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54. Classifying individuals at high-risk for psychosis based on functional brain activity during working memory processing

Author

Bendfeldt, Kerstin, primary, Smieskova, Renata, additional, Koutsouleris, Nikolaos, additional, Klöppel, Stefan, additional, Schmidt, André, additional, Walter, Anna, additional, Harrisberger, Fabienne, additional, Wrege, Johannes, additional, Simon, Andor, additional, Taschler, Bernd, additional, Nichols, Thomas, additional, Riecher-Rössler, Anita, additional, Lang, Undine E., additional, Radue, Ernst-Wilhelm, additional, and Borgwardt, Stefan, additional

Published
2015
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55. Hippocampal volume correlates with attenuated negative psychotic symptoms irrespective of antidepressant medication

Author

Bernasconi, Raffaele, primary, Smieskova, Renata, additional, Schmidt, André, additional, Harrisberger, Fabienne, additional, Raschle, Nora Maria, additional, Lenz, Claudia, additional, Walter, Anna, additional, Simon, Andor, additional, Riecher-Rössler, Anita, additional, Radue, Ernst-Wilhelm, additional, Lang, Undine E., additional, Fusar-Poli, Paolo, additional, and Borgwardt, Stefan J., additional

Published
2015
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56. Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations

Author

van Os, Jim, Rutten, Bart P., Myin-Germeys, Inez, Delespaul, Philippe, Viechtbauer, Wolfgang, van Zelst, Catherine, Bruggeman, Richard, Reininghaus, Ulrich, Morgan, Craig, Murray, Robin M., Di Forti, Marta, McGuire, Philip, Valmaggia, Lucia R., Kempton, Matthew J., Gayer-Anderson, Charlotte, Hubbard, Kathryn, Beards, Stephanie, Stilo, Simona A., Onyejiaka, Adanna, Bourque, Francois, Modinos, Gemma, Tognin, Stefania, Calem, Maria, O'Donovan, Michael C., Owen, Michael J., Holmans, Peter, Williams, Nigel, Craddock, Nicholas, Richards, Alexander, Humphreys, Isla, Meyer-Lindenberg, Andreas, Leweke, F. Markus, Tost, Heike, Akdeniz, Ceren, Rohleder, Cathrin, Bumb, J. Malte, Schwarz, Emanuel, Alptekin, Koksal, Ucok, Alp, Saka, Meram Can, Atbasoglu, E. Cem, Guloksuz, Sinan, Gumus-Akay, Guvem, Cihan, Burin, Karadag, Hasan, Soygur, Haldan, Cankurtaran, Eylem Sahin, Ulusoy, Semra, Akdede, Berna, Binbay, Tolga, Ayer, Ahmet, Noyan, Handan, Karadayi, Gulsah, Akturan, Elin, Ulas, Halis, Arango, Celso, Parellada, Mara, Bernardo, Miguel, Sanjuan, Julio, Bobes, Julio, Arrojo, Manuel, Luis Santos, Jose, Cuadrado, Pedro, Rodriguez Solano, Jose Juan, Carracedo, Angel, Garcia Bernardo, Enrique, Roldan, Laura, Lopez, Gonzalo, Cabrera, Bibiana, Cruz, Sabrina, Diaz Mesa, Eva Ma, Pouso, Maria, Jimenez, Estela, Sanchez, Teresa, Rapado, Marta, Gonzalez, Emiliano, Martinez, Covadonga, Sanchez, Emilio, Soledad Olmeda, Ma, de Haan, Lieuwe, Velthorst, Eva, van der Gaag, Mark, Selten, Jean-Paul, van Dam, Daniella, van der Ven, Elsje, van der Meer, Floor, Messchaert, Elles, Kraan, Tamar, Burger, Nadine, Leboyer, Marion, Szoke, Andrei, Schurhoff, Franck, Llorca, Pierre-Michel, Jamain, Stephane, Tortelli, Andrea, Frijda, Flora, Vilain, Jeanne, Galliot, Anne-Marie, Baudin, Gregoire, Ferchiou, Aziz, Richard, Jean-Romain, Bulzacka, Ewa, Charpeaud, Thomas, Tronche, Anne-Marie, De Hert, Marc, van Winkel, Ruud, Decoster, Jeroen, Derom, Catherine, Thiery, Evert, Stefanis, Nikos C., Sachs, Gabriele, Aschauer, Harald, Lasser, Iris, Winklbaur, Bernadette, Schlogelhofer, Monika, Riecher-Rossler, Anita, Borgwardt, Stefan, Walter, Anna, Harrisberger, Fabienne, Smieskova, Renata, Rapp, Charlotte, Ittig, Sarah, Soguel-Dit-Piquard, Fabienne, Studerus, Erich, Klosterkotter, Joachim, Ruhrmann, Stephan, Paruch, Julia, Julkowski, Dominika, Hilboll, Desiree, Sham, Pak C., Cherny, Stacey S., Chen, Eric Y. H., Campbell, Desmond D., Li, Miaoxin, Maria Romeo-Casabona, Carlos, Emaldi Cirion, Aitziber, Urruela Mora, Asier, Jones, Peter, Kirkbride, James, Cannon, Mary, Rujescu, Dan, Tarricone, Ilaria, Berardi, Domenico, Bonora, Elena, Seri, Marco, Marcacci, Thomas, Chiri, Luigi, Chierzi, Federico, Storbini, Viviana, Braca, Mauro, Minenna, Maria