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

Author: Georgiadis, Foivos, Georgiadis, Foivos, Larivière, Sara, Glahn, David, Hong, L, Kochunov, Peter, Mowry, Bryan, Loughland, Carmel, Pantelis, Christos, Henskens, Frans, Green, Melissa, Cairns, Murray, Michie, Patricia, Rasser, Paul, Catts, Stanley, Tooney, Paul, Scott, Rodney, Schall, Ulrich, Carr, Vaughan, Quidé, Yann, Krug, Axel, Stein, Frederike, Nenadić, Igor, Brosch, Katharina, Kircher, Tilo, Gur, Raquel, Gur, Ruben, Satterthwaite, Theodore, Karuk, Andriana, Pomarol-Clotet, Edith, Radua, Joaquim, Fuentes-Claramonte, Paola, Salvador, Raymond, Spalletta, Gianfranco, Voineskos, Aristotle, Sim, Kang, Crespo-Facorro, Benedicto, Tordesillas Gutiérrez, Diana, Ehrlich, Stefan, Crossley, Nicolas, Grotegerd, Dominik, Repple, Jonathan, Lencer, Rebekka, Dannlowski, Udo, Calhoun, Vince, Rootes-Murdy, Kelly, Demro, Caroline, Ramsay, Ian, Sponheim, Scott, Schmidt, Andre, Borgwardt, Stefan, Tomyshev, Alexander, Lebedeva, Irina, Höschl, Cyril, Spaniel, Filip, Preda, Adrian, Nguyen, Dana, Uhlmann, Anne, Stein, Dan, Howells, Fleur, Temmingh, Henk, Diaz Zuluaga, Ana, López Jaramillo, Carlos, Iasevoli, Felice, Ji, Ellen, Homan, Stephanie, Omlor, Wolfgang, Homan, Philipp, Kaiser, Stefan, Seifritz, Erich, Misic, Bratislav, Valk, Sofie, Thompson, Paul, Van Erp, Theodorus, Turner, Jessica, Bernhardt, Boris, Kirschner, Matthias, Georgiadis, Foivos, Georgiadis, Foivos, Larivière, Sara, Glahn, David, Hong, L, Kochunov, Peter, Mowry, Bryan, Loughland, Carmel, Pantelis, Christos, Henskens, Frans, Green, Melissa, Cairns, Murray, Michie, Patricia, Rasser, Paul, Catts, Stanley, Tooney, Paul, Scott, Rodney, Schall, Ulrich, Carr, Vaughan, Quidé, Yann, Krug, Axel, Stein, Frederike, Nenadić, Igor, Brosch, Katharina, Kircher, Tilo, Gur, Raquel, Gur, Ruben, Satterthwaite, Theodore, Karuk, Andriana, Pomarol-Clotet, Edith, Radua, Joaquim, Fuentes-Claramonte, Paola, Salvador, Raymond, Spalletta, Gianfranco, Voineskos, Aristotle, Sim, Kang, Crespo-Facorro, Benedicto, Tordesillas Gutiérrez, Diana, Ehrlich, Stefan, Crossley, Nicolas, Grotegerd, Dominik, Repple, Jonathan, Lencer, Rebekka, Dannlowski, Udo, Calhoun, Vince, Rootes-Murdy, Kelly, Demro, Caroline, Ramsay, Ian, Sponheim, Scott, Schmidt, Andre, Borgwardt, Stefan, Tomyshev, Alexander, Lebedeva, Irina, Höschl, Cyril, Spaniel, Filip, Preda, Adrian, Nguyen, Dana, Uhlmann, Anne, Stein, Dan, Howells, Fleur, Temmingh, Henk, Diaz Zuluaga, Ana, López Jaramillo, Carlos, Iasevoli, Felice, Ji, Ellen, Homan, Stephanie, Omlor, Wolfgang, Homan, Philipp, Kaiser, Stefan, Seifritz, Erich, Misic, Bratislav, Valk, Sofie, Thompson, Paul, Van Erp, Theodorus, Turner, Jessica, Bernhardt, Boris, and Kirschner, Matthias
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 schizophrenias 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 networ
Published: 2024

2. Structural brain abnormalities and aggressive behaviour in schizophrenia: Mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium

Author: Lamsma, Jelle, Lamsma, Jelle, Raine, Adrian, Kia, Seyed M, Cahn, Wiepke, Arold, Dominic, Banaj, Nerisa, Barone, Annarita, Brosch, Katharina, Brouwer, Rachel, Brunetti, Arturo, Calhoun, Vince D, Chew, Qian H, Choi, Sunah, Chung, Young-Chul, Ciccarelli, Mariateresa, Cobia, Derin, Cocozza, Sirio, Dannlowski, Udo, Dazzan, Paola, de Bartolomeis, Andrea, Di Forti, Marta, Dumais, Alexandre, Edmond, Jesse T, Ehrlich, Stefan, Evermann, Ulrika, Flinkenflügel, Kira, Georgiadis, Foivos, Glahn, David C, Goltermann, Janik, Green, Melissa J, Grotegerd, Dominik, Guerrero-Pedraza, Amalia, Ha, Minji, Hong, Elliot L, Pol, Hilleke Hulshoff, Iasevoli, Felice, Kaiser, Stefan, Kaleda, Vasily, Karuk, Andriana, Kim, Minah, Kircher, Tilo, Kirschner, Matthias, Kochunov, Peter, Kwon, Jun Soo, Lebedeva, Irina, Lencer, Rebekka, Marques, Tiago R, Meinert, Susanne, Murray, Robin, Nenadić, Igor, Nguyen, Dana, Pearlson, Godfrey, Piras, Fabrizio, Pomarol-Clotet, Edith, Pontillo, Giuseppe, Potvin, Stéphane, Preda, Adrian, Quidé, Yann, Rodrigue, Amanda, Rootes-Murdy, Kelly, Salvador, Raymond, Skoch, Antonin, Sim, Kang, Spalletta, Gianfranco, Spaniel, Filip, Stein, Frederike, Thomas-Odenthal, Florian, Tikàsz, Andràs, Tomecek, David, Tomyshev, Alexander, Tranfa, Mario, Tsogt, Uyanga, Turner, Jessica A, van Erp, Theo GM, van Haren, Neeltje EM, van Os, Jim, Vecchio, Daniela, Wang, Lei, Wroblewski, Adrian, Nickl-Jockschat, Thomas, Lamsma, Jelle, Lamsma, Jelle, Raine, Adrian, Kia, Seyed M, Cahn, Wiepke, Arold, Dominic, Banaj, Nerisa, Barone, Annarita, Brosch, Katharina, Brouwer, Rachel, Brunetti, Arturo, Calhoun, Vince D, Chew, Qian H, Choi, Sunah, Chung, Young-Chul, Ciccarelli, Mariateresa, Cobia, Derin, Cocozza, Sirio, Dannlowski, Udo, Dazzan, Paola, de Bartolomeis, Andrea, Di Forti, Marta, Dumais, Alexandre, Edmond, Jesse T, Ehrlich, Stefan, Evermann, Ulrika, Flinkenflügel, Kira, Georgiadis, Foivos, Glahn, David C, Goltermann, Janik, Green, Melissa J, Grotegerd, Dominik, Guerrero-Pedraza, Amalia, Ha, Minji, Hong, Elliot L, Pol, Hilleke Hulshoff, Iasevoli, Felice, Kaiser, Stefan, Kaleda, Vasily, Karuk, Andriana, Kim, Minah, Kircher, Tilo, Kirschner, Matthias, Kochunov, Peter, Kwon, Jun Soo, Lebedeva, Irina, Lencer, Rebekka, Marques, Tiago R, Meinert, Susanne, Murray, Robin, Nenadić, Igor, Nguyen, Dana, Pearlson, Godfrey, Piras, Fabrizio, Pomarol-Clotet, Edith, Pontillo, Giuseppe, Potvin, Stéphane, Preda, Adrian, Quidé, Yann, Rodrigue, Amanda, Rootes-Murdy, Kelly, Salvador, Raymond, Skoch, Antonin, Sim, Kang, Spalletta, Gianfranco, Spaniel, Filip, Stein, Frederike, Thomas-Odenthal, Florian, Tikàsz, Andràs, Tomecek, David, Tomyshev, Alexander, Tranfa, Mario, Tsogt, Uyanga, Turner, Jessica A, van Erp, Theo GM, van Haren, Neeltje EM, van Os, Jim, Vecchio, Daniela, Wang, Lei, Wroblewski, Adrian, and Nickl-Jockschat, Thomas
Abstract: BACKGROUND: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome. METHODS: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z-scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale. RESULTS: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10-5) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10-4). Except for inferior parietal lobule volume, these associations were largely mediated b
Published: 2024

3. 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

4. ENIGMA-DTI: Translating reproducible white matter deficits into personalized vulnerability metrics in cross-diagnostic psychiatric research.

Author: Kochunov, Peter, Kochunov, Peter, Hong, L Elliot, Dennis, Emily L, Morey, Rajendra A, Tate, David F, Wilde, Elisabeth A, Logue, Mark, Kelly, Sinead, Donohoe, Gary, Favre, Pauline, Houenou, Josselin, Ching, Christopher RK, Holleran, Laurena, Andreassen, Ole A, van Velzen, Laura S, Schmaal, Lianne, Villalón-Reina, Julio E, Bearden, Carrie E, Piras, Fabrizio, Spalletta, Gianfranco, van den Heuvel, Odile A, Veltman, Dick J, Stein, Dan J, Ryan, Meghann C, Tan, Yunlong, van Erp, Theo GM, Turner, Jessica A, Haddad, Liz, Nir, Talia M, Glahn, David C, Thompson, Paul M, Jahanshad, Neda, Kochunov, Peter, Kochunov, Peter, Hong, L Elliot, Dennis, Emily L, Morey, Rajendra A, Tate, David F, Wilde, Elisabeth A, Logue, Mark, Kelly, Sinead, Donohoe, Gary, Favre, Pauline, Houenou, Josselin, Ching, Christopher RK, Holleran, Laurena, Andreassen, Ole A, van Velzen, Laura S, Schmaal, Lianne, Villalón-Reina, Julio E, Bearden, Carrie E, Piras, Fabrizio, Spalletta, Gianfranco, van den Heuvel, Odile A, Veltman, Dick J, Stein, Dan J, Ryan, Meghann C, Tan, Yunlong, van Erp, Theo GM, Turner, Jessica A, Haddad, Liz, Nir, Talia M, Glahn, David C, Thompson, Paul M, and Jahanshad, Neda
Abstract: The ENIGMA-DTI (diffusion tensor imaging) workgroup supports analyses that examine the effects of psychiatric, neurological, and developmental disorders on the white matter pathways of the human brain, as well as the effects of normal variation and its genetic associations. The seven ENIGMA disorder-oriented working groups used the ENIGMA-DTI workflow to derive patterns of deficits using coherent and coordinated analyses that model the disease effects across cohorts worldwide. This yielded the largest studies detailing patterns of white matter deficits in schizophrenia spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and 22q11 deletion syndrome. These deficit patterns are informative of the underlying neurobiology and reproducible in independent cohorts. We reviewed these findings, demonstrated their reproducibility in independent cohorts, and compared the deficit patterns across illnesses. We discussed translating ENIGMA-defined deficit patterns on the level of individual subjects using a metric called the regional vulnerability index (RVI), a correlation of an individual's brain metrics with the expected pattern for a disorder. We discussed the similarity in white matter deficit patterns among SSD, BD, MDD, and OCD and provided a rationale for using this index in cross-diagnostic neuropsychiatric research. We also discussed the difference in deficit patterns between idiopathic schizophrenia and 22q11 deletion syndrome, which is used as a developmental and genetic model of schizophrenia. Together, these findings highlight the importance of collaborative large-scale research to provide robust and reproducible effects that offer insights into individual vulnerability and cross-diagnosis features.
Published: 2022

5. Translating ENIGMA schizophrenia findings using the regional vulnerability index: Association with cognition, symptoms, and disease trajectory.

Author: Kochunov, Peter, Kochunov, Peter, Fan, Fengmei, Ryan, Meghann C, Hatch, Kathryn S, Tan, Shuping, Jahanshad, Neda, Thompson, Paul M, van Erp, Theo GM, Turner, Jessica A, Chen, Shuo, Du, Xiaoming, Adhikari, Bhim, Bruce, Heather, Hare, Stephanie, Goldwaser, Eric, Kvarta, Mark, Huang, Junchao, Tong, Jinghui, Cui, Yimin, Cao, Baopeng, Tan, Yunlong, Hong, L Elliot, Kochunov, Peter, Kochunov, Peter, Fan, Fengmei, Ryan, Meghann C, Hatch, Kathryn S, Tan, Shuping, Jahanshad, Neda, Thompson, Paul M, van Erp, Theo GM, Turner, Jessica A, Chen, Shuo, Du, Xiaoming, Adhikari, Bhim, Bruce, Heather, Hare, Stephanie, Goldwaser, Eric, Kvarta, Mark, Huang, Junchao, Tong, Jinghui, Cui, Yimin, Cao, Baopeng, Tan, Yunlong, and Hong, L Elliot
Abstract: Patients with schizophrenia have patterns of brain deficits including reduced cortical thickness, subcortical gray matter volumes, and cerebral white matter integrity. We proposed the regional vulnerability index (RVI) to translate the results of Enhancing Neuro Imaging Genetics Meta-Analysis studies to the individual level. We calculated RVIs for cortical, subcortical, and white matter measurements and a multimodality RVI. We evaluated RVI as a measure sensitive to schizophrenia-specific neuroanatomical deficits and symptoms and studied the timeline of deficit formations in: early (≤5 years since diagnosis, N = 45, age = 28.8 ± 8.5); intermediate (6-20 years, N = 30, age 43.3 ± 8.6); and chronic (21+ years, N = 44, age = 52.5 ± 5.2) patients and healthy controls (N = 76, age = 38.6 ± 12.4). All RVIs were significantly elevated in patients compared to controls, with the multimodal RVI showing the largest effect size, followed by cortical, white matter and subcortical RVIs (d = 1.57, 1.23, 1.09, and 0.61, all p < 10-6 ). Multimodal RVI was significantly correlated with multiple cognitive variables including measures of visual learning, working memory and the total score of the MATRICS consensus cognitive battery, and with negative symptoms. The multimodality and white matter RVIs were significantly elevated in the intermediate and chronic versus early diagnosis group, consistent with ongoing progression. Cortical RVI was stable in the three disease-duration groups, suggesting neurodevelopmental origins of cortical deficits. In summary, neuroanatomical deficits in schizophrenia affect the entire brain; the heterochronicity of their appearance indicates both the neurodevelopmental and progressive nature of this illness. These deficit patterns may be useful for early diagnosis and as quantitative targets for more effective treatment strategies aiming to alter these neuroanatomical deficit
Published: 2022

6. ENIGMA-DTI: Translating reproducible white matter deficits into personalized vulnerability metrics in cross-diagnostic psychiatric research.

