilankovic, Lana, Haas, Shalaila S., Stainton, Alexandra, Ruhrmann, Stephan, Chisholm, Katharine, Kambeitz, Joseph, Riecher-Rössler, Anita, Upthegrove, Rachel, Schultze-Lutter, Frauke, Salokangas, Raimo K.R., Hietala, Jarmo, Pantelis, Christos, Lencer, Rebekka, Meisenzahl, Eva, Wood, Stephen J., Brambilla, Paolo, Borgwardt, Stefan, Falkai, Peter, Antonucci, Linda A., Bertolino, Alessandro, Liddle, Peter, Koutsouleris, Nikolaos, Buciuman, Madalina-Octavia, Oeztuerk, Oemer Faruk, Popovic, David, Enrico, Paolo, Ruef, Anne, Bieler, Nadia, Sarisik, Elif, Weiske, Johanna, Dong, Mark Sen, Dwyer, Dominic B., Kambeitz-Ilankovic, Lana, Haas, Shalaila S., Stainton, Alexandra, Ruhrmann, Stephan, Chisholm, Katharine, Kambeitz, Joseph, Riecher-Rössler, Anita, Upthegrove, Rachel, Schultze-Lutter, Frauke, Salokangas, Raimo K.R., Hietala, Jarmo, Pantelis, Christos, Lencer, Rebekka, Meisenzahl, Eva, Wood, Stephen J., Brambilla, Paolo, Borgwardt, Stefan, Falkai, Peter, Antonucci, Linda A., Bertolino, Alessandro, Liddle, Peter, and Koutsouleris, Nikolaos
Abstract: Background: Formal thought disorder (FThD) is a core feature of psychosis, and its severity and long-term persistence relates to poor clinical outcomes. However, advances in developing early recognition and management tools for FThD are hindered by a lack of insight into the brain-level predictors of FThD states and progression at the individual level. Methods: Two hundred thirty-three individuals with recent-onset psychosis were drawn from the multisite European Prognostic Tools for Early Psychosis Management study. Support vector machine classifiers were trained within a cross-validation framework to separate two FThD symptom-based subgroups (high vs. low FThD severity), using cross-sectional whole-brain multiband fractional amplitude of low frequency fluctuations, gray matter volume and white matter volume data. Moreover, we trained machine learning models on these neuroimaging readouts to predict the persistence of high FThD subgroup membership from baseline to 1-year follow-up. Results: Cross-sectionally, multivariate patterns of gray matter volume within the salience, dorsal attention, visual, and ventral attention networks separated the FThD severity subgroups (balanced accuracy [BAC] = 60.8%). Longitudinally, distributed activations/deactivations within all fractional amplitude of low frequency fluctuation sub-bands (BAC slow-5 = 73.2%, BAC slow-4 = 72.9%, BAC slow-3 = 68.0%), gray matter volume patterns overlapping with the cross-sectional ones (BAC = 62.7%), and smaller frontal white matter volume (BAC = 73.1%) predicted the persistence of high FThD severity from baseline to follow-up, with a combined multimodal balanced accuracy of BAC = 77%. Conclusions: We report the first evidence of brain structural and functional patterns predictive of FThD severity and persistence in early psychosis. These findings open up avenues for the development of neuroimaging-based diagnostic, prognostic, and treatment options for the early recognition and management of FThD
Published: 2023

19. Structural and functional brain patterns predict formal thought disorder’s severity and its persistence in recent-onset psychosis:Results from the PRONIA Study

Author: Buciuman, Madalina-Octavia, Oeztuerk, Oemer Faruk, Popovic, David, Enrico, Paolo, Ruef, Anne, Bieler, Nadia, Sarisik, Elif, Weiske, Johanna, Dong, Mark Sen, Dwyer, Dominic B., Kambeitz-Ilankovic, Lana, Haas, Shalaila S., Stainton, Alexandra, Ruhrmann, Stephan, Chisholm, Katharine, Kambeitz, Joseph, Riecher-Rössler, Anita, Upthegrove, Rachel, Schultze-Lutter, Frauke, Salokangas, Raimo K.R., Hietala, Jarmo, Pantelis, Christos, Lencer, Rebekka, Meisenzahl, Eva, Wood, Stephen J., Brambilla, Paolo, Borgwardt, Stefan, Falkai, Peter, Antonucci, Linda A., Bertolino, Alessandro, Liddle, Peter, Koutsouleris, Nikolaos, Buciuman, Madalina-Octavia, Oeztuerk, Oemer Faruk, Popovic, David, Enrico, Paolo, Ruef, Anne, Bieler, Nadia, Sarisik, Elif, Weiske, Johanna, Dong, Mark Sen, Dwyer, Dominic B., Kambeitz-Ilankovic, Lana, Haas, Shalaila S., Stainton, Alexandra, Ruhrmann, Stephan, Chisholm, Katharine, Kambeitz, Joseph, Riecher-Rössler, Anita, Upthegrove, Rachel, Schultze-Lutter, Frauke, Salokangas, Raimo K.R., Hietala, Jarmo, Pantelis, Christos, Lencer, Rebekka, Meisenzahl, Eva, Wood, Stephen J., Brambilla, Paolo, Borgwardt, Stefan, Falkai, Peter, Antonucci, Linda A., Bertolino, Alessandro, Liddle, Peter, and Koutsouleris, Nikolaos
Abstract: Background: Formal thought disorder (FThD) is a core feature of psychosis, and its severity and long-term persistence relates to poor clinical outcomes. However, advances in developing early recognition and management tools for FThD are hindered by a lack of insight into the brain-level predictors of FThD states and progression at the individual level. Methods: Two hundred thirty-three individuals with recent-onset psychosis were drawn from the multisite European Prognostic Tools for Early Psychosis Management study. Support vector machine classifiers were trained within a cross-validation framework to separate two FThD symptom-based subgroups (high vs. low FThD severity), using cross-sectional whole-brain multiband fractional amplitude of low frequency fluctuations, gray matter volume and white matter volume data. Moreover, we trained machine learning models on these neuroimaging readouts to predict the persistence of high FThD subgroup membership from baseline to 1-year follow-up. Results: Cross-sectionally, multivariate patterns of gray matter volume within the salience, dorsal attention, visual, and ventral attention networks separated the FThD severity subgroups (balanced accuracy [BAC] = 60.8%). Longitudinally, distributed activations/deactivations within all fractional amplitude of low frequency fluctuation sub-bands (BAC slow-5 = 73.2%, BAC slow-4 = 72.9%, BAC slow-3 = 68.0%), gray matter volume patterns overlapping with the cross-sectional ones (BAC = 62.7%), and smaller frontal white matter volume (BAC = 73.1%) predicted the persistence of high FThD severity from baseline to follow-up, with a combined multimodal balanced accuracy of BAC = 77%. Conclusions: We report the first evidence of brain structural and functional patterns predictive of FThD severity and persistence in early psychosis. These findings open up avenues for the development of neuroimaging-based diagnostic, prognostic, and treatment options for the early recognition and management of FThD
Published: 2023

20. The heterogeneity of attenuated and brief limited psychotic symptoms::association of contents with age, sex, country, religion, comorbidities, and functioning

Author: Theisen, Christian, Rosen, Marlene, Meisenzahl, Eva, Koutsouleris, Nikolaos, Lichtenstein, Theresa, Ruhrmann, Stephan, Kambeitz, Joseph, Kambeitz-Ilankovic, Lana, Riecher-Rössler, Anita, Chisholm, Katharine, Upthegrove, Rachel, Antonucci, Linda A., Bertolino, Alessandro, Pigoni, Alessandro, Salokangas, Raimo K. R., Pantelis, Christos, Wood, Stephen J., Lencer, Rebekka, Falkai, Peter, Hietala, Jarmo, Brambilla, Paolo, Schmidt, André, Andreou, Christina, Borgwardt, Stefan, Osman, Naweed, Schultze-Lutter, Frauke, Theisen, Christian, Rosen, Marlene, Meisenzahl, Eva, Koutsouleris, Nikolaos, Lichtenstein, Theresa, Ruhrmann, Stephan, Kambeitz, Joseph, Kambeitz-Ilankovic, Lana, Riecher-Rössler, Anita, Chisholm, Katharine, Upthegrove, Rachel, Antonucci, Linda A., Bertolino, Alessandro, Pigoni, Alessandro, Salokangas, Raimo K. R., Pantelis, Christos, Wood, Stephen J., Lencer, Rebekka, Falkai, Peter, Hietala, Jarmo, Brambilla, Paolo, Schmidt, André, Andreou, Christina, Borgwardt, Stefan, Osman, Naweed, and Schultze-Lutter, Frauke
Abstract: Introduction: The Attenuated Psychosis Symptoms (APS) syndrome mostly represents the ultra-high-risk state of psychosis but, as does the Brief Intermittent Psychotic Symptoms (BIPS) syndrome, shows a large variance in conversion rates. This may be due to the heterogeneity of APS/BIPS that may be related to the effects of culture, sex, age, and other psychiatric morbidities. Thus, we investigated the different thematic contents of APS and their association with sex, age, country, religion, comorbidity, and functioning to gain a better understanding of the psychosis-risk syndrome. Method: A sample of 232 clinical high-risk subjects according to the ultra-high risk and basic symptom criteria was recruited as part of a European study conducted in Germany, Italy, Switzerland, and Finland. Case vignettes, originally used for supervision of inclusion criteria, were investigated for APS/BIPS contents, which were compared for sex, age, country, religion, functioning, and comorbidities using chi-squared tests and regression analyses. Result: We extracted 109 different contents, mainly of APS (96.8%): 63 delusional, 29 hallucinatory, and 17 speech-disorganized contents. Only 20 contents (18.3%) were present in at least 5% of the sample, with paranoid and referential ideas being the most frequent. Thirty-one (28.5%) contents, in particular, bizarre ideas and perceptual abnormalities, demonstrated an association with age, country, comorbidity, or functioning, with regression models of country and obsessive-compulsive disorders explaining most of the variance: 55.8 and 38.3%, respectively. Contents did not differ between religious groups. Conclusion: Psychosis-risk patients report a wide range of different contents of APS/BIPS, underlining the psychopathological heterogeneity of this group but also revealing a potential core set of contents. Compared to earlier reports on North-American samples, our maximum prevalence rates of contents were considerably lower; this likely being r
Published: 2023

21. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author: Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M.C., van Haren, Neeltje E.M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T.J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo Sung, Chung, Young Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Luders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G.M., Francks, Clyde, Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M.C., van Haren, Neeltje E.M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T.J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo Sung, Chung, Young Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Luders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G.M., and Francks, Clyde
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023

22. Extreme deviations from the normative model reveal cortical heterogeneity and associations with negative symptom severity in first-episode psychosis from the OPTiMiSE and GAP studies

Author: Onderzoeksgroep 1, Onderzoeksgroep 11, Brain, Onderzoeksgroep 9, Worker, Amanda, Berthert, Pierre, Lawrence, Andrew J., Kia, Seyed Mostafa, Arango, Celso, Dinga, Richard, Galderisi, Silvana, Glenthøj, Birte, Kahn, René S., Leslie, Anoushka, Murray, Robin M., Pariante, Carmine M., Pantelis, Christos, Weiser, Mark, Winter-van Rossum, Inge, McGuire, Philip, Dazzan, Paola, Marquand, Andre F., Onderzoeksgroep 1, Onderzoeksgroep 11, Brain, Onderzoeksgroep 9, Worker, Amanda, Berthert, Pierre, Lawrence, Andrew J., Kia, Seyed Mostafa, Arango, Celso, Dinga, Richard, Galderisi, Silvana, Glenthøj, Birte, Kahn, René S., Leslie, Anoushka, Murray, Robin M., Pariante, Carmine M., Pantelis, Christos, Weiser, Mark, Winter-van Rossum, Inge, McGuire, Philip, Dazzan, Paola, and Marquand, Andre F.
Published: 2023

23. Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium

Author: Onderzoek, Brain, Dwyer, Dominic B, Chand, Ganesh B, Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S, Schnack, Hugo G, Meisenzahl, Eva, Wood, Stephen J, Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A, Upthegrove, Rachel, Kaczkurkin, Antonia N, Moore, Tyler M, Nelson, Barnaby, Gur, Raquel E, Gur, Ruben C, Ritchie, Marylyn D, Satterthwaite, Theodore D, Murray, Robin M, Di Forti, Marta, Ciufolini, Simone, Zanetti, Marcus V, Wolf, Daniel H, Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F, Davatzikos, Christos, Koutsouleris, Nikolaos, Dazzan, Paola, Onderzoek, Brain, Dwyer, Dominic B, Chand, Ganesh B, Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S, Schnack, Hugo G, Meisenzahl, Eva, Wood, Stephen J, Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A, Upthegrove, Rachel, Kaczkurkin, Antonia N, Moore, Tyler M, Nelson, Barnaby, Gur, Raquel E, Gur, Ruben C, Ritchie, Marylyn D, Satterthwaite, Theodore D, Murray, Robin M, Di Forti, Marta, Ciufolini, Simone, Zanetti, Marcus V, Wolf, Daniel H, Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F, Davatzikos, Christos, Koutsouleris, Nikolaos, and Dazzan, Paola
Published: 2023

24. Assessment of Neuroanatomical Endophenotypes of Autism Spectrum Disorder and Association With Characteristics of Individuals With Schizophrenia and the General Population