Gabriella, Donegani, Ivonne, Fioritti, Angelo, La Barbera, Daniele, La Cascia, Caterina Erika, Mule, Alice, Sideli, Lucia, Sartorio, Rachele, Ferraro, Laura, Tripoli, Giada, Seminerio, Fabio, Marinaro, Anna Maria, McGorry, Patrick, Nelson, Barnaby, Amminger, G. Paul, Pantelis, Christos, Menezes, Paulo R., Del-Ben, Cristina M., Tenan, Silvia H. Gallo, Shuhama, Rosana, Ruggeri, Mirella, Tosato, Sarah, Lasalvia, Antonio, Bonetto, Chiara, Ira, Elisa, Nordentoft, Merete, Krebs, Marie-Odile, Barrantes-Vidal, Neus, Cristobal, Paula, Kwapil, Thomas R., Brietzke, Elisa, Bressan, Rodrigo A., Gadelha, Ary, Maric, Nadja P., Andric, Sanja, Mihaljevic, Marina, Mirjanic, Tijana, van Os, Jim, Rutten, Bart P., Myin-Germeys, Inez, Delespaul, Philippe, Viechtbauer, Wolfgang, van Zelst, Catherine, Bruggeman, Richard, Reininghaus, Ulrich, Morgan, Craig, Murray, Robin M., Di Forti, Marta, McGuire, Philip, Valmaggia, Lucia R., Kempton, Matthew J., Gayer-Anderson, Charlotte, Hubbard, Kathryn, Beards, Stephanie, Stilo, Simona A., Onyejiaka, Adanna, Bourque, Francois, Modinos, Gemma, Tognin, Stefania, Calem, Maria, O'Donovan, Michael C., Owen, Michael J., Holmans, Peter, Williams, Nigel, Craddock, Nicholas, Richards, Alexander, Humphreys, Isla, Meyer-Lindenberg, Andreas, Leweke, F. Markus, Tost, Heike, Akdeniz, Ceren, Rohleder, Cathrin, Bumb, J. Malte, Schwarz, Emanuel, Alptekin, Koksal, Ucok, Alp, Saka, Meram Can, Atbasoglu, E. Cem, Guloksuz, Sinan, Gumus-Akay, Guvem, Cihan, Burin, Karadag, Hasan, Soygur, Haldan, Cankurtaran, Eylem Sahin, Ulusoy, Semra, Akdede, Berna, Binbay, Tolga, Ayer, Ahmet, Noyan, Handan, Karadayi, Gulsah, Akturan, Elin, Ulas, Halis, Arango, Celso, Parellada, Mara, Bernardo, Miguel, Sanjuan, Julio, Bobes, Julio, Arrojo, Manuel, Luis Santos, Jose, Cuadrado, Pedro, Rodriguez Solano, Jose Juan, Carracedo, Angel, Garcia Bernardo, Enrique, Roldan, Laura, Lopez, Gonzalo, Cabrera, Bibiana, Cruz, Sabrina, Diaz Mesa, Eva Ma, Pouso, Maria, Jimenez, Estela, Sanchez, Teresa, Rapado, Marta, Gonzalez, Emiliano, Martinez, Covadonga, Sanchez, Emilio, Soledad Olmeda, Ma, de Haan, Lieuwe, Velthorst, Eva, van der Gaag, Mark, Selten, Jean-Paul, van Dam, Daniella, van der Ven, Elsje, van der Meer, Floor, Messchaert, Elles, Kraan, Tamar, Burger, Nadine, Leboyer, Marion, Szoke, Andrei, Schurhoff, Franck, Llorca, Pierre-Michel, Jamain, Stephane, Tortelli, Andrea, Frijda, Flora, Vilain, Jeanne, Galliot, Anne-Marie, Baudin, Gregoire, Ferchiou, Aziz, Richard, Jean-Romain, Bulzacka, Ewa, Charpeaud, Thomas, Tronche, Anne-Marie, De Hert, Marc, van Winkel, Ruud, Decoster, Jeroen, Derom, Catherine, Thiery, Evert, Stefanis, Nikos C., Sachs, Gabriele, Aschauer, Harald, Lasser, Iris, Winklbaur, Bernadette, Schlogelhofer, Monika, Riecher-Rossler, Anita, Borgwardt, Stefan, Walter, Anna, Harrisberger, Fabienne, Smieskova, Renata, Rapp, Charlotte, Ittig, Sarah, Soguel-Dit-Piquard, Fabienne, Studerus, Erich, Klosterkotter, Joachim, Ruhrmann, Stephan, Paruch, Julia, Julkowski, Dominika, Hilboll, Desiree, Sham, Pak C., Cherny, Stacey S., Chen, Eric Y. H., Campbell, Desmond D., Li, Miaoxin, Maria Romeo-Casabona, Carlos, Emaldi Cirion, Aitziber, Urruela Mora, Asier, Jones, Peter, Kirkbride, James, Cannon, Mary, Rujescu, Dan, Tarricone, Ilaria, Berardi, Domenico, Bonora, Elena, Seri, Marco, Marcacci, Thomas, Chiri, Luigi, Chierzi, Federico, Storbini, Viviana, Braca, Mauro, Minenna, Maria Gabriella, Donegani, Ivonne, Fioritti, Angelo, La Barbera, Daniele, La Cascia, Caterina Erika, Mule, Alice, Sideli, Lucia, Sartorio, Rachele, Ferraro, Laura, Tripoli, Giada, Seminerio, Fabio, Marinaro, Anna Maria, McGorry, Patrick, Nelson, Barnaby, Amminger, G. Paul, Pantelis, Christos, Menezes, Paulo R., Del-Ben, Cristina M., Tenan, Silvia H. Gallo, Shuhama, Rosana, Ruggeri, Mirella, Tosato, Sarah, Lasalvia, Antonio, Bonetto, Chiara, Ira, Elisa, Nordentoft, Merete, Krebs, Marie-Odile, Barrantes-Vidal, Neus, Cristobal, Paula, Kwapil, Thomas R., Brietzke, Elisa, Bressan, Rodrigo A., Gadelha, Ary, Maric, Nadja P., Andric, Sanja, Mihaljevic, Marina, and Mirjanic, Tijana