Author: Kochunov, Peter, Kochunov, Peter, Hong, L Elliot, Dennis, Emily L, Morey, Rajendra A, Tate, David F, Wilde, Elisabeth A, Logue, Mark, Kelly, Sinead, Donohoe, Gary, Favre, Pauline, Houenou, Josselin, Ching, Christopher RK, Holleran, Laurena, Andreassen, Ole A, van Velzen, Laura S, Schmaal, Lianne, Villalón-Reina, Julio E, Bearden, Carrie E, Piras, Fabrizio, Spalletta, Gianfranco, van den Heuvel, Odile A, Veltman, Dick J, Stein, Dan J, Ryan, Meghann C, Tan, Yunlong, van Erp, Theo GM, Turner, Jessica A, Haddad, Liz, Nir, Talia M, Glahn, David C, Thompson, Paul M, Jahanshad, Neda, Kochunov, Peter, Kochunov, Peter, Hong, L Elliot, Dennis, Emily L, Morey, Rajendra A, Tate, David F, Wilde, Elisabeth A, Logue, Mark, Kelly, Sinead, Donohoe, Gary, Favre, Pauline, Houenou, Josselin, Ching, Christopher RK, Holleran, Laurena, Andreassen, Ole A, van Velzen, Laura S, Schmaal, Lianne, Villalón-Reina, Julio E, Bearden, Carrie E, Piras, Fabrizio, Spalletta, Gianfranco, van den Heuvel, Odile A, Veltman, Dick J, Stein, Dan J, Ryan, Meghann C, Tan, Yunlong, van Erp, Theo GM, Turner, Jessica A, Haddad, Liz, Nir, Talia M, Glahn, David C, Thompson, Paul M, and Jahanshad, Neda
Abstract: The ENIGMA-DTI (diffusion tensor imaging) workgroup supports analyses that examine the effects of psychiatric, neurological, and developmental disorders on the white matter pathways of the human brain, as well as the effects of normal variation and its genetic associations. The seven ENIGMA disorder-oriented working groups used the ENIGMA-DTI workflow to derive patterns of deficits using coherent and coordinated analyses that model the disease effects across cohorts worldwide. This yielded the largest studies detailing patterns of white matter deficits in schizophrenia spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and 22q11 deletion syndrome. These deficit patterns are informative of the underlying neurobiology and reproducible in independent cohorts. We reviewed these findings, demonstrated their reproducibility in independent cohorts, and compared the deficit patterns across illnesses. We discussed translating ENIGMA-defined deficit patterns on the level of individual subjects using a metric called the regional vulnerability index (RVI), a correlation of an individual's brain metrics with the expected pattern for a disorder. We discussed the similarity in white matter deficit patterns among SSD, BD, MDD, and OCD and provided a rationale for using this index in cross-diagnostic neuropsychiatric research. We also discussed the difference in deficit patterns between idiopathic schizophrenia and 22q11 deletion syndrome, which is used as a developmental and genetic model of schizophrenia. Together, these findings highlight the importance of collaborative large-scale research to provide robust and reproducible effects that offer insights into individual vulnerability and cross-diagnosis features.
Published: 2022

7. Translating ENIGMA schizophrenia findings using the regional vulnerability index: Association with cognition, symptoms, and disease trajectory.

Author: Kochunov, Peter, Kochunov, Peter, Fan, Fengmei, Ryan, Meghann C, Hatch, Kathryn S, Tan, Shuping, Jahanshad, Neda, Thompson, Paul M, van Erp, Theo GM, Turner, Jessica A, Chen, Shuo, Du, Xiaoming, Adhikari, Bhim, Bruce, Heather, Hare, Stephanie, Goldwaser, Eric, Kvarta, Mark, Huang, Junchao, Tong, Jinghui, Cui, Yimin, Cao, Baopeng, Tan, Yunlong, Hong, L Elliot, Kochunov, Peter, Kochunov, Peter, Fan, Fengmei, Ryan, Meghann C, Hatch, Kathryn S, Tan, Shuping, Jahanshad, Neda, Thompson, Paul M, van Erp, Theo GM, Turner, Jessica A, Chen, Shuo, Du, Xiaoming, Adhikari, Bhim, Bruce, Heather, Hare, Stephanie, Goldwaser, Eric, Kvarta, Mark, Huang, Junchao, Tong, Jinghui, Cui, Yimin, Cao, Baopeng, Tan, Yunlong, and Hong, L Elliot
Abstract: Patients with schizophrenia have patterns of brain deficits including reduced cortical thickness, subcortical gray matter volumes, and cerebral white matter integrity. We proposed the regional vulnerability index (RVI) to translate the results of Enhancing Neuro Imaging Genetics Meta-Analysis studies to the individual level. We calculated RVIs for cortical, subcortical, and white matter measurements and a multimodality RVI. We evaluated RVI as a measure sensitive to schizophrenia-specific neuroanatomical deficits and symptoms and studied the timeline of deficit formations in: early (≤5 years since diagnosis, N = 45, age = 28.8 ± 8.5); intermediate (6-20 years, N = 30, age 43.3 ± 8.6); and chronic (21+ years, N = 44, age = 52.5 ± 5.2) patients and healthy controls (N = 76, age = 38.6 ± 12.4). All RVIs were significantly elevated in patients compared to controls, with the multimodal RVI showing the largest effect size, followed by cortical, white matter and subcortical RVIs (d = 1.57, 1.23, 1.09, and 0.61, all p < 10-6 ). Multimodal RVI was significantly correlated with multiple cognitive variables including measures of visual learning, working memory and the total score of the MATRICS consensus cognitive battery, and with negative symptoms. The multimodality and white matter RVIs were significantly elevated in the intermediate and chronic versus early diagnosis group, consistent with ongoing progression. Cortical RVI was stable in the three disease-duration groups, suggesting neurodevelopmental origins of cortical deficits. In summary, neuroanatomical deficits in schizophrenia affect the entire brain; the heterochronicity of their appearance indicates both the neurodevelopmental and progressive nature of this illness. These deficit patterns may be useful for early diagnosis and as quantitative targets for more effective treatment strategies aiming to alter these neuroanatomical deficit
Published: 2022

8. ENIGMA-DTI: Translating reproducible white matter deficits into personalized vulnerability metrics in cross-diagnostic psychiatric research.

Author: Kochunov, Peter, Kochunov, Peter, Hong, L, Dennis, Emily, Morey, Rajendra, Tate, David, Wilde, Elisabeth, Logue, Mark, Kelly, Sinead, Donohoe, Gary, Favre, Pauline, Houenou, Josselin, Ching, Christopher, Holleran, Laurena, Andreassen, Ole, van Velzen, Laura, Schmaal, Lianne, Villalón-Reina, Julio, Piras, Fabrizio, Spalletta, Gianfranco, van den Heuvel, Odile, Veltman, Dick, Stein, Dan, Ryan, Meghann, Tan, Yunlong, Turner, Jessica, Haddad, Liz, Nir, Talia, Glahn, David, Thompson, Paul, Jahanshad, Neda, Bearden, Carrie, Van Erp, Theodorus, Kochunov, Peter, Kochunov, Peter, Hong, L, Dennis, Emily, Morey, Rajendra, Tate, David, Wilde, Elisabeth, Logue, Mark, Kelly, Sinead, Donohoe, Gary, Favre, Pauline, Houenou, Josselin, Ching, Christopher, Holleran, Laurena, Andreassen, Ole, van Velzen, Laura, Schmaal, Lianne, Villalón-Reina, Julio, Piras, Fabrizio, Spalletta, Gianfranco, van den Heuvel, Odile, Veltman, Dick, Stein, Dan, Ryan, Meghann, Tan, Yunlong, Turner, Jessica, Haddad, Liz, Nir, Talia, Glahn, David, Thompson, Paul, Jahanshad, Neda, Bearden, Carrie, and Van Erp, Theodorus
Abstract: The ENIGMA-DTI (diffusion tensor imaging) workgroup supports analyses that examine the effects of psychiatric, neurological, and developmental disorders on the white matter pathways of the human brain, as well as the effects of normal variation and its genetic associations. The seven ENIGMA disorder-oriented working groups used the ENIGMA-DTI workflow to derive patterns of deficits using coherent and coordinated analyses that model the disease effects across cohorts worldwide. This yielded the largest studies detailing patterns of white matter deficits in schizophrenia spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and 22q11 deletion syndrome. These deficit patterns are informative of the underlying neurobiology and reproducible in independent cohorts. We reviewed these findings, demonstrated their reproducibility in independent cohorts, and compared the deficit patterns across illnesses. We discussed translating ENIGMA-defined deficit patterns on the level of individual subjects using a metric called the regional vulnerability index (RVI), a correlation of an individuals brain metrics with the expected pattern for a disorder. We discussed the similarity in white matter deficit patterns among SSD, BD, MDD, and OCD and provided a rationale for using this index in cross-diagnostic neuropsychiatric research. We also discussed the difference in deficit patterns between idiopathic schizophrenia and 22q11 deletion syndrome, which is used as a developmental and genetic model of schizophrenia. Together, these findings highlight the importance of collaborative large-scale research to provide robust and reproducible effects that offer insights into individual vulnerability and cross-diagnosis features.
Published: 2022

9. Translating ENIGMA schizophrenia findings using the regional vulnerability index: Association with cognition, symptoms, and disease trajectory.

Author: Kochunov, Peter, Kochunov, Peter, Fan, Fengmei, Ryan, Meghann, Hatch, Kathryn, Tan, Shuping, Jahanshad, Neda, Thompson, Paul, Turner, Jessica, Chen, Shuo, Du, Xiaoming, Adhikari, Bhim, Bruce, Heather, Hare, Stephanie, Goldwaser, Eric, Kvarta, Mark, Huang, Junchao, Tong, Jinghui, Cui, Yimin, Cao, Baopeng, Tan, Yunlong, Hong, L, Van Erp, Theodorus, Kochunov, Peter, Kochunov, Peter, Fan, Fengmei, Ryan, Meghann, Hatch, Kathryn, Tan, Shuping, Jahanshad, Neda, Thompson, Paul, Turner, Jessica, Chen, Shuo, Du, Xiaoming, Adhikari, Bhim, Bruce, Heather, Hare, Stephanie, Goldwaser, Eric, Kvarta, Mark, Huang, Junchao, Tong, Jinghui, Cui, Yimin, Cao, Baopeng, Tan, Yunlong, Hong, L, and Van Erp, Theodorus
Abstract: Patients with schizophrenia have patterns of brain deficits including reduced cortical thickness, subcortical gray matter volumes, and cerebral white matter integrity. We proposed the regional vulnerability index (RVI) to translate the results of Enhancing Neuro Imaging Genetics Meta-Analysis studies to the individual level. We calculated RVIs for cortical, subcortical, and white matter measurements and a multimodality RVI. We evaluated RVI as a measure sensitive to schizophrenia-specific neuroanatomical deficits and symptoms and studied the timeline of deficit formations in: early (≤5 years since diagnosis, N = 45, age = 28.8 ± 8.5); intermediate (6-20 years, N = 30, age 43.3 ± 8.6); and chronic (21+ years, N = 44, age = 52.5 ± 5.2) patients and healthy controls (N = 76, age = 38.6 ± 12.4). All RVIs were significantly elevated in patients compared to controls, with the multimodal RVI showing the largest effect size, followed by cortical, white matter and subcortical RVIs (d = 1.57, 1.23, 1.09, and 0.61, all p < 10-6 ). Multimodal RVI was significantly correlated with multiple cognitive variables including measures of visual learning, working memory and the total score of the MATRICS consensus cognitive battery, and with negative symptoms. The multimodality and white matter RVIs were significantly elevated in the intermediate and chronic versus early diagnosis group, consistent with ongoing progression. Cortical RVI was stable in the three disease-duration groups, suggesting neurodevelopmental origins of cortical deficits. In summary, neuroanatomical deficits in schizophrenia affect the entire brain; the heterochronicity of their appearance indicates both the neurodevelopmental and progressive nature of this illness. These deficit patterns may be useful for early diagnosis and as quantitative targets for more effective treatment strategies aiming to alter these neuroanatomical deficit
Published: 2022

10. In vivo white matter microstructure in adolescents with early-onset psychosis : a multi-site mega-analysis

Author: Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A., Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E., Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Diaz-Caneja, Covadonga M., Gurholt, Tiril P., Hegarty, Catherine E., James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G., Karlsgodt, Katherine H., Kochunov, Peter, Lois, Noemi G., Lundberg, Mathias, Myhre, Anne M., Pascual-Diaz, Sauel, Piras, Fabrizio, Smelror, Runar E., Spalletta, Gianfranco, Stokkan, Therese S., Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I., Tordesillas-Gutierrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A., Thompson, Paul M., Agartz, Ingrid, Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A., Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E., Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Diaz-Caneja, Covadonga M., Gurholt, Tiril P., Hegarty, Catherine E., James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G., Karlsgodt, Katherine H., Kochunov, Peter, Lois, Noemi G., Lundberg, Mathias, Myhre, Anne M., Pascual-Diaz, Sauel, Piras, Fabrizio, Smelror, Runar E., Spalletta, Gianfranco, Stokkan, Therese S., Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I., Tordesillas-Gutierrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A., Thompson, Paul M., and Agartz, Ingrid
Abstract: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age=16.6 years, interquartile range (IQR)=2.14, 46.4% females) and 265 adolescent healthy controls (median age=16.2 years, IQR=2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d=0.37), posterior corona radiata (d=0.32), and superior fronto-occipital fasciculus (d=0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.
Published: 2023
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11. In vivo white matter microstructure in adolescents with early-onset psychosis : a multi-site mega-analysis

Author: Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A., Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E., Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Diaz-Caneja, Covadonga M., Gurholt, Tiril P., Hegarty, Catherine E., James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G., Karlsgodt, Katherine H., Kochunov, Peter, Lois, Noemi G., Lundberg, Mathias, Myhre, Anne M., Pascual-Diaz, Sauel, Piras, Fabrizio, Smelror, Runar E., Spalletta, Gianfranco, Stokkan, Therese S., Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I., Tordesillas-Gutierrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A., Thompson, Paul M., Agartz, Ingrid, Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A., Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E., Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Diaz-Caneja, Covadonga M., Gurholt, Tiril P., Hegarty, Catherine E., James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G., Karlsgodt, Katherine H., Kochunov, Peter, Lois, Noemi G., Lundberg, Mathias, Myhre, Anne M., Pascual-Diaz, Sauel, Piras, Fabrizio, Smelror, Runar E., Spalletta, Gianfranco, Stokkan, Therese S., Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I., Tordesillas-Gutierrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A., Thompson, Paul M., and Agartz, Ingrid
Abstract: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age=16.6 years, interquartile range (IQR)=2.14, 46.4% females) and 265 adolescent healthy controls (median age=16.2 years, IQR=2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d=0.37), posterior corona radiata (d=0.32), and superior fronto-occipital fasciculus (d=0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.
Published: 2023
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12. In vivo white matter microstructure in adolescents with early-onset psychosis : a multi-site mega-analysis

Author: Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A., Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E., Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Diaz-Caneja, Covadonga M., Gurholt, Tiril P., Hegarty, Catherine E., James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G., Karlsgodt, Katherine H., Kochunov, Peter, Lois, Noemi G., Lundberg, Mathias, Myhre, Anne M., Pascual-Diaz, Sauel, Piras, Fabrizio, Smelror, Runar E., Spalletta, Gianfranco, Stokkan, Therese S., Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I., Tordesillas-Gutierrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A., Thompson, Paul M., Agartz, Ingrid, Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A., Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E., Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Diaz-Caneja, Covadonga M., Gurholt, Tiril P., Hegarty, Catherine E., James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G., Karlsgodt, Katherine H., Kochunov, Peter, Lois, Noemi G., Lundberg, Mathias, Myhre, Anne M., Pascual-Diaz, Sauel, Piras, Fabrizio, Smelror, Runar E., Spalletta, Gianfranco, Stokkan, Therese S., Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I., Tordesillas-Gutierrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A., Thompson, Paul M., and Agartz, Ingrid
Abstract: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age=16.6 years, interquartile range (IQR)=2.14, 46.4% females) and 265 adolescent healthy controls (median age=16.2 years, IQR=2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d=0.37), posterior corona radiata (d=0.32), and superior fronto-occipital fasciculus (d=0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.
Published: 2023
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13. Five negative symptom domains are differentially associated with resting state amplitude of low frequency fluctuations in Schizophrenia.