Author: Onderzoek, Brain, Hwang, Gyujoon, Wen, Junhao, Sotardi, Susan, Brodkin, Edward S, Chand, Ganesh B, Dwyer, Dominic B, Erus, Guray, Doshi, Jimit, Singhal, Pankhuri, Srinivasan, Dhivya, Varol, Erdem, Sotiras, Aristeidis, Dazzan, Paola, Kahn, Rene S, Schnack, Hugo G, Zanetti, Marcus V, Meisenzahl, Eva, Busatto, Geraldo F, Crespo-Facorro, Benedicto, Pantelis, Christos, Wood, Stephen J, Zhuo, Chuanjun, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Di Martino, Adriana, Koutsouleris, Nikolaos, Gur, Raquel E, Gur, Ruben C, Satterthwaite, Theodore D, Wolf, Daniel H, Davatzikos, Christos, Onderzoek, Brain, Hwang, Gyujoon, Wen, Junhao, Sotardi, Susan, Brodkin, Edward S, Chand, Ganesh B, Dwyer, Dominic B, Erus, Guray, Doshi, Jimit, Singhal, Pankhuri, Srinivasan, Dhivya, Varol, Erdem, Sotiras, Aristeidis, Dazzan, Paola, Kahn, Rene S, Schnack, Hugo G, Zanetti, Marcus V, Meisenzahl, Eva, Busatto, Geraldo F, Crespo-Facorro, Benedicto, Pantelis, Christos, Wood, Stephen J, Zhuo, Chuanjun, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Di Martino, Adriana, Koutsouleris, Nikolaos, Gur, Raquel E, Gur, Ruben C, Satterthwaite, Theodore D, Wolf, Daniel H, and Davatzikos, Christos
Published: 2023

25. Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium

Author: National Institutes of Health (US), National Health and Medical Research Council (Australia), Council of Australian University Librarians, Dwyer, Dominic B., Chand, Ganesh B., Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S., Schnack, Hugo G., Meisenzahl, Eva, Wood, Stephen J., Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T., Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A., Upthegrove, Rachel, Kaczkurkin, Antonia N., Moore, Tyler M., Nelson, Barnaby, Gur, Rachel E., Gur, Ruben C., Ritchie, Marylyn D., Satterthwaite, Theodore D., Murray, Robin M., Forti, Marta Di, Ciufolini, Simone, Zanetti, Marcus V., Wolf, Daniel H., Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F., Davatzikos, Christos, Koutsouleris, Nikolaos, Dazzan, Paola, National Institutes of Health (US), National Health and Medical Research Council (Australia), Council of Australian University Librarians, Dwyer, Dominic B., Chand, Ganesh B., Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S., Schnack, Hugo G., Meisenzahl, Eva, Wood, Stephen J., Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T., Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A., Upthegrove, Rachel, Kaczkurkin, Antonia N., Moore, Tyler M., Nelson, Barnaby, Gur, Rachel E., Gur, Ruben C., Ritchie, Marylyn D., Satterthwaite, Theodore D., Murray, Robin M., Forti, Marta Di, Ciufolini, Simone, Zanetti, Marcus V., Wolf, Daniel H., Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F., Davatzikos, Christos, Koutsouleris, Nikolaos, and Dazzan, Paola
Abstract: Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups—a ‘lower brain volume’ subgroup (SG1) and an ‘higher striatal volume’ subgroup (SG2) with otherwise normal brain structure. In this study, we investigated whether the MRI signatures of these subgroups were also already present at the time of the first-episode of psychosis (FEP) and whether they were related to clinical presentation and clinical remission over 1-, 3-, and 5-years. We included 572 FEP and 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) of the PHENOM consortium. Our prior MRI subgrouping models (671 participants; USA, Germany, and China) were applied to both FEP and HC. Participants were assigned into 1 of 4 categories: subgroup 1 (SG1), subgroup 2 (SG2), no subgroup membership (‘None’), and mixed SG1 + SG2 subgroups (‘Mixed’). Voxel-wise analyses characterized SG1 and SG2 subgroups. Supervised machine learning analyses characterized baseline and remission signatures related to SG1 and SG2 membership. The two dominant patterns of ‘lower brain volume’ in SG1 and ‘higher striatal volume’ (with otherwise normal neuromorphology) in SG2 were identified already at the first episode of psychosis. SG1 had a significantly higher proportion of FEP (32%) vs. HC (19%) than SG2 (FEP, 21%; HC, 23%). Clinical multivariate signatures separated the SG1 and SG2 subgroups (balanced accuracy = 64%; p < 0.0001), with SG2 showing higher education but also greater positive psychosis symptoms at first presentation, and an association with symptom remission at 1-year, 5-year, and when timepoints were combined. Neuromorphological subtypes of schizophrenia are already evident at illness onset, separated by distinct clinical presentations, and differentially associated with subsequent remission. These results suggest that the subgroups may be underlying risk phenotypes that could be targeted in future t
Published: 2023

26. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author: Schijven, Dick; https://orcid.org/0000-0001-5190-7241, Postema, Merel C; https://orcid.org/0000-0002-1536-7062, Fukunaga, Masaki; https://orcid.org/0000-0003-1010-2644, Matsumoto, Junya; https://orcid.org/0000-0003-4228-3208, Miura, Kenichiro, de Zwarte, Sonja M C, van Haren, Neeltje E M, Cahn, Wiepke, Hulshoff Pol, Hilleke E, Kahn, René S, Ayesa-Arriola, Rosa; https://orcid.org/0000-0003-0570-5352, de la Foz, Víctor Ortiz-García; https://orcid.org/0000-0002-0627-1827, Tordesillas-Gutierrez, Diana; https://orcid.org/0000-0003-1458-3932, Vázquez-Bourgon, Javier; https://orcid.org/0000-0002-5478-3376, Crespo-Facorro, Benedicto, Alnæs, Dag; https://orcid.org/0000-0001-7361-5418, Dahl, Andreas; https://orcid.org/0000-0002-2668-8371, Westlye, Lars T; https://orcid.org/0000-0001-8644-956X, Agartz, Ingrid, Andreassen, Ole A; https://orcid.org/0000-0002-4461-3568, Jönsson, Erik G, Kochunov, Peter, Bruggemann, Jason M, Catts, Stanley V, Michie, Patricia T, Mowry, Bryan J, Quidé, Yann, Rasser, Paul E; https://orcid.org/0000-0003-3482-721X, Schall, Ulrich; https://orcid.org/0000-0001-9041-4562, Scott, Rodney J; https://orcid.org/0000-0001-7724-3404, Carr, Vaughan J; https://orcid.org/0000-0002-8907-5804, Green, Melissa J; https://orcid.org/0000-0002-9361-4874, Henskens, Frans A; https://orcid.org/0000-0003-2358-5630, Loughland, Carmel M, Pantelis, Christos; https://orcid.org/0000-0002-9565-0238, Weickert, Cynthia Shannon, Weickert, Thomas W, de Haan, Lieuwe, Brosch, Katharina; https://orcid.org/0000-0002-0526-8095, Pfarr, Julia-Katharina, Ringwald, Kai G, Stein, Frederike, Jansen, Andreas, Kircher, Tilo T J, Nenadić, Igor, Krämer, Bernd; https://orcid.org/0000-0002-1145-9103, Gruber, Oliver; https://orcid.org/0000-0003-1841-7413, Satterthwaite, Theodore D; https://orcid.org/0000-0001-7072-9399, Bustillo, Juan; https://orcid.org/0000-0001-8730-8152, Mathalon, Daniel H, Preda, Adrian, Calhoun, Vince D; https://orcid.org/0000-0001-9058-0747, Ford, Judith M; https://orcid.org/0000-0002-6500-6548, Potkin, Steven G, Chen, Jingxu, Tan, Yunlong; https://orcid.org/0000-0002-3522-3912, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan; https://orcid.org/0000-0003-2132-4445, Fuentes-Claramonte, Paola; https://orcid.org/0000-0002-1428-7976, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond; https://orcid.org/0000-0001-5557-1562, Sarró, Salvador; https://orcid.org/0000-0003-1835-2189, Pomarol-Clotet, Edith, Ciullo, Valentina; https://orcid.org/0000-0002-6870-6259, Piras, Fabrizio; https://orcid.org/0000-0003-3566-5494, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco; https://orcid.org/0000-0002-7432-4249, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W, Voineskos, Aristotle N; https://orcid.org/0000-0003-0156-0395, Sim, Kang; https://orcid.org/0000-0003-3209-9626, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M; https://orcid.org/0000-0003-0829-0519, Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André; https://orcid.org/0000-0001-6055-8397, Borgwardt, Stefan; https://orcid.org/0000-0002-5792-3987, McIntosh, Andrew M, Whalley, Heather C, Lawrie, Stephen M; https://orcid.org/0000-0002-2444-5675, du Plessis, Stefan, Luckhoff, Hilmar K, Scheffler, Freda; https://orcid.org/0000-0002-8898-8599, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo; https://orcid.org/0000-0002-0623-3759, Edmond, Jesse T, Rootes-Murdy, Kelly, Stephen, Julia M, Mayer, Andrew R, Antonucci, Linda A, Fazio, Leonardo; https://orcid.org/0000-0003-4000-974X, Pergola, Giulio; https://orcid.org/0000-0002-9193-1841, Bertolino, Alessandro, Díaz-Caneja, Covadonga M; https://orcid.org/0000-0001-8538-3175, Janssen, Joost, Lois, Noemi G; https://orcid.org/0000-0002-6600-072X, Arango, Celso; https://orcid.org/0000-0003-3382-4754, Tomyshev, Alexander S, Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M, Georgiadis, Foivos, Kirschner, Matthias; https://orcid.org/0000-0002-9486-1439, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin; https://orcid.org/0000-0002-1739-3256, Spaniel, Filip, Kim, Minah; https://orcid.org/0000-0001-8668-0817, Kwak, Yoo Bin, Oh, Sanghoon; https://orcid.org/0000-0002-7394-5211, Kwon, Jun Soo; https://orcid.org/0000-0002-1060-1462, James, Anthony; https://orcid.org/0000-0002-2742-8328, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne; https://orcid.org/0000-0002-1753-7811, Howells, Fleur M, Stein, Dan J; https://orcid.org/0000-0001-7218-7810, Temmingh, Henk S; https://orcid.org/0000-0002-7688-0759, Diaz-Zuluaga, Ana M, Pineda-Zapata, Julian A, López-Jaramillo, Carlos, Homan, Stephanie; https://orcid.org/0000-0003-1449-7508, Ji, Ellen; https://orcid.org/0000-0003-1527-8868, Surbeck, Werner; https://orcid.org/0000-0002-4733-795X, Homan, Philipp; https://orcid.org/0000-0001-9034-148X, Fisher, Simon E; https://orcid.org/0000-0002-3132-1996, Franke, Barbara; https://orcid.org/0000-0003-4375-6572, Glahn, David C; https://orcid.org/0000-0002-4749-6977, Gur, Ruben C; https://orcid.org/0000-0002-9657-1996, Hashimoto, Ryota, Jahanshad, Neda, Luders, Eileen; https://orcid.org/0000-0001-5659-992X, Medland, Sarah E, Thompson, Paul M; https://orcid.org/0000-0002-4720-8867, Turner, Jessica A, van Erp, Theo G M, Francks, Clyde; https://orcid.org/0000-0002-9098-890X, Schijven, Dick; https://orcid.org/0000-0001-5190-7241, Postema, Merel C; https://orcid.org/0000-0002-1536-7062, Fukunaga, Masaki; https://orcid.org/0000-0003-1010-2644, Matsumoto, Junya; https://orcid.org/0000-0003-4228-3208, Miura, Kenichiro, de Zwarte, Sonja M C, van Haren, Neeltje E M, Cahn, Wiepke, Hulshoff Pol, Hilleke E, Kahn, René S, Ayesa-Arriola, Rosa; https://orcid.org/0000-0003-0570-5352, de la Foz, Víctor Ortiz-García; https://orcid.org/0000-0002-0627-1827, Tordesillas-Gutierrez, Diana; https://orcid.org/0000-0003-1458-3932, Vázquez-Bourgon, Javier; https://orcid.org/0000-0002-5478-3376, Crespo-Facorro, Benedicto, Alnæs, Dag; https://orcid.org/0000-0001-7361-5418, Dahl, Andreas; https://orcid.org/0000-0002-2668-8371, Westlye, Lars T; https://orcid.org/0000-0001-8644-956X, Agartz, Ingrid, Andreassen, Ole A; https://orcid.org/0000-0002-4461-3568, Jönsson, Erik G, Kochunov, Peter, Bruggemann, Jason M, Catts, Stanley V, Michie, Patricia T, Mowry, Bryan J, Quidé, Yann, Rasser, Paul E; https://orcid.org/0000-0003-3482-721X, Schall, Ulrich; https://orcid.org/0000-0001-9041-4562, Scott, Rodney J; https://orcid.org/0000-0001-7724-3404, Carr, Vaughan J; https://orcid.org/0000-0002-8907-5804, Green, Melissa J; https://orcid.org/0000-0002-9361-4874, Henskens, Frans A; https://orcid.org/0000-0003-2358-5630, Loughland, Carmel M, Pantelis, Christos; https://orcid.org/0000-0002-9565-0238, Weickert, Cynthia Shannon, Weickert, Thomas W, de Haan, Lieuwe, Brosch, Katharina; https://orcid.org/0000-0002-0526-8095, Pfarr, Julia-Katharina, Ringwald, Kai G, Stein, Frederike, Jansen, Andreas, Kircher, Tilo T J, Nenadić, Igor, Krämer, Bernd; https://orcid.org/0000-0002-1145-9103, Gruber, Oliver; https://orcid.org/0000-0003-1841-7413, Satterthwaite, Theodore D; https://orcid.org/0000-0001-7072-9399, Bustillo, Juan; https://orcid.org/0000-0001-8730-8152, Mathalon, Daniel H, Preda, Adrian, Calhoun, Vince D; https://orcid.org/0000-0001-9058-0747, Ford, Judith M; https://orcid.org/0000-0002-6500-6548, Potkin, Steven G, Chen, Jingxu, Tan, Yunlong; https://orcid.org/0000-0002-3522-3912, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan; https://orcid.org/0000-0003-2132-4445, Fuentes-Claramonte, Paola; https://orcid.org/0000-0002-1428-7976, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond; https://orcid.org/0000-0001-5557-1562, Sarró, Salvador; https://orcid.org/0000-0003-1835-2189, Pomarol-Clotet, Edith, Ciullo, Valentina; https://orcid.org/0000-0002-6870-6259, Piras, Fabrizio; https://orcid.org/0000-0003-3566-5494, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco; https://orcid.org/0000-0002-7432-4249, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W, Voineskos, Aristotle N; https://orcid.org/0000-0003-0156-0395, Sim, Kang; https://orcid.org/0000-0003-3209-9626, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M; https://orcid.org/0000-0003-0829-0519, Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André; https://orcid.org/0000-0001-6055-8397, Borgwardt, Stefan; https://orcid.org/0000-0002-5792-3987, McIntosh, Andrew M, Whalley, Heather C, Lawrie, Stephen M; https://orcid.org/0000-0002-2444-5675, du Plessis, Stefan, Luckhoff, Hilmar K, Scheffler, Freda; https://orcid.org/0000-0002-8898-8599, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo; https://orcid.org/0000-0002-0623-3759, Edmond, Jesse T, Rootes-Murdy, Kelly, Stephen, Julia M, Mayer, Andrew R, Antonucci, Linda A, Fazio, Leonardo; https://orcid.org/0000-0003-4000-974X, Pergola, Giulio; https://orcid.org/0000-0002-9193-1841, Bertolino, Alessandro, Díaz-Caneja, Covadonga M; https://orcid.org/0000-0001-8538-3175, Janssen, Joost, Lois, Noemi G; https://orcid.org/0000-0002-6600-072X, Arango, Celso; https://orcid.org/0000-0003-3382-4754, Tomyshev, Alexander S, Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M, Georgiadis, Foivos, Kirschner, Matthias; https://orcid.org/0000-0002-9486-1439, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin; https://orcid.org/0000-0002-1739-3256, Spaniel, Filip, Kim, Minah; https://orcid.org/0000-0001-8668-0817, Kwak, Yoo Bin, Oh, Sanghoon; https://orcid.org/0000-0002-7394-5211, Kwon, Jun Soo; https://orcid.org/0000-0002-1060-1462, James, Anthony; https://orcid.org/0000-0002-2742-8328, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne; https://orcid.org/0000-0002-1753-7811, Howells, Fleur M, Stein, Dan J; https://orcid.org/0000-0001-7218-7810, Temmingh, Henk S; https://orcid.org/0000-0002-7688-0759, Diaz-Zuluaga, Ana M, Pineda-Zapata, Julian A, López-Jaramillo, Carlos, Homan, Stephanie; https://orcid.org/0000-0003-1449-7508, Ji, Ellen; https://orcid.org/0000-0003-1527-8868, Surbeck, Werner; https://orcid.org/0000-0002-4733-795X, Homan, Philipp; https://orcid.org/0000-0001-9034-148X, Fisher, Simon E; https://orcid.org/0000-0002-3132-1996, Franke, Barbara; https://orcid.org/0000-0003-4375-6572, Glahn, David C; https://orcid.org/0000-0002-4749-6977, Gur, Ruben C; https://orcid.org/0000-0002-9657-1996, Hashimoto, Ryota, Jahanshad, Neda, Luders, Eileen; https://orcid.org/0000-0001-5659-992X, Medland, Sarah E, Thompson, Paul M; https://orcid.org/0000-0002-4720-8867, Turner, Jessica A, van Erp, Theo G M, and Francks, Clyde; https://orcid.org/0000-0002-9098-890X
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macro-structural asymmetry may reflect differences at the molecular, cytoarchitectonic or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023