Abstract

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G x E), however, so far, thorough replication of findings is rare and G x E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G x E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G x E in schizophrenia. While such investigations are now well underway, new challenges emerge for G x E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.

Published
2014

57. Structural Network Disorganization in Subjects at Clinical High Risk for Psychosis.

Author

Schmidt, André, Crossley, Nicolas A., Harrisberger, Fabienne, Smieskova, Renata, Lenz, Claudia, Riecher-Rössler, Anita, Lang, Undine E., McGuire, Philip, Fusar-Poli, Paolo, and Borgwardt, Stefan

Subjects
PSYCHOSES risk factors, BRAIN, SIBLINGS, EXPERIMENTAL design, GENETICS, MAGNETIC resonance imaging, SCHIZOPHRENIA, STRUCTURAL models, SEVERITY of illness index, NEURAL pathways, PSYCHOLOGICAL vulnerability
Published
2017
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59. Detecting the Psychosis Prodrome Across High-Risk Populations Using Neuroanatomical Biomarkers

Author

Koutsouleris, Nikolaos, primary, Riecher-Rössler, Anita, additional, Meisenzahl, Eva M., additional, Smieskova, Renata, additional, Studerus, Erich, additional, Kambeitz-Ilankovic, Lana, additional, von Saldern, Sebastian, additional, Cabral, Carlos, additional, Reiser, Maximilian, additional, Falkai, Peter, additional, and Borgwardt, Stefan, additional

Published
2014
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66. Progression in disability and regional grey matter atrophy in relapsing–remitting multiple sclerosis

Author

Hofstetter, Louis, primary, Naegelin, Yvonne, additional, Filli, Lukas, additional, Kuster, Pascal, additional, Traud, Stefan, additional, Smieskova, Renata, additional, Mueller-Lenke, Nicole, additional, Kappos, Ludwig, additional, Gass, Achim, additional, Sprenger, Till, additional, Penner, Iris-Katharina, additional, Nichols, Thomas E, additional, Vrenken, Hugo, additional, Barkhof, Frederik, additional, Polman, Chris, additional, Radue, Ernst-Wilhelm, additional, Borgwardt, Stefan J, additional, and Bendfeldt, Kerstin, additional