Author: Cheon, Eun-Jin, Cheon, Eun-Jin, Male, Alie, Gao, Bingchen, Adhikari, Bhim, Edmond, Jesse, Hare, Stephanie, Belger, Aysenil, Potkin, Steven, Bustillo, Juan, Mathalon, Daniel, Ford, Judith, Lim, Kelvin, Mueller, Bryon, Preda, Adrian, OLeary, Daniel, Strauss, Gregory, Ahmed, Anthony, Thompson, Paul, Jahanshad, Neda, Kochunov, Peter, Calhoun, Vince, Turner, Jessica, Van Erp, Theodorus, Cheon, Eun-Jin, Cheon, Eun-Jin, Male, Alie, Gao, Bingchen, Adhikari, Bhim, Edmond, Jesse, Hare, Stephanie, Belger, Aysenil, Potkin, Steven, Bustillo, Juan, Mathalon, Daniel, Ford, Judith, Lim, Kelvin, Mueller, Bryon, Preda, Adrian, OLeary, Daniel, Strauss, Gregory, Ahmed, Anthony, Thompson, Paul, Jahanshad, Neda, Kochunov, Peter, Calhoun, Vince, Turner, Jessica, and Van Erp, Theodorus
Abstract: This study examined associations between resting-state amplitude of low frequency fluctuations (ALFF) and negative symptoms represented by total scores, second-order dimension (motivation and pleasure, expressivity), and first-order domain (anhedonia, avolition, asociality, alogia, blunted affect) factor scores in schizophrenia (n = 57). Total negative symptom scores showed positive associations with ALFF in temporal and frontal brain regions. Negative symptom domain scores showed predominantly stronger associations with regional ALFF compared to total scores, suggesting domain scores may better map to neural signatures than total scores. Improving our understanding of the neuropathology underlying negative symptoms may aid in addressing this unmet therapeutic need in schizophrenia.
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. 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

16. 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

17. A Novel Neighborhood Rough Set-Based Feature Selection Method and Its Application to Biomarker Identification of Schizophrenia.

Author: Xing, Ying, Xing, Ying, Kochunov, Peter, van Erp, Theo GM, Ma, Tianzhou, Calhoun, Vince D, Du, Yuhui, Xing, Ying, Xing, Ying, Kochunov, Peter, van Erp, Theo GM, Ma, Tianzhou, Calhoun, Vince D, and Du, Yuhui
Abstract: Feature selection can disclose biomarkers of mental disorders that have unclear biological mechanisms. Although neighborhood rough set (NRS) has been applied to discover important sparse features, it has hardly ever been utilized in neuroimaging-based biomarker identification, probably due to the inadequate feature evaluation metric and incomplete information provided under a single-granularity. Here, we propose a new NRS-based feature selection method and successfully identify brain functional connectivity biomarkers of schizophrenia (SZ) using functional magnetic resonance imaging (fMRI) data. Specifically, we develop a new weighted metric based on NRS combined with information entropy to evaluate the capacity of features in distinguishing different groups. Inspired by multi-granularity information maximization theory, we further take advantage of the complementary information from different neighborhood sizes via a multi-granularity fusion to obtain the most discriminative and stable features. For validation, we compare our method with six popular feature selection methods using three public omics datasets as well as resting-state fMRI data of 393 SZ patients and 429 healthy controls. Results show that our method obtained higher classification accuracies on both omics data (100.0%, 88.6%, and 72.2% for three omics datasets, respectively) and fMRI data (93.9% for main dataset, and 76.3% and 83.8% for two independent datasets, respectively). Moreover, our findings reveal biologically meaningful substrates of SZ, notably involving the connectivity between the thalamus and superior temporal gyrus as well as between the postcentral gyrus and calcarine gyrus. Taken together, we propose a new NRS-based feature selection method that shows the potential of exploring effective and sparse neuroimaging-based biomarkers of mental disorders.
Published: 2023

18. Multi-model order spatially constrained ICA reveals highly replicable group differences and consistent predictive results from resting data: A large N fMRI schizophrenia study.

Author: Meng, Xing, Meng, Xing, Iraji, Armin, Fu, Zening, Kochunov, Peter, Belger, Aysenil, Ford, Judy M, McEwen, Sara, Mathalon, Daniel H, Mueller, Bryon A, Pearlson, Godfrey, Potkin, Steven G, Preda, Adrian, Turner, Jessica, van Erp, Theo GM, Sui, Jing, Calhoun, Vince D, Meng, Xing, Meng, Xing, Iraji, Armin, Fu, Zening, Kochunov, Peter, Belger, Aysenil, Ford, Judy M, McEwen, Sara, Mathalon, Daniel H, Mueller, Bryon A, Pearlson, Godfrey, Potkin, Steven G, Preda, Adrian, Turner, Jessica, van Erp, Theo GM, Sui, Jing, and Calhoun, Vince D
Abstract: Brain functional networks identified from resting functional magnetic resonance imaging (fMRI) data have the potential to reveal biomarkers for brain disorders, but studies of complex mental illnesses such as schizophrenia (SZ) often yield mixed results across replication studies. This is likely due in part to the complexity of the disorder, the short data acquisition time, and the limited ability of the approaches for brain imaging data mining. Therefore, the use of analytic approaches which can both capture individual variability while offering comparability across analyses is highly preferred. Fully blind data-driven approaches such as independent component analysis (ICA) are hard to compare across studies, and approaches that use fixed atlas-based regions can have limited sensitivity to individual sensitivity. By contrast, spatially constrained ICA (scICA) provides a hybrid, fully automated solution that can incorporate spatial network priors while also adapting to new subjects. However, scICA has thus far only been used with a single spatial scale (ICA dimensionality, i.e., ICA model order). In this work, we present an approach using multi-objective optimization scICA with reference algorithm (MOO-ICAR) to extract subject-specific intrinsic connectivity networks (ICNs) from fMRI data at multiple spatial scales, which also enables us to study interactions across spatial scales. We evaluate this approach using a large N (N > 1,600) study of schizophrenia divided into separate validation and replication sets. A multi-scale ICN template was estimated and labeled, then used as input into scICA which was computed on an individual subject level. We then performed a subsequent analysis of multiscale functional network connectivity (msFNC) to evaluate the patient data, including group differences and classification. Results showed highly consistent group differences in msFNC in regions including cerebellum, thalamus, and motor/auditory networks. Importantly
Published: 2023

19. In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis.

Author: Barth, Claudia, Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A, Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Díaz-Caneja, Covadonga M, Gurholt, Tiril P, Hegarty, Catherine E, James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G, Karlsgodt, Katherine H, Kochunov, Peter, Lois, Noemi G, Lundberg, Mathias, Myhre, Anne M, Pascual-Diaz, Saül, Piras, Fabrizio, Smelror, Runar E, Spalletta, Gianfranco, Stokkan, Therese S, Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I, Tordesillas-Gutiérrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A, Thompson, Paul M, Agartz, Ingrid, Barth, Claudia, Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A, Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Díaz-Caneja, Covadonga M, Gurholt, Tiril P, Hegarty, Catherine E, James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G, Karlsgodt, Katherine H, Kochunov, Peter, Lois, Noemi G, Lundberg, Mathias, Myhre, Anne M, Pascual-Diaz, Saül, Piras, Fabrizio, Smelror, Runar E, Spalletta, Gianfranco, Stokkan, Therese S, Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I, Tordesillas-Gutiérrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A, Thompson, Paul M, and Agartz, Ingrid
Abstract: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age = 16.6 years, interquartile range (IQR) = 2.14, 46.4% females) and 265 adolescent healthy controls (median age = 16.2 years, IQR = 2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d = 0.37), posterior corona radiata (d = 0.32), and superior fronto-occipital fasciculus (d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.
Published: 2023

20. 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

21. 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

22. 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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23. In vivo white matter microstructure in adolescents with early-onset psychosis : a multi-site mega-analysis

Author: Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A., Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E., Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Diaz-Caneja, Covadonga M., Gurholt, Tiril P., Hegarty, Catherine E., James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G., Karlsgodt, Katherine H., Kochunov, Peter, Lois, Noemi G., Lundberg, Mathias, Myhre, Anne M., Pascual-Diaz, Sauel, Piras, Fabrizio, Smelror, Runar E., Spalletta, Gianfranco, Stokkan, Therese S., Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I., Tordesillas-Gutierrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A., Thompson, Paul M., Agartz, Ingrid, Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A., Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E., Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Diaz-Caneja, Covadonga M., Gurholt, Tiril P., Hegarty, Catherine E., James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G., Karlsgodt, Katherine H., Kochunov, Peter, Lois, Noemi G., Lundberg, Mathias, Myhre, Anne M., Pascual-Diaz, Sauel, Piras, Fabrizio, Smelror, Runar E., Spalletta, Gianfranco, Stokkan, Therese S., Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I., Tordesillas-Gutierrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A., Thompson, Paul M., and Agartz, Ingrid
Abstract: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age=16.6 years, interquartile range (IQR)=2.14, 46.4% females) and 265 adolescent healthy controls (median age=16.2 years, IQR=2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d=0.37), posterior corona radiata (d=0.32), and superior fronto-occipital fasciculus (d=0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.
Published: 2023
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24. Elevated blood pressure accelerates white matter brain aging among late middle-aged women: a Mendelian Randomization study in the UK Biobank

Author: Feng, Li, Ye, Zhenyao, Mo, Chen, Wang, Jingtao, Liu, Song, Gao, Si, Ke, Hongjie, Canida, Travis A, Pan, Yezhi, Greevenbroek, Marleen M J van, Houben, Alfons J H M, Wang, Kai, Hatch, Kathryn S, Ma, Yizhou, Lei, David K Y, Chen, Chixiang, Mitchell, Braxton D, Hong, L Elliot, Kochunov, Peter, Chen, Shuo, Ma, Tianzhou, Feng, Li, Ye, Zhenyao, Mo, Chen, Wang, Jingtao, Liu, Song, Gao, Si, Ke, Hongjie, Canida, Travis A, Pan, Yezhi, Greevenbroek, Marleen M J van, Houben, Alfons J H M, Wang, Kai, Hatch, Kathryn S, Ma, Yizhou, Lei, David K Y, Chen, Chixiang, Mitchell, Braxton D, Hong, L Elliot, Kochunov, Peter, Chen, Shuo, and Ma, Tianzhou
Abstract: BACKGROUND: Elevated blood pressure (BP) is a modifiable risk factor associated with cognitive impairment and cerebrovascular diseases. However, the causal effect of BP on white matter brain aging remains unclear.METHODS: In this study, we focused on N = 228 473 individuals of European ancestry who had genotype data and clinical BP measurements available (103 929 men and 124 544 women, mean age = 56.49, including 16 901 participants with neuroimaging data available) collected from UK Biobank (UKB). We first established a machine learning model to compute the outcome variable brain age gap (BAG) based on white matter microstructure integrity measured by fractional anisotropy derived from diffusion tensor imaging data. We then performed a two-sample Mendelian randomization analysis to estimate the causal effect of BP on white matter BAG in the whole population and subgroups stratified by sex and age brackets using two nonoverlapping data sets.RESULTS: The hypertension group is on average 0.31 years (95% CI = 0.13-0.49; P < 0.0001) older in white matter brain age than the nonhypertension group. Women are on average 0.81 years (95% CI = 0.68-0.95; P < 0.0001) younger in white matter brain age than men. The Mendelian randomization analyses showed an overall significant positive causal effect of DBP on white matter BAG (0.37 years/10 mmHg, 95% CI 0.034-0.71, P = 0.0311). In stratified analysis, the causal effect was found most prominent among women aged 50-59 and aged 60-69.CONCLUSION: High BP can accelerate white matter brain aging among late middle-aged women, providing insights on planning effective control of BP for women in this age group.
Published: 2023

25. Deciphering the causal relationship between blood pressure and regional white matter integrity: A two-sample Mendelian randomization study

Author: Ye, Zhenyao, Ye, Zhenyao, Mo, Chen, Liu, Song, Gao, Si, Feng, Li, Zhao, Boao, Canida, Travis, Wu, Yu-Chia, Hatch, Kathryn S., Ma, Yizhou, Mitchell, Braxton D., Hong, Elliot L., Kochunov, Peter, Chen, Chixiang, Zhao, Bingxin, Chen, Shuo, Ma, Tianzhou, Ye, Zhenyao, Ye, Zhenyao, Mo, Chen, Liu, Song, Gao, Si, Feng, Li, Zhao, Boao, Canida, Travis, Wu, Yu-Chia, Hatch, Kathryn S., Ma, Yizhou, Mitchell, Braxton D., Hong, Elliot L., Kochunov, Peter, Chen, Chixiang, Zhao, Bingxin, Chen, Shuo, and Ma, Tianzhou
Abstract: Elevated arterial blood pressure (BP) is a common risk factor for cerebrovascular and cardiovascular diseases, but no causal relationship has been established between BP and cerebral white matter (WM) integrity. In this study, we performed a two-sample Mendelian randomization (MR) analysis with individual-level data by defining two nonoverlapping sets of European ancestry individuals (genetics–exposure set: N = 203,111; mean age = 56.71 years, genetics–outcome set: N = 16,156; mean age = 54.61 years) from UK Biobank to evaluate the causal effects of BP on regional WM integrity, measured by fractional anisotropy of diffusion tensor imaging. Two BP traits: systolic and diastolic blood pressure were used as exposures. Genetic variant was carefully selected as instrumental variable (IV) under the MR analysis assumptions. We existing large-scale genome-wide association study summary data for validation. The main method used was a generalized version of inverse-variance weight method while other MR methods were also applied for consistent findings. Two additional MR analyses were performed to exclude the possibility of reverse causality. We found significantly negative causal effects (FDR-adjusted p < .05; every 10 mmHg increase in BP leads to a decrease in FA value by .4% ~ 2%) of BP traits on a union set of 17 WM tracts, including brain regions related to cognitive function and memory. Our study extended the previous findings of association to causation for regional WM integrity, providing insights into the pathological processes of elevated BP that might chronically alter the brain microstructure in different regions.
Published: 2023