27. Extreme deviations from the normative model reveal cortical heterogeneity and associations with negative symptom severity in first-episode psychosis from the OPTiMiSE and GAP studies

Author: Worker, Amanda, Berthert, Pierre, Lawrence, Andrew J., Kia, Seyed Mostafa, Arango, Celso, Dinga, Richard, Galderisi, Silvana, Glenthøj, Birte, Kahn, René S., Leslie, Anoushka, Murray, Robin M., Pariante, Carmine M., Pantelis, Christos, Weiser, Mark, Winter-van Rossum, Inge, McGuire, Philip, Dazzan, Paola, Marquand, Andre F., Worker, Amanda, Berthert, Pierre, Lawrence, Andrew J., Kia, Seyed Mostafa, Arango, Celso, Dinga, Richard, Galderisi, Silvana, Glenthøj, Birte, Kahn, René S., Leslie, Anoushka, Murray, Robin M., Pariante, Carmine M., Pantelis, Christos, Weiser, Mark, Winter-van Rossum, Inge, McGuire, Philip, Dazzan, Paola, and Marquand, Andre F.
Abstract: There is currently no quantifiable method to predict long-term clinical outcomes in patients presenting with a first episode of psychosis. A major barrier to developing useful markers for this is biological heterogeneity, where many different pathological mechanisms may underly the same set of symptoms in different individuals. Normative modelling has been used to quantify this heterogeneity in established psychotic disorders by identifying regions of the cortex which are thinner than expected based on a normative healthy population range. These brain atypicalities are measured at the individual level and therefore potentially useful in a clinical setting. However, it is still unclear whether alterations in individual brain structure can be detected at the time of the first psychotic episode, and whether they are associated with subsequent clinical outcomes. We applied normative modelling of cortical thickness to a sample of first-episode psychosis patients, with the aim of quantifying heterogeneity and to use any pattern of cortical atypicality to predict symptoms and response to antipsychotic medication at timepoints from baseline up to 95 weeks (median follow-ups = 4). T1-weighted brain magnetic resonance images from the GAP and OPTiMiSE samples were processed with Freesurfer V6.0.0 yielding 148 cortical thickness features. An existing normative model of cortical thickness (n = 37,126) was adapted to integrate data from each clinical site and account for effects of gender and site. Our test sample consisted of control participants (n = 149, mean age = 26, SD = 6.7) and patient data (n = 295, mean age = 26, SD = 6.7), this sample was used for estimating deviations from the normative model and subsequent statistical analysis. For each individual, the 148 cortical thickness features were mapped to centiles of the normative distribution and converted to z-scores reflecting the distance from the population mean. Individual cortical thickness metrics of +/– 2.6 standar, There is currently no quantifiable method to predict long-term clinical outcomes in patients presenting with a first episode of psychosis. A major barrier to developing useful markers for this is biological heterogeneity, where many different pathological mechanisms may underly the same set of symptoms in different individuals. Normative modelling has been used to quantify this heterogeneity in established psychotic disorders by identifying regions of the cortex which are thinner than expected based on a normative healthy population range. These brain atypicalities are measured at the individual level and therefore potentially useful in a clinical setting. However, it is still unclear whether alterations in individual brain structure can be detected at the time of the first psychotic episode, and whether they are associated with subsequent clinical outcomes. We applied normative modelling of cortical thickness to a sample of first-episode psychosis patients, with the aim of quantifying heterogeneity and to use any pattern of cortical atypicality to predict symptoms and response to antipsychotic medication at timepoints from baseline up to 95 weeks (median follow-ups = 4). T1-weighted brain magnetic resonance images from the GAP and OPTiMiSE samples were processed with Freesurfer V6.0.0 yielding 148 cortical thickness features. An existing normative model of cortical thickness (n = 37,126) was adapted to integrate data from each clinical site and account for effects of gender and site. Our test sample consisted of control participants (n = 149, mean age = 26, SD = 6.7) and patient data (n = 295, mean age = 26, SD = 6.7), this sample was used for estimating deviations from the normative model and subsequent statistical analysis. For each individual, the 148 cortical thickness features were mapped to centiles of the normative distribution and converted to z-scores reflecting the distance from the population mean. Individual cortical thickness metrics of +/– 2.6 stan
Published: 2023

28. Fibre density and fibre-bundle cross-section of the corticospinal tract are distinctly linked to psychosis-specific symptoms in antipsychotic-naïve patients with first-episode schizophrenia

Author: Kristensen, Tina D., Raghava, Jayachandra M., Skjerbæk, Martin W., Dhollander, Thijs, Syeda, Warda, Ambrosen, Karen S., Bojesen, Kirsten B., Nielsen, Mette, Pantelis, Christos, Glenthøj, Birte Y., Ebdrup, Bjørn H., Kristensen, Tina D., Raghava, Jayachandra M., Skjerbæk, Martin W., Dhollander, Thijs, Syeda, Warda, Ambrosen, Karen S., Bojesen, Kirsten B., Nielsen, Mette, Pantelis, Christos, Glenthøj, Birte Y., and Ebdrup, Bjørn H.
Abstract: Multiple lines of research support the dysconnectivity hypothesis of schizophrenia. However, findings on white matter (WM) alterations in patients with schizophrenia are widespread and non-specific. Confounding factors from magnetic resonance image (MRI) processing, clinical diversity, antipsychotic exposure, and substance use may underlie some of the variability. By application of refined methodology and careful sampling, we rectified common confounders investigating WM and symptom correlates in a sample of strictly antipsychotic-naïve first-episode patients with schizophrenia. Eighty-six patients and 112 matched controls underwent diffusion MRI. Using fixel-based analysis (FBA), we extracted fibre-specific measures such as fibre density and fibre-bundle cross-section. Group differences on fixel-wise measures were examined with multivariate general linear modelling. Psychopathology was assessed with the Positive and Negative Syndrome Scale. We separately tested multivariate correlations between fixel-wise measures and predefined psychosis-specific versus anxio-depressive symptoms. Results were corrected for multiple comparisons. Patients displayed reduced fibre density in the body of corpus callosum and in the middle cerebellar peduncle. Fibre density and fibre-bundle cross-section of the corticospinal tract were positively correlated with suspiciousness/persecution, and negatively correlated with delusions. Fibre-bundle cross-section of isthmus of corpus callosum and hallucinatory behaviour were negatively correlated. Fibre density and fibre-bundle cross-section of genu and splenium of corpus callosum were negative correlated with anxio-depressive symptoms. FBA revealed fibre-specific properties of WM abnormalities in patients and differentiated associations between WM and psychosis-specific versus anxio-depressive symptoms. Our findings encourage an itemised approach to investigate the relationship between WM microstructure and clinical symptoms in patients with, Multiple lines of research support the dysconnectivity hypothesis of schizophrenia. However, findings on white matter (WM) alterations in patients with schizophrenia are widespread and non-specific. Confounding factors from magnetic resonance image (MRI) processing, clinical diversity, antipsychotic exposure, and substance use may underlie some of the variability. By application of refined methodology and careful sampling, we rectified common confounders investigating WM and symptom correlates in a sample of strictly antipsychotic-naïve first-episode patients with schizophrenia. Eighty-six patients and 112 matched controls underwent diffusion MRI. Using fixel-based analysis (FBA), we extracted fibre-specific measures such as fibre density and fibre-bundle cross-section. Group differences on fixel-wise measures were examined with multivariate general linear modelling. Psychopathology was assessed with the Positive and Negative Syndrome Scale. We separately tested multivariate correlations between fixel-wise measures and predefined psychosis-specific versus anxio-depressive symptoms. Results were corrected for multiple comparisons. Patients displayed reduced fibre density in the body of corpus callosum and in the middle cerebellar peduncle. Fibre density and fibre-bundle cross-section of the corticospinal tract were positively correlated with suspiciousness/persecution, and negatively correlated with delusions. Fibre-bundle cross-section of isthmus of corpus callosum and hallucinatory behaviour were negatively correlated. Fibre density and fibre-bundle cross-section of genu and splenium of corpus callosum were negative correlated with anxio-depressive symptoms. FBA revealed fibre-specific properties of WM abnormalities in patients and differentiated associations between WM and psychosis-specific versus anxio-depressive symptoms. Our findings encourage an itemised approach to investigate the relationship between WM microstructure and clinical symptoms in patients wi
Published: 2023

29. Extreme deviations from the normative model reveal cortical heterogeneity and associations with negative symptom severity in first-episode psychosis from the OPTiMiSE and GAP studies