Published
2013
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69. Poster #56 INSULAR VOLUME ABNORMALITIES ASSOCIATED WITH DIFFERENT TRANSITION PROBABILITIES TO PSYCHOSIS – A VOXEL-BASED MORPHOMETRY STUDY

Author

Smieskova, Renata, primary, Riecher-Rössler, Anita, additional, Aston, Jacqueline, additional, Simon, Andor, additional, Bendfeldt, Kerstin, additional, Lenz, Claudia, additional, Stieglitz, Rolf-Dieter, additional, Fusar-Poil, Paolo, additional, McGuire, Philip, additional, and Borgwardt, Stefan J., additional

Published
2012
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72. Different duration of at‐risk mental state associated with neurofunctional abnormalities. A multimodal imaging study

Author

Smieskova, Renata, primary, Allen, Paul, additional, Simon, Andor, additional, Aston, Jacqueline, additional, Bendfeldt, Kerstin, additional, Drewe, Jürgen, additional, Gruber, Kerstin, additional, Gschwandtner, Ute, additional, Klarhoefer, Markus, additional, Lenz, Claudia, additional, Scheffler, Klaus, additional, Stieglitz, Rolf‐Dieter, additional, Radue, Ernst‐Wilhelm, additional, McGuire, Philip, additional, Riecher‐Rössler, Anita, additional, and Borgwardt, Stefan J., additional

Published
2011
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74. Progression in disability and regional grey matter atrophy in relapsing–remitting multiple sclerosis.

Author

Hofstetter, Louis, Naegelin, Yvonne, Filli, Lukas, Kuster, Pascal, Traud, Stefan, Smieskova, Renata, Mueller-Lenke, Nicole, Kappos, Ludwig, Gass, Achim, Sprenger, Till, Penner, Iris-Katharina, Nichols, Thomas E, Vrenken, Hugo, Barkhof, Frederik, Polman, Chris, Radue, Ernst-Wilhelm, Borgwardt, Stefan J, and Bendfeldt, Kerstin

Subjects
MULTIPLE sclerosis research, DEMYELINATION, VOXEL-based morphometry, MYELIN sheath diseases, DEGENERATION (Pathology)
Abstract

Background: In multiple sclerosis (MS) regional grey matter (GM) atrophy has been associated with disabilityprogression.Objective: The aim of this study was to compare regional GM volume changes in relapsing-remitting MS (RRMS)patients with progressive and stable disability, using voxel-based morphometry (VBM).Methods: We acquired baseline and 1-year follow-up 3-dimensional (3D) T1-weighted magnetic resonance imaging(MRI) data of RRMS patients, using two 1.5-Tesla scanners. Patients were matched pair-wise with respect to age, gender,disease duration, medication, scanner and baseline Expanded Disability Status Scale (EDSS) into 13 pairs, with eitherprogressive EDSS (≥ 1 point change y-1) or stable EDSS, as well as into 29 pairs with either progressive Multiple SclerosisFunctional Composite (MSFC) at ≥ 0.25% decrease in y-1 in any component, or stable MSFC. We analysed longitudinalregional differences in GM volumes in the progressive and stable EDSS and MSFC groups, respectively, using VBM.Results: Significant GM volume reductions occurred in the right precuneus, in the progressive EDSS group. Differentialbetween-group effects occurred in the right precuneus and in the postcentral gyrus. Further longitudinal GM volumereductions occurred in the right orbicular gyrus, in the progressive MSFC group, but no between-group differences wereobserved (non-stationary cluster-wise inference, all Pcorrected < 0.05).Conclusion: These results suggested a direct association of disability progression and regional GM atrophy in RRMS. [ABSTRACT FROM AUTHOR]

Published
2014
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75. Pituitary gland volume in at-risk mental state for psychosis: a longitudinal MRI analysis

Author

Walter, Anna, Studerus, Erich, Smieskova, Renata, Tamagni, Corinne, Rapp, Charlotte, Borgwardt, Stefan J., and Riecher-Rössler, Anita

Abstract

IntroductionPituitary enlargement has been reported in individuals with schizophrenic psychosis or an at-risk mental state for psychosis (ARMS). In a previous study, our group could show pituitary volume increase in first episode and ARMS patients with later transition to psychosis (ARMS-T). However, there are no longitudinal studies on this issue so far. We therefore examined longitudinally whether transition to psychosis would be accompanied by a further increase of pituitary volume in antipsychotic-naïve ARMS patients.MethodsMagnetic resonance imaging (MRI) data were acquired from 23 antipsychotic-naïve individuals with an ARMS. Ten subjects developed psychosis (ARMS-T) and 13 did not (ARMS-NT). ARMS-T were re-scanned after the onset of psychosis, and ARMS-NT were re-scanned at the end of the study period.ResultsThere was no significant difference of the pituitary volume between ARMS-T and ARMS-NT in our sample, and there were no significant pituitary volume changes over time.DiscussionLongitudinally, we could not detect any further volumetric changes in the pituitary volume with transition to psychosis.ConclusionsThis, together with the result of our previous study, could indicate that the perceived level of stress in ARMS patients is constantly high from very early onward.