26. In vivo white matter microstructure in adolescents with early-onset psychosis : a multi-site mega-analysis

Author: Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A., Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E., Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Diaz-Caneja, Covadonga M., Gurholt, Tiril P., Hegarty, Catherine E., James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G., Karlsgodt, Katherine H., Kochunov, Peter, Lois, Noemi G., Lundberg, Mathias, Myhre, Anne M., Pascual-Diaz, Sauel, Piras, Fabrizio, Smelror, Runar E., Spalletta, Gianfranco, Stokkan, Therese S., Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I., Tordesillas-Gutierrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A., Thompson, Paul M., Agartz, Ingrid, Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A., Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E., Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Diaz-Caneja, Covadonga M., Gurholt, Tiril P., Hegarty, Catherine E., James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G., Karlsgodt, Katherine H., Kochunov, Peter, Lois, Noemi G., Lundberg, Mathias, Myhre, Anne M., Pascual-Diaz, Sauel, Piras, Fabrizio, Smelror, Runar E., Spalletta, Gianfranco, Stokkan, Therese S., Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I., Tordesillas-Gutierrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A., Thompson, Paul M., and Agartz, Ingrid
Abstract: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age=16.6 years, interquartile range (IQR)=2.14, 46.4% females) and 265 adolescent healthy controls (median age=16.2 years, IQR=2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d=0.37), posterior corona radiata (d=0.32), and superior fronto-occipital fasciculus (d=0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.
Published: 2023
Full Text: View/download PDF

27. 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

28. 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

29. 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

30. Event‐based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross‐sectional data

Author: Lopez, Seymour M, Lopez, Seymour M, Aksman, Leon M, Oxtoby, Neil P, Vos, Sjoerd B, Rao, Jun, Kaestner, Erik, Alhusaini, Saud, Alvim, Marina, Bender, Benjamin, Bernasconi, Andrea, Bernasconi, Neda, Bernhardt, Boris, Bonilha, Leonardo, Caciagli, Lorenzo, Caldairou, Benoit, Caligiuri, Maria Eugenia, Calvet, Angels, Cendes, Fernando, Concha, Luis, Conde‐Blanco, Estefania, Davoodi‐Bojd, Esmaeil, de Bézenac, Christophe, Delanty, Norman, Desmond, Patricia M, Devinsky, Orrin, Domin, Martin, Duncan, John S, Focke, Niels K, Foley, Sonya, Fortunato, Francesco, Galovic, Marian, Gambardella, Antonio, Gleichgerrcht, Ezequiel, Guerrini, Renzo, Hamandi, Khalid, Ives‐Deliperi, Victoria, Jackson, Graeme D, Jahanshad, Neda, Keller, Simon S, Kochunov, Peter, Kotikalapudi, Raviteja, Kreilkamp, Barbara AK, Labate, Angelo, Larivière, Sara, Lenge, Matteo, Lui, Elaine, Malpas, Charles, Martin, Pascal, Mascalchi, Mario, Medland, Sarah E, Meletti, Stefano, Morita‐Sherman, Marcia E, Owen, Thomas W, Richardson, Mark, Riva, Antonella, Rüber, Theodor, Sinclair, Ben, Soltanian‐Zadeh, Hamid, Stein, Dan J, Striano, Pasquale, Taylor, Peter N, Thomopoulos, Sophia I, Thompson, Paul M, Tondelli, Manuela, Vaudano, Anna Elisabetta, Vivash, Lucy, Wang, Yujiang, Weber, Bernd, Whelan, Christopher D, Wiest, Roland, Winston, Gavin P, Yasuda, Clarissa Lin, McDonald, Carrie R, Alexander, Daniel C, Sisodiya, Sanjay M, Altmann, Andre, Bargalló, Núria, Bartolini, Emanuele, O’Brien, Terence J, Thomas, Rhys H, Lopez, Seymour M, Lopez, Seymour M, Aksman, Leon M, Oxtoby, Neil P, Vos, Sjoerd B, Rao, Jun, Kaestner, Erik, Alhusaini, Saud, Alvim, Marina, Bender, Benjamin, Bernasconi, Andrea, Bernasconi, Neda, Bernhardt, Boris, Bonilha, Leonardo, Caciagli, Lorenzo, Caldairou, Benoit, Caligiuri, Maria Eugenia, Calvet, Angels, Cendes, Fernando, Concha, Luis, Conde‐Blanco, Estefania, Davoodi‐Bojd, Esmaeil, de Bézenac, Christophe, Delanty, Norman, Desmond, Patricia M, Devinsky, Orrin, Domin, Martin, Duncan, John S, Focke, Niels K, Foley, Sonya, Fortunato, Francesco, Galovic, Marian, Gambardella, Antonio, Gleichgerrcht, Ezequiel, Guerrini, Renzo, Hamandi, Khalid, Ives‐Deliperi, Victoria, Jackson, Graeme D, Jahanshad, Neda, Keller, Simon S, Kochunov, Peter, Kotikalapudi, Raviteja, Kreilkamp, Barbara AK, Labate, Angelo, Larivière, Sara, Lenge, Matteo, Lui, Elaine, Malpas, Charles, Martin, Pascal, Mascalchi, Mario, Medland, Sarah E, Meletti, Stefano, Morita‐Sherman, Marcia E, Owen, Thomas W, Richardson, Mark, Riva, Antonella, Rüber, Theodor, Sinclair, Ben, Soltanian‐Zadeh, Hamid, Stein, Dan J, Striano, Pasquale, Taylor, Peter N, Thomopoulos, Sophia I, Thompson, Paul M, Tondelli, Manuela, Vaudano, Anna Elisabetta, Vivash, Lucy, Wang, Yujiang, Weber, Bernd, Whelan, Christopher D, Wiest, Roland, Winston, Gavin P, Yasuda, Clarissa Lin, McDonald, Carrie R, Alexander, Daniel C, Sisodiya, Sanjay M, Altmann, Andre, Bargalló, Núria, Bartolini, Emanuele, O’Brien, Terence J, and Thomas, Rhys H
Published: 2022

31. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author: Patel, Yash, Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A, Arango, Celso, Arolt, Volker, Auzias, Guillaume, Ayesa-Arriola, Rosa, Banaj, Nerisa, Banaschewski, Tobias, Bandeira, Cibele, Başgöze, Zeynep, Cupertino, Renata Basso, Bau, Claiton HD, Bauer, Jochen, Baumeister, Sarah, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Brem, Silvia, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R, Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J, Cannon, Dara M, Carmona, Susanna, Carr, Vaughan J, Catts, Stanley V, Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G, Conzelmann, Annette, Craven, Alexander R, Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Dannlowski, Udo, Davey, Christopher G, Deruelle, Christine, Díaz-Caneja, Covadonga M, Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T, Fedor, Jennifer, Fitzgerald, Jacqueline, Foran, William, Ford, Judith M, Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Gao, Bingchen, Gao, Si, Goikolea, Jose M, Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J, Green, Melissa, Grevet, Eugenio H, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Haavik, Jan, Hahn, Tim, Harrison, Ben J, Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J, Hilland, Eva, Hoekstra, Pieter J, Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M, Ipser, Jonathan C, Jahanshad, Neda, Jakobi, Babette, Jansen, Andreas, Janssen, Joost, Jonassen, Rune, Kaiser, Anna, Kaleda, Vasiliy, Karantonis, James, King, Joseph A, Kircher, Tilo, Kochunov, Peter, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, Lawrie, Stephen, Patel, Yash, Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A, Arango, Celso, Arolt, Volker, Auzias, Guillaume, Ayesa-Arriola, Rosa, Banaj, Nerisa, Banaschewski, Tobias, Bandeira, Cibele, Başgöze, Zeynep, Cupertino, Renata Basso, Bau, Claiton HD, Bauer, Jochen, Baumeister, Sarah, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Brem, Silvia, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R, Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J, Cannon, Dara M, Carmona, Susanna, Carr, Vaughan J, Catts, Stanley V, Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G, Conzelmann, Annette, Craven, Alexander R, Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Dannlowski, Udo, Davey, Christopher G, Deruelle, Christine, Díaz-Caneja, Covadonga M, Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T, Fedor, Jennifer, Fitzgerald, Jacqueline, Foran, William, Ford, Judith M, Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Gao, Bingchen, Gao, Si, Goikolea, Jose M, Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J, Green, Melissa, Grevet, Eugenio H, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Haavik, Jan, Hahn, Tim, Harrison, Ben J, Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J, Hilland, Eva, Hoekstra, Pieter J, Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M, Ipser, Jonathan C, Jahanshad, Neda, Jakobi, Babette, Jansen, Andreas, Janssen, Joost, Jonassen, Rune, Kaiser, Anna, Kaleda, Vasiliy, Karantonis, James, King, Joseph A, Kircher, Tilo, Kochunov, Peter, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, and Lawrie, Stephen
Abstract: BackgroundMorphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.MethodsInterregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.ResultsAcross the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.ConclusionsOur findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brai
Published: 2022

32. Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium.

Author: Gurholt, Tiril P, Gurholt, Tiril P, Lonning, Vera, Nerland, Stener, Jørgensen, Kjetil N, Haukvik, Unn K, Alloza, Clara, Arango, Celso, Barth, Claudia, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Dandash, Orwa, Díaz-Caneja, Covadonga M, Edbom, Carl T, van Erp, Theo GM, Fett, Anne-Kathrin J, Frangou, Sophia, Goldstein, Benjamin I, Grigorian, Anahit, Jahanshad, Neda, James, Anthony C, Janssen, Joost, Johannessen, Cecilie, Karlsgodt, Katherine H, Kempton, Matthew J, Kochunov, Peter, Krabbendam, Lydia, Kyriakopoulos, Marinos, Lundberg, Mathias, MacIntosh, Bradley J, Rund, Bjørn Rishovd, Smelror, Runar E, Sultan, Alysha, Tamnes, Christian K, Thomopoulos, Sophia I, Vajdi, Ariana, Wedervang-Resell, Kirsten, Myhre, Anne M, Andreassen, Ole A, Thompson, Paul M, Agartz, Ingrid, ENIGMA-EOP Working Group, Gurholt, Tiril P, Gurholt, Tiril P, Lonning, Vera, Nerland, Stener, Jørgensen, Kjetil N, Haukvik, Unn K, Alloza, Clara, Arango, Celso, Barth, Claudia, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Dandash, Orwa, Díaz-Caneja, Covadonga M, Edbom, Carl T, van Erp, Theo GM, Fett, Anne-Kathrin J, Frangou, Sophia, Goldstein, Benjamin I, Grigorian, Anahit, Jahanshad, Neda, James, Anthony C, Janssen, Joost, Johannessen, Cecilie, Karlsgodt, Katherine H, Kempton, Matthew J, Kochunov, Peter, Krabbendam, Lydia, Kyriakopoulos, Marinos, Lundberg, Mathias, MacIntosh, Bradley J, Rund, Bjørn Rishovd, Smelror, Runar E, Sultan, Alysha, Tamnes, Christian K, Thomopoulos, Sophia I, Vajdi, Ariana, Wedervang-Resell, Kirsten, Myhre, Anne M, Andreassen, Ole A, Thompson, Paul M, Agartz, Ingrid, and ENIGMA-EOP Working Group
Abstract: Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.
Published: 2022

33. A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium

Author: Gutman, Boris A, van Erp, Theo G M, Alpert, Kathryn, Ching, Christopher R K, Isaev, Dmitry, Ragothaman, Anjani, Jahanshad, Neda, Saremi, Arvin, Zavaliangos-Petropulu, Artemis, Glahn, David C, Shen, Li, Cong, Shan, Alnaes, Dag, Andreassen, Ole Andreas, Doan, Nhat Trung, Westlye, Lars T., Kochunov, Peter, Satterthwaite, Theodore D, Wolf, Daniel H, Huang, Alexander J, Kessler, Charles, Weideman, Andrea, Nguyen, Dana, Mueller, Bryon A, Faziola, Lawrence, Potkin, Steven G, Preda, Adrian, Mathalon, Daniel H, Bustillo, Juan, Calhoun, Vince, Ford, Judith M, Walton, Esther, Ehrlich, Stefan, Ducci, Giuseppe, Banaj, Nerisa, Piras, Fabrizio, Piras, Federica, Spalletta, Gianfranco, Canales-Rodríguez, Erick J, Fuentes-Claramonte, Paola, Pomarol-Clotet, Edith, Radua, Joaquim, Salvador, Raymond, Sarró, Salvador, Dickie, Erin W, Voineskos, Aristotle, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Setién-Suero, Esther, van Son, Jacqueline Mayoral, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Morris, Derek, Donohoe, Gary, Holleran, Laurena, Cannon, Dara, McDonald, Colm, Corvin, Aiden, Gill, Michael, Filho, Geraldo Busatto, Rosa, Pedro G P, Serpa, Mauricio H, Zanetti, Marcus V, Lebedeva, Irina, Kaleda, Vasily, Tomyshev, Alexander, Crow, Tim, James, Anthony, Cervenka, Simon, Sellgren, Carl M, Fatouros-Bergman, Helena, Agartz, Ingrid, Howells, Fleur, Stein, Dan J, Temmingh, Henk, Uhlmann, Anne, de Zubicaray, Greig I, McMahon, Katie L, Wright, Margie, Cobia, Derin, Csernansky, John G, Thompson, Paul M, Turner, Jessica A, Wang, Lei, Gutman, Boris A, van Erp, Theo G M, Alpert, Kathryn, Ching, Christopher R K, Isaev, Dmitry, Ragothaman, Anjani, Jahanshad, Neda, Saremi, Arvin, Zavaliangos-Petropulu, Artemis, Glahn, David C, Shen, Li, Cong, Shan, Alnaes, Dag, Andreassen, Ole Andreas, Doan, Nhat Trung, Westlye, Lars T., Kochunov, Peter, Satterthwaite, Theodore D, Wolf, Daniel H, Huang, Alexander J, Kessler, Charles, Weideman, Andrea, Nguyen, Dana, Mueller, Bryon A, Faziola, Lawrence, Potkin, Steven G, Preda, Adrian, Mathalon, Daniel H, Bustillo, Juan, Calhoun, Vince, Ford, Judith M, Walton, Esther, Ehrlich, Stefan, Ducci, Giuseppe, Banaj, Nerisa, Piras, Fabrizio, Piras, Federica, Spalletta, Gianfranco, Canales-Rodríguez, Erick J, Fuentes-Claramonte, Paola, Pomarol-Clotet, Edith, Radua, Joaquim, Salvador, Raymond, Sarró, Salvador, Dickie, Erin W, Voineskos, Aristotle, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Setién-Suero, Esther, van Son, Jacqueline Mayoral, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Morris, Derek, Donohoe, Gary, Holleran, Laurena, Cannon, Dara, McDonald, Colm, Corvin, Aiden, Gill, Michael, Filho, Geraldo Busatto, Rosa, Pedro G P, Serpa, Mauricio H, Zanetti, Marcus V, Lebedeva, Irina, Kaleda, Vasily, Tomyshev, Alexander, Crow, Tim, James, Anthony, Cervenka, Simon, Sellgren, Carl M, Fatouros-Bergman, Helena, Agartz, Ingrid, Howells, Fleur, Stein, Dan J, Temmingh, Henk, Uhlmann, Anne, de Zubicaray, Greig I, McMahon, Katie L, Wright, Margie, Cobia, Derin, Csernansky, John G, Thompson, Paul M, Turner, Jessica A, and Wang, Lei
Abstract: Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
Published: 2022