Author: Worker, Amanda, Berthert, Pierre, Lawrence, Andrew J., Kia, Seyed Mostafa, Arango, Celso, Dinga, Richard, Galderisi, Silvana, Glenthøj, Birte, Kahn, René S., Leslie, Anoushka, Murray, Robin M., Pariante, Carmine M., Pantelis, Christos, Weiser, Mark, Winter-van Rossum, Inge, McGuire, Philip, Dazzan, Paola, Marquand, Andre F., Worker, Amanda, Berthert, Pierre, Lawrence, Andrew J., Kia, Seyed Mostafa, Arango, Celso, Dinga, Richard, Galderisi, Silvana, Glenthøj, Birte, Kahn, René S., Leslie, Anoushka, Murray, Robin M., Pariante, Carmine M., Pantelis, Christos, Weiser, Mark, Winter-van Rossum, Inge, McGuire, Philip, Dazzan, Paola, and Marquand, Andre F.
Abstract: There is currently no quantifiable method to predict long-term clinical outcomes in patients presenting with a first episode of psychosis. A major barrier to developing useful markers for this is biological heterogeneity, where many different pathological mechanisms may underly the same set of symptoms in different individuals. Normative modelling has been used to quantify this heterogeneity in established psychotic disorders by identifying regions of the cortex which are thinner than expected based on a normative healthy population range. These brain atypicalities are measured at the individual level and therefore potentially useful in a clinical setting. However, it is still unclear whether alterations in individual brain structure can be detected at the time of the first psychotic episode, and whether they are associated with subsequent clinical outcomes. We applied normative modelling of cortical thickness to a sample of first-episode psychosis patients, with the aim of quantifying heterogeneity and to use any pattern of cortical atypicality to predict symptoms and response to antipsychotic medication at timepoints from baseline up to 95 weeks (median follow-ups = 4). T1-weighted brain magnetic resonance images from the GAP and OPTiMiSE samples were processed with Freesurfer V6.0.0 yielding 148 cortical thickness features. An existing normative model of cortical thickness (n = 37,126) was adapted to integrate data from each clinical site and account for effects of gender and site. Our test sample consisted of control participants (n = 149, mean age = 26, SD = 6.7) and patient data (n = 295, mean age = 26, SD = 6.7), this sample was used for estimating deviations from the normative model and subsequent statistical analysis. For each individual, the 148 cortical thickness features were mapped to centiles of the normative distribution and converted to z-scores reflecting the distance from the population mean. Individual cortical thickness metrics of +/– 2.6 standar, There is currently no quantifiable method to predict long-term clinical outcomes in patients presenting with a first episode of psychosis. A major barrier to developing useful markers for this is biological heterogeneity, where many different pathological mechanisms may underly the same set of symptoms in different individuals. Normative modelling has been used to quantify this heterogeneity in established psychotic disorders by identifying regions of the cortex which are thinner than expected based on a normative healthy population range. These brain atypicalities are measured at the individual level and therefore potentially useful in a clinical setting. However, it is still unclear whether alterations in individual brain structure can be detected at the time of the first psychotic episode, and whether they are associated with subsequent clinical outcomes. We applied normative modelling of cortical thickness to a sample of first-episode psychosis patients, with the aim of quantifying heterogeneity and to use any pattern of cortical atypicality to predict symptoms and response to antipsychotic medication at timepoints from baseline up to 95 weeks (median follow-ups = 4). T1-weighted brain magnetic resonance images from the GAP and OPTiMiSE samples were processed with Freesurfer V6.0.0 yielding 148 cortical thickness features. An existing normative model of cortical thickness (n = 37,126) was adapted to integrate data from each clinical site and account for effects of gender and site. Our test sample consisted of control participants (n = 149, mean age = 26, SD = 6.7) and patient data (n = 295, mean age = 26, SD = 6.7), this sample was used for estimating deviations from the normative model and subsequent statistical analysis. For each individual, the 148 cortical thickness features were mapped to centiles of the normative distribution and converted to z-scores reflecting the distance from the population mean. Individual cortical thickness metrics of +/– 2.6 stan
Published: 2023

30. Fibre density and fibre-bundle cross-section of the corticospinal tract are distinctly linked to psychosis-specific symptoms in antipsychotic-naïve patients with first-episode schizophrenia

Author: Kristensen, Tina D., Raghava, Jayachandra M., Skjerbæk, Martin W., Dhollander, Thijs, Syeda, Warda, Ambrosen, Karen S., Bojesen, Kirsten B., Nielsen, Mette, Pantelis, Christos, Glenthøj, Birte Y., Ebdrup, Bjørn H., Kristensen, Tina D., Raghava, Jayachandra M., Skjerbæk, Martin W., Dhollander, Thijs, Syeda, Warda, Ambrosen, Karen S., Bojesen, Kirsten B., Nielsen, Mette, Pantelis, Christos, Glenthøj, Birte Y., and Ebdrup, Bjørn H.
Abstract: Multiple lines of research support the dysconnectivity hypothesis of schizophrenia. However, findings on white matter (WM) alterations in patients with schizophrenia are widespread and non-specific. Confounding factors from magnetic resonance image (MRI) processing, clinical diversity, antipsychotic exposure, and substance use may underlie some of the variability. By application of refined methodology and careful sampling, we rectified common confounders investigating WM and symptom correlates in a sample of strictly antipsychotic-naïve first-episode patients with schizophrenia. Eighty-six patients and 112 matched controls underwent diffusion MRI. Using fixel-based analysis (FBA), we extracted fibre-specific measures such as fibre density and fibre-bundle cross-section. Group differences on fixel-wise measures were examined with multivariate general linear modelling. Psychopathology was assessed with the Positive and Negative Syndrome Scale. We separately tested multivariate correlations between fixel-wise measures and predefined psychosis-specific versus anxio-depressive symptoms. Results were corrected for multiple comparisons. Patients displayed reduced fibre density in the body of corpus callosum and in the middle cerebellar peduncle. Fibre density and fibre-bundle cross-section of the corticospinal tract were positively correlated with suspiciousness/persecution, and negatively correlated with delusions. Fibre-bundle cross-section of isthmus of corpus callosum and hallucinatory behaviour were negatively correlated. Fibre density and fibre-bundle cross-section of genu and splenium of corpus callosum were negative correlated with anxio-depressive symptoms. FBA revealed fibre-specific properties of WM abnormalities in patients and differentiated associations between WM and psychosis-specific versus anxio-depressive symptoms. Our findings encourage an itemised approach to investigate the relationship between WM microstructure and clinical symptoms in patients with, Multiple lines of research support the dysconnectivity hypothesis of schizophrenia. However, findings on white matter (WM) alterations in patients with schizophrenia are widespread and non-specific. Confounding factors from magnetic resonance image (MRI) processing, clinical diversity, antipsychotic exposure, and substance use may underlie some of the variability. By application of refined methodology and careful sampling, we rectified common confounders investigating WM and symptom correlates in a sample of strictly antipsychotic-naïve first-episode patients with schizophrenia. Eighty-six patients and 112 matched controls underwent diffusion MRI. Using fixel-based analysis (FBA), we extracted fibre-specific measures such as fibre density and fibre-bundle cross-section. Group differences on fixel-wise measures were examined with multivariate general linear modelling. Psychopathology was assessed with the Positive and Negative Syndrome Scale. We separately tested multivariate correlations between fixel-wise measures and predefined psychosis-specific versus anxio-depressive symptoms. Results were corrected for multiple comparisons. Patients displayed reduced fibre density in the body of corpus callosum and in the middle cerebellar peduncle. Fibre density and fibre-bundle cross-section of the corticospinal tract were positively correlated with suspiciousness/persecution, and negatively correlated with delusions. Fibre-bundle cross-section of isthmus of corpus callosum and hallucinatory behaviour were negatively correlated. Fibre density and fibre-bundle cross-section of genu and splenium of corpus callosum were negative correlated with anxio-depressive symptoms. FBA revealed fibre-specific properties of WM abnormalities in patients and differentiated associations between WM and psychosis-specific versus anxio-depressive symptoms. Our findings encourage an itemised approach to investigate the relationship between WM microstructure and clinical symptoms in patients wi
Published: 2023

31. Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study.

Author: Kirschner, Matthias, Kirschner, Matthias, Hodzic-Santor, Benazir, Antoniades, Mathilde, Nenadic, Igor, Kircher, Tilo, Krug, Axel, Meller, Tina, Grotegerd, Dominik, Fornito, Alex, Arnatkeviciute, Aurina, Bellgrove, Mark A, Tiego, Jeggan, Dannlowski, Udo, Koch, Katharina, Hülsmann, Carina, Kugel, Harald, Enneking, Verena, Klug, Melissa, Leehr, Elisabeth J, Böhnlein, Joscha, Gruber, Marius, Mehler, David, DeRosse, Pamela, Moyett, Ashley, Baune, Bernhard T, Green, Melissa, Quidé, Yann, Pantelis, Christos, Chan, Raymond, Wang, Yi, Ettinger, Ulrich, Debbané, Martin, Derome, Melodie, Gaser, Christian, Besteher, Bianca, Diederen, Kelly, Spencer, Tom J, Fletcher, Paul, Rössler, Wulf, Smigielski, Lukasz, Kumari, Veena, Premkumar, Preethi, Park, Haeme RP, Wiebels, Kristina, Lemmers-Jansen, Imke, Gilleen, James, Allen, Paul, Kozhuharova, Petya, Marsman, Jan-Bernard, Lebedeva, Irina, Tomyshev, Alexander, Mukhorina, Anna, Kaiser, Stefan, Fett, Anne-Kathrin, Sommer, Iris, Schuite-Koops, Sanne, Paquola, Casey, Larivière, Sara, Bernhardt, Boris, Dagher, Alain, Grant, Phillip, van Erp, Theo GM, Turner, Jessica A, Thompson, Paul M, Aleman, André, Modinos, Gemma, Kirschner, Matthias, Kirschner, Matthias, Hodzic-Santor, Benazir, Antoniades, Mathilde, Nenadic, Igor, Kircher, Tilo, Krug, Axel, Meller, Tina, Grotegerd, Dominik, Fornito, Alex, Arnatkeviciute, Aurina, Bellgrove, Mark A, Tiego, Jeggan, Dannlowski, Udo, Koch, Katharina, Hülsmann, Carina, Kugel, Harald, Enneking, Verena, Klug, Melissa, Leehr, Elisabeth J, Böhnlein, Joscha, Gruber, Marius, Mehler, David, DeRosse, Pamela, Moyett, Ashley, Baune, Bernhard T, Green, Melissa, Quidé, Yann, Pantelis, Christos, Chan, Raymond, Wang, Yi, Ettinger, Ulrich, Debbané, Martin, Derome, Melodie, Gaser, Christian, Besteher, Bianca, Diederen, Kelly, Spencer, Tom J, Fletcher, Paul, Rössler, Wulf, Smigielski, Lukasz, Kumari, Veena, Premkumar, Preethi, Park, Haeme RP, Wiebels, Kristina, Lemmers-Jansen, Imke, Gilleen, James, Allen, Paul, Kozhuharova, Petya, Marsman, Jan-Bernard, Lebedeva, Irina, Tomyshev, Alexander, Mukhorina, Anna, Kaiser, Stefan, Fett, Anne-Kathrin, Sommer, Iris, Schuite-Koops, Sanne, Paquola, Casey, Larivière, Sara, Bernhardt, Boris, Dagher, Alain, Grant, Phillip, van Erp, Theo GM, Turner, Jessica A, Thompson, Paul M, Aleman, André, and Modinos, Gemma
Abstract: Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.
Published: 2022

32. Impact of Comorbid Affective Disorders on Longitudinal Clinical Outcomes in Individuals at Ultra-high Risk for Psychosis

Author: Schirmbeck, Frederike, van der Burg, Nadine C., Blankers, Matthijs, Vermeulen, Jentien M., McGuire, Philip, Valmaggia, Lucia R., Kempton, Matthew J., van der Gaag, Mark, Riecher-Rossler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Nelson, Barnaby, Amminger, G. Paul, McGorry, Patrick, Pantelis, Christos, Krebs, Marie-Odile, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P. F., van Os, Jim, Nordentoft, Merete, Glenthoj, Birte, Fusar-Poli, Paolo, de Haan, Lieuwe, Schirmbeck, Frederike, van der Burg, Nadine C., Blankers, Matthijs, Vermeulen, Jentien M., McGuire, Philip, Valmaggia, Lucia R., Kempton, Matthew J., van der Gaag, Mark, Riecher-Rossler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Nelson, Barnaby, Amminger, G. Paul, McGorry, Patrick, Pantelis, Christos, Krebs, Marie-Odile, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P. F., van Os, Jim, Nordentoft, Merete, Glenthoj, Birte, Fusar-Poli, Paolo, and de Haan, Lieuwe
Abstract: Introduction: Diagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS). Method: Latent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk. Results: 46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298-7.642]) or decreasing group (OR = 3.137, [1.165-8.450]). In contrast, past (OR =.443, [.179-1.094]) or current (OR =.414, [.156-1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178-3.828]). Conclusion: A past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.
Published: 2022

33. The clinical relevance of formal thought disorder in the early stages of psychosis: results from the PRONIA study

Author: Oeztuerk, Oemer Faruk, Pigoni, Alessandro, Wenzel, Julian, Haas, Shalaila S., Popovic, David, Ruef, Anne, Dwyer, Dominic B., Kambeitz-Ilankovic, Lana, Ruhrmann, Stephan, Chisholm, Katharine, Lalousis, Paris, Griffiths, Sian Lowri, Lichtenstein, Theresa, Rosen, Marlene, Kambeitz, Joseph, Schultze-Lutter, Frauke, Liddle, Peter, Upthegrove, Rachel, Salokangas, Raimo K. R., Pantelis, Christos, Meisenzahl, Eva, Wood, Stephen J., Brambilla, Paolo, Borgwardt, Stefan, Falkai, Peter, Antonucci, Linda A., Koutsouleris, Nikolaos, Oeztuerk, Oemer Faruk, Pigoni, Alessandro, Wenzel, Julian, Haas, Shalaila S., Popovic, David, Ruef, Anne, Dwyer, Dominic B., Kambeitz-Ilankovic, Lana, Ruhrmann, Stephan, Chisholm, Katharine, Lalousis, Paris, Griffiths, Sian Lowri, Lichtenstein, Theresa, Rosen, Marlene, Kambeitz, Joseph, Schultze-Lutter, Frauke, Liddle, Peter, Upthegrove, Rachel, Salokangas, Raimo K. R., Pantelis, Christos, Meisenzahl, Eva, Wood, Stephen J., Brambilla, Paolo, Borgwardt, Stefan, Falkai, Peter, Antonucci, Linda A., and Koutsouleris, Nikolaos
Abstract: Background Formal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This study aimed to identify stable and generalizable FTD-subgroups of patients with recent-onset psychosis (ROP) by applying a comprehensive data-driven clustering approach and to test the validity of these subgroups by assessing associations between this FTD-related stratification, social and occupational functioning, and neurocognition. Methods 279 patients with ROP were recruited as part of the multi-site European PRONIA study (Personalised Prognostic Tools for Early Psychosis Management; www.pronia.eu). Five FTD-related symptoms (conceptual disorganization, poverty of content of speech, difficulty in abstract thinking, increased latency of response and poverty of speech) were assessed with Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Results The results with two patient subgroups showing different levels of FTD were the most stable and generalizable clustering solution (predicted clustering strength value = 0.86). FTD-High subgroup had lower scores in social (p(fdr) < 0.001) and role (p(fdr) < 0.001) functioning, as well as worse neurocognitive performance in semantic (p(fdr) < 0.001) and phonological verbal fluency (p(fdr) < 0.001), short-term verbal memory (p(fdr) = 0.002) and abstract thinking (p(fdr) = 0.010), in comparison to FTD-Low group. Conclusions Clustering techniques allowed us to identify patients with more pronounced FTD showing more severe deficits in functioning and neurocognition, thus suggesting that FTD may be a relevant marker of illness severity in the early psychosis pathway.
Published: 2022