Published
2015
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76. Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis

Author

Pollak, Thomas A., Kempton, Matthew J., Iyegbe, Conrad, Vincent, Angela, Irani, Sarosh R., Coutinho, Ester, Menassa, David A., Jacobson, Leslie, de Haan, Lieuwe, Ruhrmann, Stephan, Sachs, Gabriele, Riecher-Roessler, Anita, Krebs, Marie-Odile, Amminger, Paul, Glenthoj, Birte, Barrantes-Vidal, Neus, van Os, Jim, Rutten, Bart P. F., Bressan, Rodrigo A., van der Gaag, Mark, Yolken, Robert, Hotopf, Matthew, Valmaggia, Lucia, Stone, James, David, Anthony S., McGuire, Philip, Calem, Maria, Tognin, Stefania, Modinos, Gemma, Velthorst, Eva, Kraan, Tamar C., van Dam, Daniella S., Burger, Nadine, Nelson, Barnaby, McGorry, Patrick, Pantelis, Christos, Politis, Athena, Goodall, Joanne, Borgwardt, Stefan, Ittig, Sarah, Studerus, Erich, Smieskova, Renata, Gadelha, Ary, Brietzke, Elisa, Asevedo, Graccielle, Asevedo, Elson, Zugman, Andre, Rosa, Araceli, Racioppi, Anna, Monsonet, Manel, Hinojosa-Marques, Lidia, Kwapil, Thomas R., Kazes, Mathilde, Daban, Claire, Bourgin, Julie, Gay, Olivier, Mam-Lam-Fook, Celia, Nordholm, Dorte, Randers, Lasse, Krakauer, Kristine, Glenthoj, Louise, Nordentoft, Merete, Gebhard, Dominika, Arnhold, Julia, Klosterkoetter, Joachim, Lasser, Iris, Winklbaur, Bernadette, Delespaul, Philippe A., Pollak, Thomas A., Kempton, Matthew J., Iyegbe, Conrad, Vincent, Angela, Irani, Sarosh R., Coutinho, Ester, Menassa, David A., Jacobson, Leslie, de Haan, Lieuwe, Ruhrmann, Stephan, Sachs, Gabriele, Riecher-Roessler, Anita, Krebs, Marie-Odile, Amminger, Paul, Glenthoj, Birte, Barrantes-Vidal, Neus, van Os, Jim, Rutten, Bart P. F., Bressan, Rodrigo A., van der Gaag, Mark, Yolken, Robert, Hotopf, Matthew, Valmaggia, Lucia, Stone, James, David, Anthony S., McGuire, Philip, Calem, Maria, Tognin, Stefania, Modinos, Gemma, Velthorst, Eva, Kraan, Tamar C., van Dam, Daniella S., Burger, Nadine, Nelson, Barnaby, McGorry, Patrick, Pantelis, Christos, Politis, Athena, Goodall, Joanne, Borgwardt, Stefan, Ittig, Sarah, Studerus, Erich, Smieskova, Renata, Gadelha, Ary, Brietzke, Elisa, Asevedo, Graccielle, Asevedo, Elson, Zugman, Andre, Rosa, Araceli, Racioppi, Anna, Monsonet, Manel, Hinojosa-Marques, Lidia, Kwapil, Thomas R., Kazes, Mathilde, Daban, Claire, Bourgin, Julie, Gay, Olivier, Mam-Lam-Fook, Celia, Nordholm, Dorte, Randers, Lasse, Krakauer, Kristine, Glenthoj, Louise, Nordentoft, Merete, Gebhard, Dominika, Arnhold, Julia, Klosterkoetter, Joachim, Lasser, Iris, Winklbaur, Bernadette, and Delespaul, Philippe A.