34. Multi-spatial-scale dynamic interactions between functional sources reveal sex-specific changes in schizophrenia.

Author: Iraji, Armin, Iraji, Armin, Faghiri, Ashkan, Fu, Zening, Rachakonda, Srinivas, Kochunov, Peter, Belger, Aysenil, Ford, Judy M, McEwen, Sarah, Mathalon, Daniel H, Mueller, Bryon A, Pearlson, Godfrey D, Potkin, Steven G, Preda, Adrian, Turner, Jessica A, van Erp, Theodorus GM, Calhoun, Vince D, Iraji, Armin, Iraji, Armin, Faghiri, Ashkan, Fu, Zening, Rachakonda, Srinivas, Kochunov, Peter, Belger, Aysenil, Ford, Judy M, McEwen, Sarah, Mathalon, Daniel H, Mueller, Bryon A, Pearlson, Godfrey D, Potkin, Steven G, Preda, Adrian, Turner, Jessica A, van Erp, Theodorus GM, and Calhoun, Vince D
Abstract: We introduce an extension of independent component analysis (ICA), called multiscale ICA, and design an approach to capture dynamic functional source interactions within and between multiple spatial scales. Multiscale ICA estimates functional sources at multiple spatial scales without imposing direct constraints on the size of functional sources, overcomes the limitation of using fixed anatomical locations, and eliminates the need for model-order selection in ICA analysis. We leveraged this approach to study sex-specific and sex-common connectivity patterns in schizophrenia. Results show dynamic reconfiguration and interaction within and between multi-spatial scales. Sex-specific differences occur (a) within the subcortical domain, (b) between the somatomotor and cerebellum domains, and (c) between the temporal domain and several others, including the subcortical, visual, and default mode domains. Most of the sex-specific differences belong to between-spatial-scale functional interactions and are associated with a dynamic state with strong functional interactions between the visual, somatomotor, and temporal domains and their anticorrelation patterns with the rest of the brain. We observed significant correlations between multi-spatial-scale functional interactions and symptom scores, highlighting the importance of multiscale analyses to identify potential biomarkers for schizophrenia. As such, we recommend such analyses as an important option for future functional connectivity studies.
Published: 2022

35. A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium.

Author: Gutman, Boris A, Gutman, Boris A, van Erp, Theo GM, Alpert, Kathryn, Ching, Christopher RK, Isaev, Dmitry, Ragothaman, Anjani, Jahanshad, Neda, Saremi, Arvin, Zavaliangos-Petropulu, Artemis, Glahn, David C, Shen, Li, Cong, Shan, Alnaes, Dag, Andreassen, Ole Andreas, Doan, Nhat Trung, Westlye, Lars T, Kochunov, Peter, Satterthwaite, Theodore D, Wolf, Daniel H, Huang, Alexander J, Kessler, Charles, Weideman, Andrea, Nguyen, Dana, Mueller, Bryon A, Faziola, Lawrence, Potkin, Steven G, Preda, Adrian, Mathalon, Daniel H, Bustillo, Juan, Calhoun, Vince, Ford, Judith M, Walton, Esther, Ehrlich, Stefan, Ducci, Giuseppe, Banaj, Nerisa, Piras, Fabrizio, Piras, Federica, Spalletta, Gianfranco, Canales-Rodríguez, Erick J, Fuentes-Claramonte, Paola, Pomarol-Clotet, Edith, Radua, Joaquim, Salvador, Raymond, Sarró, Salvador, Dickie, Erin W, Voineskos, Aristotle, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Setién-Suero, Esther, van Son, Jacqueline Mayoral, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Morris, Derek, Donohoe, Gary, Holleran, Laurena, Cannon, Dara, McDonald, Colm, Corvin, Aiden, Gill, Michael, Filho, Geraldo Busatto, Rosa, Pedro GP, Serpa, Mauricio H, Zanetti, Marcus V, Lebedeva, Irina, Kaleda, Vasily, Tomyshev, Alexander, Crow, Tim, James, Anthony, Cervenka, Simon, Sellgren, Carl M, Fatouros-Bergman, Helena, Agartz, Ingrid, Howells, Fleur, Stein, Dan J, Temmingh, Henk, Uhlmann, Anne, de Zubicaray, Greig I, McMahon, Katie L, Wright, Margie, Cobia, Derin, Csernansky, John G, Thompson, Paul M, Turner, Jessica A, Wang, Lei, Gutman, Boris A, Gutman, Boris A, van Erp, Theo GM, Alpert, Kathryn, Ching, Christopher RK, Isaev, Dmitry, Ragothaman, Anjani, Jahanshad, Neda, Saremi, Arvin, Zavaliangos-Petropulu, Artemis, Glahn, David C, Shen, Li, Cong, Shan, Alnaes, Dag, Andreassen, Ole Andreas, Doan, Nhat Trung, Westlye, Lars T, Kochunov, Peter, Satterthwaite, Theodore D, Wolf, Daniel H, Huang, Alexander J, Kessler, Charles, Weideman, Andrea, Nguyen, Dana, Mueller, Bryon A, Faziola, Lawrence, Potkin, Steven G, Preda, Adrian, Mathalon, Daniel H, Bustillo, Juan, Calhoun, Vince, Ford, Judith M, Walton, Esther, Ehrlich, Stefan, Ducci, Giuseppe, Banaj, Nerisa, Piras, Fabrizio, Piras, Federica, Spalletta, Gianfranco, Canales-Rodríguez, Erick J, Fuentes-Claramonte, Paola, Pomarol-Clotet, Edith, Radua, Joaquim, Salvador, Raymond, Sarró, Salvador, Dickie, Erin W, Voineskos, Aristotle, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Setién-Suero, Esther, van Son, Jacqueline Mayoral, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Morris, Derek, Donohoe, Gary, Holleran, Laurena, Cannon, Dara, McDonald, Colm, Corvin, Aiden, Gill, Michael, Filho, Geraldo Busatto, Rosa, Pedro GP, Serpa, Mauricio H, Zanetti, Marcus V, Lebedeva, Irina, Kaleda, Vasily, Tomyshev, Alexander, Crow, Tim, James, Anthony, Cervenka, Simon, Sellgren, Carl M, Fatouros-Bergman, Helena, Agartz, Ingrid, Howells, Fleur, Stein, Dan J, Temmingh, Henk, Uhlmann, Anne, de Zubicaray, Greig I, McMahon, Katie L, Wright, Margie, Cobia, Derin, Csernansky, John G, Thompson, Paul M, Turner, Jessica A, and Wang, Lei
Abstract: Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
Published: 2022

36. A new multimodality fusion classification approach to explore the uniqueness of schizophrenia and autism spectrum disorder.

Author: Du, Yuhui, Du, Yuhui, He, Xingyu, Kochunov, Peter, Pearlson, Godfrey, Hong, L Elliot, van Erp, Theo GM, Belger, Aysenil, Calhoun, Vince D, Du, Yuhui, Du, Yuhui, He, Xingyu, Kochunov, Peter, Pearlson, Godfrey, Hong, L Elliot, van Erp, Theo GM, Belger, Aysenil, and Calhoun, Vince D
Abstract: Schizophrenia (SZ) and autism spectrum disorder (ASD) sharing overlapping symptoms have a long history of diagnostic confusion. It is unclear what their differences at a brain level are. Here, we propose a multimodality fusion classification approach to investigate their divergence in brain function and structure. Using brain functional network connectivity (FNC) calculated from resting-state fMRI data and gray matter volume (GMV) estimated from sMRI data, we classify the two disorders using the main data (335 SZ and 380 ASD patients) via an unbiased 10-fold cross-validation pipeline, and also validate the classification generalization ability on an independent cohort (120 SZ and 349 ASD patients). The classification accuracy reached up to 83.08% for the testing data and 72.10% for the independent data, significantly better than the results from using the single-modality features. The discriminative FNCs that were automatically selected primarily involved the sub-cortical, default mode, and visual domains. Interestingly, all discriminative FNCs relating to the default mode network showed an intermediate strength in healthy controls (HCs) between SZ and ASD patients. Their GMV differences were mainly driven by the frontal gyrus, temporal gyrus, and insula. Regarding these regions, the mean GMV of HC fell intermediate between that of SZ and ASD, and ASD showed the highest GMV. The middle frontal gyrus was associated with both functional and structural differences. In summary, our work reveals the unique neuroimaging characteristics of SZ and ASD that can achieve high and generalizable classification accuracy, supporting their potential as disorder-specific neural substrates of the two entwined disorders.
Published: 2022

37. Multi-spatial-scale dynamic interactions between functional sources reveal sex-specific changes in schizophrenia.

Author: Iraji, Armin, Iraji, Armin, Faghiri, Ashkan, Fu, Zening, Rachakonda, Srinivas, Kochunov, Peter, Belger, Aysenil, Ford, Judy M, McEwen, Sarah, Mathalon, Daniel H, Mueller, Bryon A, Pearlson, Godfrey D, Potkin, Steven G, Preda, Adrian, Turner, Jessica A, van Erp, Theodorus GM, Calhoun, Vince D, Iraji, Armin, Iraji, Armin, Faghiri, Ashkan, Fu, Zening, Rachakonda, Srinivas, Kochunov, Peter, Belger, Aysenil, Ford, Judy M, McEwen, Sarah, Mathalon, Daniel H, Mueller, Bryon A, Pearlson, Godfrey D, Potkin, Steven G, Preda, Adrian, Turner, Jessica A, van Erp, Theodorus GM, and Calhoun, Vince D
Abstract: We introduce an extension of independent component analysis (ICA), called multiscale ICA, and design an approach to capture dynamic functional source interactions within and between multiple spatial scales. Multiscale ICA estimates functional sources at multiple spatial scales without imposing direct constraints on the size of functional sources, overcomes the limitation of using fixed anatomical locations, and eliminates the need for model-order selection in ICA analysis. We leveraged this approach to study sex-specific and sex-common connectivity patterns in schizophrenia. Results show dynamic reconfiguration and interaction within and between multi-spatial scales. Sex-specific differences occur (a) within the subcortical domain, (b) between the somatomotor and cerebellum domains, and (c) between the temporal domain and several others, including the subcortical, visual, and default mode domains. Most of the sex-specific differences belong to between-spatial-scale functional interactions and are associated with a dynamic state with strong functional interactions between the visual, somatomotor, and temporal domains and their anticorrelation patterns with the rest of the brain. We observed significant correlations between multi-spatial-scale functional interactions and symptom scores, highlighting the importance of multiscale analyses to identify potential biomarkers for schizophrenia. As such, we recommend such analyses as an important option for future functional connectivity studies.
Published: 2022

38. A new multimodality fusion classification approach to explore the uniqueness of schizophrenia and autism spectrum disorder.

Author: Du, Yuhui, Du, Yuhui, He, Xingyu, Kochunov, Peter, Pearlson, Godfrey, Hong, L Elliot, van Erp, Theo GM, Belger, Aysenil, Calhoun, Vince D, Du, Yuhui, Du, Yuhui, He, Xingyu, Kochunov, Peter, Pearlson, Godfrey, Hong, L Elliot, van Erp, Theo GM, Belger, Aysenil, and Calhoun, Vince D
Abstract: Schizophrenia (SZ) and autism spectrum disorder (ASD) sharing overlapping symptoms have a long history of diagnostic confusion. It is unclear what their differences at a brain level are. Here, we propose a multimodality fusion classification approach to investigate their divergence in brain function and structure. Using brain functional network connectivity (FNC) calculated from resting-state fMRI data and gray matter volume (GMV) estimated from sMRI data, we classify the two disorders using the main data (335 SZ and 380 ASD patients) via an unbiased 10-fold cross-validation pipeline, and also validate the classification generalization ability on an independent cohort (120 SZ and 349 ASD patients). The classification accuracy reached up to 83.08% for the testing data and 72.10% for the independent data, significantly better than the results from using the single-modality features. The discriminative FNCs that were automatically selected primarily involved the sub-cortical, default mode, and visual domains. Interestingly, all discriminative FNCs relating to the default mode network showed an intermediate strength in healthy controls (HCs) between SZ and ASD patients. Their GMV differences were mainly driven by the frontal gyrus, temporal gyrus, and insula. Regarding these regions, the mean GMV of HC fell intermediate between that of SZ and ASD, and ASD showed the highest GMV. The middle frontal gyrus was associated with both functional and structural differences. In summary, our work reveals the unique neuroimaging characteristics of SZ and ASD that can achieve high and generalizable classification accuracy, supporting their potential as disorder-specific neural substrates of the two entwined disorders.
Published: 2022

39. A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium.

Author: Gutman, Boris A, Gutman, Boris A, van Erp, Theo GM, Alpert, Kathryn, Ching, Christopher RK, Isaev, Dmitry, Ragothaman, Anjani, Jahanshad, Neda, Saremi, Arvin, Zavaliangos-Petropulu, Artemis, Glahn, David C, Shen, Li, Cong, Shan, Alnaes, Dag, Andreassen, Ole Andreas, Doan, Nhat Trung, Westlye, Lars T, Kochunov, Peter, Satterthwaite, Theodore D, Wolf, Daniel H, Huang, Alexander J, Kessler, Charles, Weideman, Andrea, Nguyen, Dana, Mueller, Bryon A, Faziola, Lawrence, Potkin, Steven G, Preda, Adrian, Mathalon, Daniel H, Bustillo, Juan, Calhoun, Vince, Ford, Judith M, Walton, Esther, Ehrlich, Stefan, Ducci, Giuseppe, Banaj, Nerisa, Piras, Fabrizio, Piras, Federica, Spalletta, Gianfranco, Canales-Rodríguez, Erick J, Fuentes-Claramonte, Paola, Pomarol-Clotet, Edith, Radua, Joaquim, Salvador, Raymond, Sarró, Salvador, Dickie, Erin W, Voineskos, Aristotle, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Setién-Suero, Esther, van Son, Jacqueline Mayoral, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Morris, Derek, Donohoe, Gary, Holleran, Laurena, Cannon, Dara, McDonald, Colm, Corvin, Aiden, Gill, Michael, Filho, Geraldo Busatto, Rosa, Pedro GP, Serpa, Mauricio H, Zanetti, Marcus V, Lebedeva, Irina, Kaleda, Vasily, Tomyshev, Alexander, Crow, Tim, James, Anthony, Cervenka, Simon, Sellgren, Carl M, Fatouros-Bergman, Helena, Agartz, Ingrid, Howells, Fleur, Stein, Dan J, Temmingh, Henk, Uhlmann, Anne, de Zubicaray, Greig I, McMahon, Katie L, Wright, Margie, Cobia, Derin, Csernansky, John G, Thompson, Paul M, Turner, Jessica A, Wang, Lei, Gutman, Boris A, Gutman, Boris A, van Erp, Theo GM, Alpert, Kathryn, Ching, Christopher RK, Isaev, Dmitry, Ragothaman, Anjani, Jahanshad, Neda, Saremi, Arvin, Zavaliangos-Petropulu, Artemis, Glahn, David C, Shen, Li, Cong, Shan, Alnaes, Dag, Andreassen, Ole Andreas, Doan, Nhat Trung, Westlye, Lars T, Kochunov, Peter, Satterthwaite, Theodore D, Wolf, Daniel H, Huang, Alexander J, Kessler, Charles, Weideman, Andrea, Nguyen, Dana, Mueller, Bryon A, Faziola, Lawrence, Potkin, Steven G, Preda, Adrian, Mathalon, Daniel H, Bustillo, Juan, Calhoun, Vince, Ford, Judith M, Walton, Esther, Ehrlich, Stefan, Ducci, Giuseppe, Banaj, Nerisa, Piras, Fabrizio, Piras, Federica, Spalletta, Gianfranco, Canales-Rodríguez, Erick J, Fuentes-Claramonte, Paola, Pomarol-Clotet, Edith, Radua, Joaquim, Salvador, Raymond, Sarró, Salvador, Dickie, Erin W, Voineskos, Aristotle, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Setién-Suero, Esther, van Son, Jacqueline Mayoral, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Morris, Derek, Donohoe, Gary, Holleran, Laurena, Cannon, Dara, McDonald, Colm, Corvin, Aiden, Gill, Michael, Filho, Geraldo Busatto, Rosa, Pedro GP, Serpa, Mauricio H, Zanetti, Marcus V, Lebedeva, Irina, Kaleda, Vasily, Tomyshev, Alexander, Crow, Tim, James, Anthony, Cervenka, Simon, Sellgren, Carl M, Fatouros-Bergman, Helena, Agartz, Ingrid, Howells, Fleur, Stein, Dan J, Temmingh, Henk, Uhlmann, Anne, de Zubicaray, Greig I, McMahon, Katie L, Wright, Margie, Cobia, Derin, Csernansky, John G, Thompson, Paul M, Turner, Jessica A, and Wang, Lei
Abstract: Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
Published: 2022

40. Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium.