34. Relationship between jumping to conclusions and clinical outcomes in people at clinical high-risk for psychosis

Author: Neurociencias, Neurozientziak, Catalán Alcántara, Ana, Tognin, Stefania, Kempton, Matthew J., Stahl, Daniel, Salazar de Pablo, Gonzalo, Nelson, Barnaby, Pantelis, Christos, Riecher-Rössler, Anita, Bressan, Rodrigo, Barrantes-Vidal, Neus, Krebs, Marie-Odile, Nordentoft, Merete, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P. F., Van Os, Jim, De Haan, Lieuwe, Van der Gaag, Mark, Valmaggia, Lucia R., McGuire, Philip, Neurociencias, Neurozientziak, Catalán Alcántara, Ana, Tognin, Stefania, Kempton, Matthew J., Stahl, Daniel, Salazar de Pablo, Gonzalo, Nelson, Barnaby, Pantelis, Christos, Riecher-Rössler, Anita, Bressan, Rodrigo, Barrantes-Vidal, Neus, Krebs, Marie-Odile, Nordentoft, Merete, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P. F., Van Os, Jim, De Haan, Lieuwe, Van der Gaag, Mark, Valmaggia, Lucia R., and McGuire, Philip
Abstract: Background Psychosis is associated with a reasoning bias, which manifests as a tendency to 'jump to conclusions'. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes. Methods In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A 'beads' task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point. Results There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; chi 2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ. Conclusions In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.
Published: 2022

35. Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

Author: Baldwin, Helen, Baldwin, Helen, Radua, Joaquim, Antoniades, Mathilde, Haas, Shalaila S, Frangou, Sophia, Agartz, Ingrid, Allen, Paul, Andreassen, Ole A, Atkinson, Kimberley, Bachman, Peter, Baeza, Inmaculada, Bartholomeusz, Cali F, Chee, Michael WL, Colibazzi, Tiziano, Cooper, Rebecca E, Corcoran, Cheryl M, Cropley, Vanessa L, Ebdrup, Bjørn H, Fortea, Adriana, Glenthøj, Louise Birkedal, Hamilton, Holly K, Haut, Kristen M, Hayes, Rebecca A, He, Ying, Heekeren, Karsten, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Klaunig, Mallory J, Koike, Shinsuke, Koppel, Alex, Kristensen, Tina D, Bin Kwak, Yoo, Kwon, Jun Soo, Lawrie, Stephen M, Lebedeva, Irina, Lee, Jimmy, Lin, Ashleigh, Loewy, Rachel L, Mathalon, Daniel H, Michel, Chantal, Mizrahi, Romina, Møller, Paul, Nelson, Barnaby, Nemoto, Takahiro, Nordholm, Dorte, Omelchenko, Maria A, Pantelis, Christos, Raghava, Jayachandra M, Røssberg, Jan I, Rössler, Wulf, Salisbury, Dean F, Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K, Tang, Jinsong, Theodoridou, Anastasia, Thomopoulos, Sophia I, Tomyshev, Alexander S, Uhlhaas, Peter J, Værnes, Tor G, van Amelsvoort, Therese AMJ, Van Erp, Theo GM, Waltz, James A, Westlye, Lars T, Wood, Stephen J, Zhou, Juan H, McGuire, Philip, Thompson, Paul M, Jalbrzikowski, Maria, Hernaus, Dennis, Fusar-Poli, Paolo, ENIGMA Clinical High Risk for Psychosis Working Group, Baldwin, Helen, Baldwin, Helen, Radua, Joaquim, Antoniades, Mathilde, Haas, Shalaila S, Frangou, Sophia, Agartz, Ingrid, Allen, Paul, Andreassen, Ole A, Atkinson, Kimberley, Bachman, Peter, Baeza, Inmaculada, Bartholomeusz, Cali F, Chee, Michael WL, Colibazzi, Tiziano, Cooper, Rebecca E, Corcoran, Cheryl M, Cropley, Vanessa L, Ebdrup, Bjørn H, Fortea, Adriana, Glenthøj, Louise Birkedal, Hamilton, Holly K, Haut, Kristen M, Hayes, Rebecca A, He, Ying, Heekeren, Karsten, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Klaunig, Mallory J, Koike, Shinsuke, Koppel, Alex, Kristensen, Tina D, Bin Kwak, Yoo, Kwon, Jun Soo, Lawrie, Stephen M, Lebedeva, Irina, Lee, Jimmy, Lin, Ashleigh, Loewy, Rachel L, Mathalon, Daniel H, Michel, Chantal, Mizrahi, Romina, Møller, Paul, Nelson, Barnaby, Nemoto, Takahiro, Nordholm, Dorte, Omelchenko, Maria A, Pantelis, Christos, Raghava, Jayachandra M, Røssberg, Jan I, Rössler, Wulf, Salisbury, Dean F, Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K, Tang, Jinsong, Theodoridou, Anastasia, Thomopoulos, Sophia I, Tomyshev, Alexander S, Uhlhaas, Peter J, Værnes, Tor G, van Amelsvoort, Therese AMJ, Van Erp, Theo GM, Waltz, James A, Westlye, Lars T, Wood, Stephen J, Zhou, Juan H, McGuire, Philip, Thompson, Paul M, Jalbrzikowski, Maria, Hernaus, Dennis, Fusar-Poli, Paolo, and ENIGMA Clinical High Risk for Psychosis Working Group
Abstract: Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, i
Published: 2022

36. Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study.

Author: Kirschner, Matthias, Kirschner, Matthias, Hodzic-Santor, Benazir, Antoniades, Mathilde, Nenadic, Igor, Kircher, Tilo, Krug, Axel, Meller, Tina, Grotegerd, Dominik, Fornito, Alex, Arnatkeviciute, Aurina, Bellgrove, Mark A, Tiego, Jeggan, Dannlowski, Udo, Koch, Katharina, Hülsmann, Carina, Kugel, Harald, Enneking, Verena, Klug, Melissa, Leehr, Elisabeth J, Böhnlein, Joscha, Gruber, Marius, Mehler, David, DeRosse, Pamela, Moyett, Ashley, Baune, Bernhard T, Green, Melissa, Quidé, Yann, Pantelis, Christos, Chan, Raymond, Wang, Yi, Ettinger, Ulrich, Debbané, Martin, Derome, Melodie, Gaser, Christian, Besteher, Bianca, Diederen, Kelly, Spencer, Tom J, Fletcher, Paul, Rössler, Wulf, Smigielski, Lukasz, Kumari, Veena, Premkumar, Preethi, Park, Haeme RP, Wiebels, Kristina, Lemmers-Jansen, Imke, Gilleen, James, Allen, Paul, Kozhuharova, Petya, Marsman, Jan-Bernard, Lebedeva, Irina, Tomyshev, Alexander, Mukhorina, Anna, Kaiser, Stefan, Fett, Anne-Kathrin, Sommer, Iris, Schuite-Koops, Sanne, Paquola, Casey, Larivière, Sara, Bernhardt, Boris, Dagher, Alain, Grant, Phillip, van Erp, Theo GM, Turner, Jessica A, Thompson, Paul M, Aleman, André, Modinos, Gemma, Kirschner, Matthias, Kirschner, Matthias, Hodzic-Santor, Benazir, Antoniades, Mathilde, Nenadic, Igor, Kircher, Tilo, Krug, Axel, Meller, Tina, Grotegerd, Dominik, Fornito, Alex, Arnatkeviciute, Aurina, Bellgrove, Mark A, Tiego, Jeggan, Dannlowski, Udo, Koch, Katharina, Hülsmann, Carina, Kugel, Harald, Enneking, Verena, Klug, Melissa, Leehr, Elisabeth J, Böhnlein, Joscha, Gruber, Marius, Mehler, David, DeRosse, Pamela, Moyett, Ashley, Baune, Bernhard T, Green, Melissa, Quidé, Yann, Pantelis, Christos, Chan, Raymond, Wang, Yi, Ettinger, Ulrich, Debbané, Martin, Derome, Melodie, Gaser, Christian, Besteher, Bianca, Diederen, Kelly, Spencer, Tom J, Fletcher, Paul, Rössler, Wulf, Smigielski, Lukasz, Kumari, Veena, Premkumar, Preethi, Park, Haeme RP, Wiebels, Kristina, Lemmers-Jansen, Imke, Gilleen, James, Allen, Paul, Kozhuharova, Petya, Marsman, Jan-Bernard, Lebedeva, Irina, Tomyshev, Alexander, Mukhorina, Anna, Kaiser, Stefan, Fett, Anne-Kathrin, Sommer, Iris, Schuite-Koops, Sanne, Paquola, Casey, Larivière, Sara, Bernhardt, Boris, Dagher, Alain, Grant, Phillip, van Erp, Theo GM, Turner, Jessica A, Thompson, Paul M, Aleman, André, and Modinos, Gemma
Abstract: Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.
Published: 2022

37. Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

Author: Baldwin, Helen, Baldwin, Helen, Radua, Joaquim, Antoniades, Mathilde, Haas, Shalaila S, Frangou, Sophia, Agartz, Ingrid, Allen, Paul, Andreassen, Ole A, Atkinson, Kimberley, Bachman, Peter, Baeza, Inmaculada, Bartholomeusz, Cali F, Chee, Michael WL, Colibazzi, Tiziano, Cooper, Rebecca E, Corcoran, Cheryl M, Cropley, Vanessa L, Ebdrup, Bjørn H, Fortea, Adriana, Glenthøj, Louise Birkedal, Hamilton, Holly K, Haut, Kristen M, Hayes, Rebecca A, He, Ying, Heekeren, Karsten, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Klaunig, Mallory J, Koike, Shinsuke, Koppel, Alex, Kristensen, Tina D, Bin Kwak, Yoo, Kwon, Jun Soo, Lawrie, Stephen M, Lebedeva, Irina, Lee, Jimmy, Lin, Ashleigh, Loewy, Rachel L, Mathalon, Daniel H, Michel, Chantal, Mizrahi, Romina, Møller, Paul, Nelson, Barnaby, Nemoto, Takahiro, Nordholm, Dorte, Omelchenko, Maria A, Pantelis, Christos, Raghava, Jayachandra M, Røssberg, Jan I, Rössler, Wulf, Salisbury, Dean F, Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K, Tang, Jinsong, Theodoridou, Anastasia, Thomopoulos, Sophia I, Tomyshev, Alexander S, Uhlhaas, Peter J, Værnes, Tor G, van Amelsvoort, Therese AMJ, Van Erp, Theo GM, Waltz, James A, Westlye, Lars T, Wood, Stephen J, Zhou, Juan H, McGuire, Philip, Thompson, Paul M, Jalbrzikowski, Maria, Hernaus, Dennis, Fusar-Poli, Paolo, ENIGMA Clinical High Risk for Psychosis Working Group, Baldwin, Helen, Baldwin, Helen, Radua, Joaquim, Antoniades, Mathilde, Haas, Shalaila S, Frangou, Sophia, Agartz, Ingrid, Allen, Paul, Andreassen, Ole A, Atkinson, Kimberley, Bachman, Peter, Baeza, Inmaculada, Bartholomeusz, Cali F, Chee, Michael WL, Colibazzi, Tiziano, Cooper, Rebecca E, Corcoran, Cheryl M, Cropley, Vanessa L, Ebdrup, Bjørn H, Fortea, Adriana, Glenthøj, Louise Birkedal, Hamilton, Holly K, Haut, Kristen M, Hayes, Rebecca A, He, Ying, Heekeren, Karsten, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Klaunig, Mallory J, Koike, Shinsuke, Koppel, Alex, Kristensen, Tina D, Bin Kwak, Yoo, Kwon, Jun Soo, Lawrie, Stephen M, Lebedeva, Irina, Lee, Jimmy, Lin, Ashleigh, Loewy, Rachel L, Mathalon, Daniel H, Michel, Chantal, Mizrahi, Romina, Møller, Paul, Nelson, Barnaby, Nemoto, Takahiro, Nordholm, Dorte, Omelchenko, Maria A, Pantelis, Christos, Raghava, Jayachandra M, Røssberg, Jan I, Rössler, Wulf, Salisbury, Dean F, Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K, Tang, Jinsong, Theodoridou, Anastasia, Thomopoulos, Sophia I, Tomyshev, Alexander S, Uhlhaas, Peter J, Værnes, Tor G, van Amelsvoort, Therese AMJ, Van Erp, Theo GM, Waltz, James A, Westlye, Lars T, Wood, Stephen J, Zhou, Juan H, McGuire, Philip, Thompson, Paul M, Jalbrzikowski, Maria, Hernaus, Dennis, Fusar-Poli, Paolo, and ENIGMA Clinical High Risk for Psychosis Working Group
Abstract: Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, i
Published: 2022