Abstract

Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58-3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current

77. Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis

Author

Pollak, Thomas A., Kempton, Matthew J., Iyegbe, Conrad, Vincent, Angela, Irani, Sarosh R., Coutinho, Ester, Menassa, David A., Jacobson, Leslie, de Haan, Lieuwe, Ruhrmann, Stephan, Sachs, Gabriele, Riecher-Roessler, Anita, Krebs, Marie-Odile, Amminger, Paul, Glenthoj, Birte, Barrantes-Vidal, Neus, van Os, Jim, Rutten, Bart P. F., Bressan, Rodrigo A., van der Gaag, Mark, Yolken, Robert, Hotopf, Matthew, Valmaggia, Lucia, Stone, James, David, Anthony S., McGuire, Philip, Calem, Maria, Tognin, Stefania, Modinos, Gemma, Velthorst, Eva, Kraan, Tamar C., van Dam, Daniella S., Burger, Nadine, Nelson, Barnaby, McGorry, Patrick, Pantelis, Christos, Politis, Athena, Goodall, Joanne, Borgwardt, Stefan, Ittig, Sarah, Studerus, Erich, Smieskova, Renata, Gadelha, Ary, Brietzke, Elisa, Asevedo, Graccielle, Asevedo, Elson, Zugman, Andre, Rosa, Araceli, Racioppi, Anna, Monsonet, Manel, Hinojosa-Marques, Lidia, Kwapil, Thomas R., Kazes, Mathilde, Daban, Claire, Bourgin, Julie, Gay, Olivier, Mam-Lam-Fook, Celia, Nordholm, Dorte, Randers, Lasse, Krakauer, Kristine, Glenthoj, Louise, Nordentoft, Merete, Gebhard, Dominika, Arnhold, Julia, Klosterkoetter, Joachim, Lasser, Iris, Winklbaur, Bernadette, Delespaul, Philippe A., Pollak, Thomas A., Kempton, Matthew J., Iyegbe, Conrad, Vincent, Angela, Irani, Sarosh R., Coutinho, Ester, Menassa, David A., Jacobson, Leslie, de Haan, Lieuwe, Ruhrmann, Stephan, Sachs, Gabriele, Riecher-Roessler, Anita, Krebs, Marie-Odile, Amminger, Paul, Glenthoj, Birte, Barrantes-Vidal, Neus, van Os, Jim, Rutten, Bart P. F., Bressan, Rodrigo A., van der Gaag, Mark, Yolken, Robert, Hotopf, Matthew, Valmaggia, Lucia, Stone, James, David, Anthony S., McGuire, Philip, Calem, Maria, Tognin, Stefania, Modinos, Gemma, Velthorst, Eva, Kraan, Tamar C., van Dam, Daniella S., Burger, Nadine, Nelson, Barnaby, McGorry, Patrick, Pantelis, Christos, Politis, Athena, Goodall, Joanne, Borgwardt, Stefan, Ittig, Sarah, Studerus, Erich, Smieskova, Renata, Gadelha, Ary, Brietzke, Elisa, Asevedo, Graccielle, Asevedo, Elson, Zugman, Andre, Rosa, Araceli, Racioppi, Anna, Monsonet, Manel, Hinojosa-Marques, Lidia, Kwapil, Thomas R., Kazes, Mathilde, Daban, Claire, Bourgin, Julie, Gay, Olivier, Mam-Lam-Fook, Celia, Nordholm, Dorte, Randers, Lasse, Krakauer, Kristine, Glenthoj, Louise, Nordentoft, Merete, Gebhard, Dominika, Arnhold, Julia, Klosterkoetter, Joachim, Lasser, Iris, Winklbaur, Bernadette, and Delespaul, Philippe A.

Abstract

Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58-3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current

78. Pituitary gland volume in at-risk mental state for psychosis: a longitudinal MRI analysis

Author

Walter, Anna, Studerus, Erich, Smieskova, Renata, Tamagni, Corinne, Rapp, Charlotte, Borgwardt, Stefan J., Riecher-Rössler, Anita, Walter, Anna, Studerus, Erich, Smieskova, Renata, Tamagni, Corinne, Rapp, Charlotte, Borgwardt, Stefan J., and Riecher-Rössler, Anita

Abstract

Introduction Pituitary enlargement has been reported in individuals with schizophrenic psychosis or an at-risk mental state for psychosis (ARMS). In a previous study, our group could show pituitary volume increase in first episode and ARMS patients with later transition to psychosis (ARMS-T). However, there are no longitudinal studies on this issue so far. We therefore examined longitudinally whether transition to psychosis would be accompanied by a further increase of pituitary volume in antipsychotic-naïve ARMS patients. Methods Magnetic resonance imaging (MRI) data were acquired from 23 antipsychotic-naïve individuals with an ARMS. Ten subjects developed psychosis (ARMS-T) and 13 did not (ARMS-NT). ARMS-T were re-scanned after the onset of psychosis, and ARMS-NT were re-scanned at the end of the study period. Results There was no significant difference of the pituitary volume between ARMS-T and ARMS-NT in our sample, and there were no significant pituitary volume changes over time. Discussion Longitudinally, we could not detect any further volumetric changes in the pituitary volume with transition to psychosis. Conclusions This, together with the result of our previous study, could indicate that the perceived level of stress in ARMS patients is constantly high from very early onward