Author: Gurholt, Tiril P, Gurholt, Tiril P, Lonning, Vera, Nerland, Stener, Jørgensen, Kjetil N, Haukvik, Unn K, Alloza, Clara, Arango, Celso, Barth, Claudia, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Dandash, Orwa, Díaz-Caneja, Covadonga M, Edbom, Carl T, van Erp, Theo GM, Fett, Anne-Kathrin J, Frangou, Sophia, Goldstein, Benjamin I, Grigorian, Anahit, Jahanshad, Neda, James, Anthony C, Janssen, Joost, Johannessen, Cecilie, Karlsgodt, Katherine H, Kempton, Matthew J, Kochunov, Peter, Krabbendam, Lydia, Kyriakopoulos, Marinos, Lundberg, Mathias, MacIntosh, Bradley J, Rund, Bjørn Rishovd, Smelror, Runar E, Sultan, Alysha, Tamnes, Christian K, Thomopoulos, Sophia I, Vajdi, Ariana, Wedervang-Resell, Kirsten, Myhre, Anne M, Andreassen, Ole A, Thompson, Paul M, Agartz, Ingrid, ENIGMA-EOP Working Group, Gurholt, Tiril P, Gurholt, Tiril P, Lonning, Vera, Nerland, Stener, Jørgensen, Kjetil N, Haukvik, Unn K, Alloza, Clara, Arango, Celso, Barth, Claudia, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Dandash, Orwa, Díaz-Caneja, Covadonga M, Edbom, Carl T, van Erp, Theo GM, Fett, Anne-Kathrin J, Frangou, Sophia, Goldstein, Benjamin I, Grigorian, Anahit, Jahanshad, Neda, James, Anthony C, Janssen, Joost, Johannessen, Cecilie, Karlsgodt, Katherine H, Kempton, Matthew J, Kochunov, Peter, Krabbendam, Lydia, Kyriakopoulos, Marinos, Lundberg, Mathias, MacIntosh, Bradley J, Rund, Bjørn Rishovd, Smelror, Runar E, Sultan, Alysha, Tamnes, Christian K, Thomopoulos, Sophia I, Vajdi, Ariana, Wedervang-Resell, Kirsten, Myhre, Anne M, Andreassen, Ole A, Thompson, Paul M, Agartz, Ingrid, and ENIGMA-EOP Working Group
Abstract: Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.
Published: 2022

41. A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium

Author: Gutman, Boris A, van Erp, Theo G M, Alpert, Kathryn, Ching, Christopher R K, Isaev, Dmitry, Ragothaman, Anjani, Jahanshad, Neda, Saremi, Arvin, Zavaliangos-Petropulu, Artemis, Glahn, David C, Shen, Li, Cong, Shan, Alnaes, Dag, Andreassen, Ole Andreas, Doan, Nhat Trung, Westlye, Lars T, Kochunov, Peter, Satterthwaite, Theodore D, Wolf, Daniel H, Huang, Alexander J, Kessler, Charles, Weideman, Andrea, Nguyen, Dana, Mueller, Bryon A, Faziola, Lawrence, Potkin, Steven G, Preda, Adrian, Mathalon, Daniel H, Bustillo, Juan, Calhoun, Vince, Ford, Judith M, Walton, Esther, Ehrlich, Stefan, Ducci, Giuseppe, Banaj, Nerisa, Piras, Fabrizio, Piras, Federica, Spalletta, Gianfranco, Canales-Rodríguez, Erick J, Fuentes-Claramonte, Paola, Pomarol-Clotet, Edith, Radua, Joaquim, Salvador, Raymond, Sarró, Salvador, Dickie, Erin W, Voineskos, Aristotle, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Setién-Suero, Esther, van Son, Jacqueline Mayoral, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Morris, Derek, Donohoe, Gary, Holleran, Laurena, Cannon, Dara, McDonald, Colm, Corvin, Aiden, Gill, Michael, Filho, Geraldo Busatto, Rosa, Pedro G P, Serpa, Mauricio H, Zanetti, Marcus V, Lebedeva, Irina, Kaleda, Vasily, Tomyshev, Alexander, Crow, Tim, James, Anthony, Cervenka, Simon, Sellgren, Carl M, Fatouros-Bergman, Helena, Agartz, Ingrid, Howells, Fleur, Stein, Dan J, Temmingh, Henk, Uhlmann, Anne, de Zubicaray, Greig I, McMahon, Katie L, Wright, Margie, Cobia, Derin, Csernansky, John G, Thompson, Paul M, Turner, Jessica A, Wang, Lei, Gutman, Boris A, van Erp, Theo G M, Alpert, Kathryn, Ching, Christopher R K, Isaev, Dmitry, Ragothaman, Anjani, Jahanshad, Neda, Saremi, Arvin, Zavaliangos-Petropulu, Artemis, Glahn, David C, Shen, Li, Cong, Shan, Alnaes, Dag, Andreassen, Ole Andreas, Doan, Nhat Trung, Westlye, Lars T, Kochunov, Peter, Satterthwaite, Theodore D, Wolf, Daniel H, Huang, Alexander J, Kessler, Charles, Weideman, Andrea, Nguyen, Dana, Mueller, Bryon A, Faziola, Lawrence, Potkin, Steven G, Preda, Adrian, Mathalon, Daniel H, Bustillo, Juan, Calhoun, Vince, Ford, Judith M, Walton, Esther, Ehrlich, Stefan, Ducci, Giuseppe, Banaj, Nerisa, Piras, Fabrizio, Piras, Federica, Spalletta, Gianfranco, Canales-Rodríguez, Erick J, Fuentes-Claramonte, Paola, Pomarol-Clotet, Edith, Radua, Joaquim, Salvador, Raymond, Sarró, Salvador, Dickie, Erin W, Voineskos, Aristotle, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Setién-Suero, Esther, van Son, Jacqueline Mayoral, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Morris, Derek, Donohoe, Gary, Holleran, Laurena, Cannon, Dara, McDonald, Colm, Corvin, Aiden, Gill, Michael, Filho, Geraldo Busatto, Rosa, Pedro G P, Serpa, Mauricio H, Zanetti, Marcus V, Lebedeva, Irina, Kaleda, Vasily, Tomyshev, Alexander, Crow, Tim, James, Anthony, Cervenka, Simon, Sellgren, Carl M, Fatouros-Bergman, Helena, Agartz, Ingrid, Howells, Fleur, Stein, Dan J, Temmingh, Henk, Uhlmann, Anne, de Zubicaray, Greig I, McMahon, Katie L, Wright, Margie, Cobia, Derin, Csernansky, John G, Thompson, Paul M, Turner, Jessica A, and Wang, Lei
Abstract: Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
Published: 2022
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42. Cross disorder comparisons of brain structure in schizophrenia, bipolar disorder, major depressive disorder, and 22q11.2 deletion syndrome: A review of ENIGMA findings.

Author: Cheon, Eun-Jin, Cheon, Eun-Jin, Bearden, Carrie E, Sun, Daqiang, Ching, Christopher RK, Andreassen, Ole A, Schmaal, Lianne, Veltman, Dick J, Thomopoulos, Sophia I, Kochunov, Peter, Jahanshad, Neda, Thompson, Paul M, Turner, Jessica A, van Erp, Theo GM, Cheon, Eun-Jin, Cheon, Eun-Jin, Bearden, Carrie E, Sun, Daqiang, Ching, Christopher RK, Andreassen, Ole A, Schmaal, Lianne, Veltman, Dick J, Thomopoulos, Sophia I, Kochunov, Peter, Jahanshad, Neda, Thompson, Paul M, Turner, Jessica A, and van Erp, Theo GM
Abstract: This review compares the main brain abnormalities in schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and 22q11.2 Deletion Syndrome (22q11DS) determined by ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium investigations. We obtained ranked effect sizes for subcortical volumes, regional cortical thickness, cortical surface area, and diffusion tensor imaging abnormalities, comparing each of these disorders relative to healthy controls. In addition, the studies report on significant associations between brain imaging metrics and disorder-related factors such as symptom severity and treatments. Visual comparison of effect size profiles shows that effect sizes are generally in the same direction and scale in severity with the disorders (in the order SZ > BD > MDD). The effect sizes for 22q11DS, a rare genetic syndrome that increases the risk for psychiatric disorders, appear to be much larger than for either of the complex psychiatric disorders. This is consistent with the idea of generally larger effects on the brain of rare compared to common genetic variants. Cortical thickness and surface area effect sizes for 22q11DS with psychosis compared to 22q11DS without psychosis are more similar to those of SZ and BD than those of MDD; a pattern not observed for subcortical brain structures and fractional anisotropy effect sizes. The observed similarities in effect size profiles for cortical measures across the psychiatric disorders mimic those observed for shared genetic variance between these disorders reported based on family and genetic studies and are consistent with shared genetic risk for SZ and BD and structural brain phenotypes.
Published: 2022

43. Multimodel Order Independent Component Analysis: A Data-Driven Method for Evaluating Brain Functional Network Connectivity Within and Between Multiple Spatial Scales.

Author: Meng, Xing, Meng, Xing, Iraji, Armin, Fu, Zening, Kochunov, Peter, Belger, Aysenil, Mueller, Bryon, Pearlson, Godfrey, Turner, Jessica, Erp, Theo, Sui, Jing, Calhoun, Vince, McEwen, Sara, Mathalon, Daniel, Ford, Judith, Potkin, Steven, Preda, Adrian, Meng, Xing, Meng, Xing, Iraji, Armin, Fu, Zening, Kochunov, Peter, Belger, Aysenil, Mueller, Bryon, Pearlson, Godfrey, Turner, Jessica, Erp, Theo, Sui, Jing, Calhoun, Vince, McEwen, Sara, Mathalon, Daniel, Ford, Judith, Potkin, Steven, and Preda, Adrian
Abstract: Background: While functional connectivity is widely studied, there has been little work studying functional connectivity at different spatial scales. Likewise, the relationship of functional connectivity between spatial scales is unknown. Methods: We proposed an independent component analysis (ICA)-based approach to capture information at multiple-model orders (component numbers), and to evaluate functional network connectivity (FNC) both within and between model orders. We evaluated the approach by studying group differences in the context of a study of resting-state functional magnetic resonance imaging (rsfMRI) data collected from schizophrenia (SZ) individuals and healthy controls (HC). The predictive ability of FNC at multiple spatial scales was assessed using support vector machine-based classification. Results: In addition to consistent predictive patterns at both multiple-model orders and single-model orders, unique predictive information was seen at multiple-model orders and in the interaction between model orders. We observed that the FNC between model orders 25 and 50 maintained the highest predictive information between HC and SZ. Results highlighted the predictive ability of the somatomotor and visual domains both within and between model orders compared with other functional domains. Also, subcortical-somatomotor, temporal-somatomotor, and temporal-subcortical FNCs had relatively high weights in predicting SZ. Conclusions: In sum, multimodel order ICA provides a more comprehensive way to study FNC, produces meaningful and interesting results, which are applicable to future studies. We shared the spatial templates from this work at different model orders to provide a reference for the community, which can be leveraged in regression-based or fully automated (spatially constrained) ICA approaches. Impact statement Multimodel order independent component analysis (ICA) provides a comprehensive way to study brain functional network connectivity within and be
Published: 2022

44. Genome-Transcriptome-Functional Connectivity-Cognition Link Differentiates Schizophrenia From Bipolar Disorder.

Author: Chen, Jiayu, Chen, Jiayu, Fu, Zening, Bustillo, Juan, Perrone-Bizzozero, Nora, Lin, Dongdong, Canive, Jose, Pearlson, Godfrey, Stephen, Julia, Mayer, Andrew, Potkin, Steven, Kochunov, Peter, Elliot Hong, L, Adhikari, Bhim, Andreassen, Ole, Agartz, Ingrid, Westlye, Lars, Sui, Jing, Du, Yuhui, Hanlon, Faith, Jung, Rex, Turner, Jessica, Liu, Jingyu, Calhoun, Vince, Van Erp, Theodorus, Macciardi, Fabio, Chen, Jiayu, Chen, Jiayu, Fu, Zening, Bustillo, Juan, Perrone-Bizzozero, Nora, Lin, Dongdong, Canive, Jose, Pearlson, Godfrey, Stephen, Julia, Mayer, Andrew, Potkin, Steven, Kochunov, Peter, Elliot Hong, L, Adhikari, Bhim, Andreassen, Ole, Agartz, Ingrid, Westlye, Lars, Sui, Jing, Du, Yuhui, Hanlon, Faith, Jung, Rex, Turner, Jessica, Liu, Jingyu, Calhoun, Vince, Van Erp, Theodorus, and Macciardi, Fabio
Abstract: BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) and bipolar disorder (BD) share genetic risk factors, yet patients display differential levels of cognitive impairment. We hypothesized a genome-transcriptome-functional connectivity (frontoparietal)-cognition pathway linked to SZ-versus-BD differences, and conducted a multiscale study to delineate this pathway. STUDY DESIGNS: Large genome-wide studies provided single nucleotide polymorphisms (SNPs) conferring more risk for SZ than BD, and we identified their regulated genes, namely SZ-biased SNPs and genes. We then (a) computed the polygenic risk score for SZ (PRSSZ) of SZ-biased SNPs and examined its associations with imaging-based frontoparietal functional connectivity (FC) and cognitive performances; (b) examined the spatial correlation between ex vivo postmortem expressions of SZ-biased genes and in vivo, SZ-related FC disruptions across frontoparietal regions; (c) investigated SZ-versus-BD differences in frontoparietal FC; and (d) assessed the associations of frontoparietal FC with cognitive performances. STUDY RESULTS: PRSSZ of SZ-biased SNPs was significantly associated with frontoparietal FC and working memory test scores. SZ-biased genes expressions significantly correlated with SZ-versus-BD differences in FC across frontoparietal regions. SZ patients showed more reductions in frontoparietal FC than BD patients compared to controls. Frontoparietal FC was significantly associated with test scores of multiple cognitive domains including working memory, and with the composite scores of all cognitive domains. CONCLUSIONS: Collectively, these multiscale findings support the hypothesis that SZ-biased genetic risk, through transcriptome regulation, is linked to frontoparietal dysconnectivity, which in turn contributes to differential cognitive deficits in SZ-versus BD, suggesting that potential biomarkers for more precise patient stratification and treatment.
Published: 2022