38. Cell type-specific manifestations of cortical thickness heterogeneity in schizophrenia

Author: Di Biase, Maria A., Geaghan, Michael P., Reay, William R., Seidlitz, Jakob, Weickert, Cynthia Shannon, Pébay, Alice, Green, Melissa J., Quidé, Yann, Atkins, Joshua R., Coleman, Michael J., Bouix, Sylvain, Knyazhanskaya, Evdokiya E., Lyall, Amanda E., Pasternak, Ofer, Kubicki, Marek, Rathi, Yogesh, Visco, Andrew, Gaunnac, Megan, Lv, Jinglei, Mesholam-Gately, Raquelle I., Lewandowski, Kathryn E., Holt, Daphne J., Keshavan, Matcheri S., Pantelis, Christos, Öngür, Dost, Breier, Alan, Cairns, Murray J., Shenton, Martha E., Zalesky, Andrew, Di Biase, Maria A., Geaghan, Michael P., Reay, William R., Seidlitz, Jakob, Weickert, Cynthia Shannon, Pébay, Alice, Green, Melissa J., Quidé, Yann, Atkins, Joshua R., Coleman, Michael J., Bouix, Sylvain, Knyazhanskaya, Evdokiya E., Lyall, Amanda E., Pasternak, Ofer, Kubicki, Marek, Rathi, Yogesh, Visco, Andrew, Gaunnac, Megan, Lv, Jinglei, Mesholam-Gately, Raquelle I., Lewandowski, Kathryn E., Holt, Daphne J., Keshavan, Matcheri S., Pantelis, Christos, Öngür, Dost, Breier, Alan, Cairns, Murray J., Shenton, Martha E., and Zalesky, Andrew
Abstract: Brain morphology differs markedly between individuals with schizophrenia, but the cellular and genetic basis of this heterogeneity is poorly understood. Here, we sought to determine whether cortical thickness (CTh) heterogeneity in schizophrenia relates to interregional variation in distinct neural cell types, as inferred from established gene expression data and person-specific genomic variation. This study comprised 1849 participants in total, including a discovery (140 cases and 1267 controls) and a validation cohort (335 cases and 185 controls). To characterize CTh heterogeneity, normative ranges were established for 34 cortical regions and the extent of deviation from these ranges was measured for each individual with schizophrenia. CTh deviations were explained by interregional gene expression levels of five out of seven neural cell types examined: (1) astrocytes; (2) endothelial cells; (3) oligodendrocyte progenitor cells (OPCs); (4) excitatory neurons; and (5) inhibitory neurons. Regional alignment between CTh alterations with cell type transcriptional maps distinguished broad patient subtypes, which were validated against genomic data drawn from the same individuals. In a predominantly neuronal/endothelial subtype (22% of patients), CTh deviations covaried with polygenic risk for schizophrenia (sczPRS) calculated specifically from genes marking neuronal and endothelial cells (r = −0.40, p = 0.010). Whereas, in a predominantly glia/OPC subtype (43% of patients), CTh deviations covaried with sczPRS calculated from glia and OPC-linked genes (r = −0.30, p = 0.028). This multi-scale analysis of genomic, transcriptomic, and brain phenotypic data may indicate that CTh heterogeneity in schizophrenia relates to inter-individual variation in cell-type specific functions. Decomposing heterogeneity in relation to cortical cell types enables prioritization of schizophrenia subsets for future disease modeling efforts.
Published: 2022

39. Neurobiologically Based Stratification of Recent Onset Depression and Psychosis: Identification of Two Distinct Transdiagnostic Phenotypes

Author: Lalousis, Paris Alexandros, Schmaal, Lianne, Wood, Stephen J., Reniers, Renate L.E.P., Barnes, Nicholas M., Chisholm, Katharine, Griffiths, Sian Lowri, Stainton, Alexandra, Wen, Junhao, Hwang, Gyujoon, Davatzikos, Christos, Wenzel, Julian, Kambeitz-Ilankovic, Lana, Andreou, Christina, Bonivento, Carolina, Dannlowski, Udo, Ferro, Adele, Liechtenstein, Theresa, Riecher-Rössler, Anita, Romer, Georg, Rosen, Marlene, Bertolino, Alessandro, Borgwardt, Stefan, Brambilla, Paolo, Kambeitz, Joseph, Lencer, Rebekka, Pantelis, Christos, Ruhrmann, Stephan, Salokangas, Raimo K.R., Schultze-Lutter, Frauke, Schmidt, André, Meisenzahl, Eva, Koutsouleris, Nikolaos, Dwyer, Dominic, Upthegrove, Rachel, Lalousis, Paris Alexandros, Schmaal, Lianne, Wood, Stephen J., Reniers, Renate L.E.P., Barnes, Nicholas M., Chisholm, Katharine, Griffiths, Sian Lowri, Stainton, Alexandra, Wen, Junhao, Hwang, Gyujoon, Davatzikos, Christos, Wenzel, Julian, Kambeitz-Ilankovic, Lana, Andreou, Christina, Bonivento, Carolina, Dannlowski, Udo, Ferro, Adele, Liechtenstein, Theresa, Riecher-Rössler, Anita, Romer, Georg, Rosen, Marlene, Bertolino, Alessandro, Borgwardt, Stefan, Brambilla, Paolo, Kambeitz, Joseph, Lencer, Rebekka, Pantelis, Christos, Ruhrmann, Stephan, Salokangas, Raimo K.R., Schultze-Lutter, Frauke, Schmidt, André, Meisenzahl, Eva, Koutsouleris, Nikolaos, Dwyer, Dominic, and Upthegrove, Rachel
Abstract: Background: Identifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity and provide better candidates for predictive modeling. We aimed to identify clusters across patients with recent-onset depression (ROD) and recent-onset psychosis (ROP) based on structural neuroimaging data. We hypothesized that these transdiagnostic clusters would identify patients with poor outcome and allow more accurate prediction of symptomatic remission than traditional diagnostic structures. Methods: HYDRA (Heterogeneity through Discriminant Analysis) was trained on whole-brain volumetric measures from 577 participants from the discovery sample of the multisite PRONIA study to identify neurobiologically driven clusters, which were then externally validated in the PRONIA replication sample (n = 404) and three datasets of chronic samples (Centre for Biomedical Research Excellence, n = 146; Mind Clinical Imaging Consortium, n = 202; Munich, n = 470). Results: The optimal clustering solution was two transdiagnostic clusters (cluster 1: n = 153, 67 ROP, 86 ROD; cluster 2: n = 149, 88 ROP, 61 ROD; adjusted Rand index = 0.618). The two clusters contained both patients with ROP and patients with ROD. One cluster had widespread gray matter volume deficits and more positive, negative, and functional deficits (impaired cluster), and one cluster revealed a more preserved neuroanatomical signature and more core depressive symptomatology (preserved cluster). The clustering solution was internally and externally validated and assessed for clinical utility in predicting 9-month symptomatic remission, outperforming traditional diagnostic structures. Conclusions: We identified two transdiagnostic neuroanatomically informed clusters that are clinically and biologically distinct, challenging current diagnostic boundaries in recent-onset mental health disorders. These results may aid understanding of the etiology of poor outcome patients transdiagnost
Published: 2022

40. Neurobiologically Based Stratification of Recent Onset Depression and Psychosis: Identification of Two Distinct Transdiagnostic Phenotypes

Author: Lalousis, Paris Alexandros, Schmaal, Lianne, Wood, Stephen J., Reniers, Renate L.E.P., Barnes, Nicholas M., Chisholm, Katharine, Griffiths, Sian Lowri, Stainton, Alexandra, Wen, Junhao, Hwang, Gyujoon, Davatzikos, Christos, Wenzel, Julian, Kambeitz-Ilankovic, Lana, Andreou, Christina, Bonivento, Carolina, Dannlowski, Udo, Ferro, Adele, Liechtenstein, Theresa, Riecher-Rössler, Anita, Romer, Georg, Rosen, Marlene, Bertolino, Alessandro, Borgwardt, Stefan, Brambilla, Paolo, Kambeitz, Joseph, Lencer, Rebekka, Pantelis, Christos, Ruhrmann, Stephan, Salokangas, Raimo K.R., Schultze-Lutter, Frauke, Schmidt, André, Meisenzahl, Eva, Koutsouleris, Nikolaos, Dwyer, Dominic, Upthegrove, Rachel, Lalousis, Paris Alexandros, Schmaal, Lianne, Wood, Stephen J., Reniers, Renate L.E.P., Barnes, Nicholas M., Chisholm, Katharine, Griffiths, Sian Lowri, Stainton, Alexandra, Wen, Junhao, Hwang, Gyujoon, Davatzikos, Christos, Wenzel, Julian, Kambeitz-Ilankovic, Lana, Andreou, Christina, Bonivento, Carolina, Dannlowski, Udo, Ferro, Adele, Liechtenstein, Theresa, Riecher-Rössler, Anita, Romer, Georg, Rosen, Marlene, Bertolino, Alessandro, Borgwardt, Stefan, Brambilla, Paolo, Kambeitz, Joseph, Lencer, Rebekka, Pantelis, Christos, Ruhrmann, Stephan, Salokangas, Raimo K.R., Schultze-Lutter, Frauke, Schmidt, André, Meisenzahl, Eva, Koutsouleris, Nikolaos, Dwyer, Dominic, and Upthegrove, Rachel
Abstract: Background: Identifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity and provide better candidates for predictive modeling. We aimed to identify clusters across patients with recent-onset depression (ROD) and recent-onset psychosis (ROP) based on structural neuroimaging data. We hypothesized that these transdiagnostic clusters would identify patients with poor outcome and allow more accurate prediction of symptomatic remission than traditional diagnostic structures. Methods: HYDRA (Heterogeneity through Discriminant Analysis) was trained on whole-brain volumetric measures from 577 participants from the discovery sample of the multisite PRONIA study to identify neurobiologically driven clusters, which were then externally validated in the PRONIA replication sample (n = 404) and three datasets of chronic samples (Centre for Biomedical Research Excellence, n = 146; Mind Clinical Imaging Consortium, n = 202; Munich, n = 470). Results: The optimal clustering solution was two transdiagnostic clusters (cluster 1: n = 153, 67 ROP, 86 ROD; cluster 2: n = 149, 88 ROP, 61 ROD; adjusted Rand index = 0.618). The two clusters contained both patients with ROP and patients with ROD. One cluster had widespread gray matter volume deficits and more positive, negative, and functional deficits (impaired cluster), and one cluster revealed a more preserved neuroanatomical signature and more core depressive symptomatology (preserved cluster). The clustering solution was internally and externally validated and assessed for clinical utility in predicting 9-month symptomatic remission, outperforming traditional diagnostic structures. Conclusions: We identified two transdiagnostic neuroanatomically informed clusters that are clinically and biologically distinct, challenging current diagnostic boundaries in recent-onset mental health disorders. These results may aid understanding of the etiology of poor outcome patients transdiagnost
Published: 2022

41. Exploring Links Between Psychosis and Frontotemporal Dementia Using Multimodal Machine Learning Dementia Praecox Revisited

Author: Koutsouleris, Nikolaos, Pantelis, Christos, Velakoulis, Dennis, McGuire, Philip, Dwyer, Dominic B., Urquijo-Castro, Maria-Fernanda, Paul, Riya, Popovic, David, Oeztuerk, Oemer, Kambeitz, Joseph, Salokangas, Raimo K. R., Hietala, Jarmo, Bertolino, Alessandro, Brambilla, Paolo, Upthegrove, Rachel, Wood, Stephen J., Lencer, Rebekka, Borgwardt, Stefan, Maj, Carlo, Nothen, Markus, Degenhardt, Franziska, Polyakova, Maryna, Mueller, Karsten, Villringer, Arno, Danek, Adrian, Fassbender, Klaus, Fliessbach, Klaus, Jahn, Holger, Kornhuber, Johannes, Landwehrmeyer, Bernhard, Anderl-Straub, Sarah, Prudlo, Johannes, Synofzik, Matthis, Wiltfang, Jens, Riedl, Lina, Diehl-Schmid, Janine, Otto, Markus, Meisenzahl, Eva, Falkai, Peter, Schroeter, Matthias L., Koutsouleris, Nikolaos, Pantelis, Christos, Velakoulis, Dennis, McGuire, Philip, Dwyer, Dominic B., Urquijo-Castro, Maria-Fernanda, Paul, Riya, Popovic, David, Oeztuerk, Oemer, Kambeitz, Joseph, Salokangas, Raimo K. R., Hietala, Jarmo, Bertolino, Alessandro, Brambilla, Paolo, Upthegrove, Rachel, Wood, Stephen J., Lencer, Rebekka, Borgwardt, Stefan, Maj, Carlo, Nothen, Markus, Degenhardt, Franziska, Polyakova, Maryna, Mueller, Karsten, Villringer, Arno, Danek, Adrian, Fassbender, Klaus, Fliessbach, Klaus, Jahn, Holger, Kornhuber, Johannes, Landwehrmeyer, Bernhard, Anderl-Straub, Sarah, Prudlo, Johannes, Synofzik, Matthis, Wiltfang, Jens, Riedl, Lina, Diehl-Schmid, Janine, Otto, Markus, Meisenzahl, Eva, Falkai, Peter, and Schroeter, Matthias L.
Abstract: IMPORTANCE The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far. OBJECTIVE To use machine learning to compare the expression of structural magnetic resonance imaging (MRI) patterns of behavioral-variant frontotemporal dementia (bvFTD), Alzheimer disease (AD). and schizophrenia; estimate predictability in patients with bvFTD and schizophrenia based on sociodemographic, clinical, and biological data; and examine prognostic value, genetic underpinnings, and progression in patients with clinical high-risk (CHR) states for psychosis or recent-onset depression (ROD). DESIGN, SETTING, AND PARTICIPANTS This study included 1870 individuals from S cohorts, including (1) patients with bvFTD (n =108), established AD (n = 44), mild cognitive impairment or early-stage AD (n = 96), schizophrenia (n = 157), or major depression (n = 102) to derive and compare diagnostic patterns and (2) patients with CHR (n = 160) or ROD (n = 161) to test patterns' prognostic relevance and progression. Healthy individuals (n = 1042) were used for age-related and cohort-related data calibration. Data were collected from January 1996 to July 2019 and analyzed between April 2020 and April 2022. MAIN OUTCOMES AND MEASURES Case assignments based on diagnostic patterns; sociodemographic, clinical, and biological data; 2-year functional outcomes and genetic separability of patients with CHR and ROD with high vs low pattern expression; and pattern progression from baseline to follow-up MRI scans in patients with nonrecovery vs preserved recovery. RESULTS Of 1870 included patients, 902 (48.2%) were female, and the mean (SD) age was 38.0 (19.3) years. The bvFTD pattern comprising prefrontal, insular, and limbic volume reductions was more expressed in patients with schizophrenia (65 of 157 [41.2%]) and major depression (22
Published: 2022