79. Detecting the Psychosis Prodrome Across High-Risk Populations Using Neuroanatomical Biomarkers

Author

Koutsouleris, Nikolaos, Riecher-Rössler, Anita, Meisenzahl, Eva M., Smieskova, Renata, Studerus, Erich, Kambeitz-Ilankovic, Lana, von Saldern, Sebastian, Cabral, Carlos, Reiser, Maximilian, Falkai, Peter, Borgwardt, Stefan, Koutsouleris, Nikolaos, Riecher-Rössler, Anita, Meisenzahl, Eva M., Smieskova, Renata, Studerus, Erich, Kambeitz-Ilankovic, Lana, von Saldern, Sebastian, Cabral, Carlos, Reiser, Maximilian, Falkai, Peter, and Borgwardt, Stefan

Abstract

To date, the MRI-based individualized prediction of psychosis has only been demonstrated in single-site studies. It remains unclear if MRI biomarkers generalize across different centers and MR scanners and represent accurate surrogates of the risk for developing this devastating illness. Therefore, we assessed whether a MRI-based prediction system identified patients with a later disease transition among 73 clinically defined high-risk persons recruited at two different early recognition centers. Prognostic performance was measured using cross-validation, independent test validation, and Kaplan-Meier survival analysis. Transition outcomes were correctly predicted in 80% of test cases (sensitivity: 76%, specificity: 85%, positive likelihood ratio: 5.1). Thus, given a 54-month transition risk of 45% across both centers, MRI-based predictors provided a 36%-increase of prognostic certainty. After stratifying individuals into low-, intermediate-, and high-risk groups using the predictor's decision score, the high- vs low-risk groups had median psychosis-free survival times of 5 vs 51 months and transition rates of 88% vs 8%. The predictor's decision function involved gray matter volume alterations in prefrontal, perisylvian, and subcortical structures. Our results support the existence of a cross-center neuroanatomical signature of emerging psychosis enabling individualized risk staging across different high-risk populations. Supplementary results revealed that (1) potentially confounding between-site differences were effectively mitigated using statistical correction methods, and (2) the detection of the prodromal signature considerably depended on the available sample sizes. These observations pave the way for future multicenter studies, which may ultimately facilitate the neurobiological refinement of risk criteria and personalized preventive therapies based on individualized risk profiling tools

80. Gender differences of patients at-risk for psychosis regarding symptomatology, drug use, comorbidity and functioning - Results from the EU-GEI study.

Author

Menghini-Müller S, Studerus E, Ittig S, Heitz U, Egloff L, Andreou C, Valmaggia LR, Kempton MJ, van der Gaag M, de Haan L, Nelson B, Barrantes-Vidal N, Nordentoft M, Ruhrmann S, Sachs G, Rutten BP, Os JV, Riecher-Rössler A, McGuire P, Valmaggia LR, Kempton MJ, Calem M, Tognin S, Modinos G, de Haan L, van der Gaag M, Velthorst E, Kraan TC, van Dam DS, Burger N, Nelson B, McGorry P, Amminger GP, Pantelis C, Politis A, Goodall J, Riecher-Rössler A, Borgwardt S, Rapp C, Ittig S, Studerus E, Smieskova R, Bressan R, Gadelha A, Brietzke E, Asevedo G, Asevedo E, Zugman A, Barrantes-Vidal N, Domínguez-Martínez T, Racioppi A, Cristóbal-Narváez P, Kwapil TR, Monsonet M, Kazes M, Daban C, Bourgin J, Gay O, Mam-Lam-Fook C, Krebs MO, Nordholm D, Randers L, Krakauer K, Glenthøj L, Glenthøj B, Nordentoft M, Ruhrmann S, Gebhard D, Arnhold J, Klosterkötter J, Sachs G, Lasser I, Winklbaur B, Delespaul PA, Rutten BP, and van Os J

Subjects
Adolescent, Adult, Anxiety Disorders epidemiology, Comorbidity, Europe epidemiology, Female, Humans, Male, Psychotic Disorders psychology, Schizophrenia diagnosis, Sex Distribution, Sex Factors, Substance-Related Disorders epidemiology, Young Adult, Early Diagnosis, Psychotic Disorders epidemiology, Schizophrenia epidemiology
Abstract