45. Clinical and cortical similarities identified between bipolar disorder I and schizophrenia: A multivariate approach.

Author: Rootes-Murdy, Kelly, Rootes-Murdy, Kelly, Edmond, Jesse T, Jiang, Wenhao, Rahaman, Md A, Chen, Jiayu, Perrone-Bizzozero, Nora I, Calhoun, Vince D, van Erp, Theo GM, Ehrlich, Stefan, Agartz, Ingrid, Jönsson, Erik G, Andreassen, Ole A, Westlye, Lars T, Wang, Lei, Pearlson, Godfrey D, Glahn, David C, Hong, Elliot, Buchanan, Robert W, Kochunov, Peter, Voineskos, Aristotle, Malhotra, Anil, Tamminga, Carol A, Liu, Jingyu, Turner, Jessica A, Rootes-Murdy, Kelly, Rootes-Murdy, Kelly, Edmond, Jesse T, Jiang, Wenhao, Rahaman, Md A, Chen, Jiayu, Perrone-Bizzozero, Nora I, Calhoun, Vince D, van Erp, Theo GM, Ehrlich, Stefan, Agartz, Ingrid, Jönsson, Erik G, Andreassen, Ole A, Westlye, Lars T, Wang, Lei, Pearlson, Godfrey D, Glahn, David C, Hong, Elliot, Buchanan, Robert W, Kochunov, Peter, Voineskos, Aristotle, Malhotra, Anil, Tamminga, Carol A, Liu, Jingyu, and Turner, Jessica A
Abstract: BackgroundStructural neuroimaging studies have identified similarities in the brains of individuals diagnosed with schizophrenia (SZ) and bipolar I disorder (BP), with overlap in regions of gray matter (GM) deficits between the two disorders. Recent studies have also shown that the symptom phenotypes associated with SZ and BP may allow for a more precise categorization than the current diagnostic criteria. In this study, we sought to identify GM alterations that were unique to each disorder and whether those alterations were also related to unique symptom profiles.Materials and methodsWe analyzed the GM patterns and clinical symptom presentations using independent component analysis (ICA), hierarchical clustering, and n-way biclustering in a large (N ∼ 3,000), merged dataset of neuroimaging data from healthy volunteers (HV), and individuals with either SZ or BP.ResultsComponent A showed a SZ and BP < HV GM pattern in the bilateral insula and cingulate gyrus. Component B showed a SZ and BP < HV GM pattern in the cerebellum and vermis. There were no significant differences between diagnostic groups in these components. Component C showed a SZ < HV and BP GM pattern bilaterally in the temporal poles. Hierarchical clustering of the PANSS scores and the ICA components did not yield new subgroups. N-way biclustering identified three unique subgroups of individuals within the sample that mapped onto different combinations of ICA components and symptom profiles categorized by the PANSS but no distinct diagnostic group differences.ConclusionThese multivariate results show that diagnostic boundaries are not clearly related to structural differences or distinct symptom profiles. Our findings add support that (1) BP tend to have less severe symptom profiles when compared to SZ on the PANSS without a clear distinction, and (2) all the gray matter alterations follow the pattern of SZ < BP < HV without a clear distinction between SZ and BP.
Published: 2022

46. Virtual ontogeny of cortical growth preceding mental illness

Author: German Research Foundation, University of Münster, National Health and Medical Research Council (Australia), University of Cape Town, National Research Foundation (South Africa), Swinburne University of Technology, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L. Cooper Medical Research Foundation, Society for Mental Health Research (Australia), Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Brain Foundation, Health Research Board (Ireland), Russian Foundation for Basic Research, University of Zurich, Pratt Foundation, Ramsay Health Care, Viertel Charitable Foundation, Schizophrenia Research Institute (Australia), European Commission, Australian Research Council, Instituto de Salud Carlos III, National Institute for Health and Care Research (US), National Institute for Health Research (UK), Ministry of Health of the Czech Republic, Bill & Melinda Gates Foundation, South African Medical Research Council, Carnegie Corporation of New York, Wellcome Trust, Medical Research Council (UK), Medical Research Scotland, Netherlands Organization for Scientific Research, Ambrogi, Sonia [0000-0002-2897-358X], Banaschewski, Tobias [0000-0003-4595-1144], Bandeira, Cibele Edom [0000-0003-0681-1309], Cupertino, Renata [0000-0002-3452-0632], Calderoni, Sara [0000-0002-6250-5739], Cannon, Dara [0000-0001-7378-3411], Carr, Vaughan [0000-0002-8907-5804], Chew, Qian Hui [0000-0003-0969-7994], Coghill, David [0000-0003-3017-9737], Cullen, Kathryn [0000-0001-9631-3770], Dahl, Andreas [0000-0002-8097-2082], Epstein, Jeffery [0000-0003-3464-5256], Foran, William [0000-0001-7491-9798], Fortea, Lydia [0000-0001-6778-2316], Fuentes-Claramonte, Paola [0000-0002-1428-7976], Fullerton, Janice M. [0000-0003-4014-4490], Furlong, Lisa [0000-0001-6196-4565], Gallagher, Louise [0000-0001-9462-2836], Gao, Si [0000-0002-4473-1142], Gotlib, Ian [0000-0002-3622-3199], Haavik, Jan [0000-0001-7865-2808], Henskens, Frans [0000-0003-2358-5630], Hilland, Eva [0000-0002-7102-8372], Hoekstra, Pieter J [0000-0001-7260-4119], Howells, Fleur M [0000-0001-9759-2556], Ipser, Jonathan [0000-0003-1272-0032], Jørgensen, Jes Kristian [0000-0001-9133-1670], Karantonis, James A. [0000-0003-2281-0912], Lawrie, Stephen [0000-0002-2444-5675], Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A., Arango, Celso, Arolt, Volker, Auzias, Guillaume, Gruber, Oliver, Haavik, Jan, McDonald, Colm, Hahn, Tim, Harrison, Ben J., Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J., Hilland, Eva, King, Joseph A., Vernooij, Meike W., Hoekstra, Pieter J., Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M., McIntosh, Andrew, Ipser, Jonathan C., Meinert, Susanne, Hoogman, Martine, Kircher, Tilo, Kochunov, Peter, Vieta, Eduard, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, Lawrie, Stephen, Michie, Patricia T., Ayesa Arriola, Rosa, Mitchell, Philip, Moreno-Alcázar, Ana, Franke, Barbara, Mowry, Bryan, Bau, Claiton H. D., Muratori, Filippo, Nabulsi, Leila, Nenadić, Igor, O'Gorman Tuura, Ruth, Oosterlaan, Jaap, Overs, Bronwyn, Pantelis, Christos, Banaj, Nerisa, Parellada, Mara, van Rooij, Daan, Vilarroya, Oscar, Pariente, Jose C., Pauli, Paul, Pergola, Giulio, Piarulli, Francesco Maria, Picon, Felipe, Piras, Fabrizio, Pomarol-Clotet, Edith, Pretus, Clara, Quidé, Yann, Banaschewski, Tobias, Weickert, Cynthia, Buitelaar, Jan, Radua, Joaquim, Ramos-Quiroga, J. Antoni, Rasser, Paul E., Reif, Andreas, Retico, Alessandra, Roberts, Gloria, Rossell, Susan, Rovaris, Diego Luiz, Rubia, Katya, Weickert, Thomas, Sacchet, Matthew, Ching, Christopher R. K., Bandeira, Cibele, Salavert, Josep, Salvador, Raymond, Sarró, Salvador, Sawa, Akira, Schall, Ulrich, Scott, Rodney, Selvaggi, Pierluigi, Westlye, Lars T., Silk, Tim, Sim, Kang, Andreassen, Ole A., Skoch, Antonin, Başgöze, Zeynep, Spalletta, Gianfranco, Spaniel, Filip, Stein, Dan J., Steinsträter, Olaf, Stolicyn, Aleks, Whalley, Heather, Takayanagi, Yoichiro, Tamm, Leanne, Tavares, Maria, Pozzi, Elena, Teumer, Alexander, Thiel, Katharina, Cupertino, Renata Basso, Thomopoulos, Sophia I., Tomecek, David, Tomyshev, Alexander S., Willinger, David, Tordesillas-Gutiérrez, Diana, Tosetti, Michela, Uhlmann, Anne, Van Rheenen, Tamsyn, Veltman, Dick, Vázquez-Bourgon, Javier, Schmaal, Lianne, Jahanshad, Neda, Winter, Alexandra, Wittfeld, Katharina, Yang, Tony T., Yoncheva, Yuliya, Bauer, Jochen, Zijlmans, Jendé L., Baumeister, Sarah, Lebedeva, Irina, van Erp, Theo G. M., Turner, Jessica, Jakobi, Babette, Castellanos, F. Xavier, Pausova, Zdenka, Thompson, Paul, Paus, Tomas, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Luna, Beatriz, Brem, Silvia, Jansen, Andreas, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R., Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J., Cannon, Dara M., Carmona, Susanna, Carr, Vaughan J., Lundervold, Astri J., Janssen, Joost, Catts, Stanley V., Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G., Conzelmann, Annette, Craven, Alexander R., Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Jonassen, Rune, MacMaster, Frank P., Dannlowski, Udo, Davey, Christopher G., Deruelle, Christine, Díaz-Caneja, Covadonga M., Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T., Kaiser, Anna, Fedor, Jennifer, Maglanoc, Luigi A., Fitzgerald, Jacqueline, Foran, William, Ford, Judith M., Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Kaleda, Vasiliy, Gao, Bingchen, Gao, Si, Mathalon, Daniel H., Goikolea, Jose M., Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J., Green, Melissa, Grevet, Eugenio H., Groenewold, Nynke A., Karantonis, James, Grotegerd, Dominik., German Research Foundation, University of Münster, National Health and Medical Research Council (Australia), University of Cape Town, National Research Foundation (South Africa), Swinburne University of Technology, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L. Cooper Medical Research Foundation, Society for Mental Health Research (Australia), Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Brain Foundation, Health Research Board (Ireland), Russian Foundation for Basic Research, University of Zurich, Pratt Foundation, Ramsay Health Care, Viertel Charitable Foundation, Schizophrenia Research Institute (Australia), European Commission, Australian Research Council, Instituto de Salud Carlos III, National Institute for Health and Care Research (US), National Institute for Health Research (UK), Ministry of Health of the Czech Republic, Bill & Melinda Gates Foundation, South African Medical Research Council, Carnegie Corporation of New York, Wellcome Trust, Medical Research Council (UK), Medical Research Scotland, Netherlands Organization for Scientific Research, Ambrogi, Sonia [0000-0002-2897-358X], Banaschewski, Tobias [0000-0003-4595-1144], Bandeira, Cibele Edom [0000-0003-0681-1309], Cupertino, Renata [0000-0002-3452-0632], Calderoni, Sara [0000-0002-6250-5739], Cannon, Dara [0000-0001-7378-3411], Carr, Vaughan [0000-0002-8907-5804], Chew, Qian Hui [0000-0003-0969-7994], Coghill, David [0000-0003-3017-9737], Cullen, Kathryn [0000-0001-9631-3770], Dahl, Andreas [0000-0002-8097-2082], Epstein, Jeffery [0000-0003-3464-5256], Foran, William [0000-0001-7491-9798], Fortea, Lydia [0000-0001-6778-2316], Fuentes-Claramonte, Paola [0000-0002-1428-7976], Fullerton, Janice M. [0000-0003-4014-4490], Furlong, Lisa [0000-0001-6196-4565], Gallagher, Louise [0000-0001-9462-2836], Gao, Si [0000-0002-4473-1142], Gotlib, Ian [0000-0002-3622-3199], Haavik, Jan [0000-0001-7865-2808], Henskens, Frans [0000-0003-2358-5630], Hilland, Eva [0000-0002-7102-8372], Hoekstra, Pieter J [0000-0001-7260-4119], Howells, Fleur M [0000-0001-9759-2556], Ipser, Jonathan [0000-0003-1272-0032], Jørgensen, Jes Kristian [0000-0001-9133-1670], Karantonis, James A. [0000-0003-2281-0912], Lawrie, Stephen [0000-0002-2444-5675], Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A., Arango, Celso, Arolt, Volker, Auzias, Guillaume, Gruber, Oliver, Haavik, Jan, McDonald, Colm, Hahn, Tim, Harrison, Ben J., Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J., Hilland, Eva, King, Joseph A., Vernooij, Meike W., Hoekstra, Pieter J., Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M., McIntosh, Andrew, Ipser, Jonathan C., Meinert, Susanne, Hoogman, Martine, Kircher, Tilo, Kochunov, Peter, Vieta, Eduard, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, Lawrie, Stephen, Michie, Patricia T., Ayesa Arriola, Rosa, Mitchell, Philip, Moreno-Alcázar, Ana, Franke, Barbara, Mowry, Bryan, Bau, Claiton H. D., Muratori, Filippo, Nabulsi, Leila, Nenadić, Igor, O'Gorman Tuura, Ruth, Oosterlaan, Jaap, Overs, Bronwyn, Pantelis, Christos, Banaj, Nerisa, Parellada, Mara, van Rooij, Daan, Vilarroya, Oscar, Pariente, Jose C., Pauli, Paul, Pergola, Giulio, Piarulli, Francesco Maria, Picon, Felipe, Piras, Fabrizio, Pomarol-Clotet, Edith, Pretus, Clara, Quidé, Yann, Banaschewski, Tobias, Weickert, Cynthia, Buitelaar, Jan, Radua, Joaquim, Ramos-Quiroga, J. Antoni, Rasser, Paul E., Reif, Andreas, Retico, Alessandra, Roberts, Gloria, Rossell, Susan, Rovaris, Diego Luiz, Rubia, Katya, Weickert, Thomas, Sacchet, Matthew, Ching, Christopher R. K., Bandeira, Cibele, Salavert, Josep, Salvador, Raymond, Sarró, Salvador, Sawa, Akira, Schall, Ulrich, Scott, Rodney, Selvaggi, Pierluigi, Westlye, Lars T., Silk, Tim, Sim, Kang, Andreassen, Ole A., Skoch, Antonin, Başgöze, Zeynep, Spalletta, Gianfranco, Spaniel, Filip, Stein, Dan J., Steinsträter, Olaf, Stolicyn, Aleks, Whalley, Heather, Takayanagi, Yoichiro, Tamm, Leanne, Tavares, Maria, Pozzi, Elena, Teumer, Alexander, Thiel, Katharina, Cupertino, Renata Basso, Thomopoulos, Sophia I., Tomecek, David, Tomyshev, Alexander S., Willinger, David, Tordesillas-Gutiérrez, Diana, Tosetti, Michela, Uhlmann, Anne, Van Rheenen, Tamsyn, Veltman, Dick, Vázquez-Bourgon, Javier, Schmaal, Lianne, Jahanshad, Neda, Winter, Alexandra, Wittfeld, Katharina, Yang, Tony T., Yoncheva, Yuliya, Bauer, Jochen, Zijlmans, Jendé L., Baumeister, Sarah, Lebedeva, Irina, van Erp, Theo G. M., Turner, Jessica, Jakobi, Babette, Castellanos, F. Xavier, Pausova, Zdenka, Thompson, Paul, Paus, Tomas, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Luna, Beatriz, Brem, Silvia, Jansen, Andreas, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R., Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J., Cannon, Dara M., Carmona, Susanna, Carr, Vaughan J., Lundervold, Astri J., Janssen, Joost, Catts, Stanley V., Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G., Conzelmann, Annette, Craven, Alexander R., Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Jonassen, Rune, MacMaster, Frank P., Dannlowski, Udo, Davey, Christopher G., Deruelle, Christine, Díaz-Caneja, Covadonga M., Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T., Kaiser, Anna, Fedor, Jennifer, Maglanoc, Luigi A., Fitzgerald, Jacqueline, Foran, William, Ford, Judith M., Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Kaleda, Vasiliy, Gao, Bingchen, Gao, Si, Mathalon, Daniel H., Goikolea, Jose M., Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J., Green, Melissa, Grevet, Eugenio H., Groenewold, Nynke A., Karantonis, James, and Grotegerd, Dominik.
Abstract: [Background]: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life., [Methods]: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed., [Results]: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth., [Conclusions]: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
Published: 2022