42. Relationship between jumping to conclusions and clinical outcomes in people at clinical high-risk for psychosis

Author: Catalan, Ana, Tognin, Stefania, Kempton, Matthew J., Stahl, Daniel, Salazar de Pablo, Gonzalo, Nelson, Barnaby, Pantelis, Christos, Riecher-Rossler, Anita, Bressan, Rodrigo, Barrantes-Vidal, Neus, Krebs, Marie-Odile, Nordentoft, Merete, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P. F., van Os, Jim, de Haan, Lieuwe, van der Gaag, Mark, Valmaggia, Lucia R., McGuire, Philip, Catalan, Ana, Tognin, Stefania, Kempton, Matthew J., Stahl, Daniel, Salazar de Pablo, Gonzalo, Nelson, Barnaby, Pantelis, Christos, Riecher-Rossler, Anita, Bressan, Rodrigo, Barrantes-Vidal, Neus, Krebs, Marie-Odile, Nordentoft, Merete, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P. F., van Os, Jim, de Haan, Lieuwe, van der Gaag, Mark, Valmaggia, Lucia R., and McGuire, Philip
Abstract: Background Psychosis is associated with a reasoning bias, which manifests as a tendency to 'jump to conclusions'. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes. Methods In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A 'beads' task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point. Results There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; chi 2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ. Conclusions In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.
Published: 2022

43. Pattern of predictive features of continued cannabis use in patients with recent-onset psychosis and clinical high-risk for psychosis

Author: Penzel, Nora, Sanfelici, Rachele, Antonucci, Linda A., Betz, Linda T., Dwyer, Dominic, Ruef, Anne, Cho, Kang Ik K., Cumming, Paul, Pogarell, Oliver, Howes, Oliver, Falkai, Peter, Upthegrove, Rachel, Borgwardt, Stefan, Brambilla, Paolo, Lencer, Rebekka, Meisenzahl, Eva, Schultze-Lutter, Frauke, Rosen, Marlene, Lichtenstein, Theresa, Kambeitz-Ilankovic, Lana, Ruhrmann, Stephan, Salokangas, Raimo K. R., Pantelis, Christos, Wood, Stephen J., Quednow, Boris B., Pergola, Giulio, Bertolino, Alessandro, Koutsouleris, Nikolaos, Kambeitz, Joseph, Penzel, Nora, Sanfelici, Rachele, Antonucci, Linda A., Betz, Linda T., Dwyer, Dominic, Ruef, Anne, Cho, Kang Ik K., Cumming, Paul, Pogarell, Oliver, Howes, Oliver, Falkai, Peter, Upthegrove, Rachel, Borgwardt, Stefan, Brambilla, Paolo, Lencer, Rebekka, Meisenzahl, Eva, Schultze-Lutter, Frauke, Rosen, Marlene, Lichtenstein, Theresa, Kambeitz-Ilankovic, Lana, Ruhrmann, Stephan, Salokangas, Raimo K. R., Pantelis, Christos, Wood, Stephen J., Quednow, Boris B., Pergola, Giulio, Bertolino, Alessandro, Koutsouleris, Nikolaos, and Kambeitz, Joseph
Abstract: Continued cannabis use (CCu) is an important predictor for poor long-term outcomes in psychosis and clinically high-risk patients, but no generalizable model has hitherto been tested for its ability to predict CCu in these vulnerable patient groups. In the current study, we investigated how structured clinical and cognitive assessments and structural magnetic resonance imaging (sMRI) contributed to the prediction of CCu in a group of 109 patients with recent-onset psychosis (ROP). We tested the generalizability of our predictors in 73 patients at clinical high-risk for psychosis (CHR). Here, CCu was defined as any cannabis consumption between baseline and 9-month follow-up, as assessed in structured interviews. All patients reported lifetime cannabis use at baseline. Data from clinical assessment alone correctly classified 73% (p < 0.001) of ROP and 59 % of CHR patients. The classifications of CCu based on sMRI and cognition were non-significant (ps > 0.093), and their addition to the interview-based predictor via stacking did not improve prediction significantly, either in the ROP or CHR groups (ps > 0.065). Lower functioning, specific substance use patterns, urbanicity and a lack of other coping strategies contributed reliably to the prediction of CCu and might thus represent important factors for guiding preventative efforts. Our results suggest that it may be possible to identify by clinical measures those psychosis-spectrum patients at high risk for CCu, potentially allowing to improve clinical care through targeted interventions. However, our model needs further testing in larger samples including more diverse clinical populations before being transferred into clinical practice.
Published: 2022

44. Novel Gyrification Networks Reveal Links with Psychiatric Risk Factors in Early Illness

Author: Sanfelici, Rachele, Ruef, Anne, Antonucci, Linda A., Penzel, Nora, Sotiras, Aristeidis, Sen Dong, Mark, Urquijo-Castro, Maria, Wenzel, Julian, Kambeitz-Ilankovic, Lana, Hettwer, Meike D., Ruhrmann, Stephan, Chisholm, Katharine, Riecher-Rossler, Anita, Falkai, Peter, Pantelis, Christos, Salokangas, Raimo K. R., Lencer, Rebekka, Bertolino, Alessandro, Kambeitz, Joseph, Meisenzahl, Eva, Borgwardt, Stefan, Brambilla, Paolo, Wood, Stephen J., Upthegrove, Rachel, Schultze-Lutter, Frauke, Koutsouleris, Nikolaos, Dwyer, Dominic B., Sanfelici, Rachele, Ruef, Anne, Antonucci, Linda A., Penzel, Nora, Sotiras, Aristeidis, Sen Dong, Mark, Urquijo-Castro, Maria, Wenzel, Julian, Kambeitz-Ilankovic, Lana, Hettwer, Meike D., Ruhrmann, Stephan, Chisholm, Katharine, Riecher-Rossler, Anita, Falkai, Peter, Pantelis, Christos, Salokangas, Raimo K. R., Lencer, Rebekka, Bertolino, Alessandro, Kambeitz, Joseph, Meisenzahl, Eva, Borgwardt, Stefan, Brambilla, Paolo, Wood, Stephen J., Upthegrove, Rachel, Schultze-Lutter, Frauke, Koutsouleris, Nikolaos, and Dwyer, Dominic B.
Abstract: Adult gyrification provides a window into coordinated early neurodevelopment when disruptions predispose individuals to psychiatric illness. We hypothesized that the echoes of such disruptions should be observed within structural gyrification networks in early psychiatric illness that would demonstrate associations with developmentally relevant variables rather than specific psychiatric symptoms. We employed a new data-driven method (Orthogonal Projective Non-Negative Matrix Factorization) to delineate novel gyrification-based networks of structural covariance in 308 healthy controls. Gyrification within the networks was then compared to 713 patients with recent onset psychosis or depression, and at clinical high-risk. Associations with diagnosis, symptoms, cognition, and functioning were investigated using linear models. Results demonstrated 18 novel gyrification networks in controls as verified by internal and external validation. Gyrification was reduced in patients in temporal-insular, lateral occipital, and lateral fronto-parietal networks (p(FDR) < 0.01) and was not moderated by illness group. Higher gyrification was associated with better cognitive performance and lifetime role functioning, but not with symptoms. The findings demonstrated that gyrification can be parsed into novel brain networks that highlight generalized illness effects linked to developmental vulnerability. When combined, our study widens the window into the etiology of psychiatric risk and its expression in adulthood.
Published: 2022

45. Using combined environmental-clinical classification models to predict role functioning outcome in clinical high-risk states for psychosis and recent-onset depression

Author: Antonucci, Linda A., Penzel, Nora, Sanfelici, Rachele, Pigoni, Alessandro, Kambeitz-Ilankovic, Lana, Dwyer, Dominic, Ruef, Anne, Sen Dong, Mark, Ozturk, Omer Faruk, Chisholm, Katharine, Haidl, Theresa, Rosen, Marlene, Ferro, Adele, Pergola, Giulio, Andriola, Ileana, Blasi, Giuseppe, Ruhrmann, Stephan, Schultze-Lutter, Frauke, Falkai, Peter, Kambeitz, Joseph, Lencer, Rebekka, Dannlowski, Udo, Upthegrove, Rachel, Salokangas, Raimo K. R., Pantelis, Christos, Meisenzahl, Eva, Wood, Stephen J., Brambilla, Paolo, Borgwardt, Stefan, Bertolino, Alessandro, Koutsouleris, Nikolaos, Antonucci, Linda A., Penzel, Nora, Sanfelici, Rachele, Pigoni, Alessandro, Kambeitz-Ilankovic, Lana, Dwyer, Dominic, Ruef, Anne, Sen Dong, Mark, Ozturk, Omer Faruk, Chisholm, Katharine, Haidl, Theresa, Rosen, Marlene, Ferro, Adele, Pergola, Giulio, Andriola, Ileana, Blasi, Giuseppe, Ruhrmann, Stephan, Schultze-Lutter, Frauke, Falkai, Peter, Kambeitz, Joseph, Lencer, Rebekka, Dannlowski, Udo, Upthegrove, Rachel, Salokangas, Raimo K. R., Pantelis, Christos, Meisenzahl, Eva, Wood, Stephen J., Brambilla, Paolo, Borgwardt, Stefan, Bertolino, Alessandro, and Koutsouleris, Nikolaos
Abstract: Background Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to accurate role functioning prediction, calling for the investigation of additional risk dimensions. Role functioning may be more strongly associated with environmental adverse events than social functioning. Aims We aimed to predict role functioning in CHR, ROD and transdiagnostically, by adding environmental adverse events-related variables to clinical and sMRI data domains within the PRONIA sample. Method Baseline clinical, environmental and sMRI data collected in 92 CHR and 95 ROD samples were trained to predict lower versus higher follow-up role functioning, using support vector classification and mixed k-fold/leave-site-out cross-validation. We built separate predictions for each domain, created multimodal predictions and validated them in independent cohorts (74 CHR, 66 ROD). Results Models combining clinical and environmental data predicted role outcome in discovery and replication samples of CHR (balanced accuracies: 65.4% and 67.7%, respectively), ROD (balanced accuracies: 58.9% and 62.5%, respectively), and transdiagnostically (balanced accuracies: 62.4% and 68.2%, respectively). The most reliable environmental features for role outcome prediction were adult environmental adjustment, childhood trauma in CHR and childhood environmental adjustment in ROD. Conclusions Findings support the hypothesis that environmental variables inform role outcome prediction, highlight the existence of both transdiagnostic and syndrome-specific predictive environmental adverse events, and emphasise the importance of implementing real-world models by measuring multiple risk dimensions.
Published: 2022

46. The impact of visual dysfunctions in recent-onset psychosis and clinical high-risk state for psychosis

Author: Schwarzer, Johanna M., Meyhoefer, Inga, Antonucci, Linda A., Kambeitz-Ilankovic, Lana, Surmann, Marian, Bienek, Olga, Romer, Georg, Dannlowski, Udo, Hahn, Tim, Korda, Alexandra, Dwyer, Dominic B., Ruef, Anne, Haas, Shalaila S., Rosen, Marlene, Lichtenstein, Theresa, Ruhrmann, Stephan, Kambeitz, Joseph, Salokangas, Raimo K. R., Pantelis, Christos, Schultze-Lutter, Frauke, Meisenzahl, Eva, Brambilla, Paolo, Bertolino, Alessandro, Borgwardt, Stefan, Upthegrove, Rachel, Koutsouleris, Nikolaos, Lencer, Rebekka, Schwarzer, Johanna M., Meyhoefer, Inga, Antonucci, Linda A., Kambeitz-Ilankovic, Lana, Surmann, Marian, Bienek, Olga, Romer, Georg, Dannlowski, Udo, Hahn, Tim, Korda, Alexandra, Dwyer, Dominic B., Ruef, Anne, Haas, Shalaila S., Rosen, Marlene, Lichtenstein, Theresa, Ruhrmann, Stephan, Kambeitz, Joseph, Salokangas, Raimo K. R., Pantelis, Christos, Schultze-Lutter, Frauke, Meisenzahl, Eva, Brambilla, Paolo, Bertolino, Alessandro, Borgwardt, Stefan, Upthegrove, Rachel, Koutsouleris, Nikolaos, and Lencer, Rebekka
Abstract: Subtle subjective visual dysfunctions (VisDys) are reported by about 50% of patients with schizophrenia and are suggested to predict psychosis states. Deeper insight into VisDys, particularly in early psychosis states, could foster the understanding of basic disease mechanisms mediating susceptibility to psychosis, and thereby inform preventive interventions. We systematically investigated the relationship between VisDys and core clinical measures across three early phase psychiatric conditions. Second, we used a novel multivariate pattern analysis approach to predict VisDys by resting-state functional connectivity within relevant brain systems. VisDys assessed with the Schizophrenia Proneness Instrument (SPI-A), clinical measures, and resting-state fMRI data were examined in recent-onset psychosis (ROP, n = 147), clinical high-risk states of psychosis (CHR, n = 143), recent-onset depression (ROD, n = 151), and healthy controls (HC, n = 280). Our multivariate pattern analysis approach used pairwise functional connectivity within occipital (ON) and frontoparietal (FPN) networks implicated in visual information processing to predict VisDys. VisDys were reported more often in ROP (50.34%), and CHR (55.94%) than in ROD (16.56%), and HC (4.28%). Higher severity of VisDys was associated with less functional remission in both CHR and ROP, and, in CHR specifically, lower quality of life (Qol), higher depressiveness, and more severe impairment of visuospatial constructability. ON functional connectivity predicted presence of VisDys in ROP (balanced accuracy 60.17%, p = 0.0001) and CHR (67.38%, p = 0.029), while in the combined ROP + CHR sample VisDys were predicted by FPN (61.11%, p = 0.006). These large-sample study findings suggest that VisDys are clinically highly relevant not only in ROP but especially in CHR, being closely related to aspects of functional outcome, depressiveness, and Qol. Findings from multivariate pattern analysis support a model of functional integrit
Published: 2022