Background: Gender differences in symptomatology in chronic schizophrenia and first episode psychosis patients have often been reported. However, little is known about gender differences in those at risk of psychotic disorders. This study investigated gender differences in symptomatology, drug use, comorbidity (i.e. substance use, affective and anxiety disorders) and global functioning in patients with an at-risk mental state (ARMS) for psychosis., Methods: The sample consisted of 336 ARMS patients (159 women) from the prodromal work package of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI; 11 centers). Clinical symptoms, drug use, comorbidity and functioning were assessed at first presentation to an early detection center using structured interviews., Results: In unadjusted analyses, men were found to have significantly higher rates of negative symptoms and current cannabis use while women showed higher rates of general psychopathology and more often displayed comorbid affective and anxiety disorders. No gender differences were found for global functioning. The results generally did not change when corrected for possible cofounders (e.g. cannabis use). However, most differences did not withstand correction for multiple testing., Conclusions: Findings indicate that gender differences in symptomatology and comorbidity in ARMS are similar to those seen in overt psychosis and in healthy controls. However, observed differences are small and would only be reliably detected in studies with high statistical power. Moreover, such small effects would likely not be clinically meaningful., (Copyright © 2019. Published by Elsevier Masson SAS.)

Published
2019
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81. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.

Author

van Os J, Rutten BP, Myin-Germeys I, Delespaul P, Viechtbauer W, van Zelst C, Bruggeman R, Reininghaus U, Morgan C, Murray RM, Di Forti M, McGuire P, Valmaggia LR, Kempton MJ, Gayer-Anderson C, Hubbard K, Beards S, Stilo SA, Onyejiaka A, Bourque F, Modinos G, Tognin S, Calem M, O'Donovan MC, Owen MJ, Holmans P, Williams N, Craddock N, Richards A, Humphreys I, Meyer-Lindenberg A, Leweke FM, Tost H, Akdeniz C, Rohleder C, Bumb JM, Schwarz E, Alptekin K, Üçok A, Saka MC, Atbaşoğlu EC, Gülöksüz S, Gumus-Akay G, Cihan B, Karadağ H, Soygür H, Cankurtaran EŞ, Ulusoy S, Akdede B, Binbay T, Ayer A, Noyan H, Karadayı G, Akturan E, Ulaş H, Arango C, Parellada M, Bernardo M, Sanjuán J, Bobes J, Arrojo M, Santos JL, Cuadrado P, Rodríguez Solano JJ, Carracedo A, García Bernardo E, Roldán L, López G, Cabrera B, Cruz S, Díaz Mesa EM, Pouso M, Jiménez E, Sánchez T, Rapado M, González E, Martínez C, Sánchez E, Olmeda MS, de Haan L, Velthorst E, van der Gaag M, Selten JP, van Dam D, van der Ven E, van der Meer F, Messchaert E, Kraan T, Burger N, Leboyer M, Szoke A, Schürhoff F, Llorca PM, Jamain S, Tortelli A, Frijda F, Vilain J, Galliot AM, Baudin G, Ferchiou A, Richard JR, Bulzacka E, Charpeaud T, Tronche AM, De Hert M, van Winkel R, Decoster J, Derom C, Thiery E, Stefanis NC, Sachs G, Aschauer H, Lasser I, Winklbaur B, Schlögelhofer M, Riecher-Rössler A, Borgwardt S, Walter A, Harrisberger F, Smieskova R, Rapp C, Ittig S, Soguel-dit-Piquard F, Studerus E, Klosterkötter J, Ruhrmann S, Paruch J, Julkowski D, Hilboll D, Sham PC, Cherny SS, Chen EY, Campbell DD, Li M, Romeo-Casabona CM, Emaldi Cirión A, Urruela Mora A, Jones P, Kirkbride J, Cannon M, Rujescu D, Tarricone I, Berardi D, Bonora E, Seri M, Marcacci T, Chiri L, Chierzi F, Storbini V, Braca M, Minenna MG, Donegani I, Fioritti A, La Barbera D, La Cascia CE, Mulè A, Sideli L, Sartorio R, Ferraro L, Tripoli G, Seminerio F, Marinaro AM, McGorry P, Nelson B, Amminger GP, Pantelis C, Menezes PR, Del-Ben CM, Gallo Tenan SH, Shuhama R, Ruggeri M, Tosato S, Lasalvia A, Bonetto C, Ira E, Nordentoft M, Krebs MO, Barrantes-Vidal N, Cristóbal P, Kwapil TR, Brietzke E, Bressan RA, Gadelha A, Maric NP, Andric S, Mihaljevic M, and Mirjanic T

Subjects
Genetic Predisposition to Disease, Humans, Schizophrenia epidemiology, Social Environment, Gene-Environment Interaction, Schizophrenia genetics, Schizophrenic Psychology
Abstract

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2014
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