47. Relationships between global functioning and neuropsychological predictors in subjects at high risk of psychosis or with a recent onset of depression

Author: Squarcina, Letizia, Kambeitz-Ilankovic, Lana, Bonivento, Carolina, Prunas, Cecilia, Oldani, Lucio, Wenzel, Julian, Ruef, Anne, Dwyer, Dominic, Ferro, Adele, Borgwardt, Stefan, Kambeitz, Joseph, Lichtenstein, Theresa Katharina, Meisenzahl, Eva, Pantelis, Christos, Rosen, Marlene, Upthegrove, Rachel, Antonucci, Linda A., Bertolino, Alessandro, Lencer, Rebekka, Ruhrmann, Stephan, Salokangas, Raimo R. K., Schultze-Lutter, Frauke, Chisholm, Katharine, Stainton, Alexandra, Wood, Stephen J., Koutsouleris, Nikolaos, Brambilla, Paolo, Squarcina, Letizia, Kambeitz-Ilankovic, Lana, Bonivento, Carolina, Prunas, Cecilia, Oldani, Lucio, Wenzel, Julian, Ruef, Anne, Dwyer, Dominic, Ferro, Adele, Borgwardt, Stefan, Kambeitz, Joseph, Lichtenstein, Theresa Katharina, Meisenzahl, Eva, Pantelis, Christos, Rosen, Marlene, Upthegrove, Rachel, Antonucci, Linda A., Bertolino, Alessandro, Lencer, Rebekka, Ruhrmann, Stephan, Salokangas, Raimo R. K., Schultze-Lutter, Frauke, Chisholm, Katharine, Stainton, Alexandra, Wood, Stephen J., Koutsouleris, Nikolaos, and Brambilla, Paolo
Abstract: Objective Psychotic disorders are frequently associated with decline in functioning and cognitive difficulties are observed in subjects at clinical high risk (CHR) for psychosis. In this work, we applied automatic approaches to neurocognitive and functioning measures, with the aim of investigating the link between global, social and occupational functioning, and cognition. Methods 102 CHR subjects and 110 patients with recent onset depression (ROD) were recruited. Global assessment of functioning (GAF) related to symptoms (GAF-S) and disability (GAF-D). and global functioning social (GF-S) and role (GF-R), at baseline and of the previous month and year, and a set of neurocognitive measures, were used for classification and regression. Results Neurocognitive measures related to GF-R at baseline (r = 0.20, p = 0.004), GF-S at present (r = 0.14, p = 0.042) and of the past year (r = 0.19, p = 0.005), for GAF-F of the past month (r = 0.24, p < 0.001) and GAF-D of the past year (r = 0.28, p = 0.002). Classification reached values of balanced accuracy of 61% for GF-R and GAF-D. Conclusion We found that neurocognition was related to psychosocial functioning. More specifically, a deficit in executive functions was associated to poor social and occupational functioning.
Published: 2022

48. Verbal memory performance predicts remission and functional outcome in people at clinical high-risk for psychosis

Author: Hedges, Emily P., Dickson, Hannah, Tognin, Stefania, Modinos, Gemma, Antoniades, Mathilde, van der Gaag, Mark, de Haan, Lieuwe, McGorry, Patrick, Pantelis, Christos, Riecher-Rossler, Anita, Bressan, Rodrigo, Barrantes-Vidal, Neus, Krebs, Marie-Odile, Nordentoft, Merete, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P., van Os, Jim, Valmaggia, Lucia R., McGuire, Philip, Kempton, Matthew J., Hedges, Emily P., Dickson, Hannah, Tognin, Stefania, Modinos, Gemma, Antoniades, Mathilde, van der Gaag, Mark, de Haan, Lieuwe, McGorry, Patrick, Pantelis, Christos, Riecher-Rossler, Anita, Bressan, Rodrigo, Barrantes-Vidal, Neus, Krebs, Marie-Odile, Nordentoft, Merete, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P., van Os, Jim, Valmaggia, Lucia R., McGuire, Philip, and Kempton, Matthew J.
Abstract: Robust deficits in cognitive functioning are present in people with psychosis and are evident in the early stages of the disorder. Impairments in verbal memory and verbal fluency are reliably seen in individuals at clinical high risk for psychosis (CHR) compared to healthy populations. As previous studies have shown a relationship between cognition and longer-term outcomes in schizophrenia, the aim of this paper was to explore whether verbal memory and verbal fluency performance predicted outcomes in a large CHR sample recruited as part of the EUGEI High Risk Study. Participants included 316 CHR individuals, 90.8% of whom were not currently on anti psychotic medication, and 60 healthy controls. Verbal memory and verbal fluency performance were measured at baseline. At two-year follow-up, CHR individuals were assessed by three different outcome measures, those who did and did not (1) transition to psychosis, (2) experience burdening impairment or disabilities, or (3) remit clinically from CHR status. Individuals with CHR displayed significant verbal memory and verbal fluency deficits at baseline compared to healthy controls (Hedges' g effect size = 0.24 to 0.66). There were no significant dif-ferences in cognitive performance of those who did , did not transition to psychosis. However, impaired immediate verbal recall predicted both functional disability and non-remission from the CHR state. Results remained significant when analyses were restricted to only include antipsychotic-free CHR participants. These findings may inform the development of early interventions designed to improve cognitive deficits in the early stages of psychosis.
Published: 2022

49. Neurobiologically Based Stratification of Recent- Onset Depression and Psychosis: Identification of Two Distinct Transdiagnostic Phenotypes

Author: Lalousis, Paris Alexandros, Schmaal, Lianne, Wood, Stephen J., Reniers, Renate L. E. P., Barnes, Nicholas M., Chisholm, Katharine, Griffiths, Sian Lowri, Stainton, Alexandra, Wen, Junhao, Hwang, Gyujoon, Davatzikos, Christos, Wenzel, Julian, Kambeitz-Ilankovic, Lana, Andreou, Christina, Bonivento, Carolina, Dannlowski, Udo, Ferro, Adele, Lichtenstein, Theresa, Riecher-Rossler, Anita, Romer, Georg, Upthegrove, Rachel, Lencer, Rebekka, Pantelis, Christos, Ruhrmann, Stephan, Salokangas, Raimo K. R., Schultze-Lutter, Frauke, Schmidt, Andre, Meisenzahl, Eva, Koutsouleris, Nikolaos, Dwyer, Dominic, Rosen, Marlene, Bertolino, Alessandro, Borgwardt, Stefan, Brambilla, Paolo, Kambeitz, Joseph, Lalousis, Paris Alexandros, Schmaal, Lianne, Wood, Stephen J., Reniers, Renate L. E. P., Barnes, Nicholas M., Chisholm, Katharine, Griffiths, Sian Lowri, Stainton, Alexandra, Wen, Junhao, Hwang, Gyujoon, Davatzikos, Christos, Wenzel, Julian, Kambeitz-Ilankovic, Lana, Andreou, Christina, Bonivento, Carolina, Dannlowski, Udo, Ferro, Adele, Lichtenstein, Theresa, Riecher-Rossler, Anita, Romer, Georg, Upthegrove, Rachel, Lencer, Rebekka, Pantelis, Christos, Ruhrmann, Stephan, Salokangas, Raimo K. R., Schultze-Lutter, Frauke, Schmidt, Andre, Meisenzahl, Eva, Koutsouleris, Nikolaos, Dwyer, Dominic, Rosen, Marlene, Bertolino, Alessandro, Borgwardt, Stefan, Brambilla, Paolo, and Kambeitz, Joseph
Abstract: BACKGROUND: Identifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity and provide better candidates for predictive modeling. We aimed to identify clusters across patients with recent-onset depression (ROD) and recent-onset psychosis (ROP) based on structural neuroimaging data. We hypothesized that these transdiagnostic clusters would identify patients with poor outcome and allow more accurate prediction of symptomatic remission than traditional diagnostic structures.METHODS: HYDRA (Heterogeneity through Discriminant Analysis) was trained on whole-brain volumetric measures from 577 participants from the discovery sample of the multisite PRONIA study to identify neurobiologically driven clusters, which were then externally validated in the PRONIA replication sample (n = 404) and three datasets of chronic samples (Centre for Biomedical Research Excellence, n = 146; Mind Clinical Imaging Consortium, n = 202; Munich, n = 470).RESULTS: The optimal clustering solution was two transdiagnostic clusters (cluster 1: n = 153, 67 ROP, 86 ROD; cluster 2: n = 149, 88 ROP, 61 ROD; adjusted Rand index = 0.618). The two clusters contained both patients with ROP and patients with ROD. One cluster had widespread gray matter volume deficits and more positive, negative, and functional deficits (impaired cluster), and one cluster revealed a more preserved neuroanatomical signature and more core depressive symptomatology (preserved cluster). The clustering solution was internally and externally validated and assessed for clinical utility in predicting 9-month symptomatic remission, outperforming traditional diagnostic structures.CONCLUSIONS: We identified two transdiagnostic neuroanatomically informed clusters that are clinically and bio-logically distinct, challenging current diagnostic boundaries in recent-onset mental health disorders. These results may aid understanding of the etiology of poor outcome patients transdiagnostic
Published: 2022

50. Clinical, Brain, and Multilevel Clustering in Early Psychosis and Affective Stages

Author: Dwyer, Dominic B., Buciuman, Madalina-Octavia, Ruef, Anne, Kambeitz, Joseph, Sen Dong, Mark, Stinson, Caedyn, Kambeitz-Ilankovic, Lana, Degenhardt, Franziska, Sanfelici, Rachele, Antonucci, Linda A., Lalousis, Paris Alexandros, Wenzel, Julian, Urquijo-Castro, Maria Fernanda, Popovic, David, Oeztuerk, Oemer Faruk, Haas, Shalaila S., Weiske, Johanna, Hauke, Daniel, Neufang, Susanne, Schmidt-Kraepelin, Christian, Ruhrmann, Stephan, Penzel, Nora, Lichtenstein, Theresa, Rosen, Marlene, Chisholm, Katharine, Riecher-Roessler, Anita, Egloff, Laura, Schmidt, Andre, Andreou, Christina, Hietala, Jarmo, Schirmer, Timo, Romer, Georg, Michel, Chantal, Rossler, Wulf, Maj, Carlo, Borisov, Oleg, Krawitz, Peter M., Falkai, Peter, Pantelis, Christos, Lencer, Rebekka, Bertolino, Alessandro, Borgwardt, Stefan, Noethen, Markus, Brambilla, Paolo, Schultze-Lutter, Frauke, Meisenzahl, Eva, Wood, Stephen J., Davatzikos, Christos, Upthegrove, Rachel, Salokangas, Raimo K. R., Koutsouleris, Nikolaos, Dwyer, Dominic B., Buciuman, Madalina-Octavia, Ruef, Anne, Kambeitz, Joseph, Sen Dong, Mark, Stinson, Caedyn, Kambeitz-Ilankovic, Lana, Degenhardt, Franziska, Sanfelici, Rachele, Antonucci, Linda A., Lalousis, Paris Alexandros, Wenzel, Julian, Urquijo-Castro, Maria Fernanda, Popovic, David, Oeztuerk, Oemer Faruk, Haas, Shalaila S., Weiske, Johanna, Hauke, Daniel, Neufang, Susanne, Schmidt-Kraepelin, Christian, Ruhrmann, Stephan, Penzel, Nora, Lichtenstein, Theresa, Rosen, Marlene, Chisholm, Katharine, Riecher-Roessler, Anita, Egloff, Laura, Schmidt, Andre, Andreou, Christina, Hietala, Jarmo, Schirmer, Timo, Romer, Georg, Michel, Chantal, Rossler, Wulf, Maj, Carlo, Borisov, Oleg, Krawitz, Peter M., Falkai, Peter, Pantelis, Christos, Lencer, Rebekka, Bertolino, Alessandro, Borgwardt, Stefan, Noethen, Markus, Brambilla, Paolo, Schultze-Lutter, Frauke, Meisenzahl, Eva, Wood, Stephen J., Davatzikos, Christos, Upthegrove, Rachel, Salokangas, Raimo K. R., and Koutsouleris, Nikolaos
Abstract: IMPORTANCE Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures. OBJECTIVE To use machine learning techniques to cluster, compare, and combine subgroup solutions using clinical and brain structural imaging data from early psychosis and depression stages. DESIGN, SETTING, AND PARTICIPANTS A multisite, naturalistic, longitudinal cohort study (10 sites in 5 European countries; including major follow-up intervals at 9 and 18 months) with a referred patient sample of those with clinical high risk for psychosis (CHR-P), recent-onset psychosis (ROP), recent-onset depression (ROD), and healthy controls were recruited between February 1, 2014, to July 1, 2019. Data were analyzed between January 2020 and January 2022. MAIN OUTCOMES AND MEASURES A nonnegative matrix factorization technique separately decomposed clinical (287 variables) and parcellated brain structural volume (204 gray, white, and cerebrospinal fluid regions) data across CHR-P, ROP, ROD, and healthy controls study groups. Stability criteria determined cluster number using nested cross-validation. Validation targets were compared across subgroup solutions (premorbid, longitudinal, and schizophrenia polygenic risk scores). Multiclass supervised machine learning produced a transferable solution to the validation sample. RESULTS There were a total of 749 individuals in the discovery group and 610 individuals in the validation group. Individuals included those with CHR-P (n = 287), ROP (n = 323), ROD (n = 285), and healthy controls (n = 464), The mean (SD) age was 25.1 (5.9) years, and 702 (51.7%) were female. A clinical 4-dimensional solution separated individuals based on positive symptoms, negative symptoms, depression, and functioning, demonstrating associations with all validation targets. Brain clustering re
Published: 2022

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