47. A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium

Author: US Department of Veterans Affairs, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Swedish Research Council for Health, Working Life and Welfare, Fundação Amazônia de Amparo a Estudos e Pesquisas, Instituto de Salud Carlos III, National Health and Medical Research Council (Australia), National Institutes of Health (US), National Science Foundation (US), Research Council of Norway, Science Foundation Ireland, Wellcome Trust, Gutman, Boris A., van Erp, Theo G. M., Alpert, Kathryn I., Ching, Christopher R. K., Isaev, Dmitry, Ragothaman, Anjani, Jahanshad, Neda, Saremi, Arvin, Zavaliangos-Petropulu, Artemis, Glahn, David C., Shen, Li, Cong, Shan, Alnæs, Dag, Andreassen, Ole A., DoanNhat Trung, Westlye, Lars T., Kochunov, Peter, Satterthwaite, Theodore D., Wolf, Daniel H., Huang, Alexander J., Kessler, Charles, Weideman, Andrea, Nguyen, Dana, Mueller, Bryon A., Faziola, Lawrence, Potkin, Steven G., Preda Adrian, Mathalon, Daniel H., Bustillo Juan, Calhoun, Vincent, Ford, Judith M., Walton, Esther, Ehrlich, Stefan, Ducci, Giuseppe, Banaj, Nerisa, Piras, Fabrizio, Piras, Federica, Spalletta, Gianfranco, Canales-Rodríguez, Erick J., Fuentes-Claramonte, Paola, Pomarol-Clotet, Edith, Radua, Joaquim, Salvador, Raymond, Sarró, Salvador, Dickie, Erin W., Voineskos, Aristotle, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Setién-Suero, Esther, Mayoral-van Son, Jacqueline, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Morris, Derek, Donohoe, Gary, Holleran, Laurena, Cannon, Dara M., McDonald, Colm, Corvin, Aiden, Gill, Michael, Busatto, Geraldo F., Rosa, Pedro G. P., Serpa, Mauricio H., Zanetti, Marcus V., Lebedeva, Irina, Kaleda, Vasiliy G., Tomyshev, Alexander S., Crow, Tim, James, Anthony, Cervenka, Simon, Sellgren, Carl M., Fatouros-Bergman, Helena, Agartz, Ingrid, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Uhlmann, Anne, Zubicaray, Greig I. de, McMahon, Katie L., Wright, Margaret J., Cobia, Derin, Csernansky, John G., Thompson, Paul M., Turner, Jessica A., Wang, Lei, US Department of Veterans Affairs, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Swedish Research Council for Health, Working Life and Welfare, Fundação Amazônia de Amparo a Estudos e Pesquisas, Instituto de Salud Carlos III, National Health and Medical Research Council (Australia), National Institutes of Health (US), National Science Foundation (US), Research Council of Norway, Science Foundation Ireland, Wellcome Trust, Gutman, Boris A., van Erp, Theo G. M., Alpert, Kathryn I., Ching, Christopher R. K., Isaev, Dmitry, Ragothaman, Anjani, Jahanshad, Neda, Saremi, Arvin, Zavaliangos-Petropulu, Artemis, Glahn, David C., Shen, Li, Cong, Shan, Alnæs, Dag, Andreassen, Ole A., DoanNhat Trung, Westlye, Lars T., Kochunov, Peter, Satterthwaite, Theodore D., Wolf, Daniel H., Huang, Alexander J., Kessler, Charles, Weideman, Andrea, Nguyen, Dana, Mueller, Bryon A., Faziola, Lawrence, Potkin, Steven G., Preda Adrian, Mathalon, Daniel H., Bustillo Juan, Calhoun, Vincent, Ford, Judith M., Walton, Esther, Ehrlich, Stefan, Ducci, Giuseppe, Banaj, Nerisa, Piras, Fabrizio, Piras, Federica, Spalletta, Gianfranco, Canales-Rodríguez, Erick J., Fuentes-Claramonte, Paola, Pomarol-Clotet, Edith, Radua, Joaquim, Salvador, Raymond, Sarró, Salvador, Dickie, Erin W., Voineskos, Aristotle, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Setién-Suero, Esther, Mayoral-van Son, Jacqueline, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Morris, Derek, Donohoe, Gary, Holleran, Laurena, Cannon, Dara M., McDonald, Colm, Corvin, Aiden, Gill, Michael, Busatto, Geraldo F., Rosa, Pedro G. P., Serpa, Mauricio H., Zanetti, Marcus V., Lebedeva, Irina, Kaleda, Vasiliy G., Tomyshev, Alexander S., Crow, Tim, James, Anthony, Cervenka, Simon, Sellgren, Carl M., Fatouros-Bergman, Helena, Agartz, Ingrid, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Uhlmann, Anne, Zubicaray, Greig I. de, McMahon, Katie L., Wright, Margaret J., Cobia, Derin, Csernansky, John G., Thompson, Paul M., Turner, Jessica A., and Wang, Lei
Abstract: Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
Published: 2022

48. ENIGMA-Sleep: Challenges, opportunities, and the road map

Author: Tahmasian, Masoud, Aleman, André, Andreassen, Ole A, Arab, Zahra, Baillet, Marion, Benedetti, Francesco, Bresser, Tom, Bright, Joanna, Chee, Michael W L, Chylinski, Daphne, Cheng, Wei, Deantoni, Michele, Dresler, Martin, Eickhoff, Simon B, Eickhoff, Claudia R, Elvsåshagen, Torbjørn, Feng, Jianfeng, Foster-Dingley, Jessica C, Ganjgahi, Habib, Grabe, Hans J, Groenewold, Nynke A, Ho, Tiffany C, Bong Hong, Seung, Houenou, Josselin, Irungu, Benson, Jahanshad, Neda, Khazaie, Habibolah, Kim, Hosung, Koshmanova, Ekaterina, Kocevska, Desi, Kochunov, Peter, Lakbila-Kamal, Oti, Leerssen, Jeanne, Li, Meng, Luik, Annemarie I, Muto, Vincenzo, Narbutas, Justinas, Nilsonne, Gustav, O'Callaghan, Victoria S, Olsen, Alexander, Osorio, Ricardo S, Poletti, Sara, Poudel, Govinda, Reesen, Joyce E, Reneman, Liesbeth, Reyt, Mathilde, Riemann, Dieter, Rosenzweig, Ivana, Rostampour, Masoumeh, Saberi, Amin, Schiel, Julian, Schmidt, Christina, Schrantee, Anouk, Sciberras, Emma, Silk, Tim J, Sim, Kang, Smevik, Hanne, Soares, Jair C, Spiegelhalder, Kai, Stein, Dan J, Talwar, Puneet, Tamm, Sandra, Teresi, Giana L, Valk, Sofie L, Van Someren, Eus, Vandewalle, Gilles, Van Egroo, Maxime, Völzke, Henry, Walter, Martin, Wassing, Rick, Weber, Frederik D, Weihs, Antoine, Westlye, Lars Tjelta, Wright, Margaret J, Wu, Mon-Ju, Zak, Nathalia, Zarei, Mojtaba, Tahmasian, Masoud, Aleman, André, Andreassen, Ole A, Arab, Zahra, Baillet, Marion, Benedetti, Francesco, Bresser, Tom, Bright, Joanna, Chee, Michael W L, Chylinski, Daphne, Cheng, Wei, Deantoni, Michele, Dresler, Martin, Eickhoff, Simon B, Eickhoff, Claudia R, Elvsåshagen, Torbjørn, Feng, Jianfeng, Foster-Dingley, Jessica C, Ganjgahi, Habib, Grabe, Hans J, Groenewold, Nynke A, Ho, Tiffany C, Bong Hong, Seung, Houenou, Josselin, Irungu, Benson, Jahanshad, Neda, Khazaie, Habibolah, Kim, Hosung, Koshmanova, Ekaterina, Kocevska, Desi, Kochunov, Peter, Lakbila-Kamal, Oti, Leerssen, Jeanne, Li, Meng, Luik, Annemarie I, Muto, Vincenzo, Narbutas, Justinas, Nilsonne, Gustav, O'Callaghan, Victoria S, Olsen, Alexander, Osorio, Ricardo S, Poletti, Sara, Poudel, Govinda, Reesen, Joyce E, Reneman, Liesbeth, Reyt, Mathilde, Riemann, Dieter, Rosenzweig, Ivana, Rostampour, Masoumeh, Saberi, Amin, Schiel, Julian, Schmidt, Christina, Schrantee, Anouk, Sciberras, Emma, Silk, Tim J, Sim, Kang, Smevik, Hanne, Soares, Jair C, Spiegelhalder, Kai, Stein, Dan J, Talwar, Puneet, Tamm, Sandra, Teresi, Giana L, Valk, Sofie L, Van Someren, Eus, Vandewalle, Gilles, Van Egroo, Maxime, Völzke, Henry, Walter, Martin, Wassing, Rick, Weber, Frederik D, Weihs, Antoine, Westlye, Lars Tjelta, Wright, Margaret J, Wu, Mon-Ju, Zak, Nathalia, and Zarei, Mojtaba
Abstract: Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
Published: 2021

49. ENIGMA-Sleep : Challenges, opportunities, and the road map

Author: Tahmasian, Masoud, Aleman, André, Andreassen, Ole A., Arab, Zahra, Baillet, Marion, Benedetti, Francesco, Bresser, Tom, Bright, Joanna, Chee, Michael W. L., Chylinski, Daphne, Cheng, Wei, Deantoni, Michele, Dresler, Martin, Eickhoff, Simon B., Eickhoff, Claudia R., Elvsåshagen, Torbjørn, Feng, Jianfeng, Foster-Dingley, Jessica C., Ganjgahi, Habib, Grabe, Hans J., Groenewold, Nynke A., Ho, Tiffany C., Hong, Seung Bong, Houenou, Josselin, Irungu, Benson, Jahanshad, Neda, Khazaie, Habibolah, Kim, Hosung, Koshmanova, Ekaterina, Kocevska, Desi, Kochunov, Peter, Lakbila-Kamal, Oti, Leerssen, Jeanne, Li, Meng, Luik, Annemarie, Muto, Vincenzo, Narbutas, Justinas, Nilsonne, Gustav, O'Callaghan, Victoria S., Olsen, Alexander, Osorio, Ricardo S., Poletti, Sara, Poudel, Govinda, Reesen, Joyce E., Reneman, Liesbeth, Reyt, Mathilde, Riemann, Dieter, Rosenzweig, Ivana, Rostampour, Masoumeh, Saberi, Amin, Schiel, Julian, Schmidt, Christina, Schrantee, Anouk, Sciberras, Emma, Silk, Tim J., Sim, Kang, Smevik, Hanne, Soares, Jair C., Spiegelhalder, Kai, Stein, Dan J., Talwar, Puneet, Tamm, Sandra, Teresi, Giana L., Valk, Sofie L., Van Someren, Eus, Vandewalle, Gilles, Van Egroo, Maxime, Völzke, Henry, Walter, Martin, Wassing, Rick, Weber, Frederik D., Weihs, Antoine, Westlye, Lars Tjelta, Wright, Margaret J., Wu, Mon-Ju, Zak, Nathalia, Zarei, Mojtaba, Tahmasian, Masoud, Aleman, André, Andreassen, Ole A., Arab, Zahra, Baillet, Marion, Benedetti, Francesco, Bresser, Tom, Bright, Joanna, Chee, Michael W. L., Chylinski, Daphne, Cheng, Wei, Deantoni, Michele, Dresler, Martin, Eickhoff, Simon B., Eickhoff, Claudia R., Elvsåshagen, Torbjørn, Feng, Jianfeng, Foster-Dingley, Jessica C., Ganjgahi, Habib, Grabe, Hans J., Groenewold, Nynke A., Ho, Tiffany C., Hong, Seung Bong, Houenou, Josselin, Irungu, Benson, Jahanshad, Neda, Khazaie, Habibolah, Kim, Hosung, Koshmanova, Ekaterina, Kocevska, Desi, Kochunov, Peter, Lakbila-Kamal, Oti, Leerssen, Jeanne, Li, Meng, Luik, Annemarie, Muto, Vincenzo, Narbutas, Justinas, Nilsonne, Gustav, O'Callaghan, Victoria S., Olsen, Alexander, Osorio, Ricardo S., Poletti, Sara, Poudel, Govinda, Reesen, Joyce E., Reneman, Liesbeth, Reyt, Mathilde, Riemann, Dieter, Rosenzweig, Ivana, Rostampour, Masoumeh, Saberi, Amin, Schiel, Julian, Schmidt, Christina, Schrantee, Anouk, Sciberras, Emma, Silk, Tim J., Sim, Kang, Smevik, Hanne, Soares, Jair C., Spiegelhalder, Kai, Stein, Dan J., Talwar, Puneet, Tamm, Sandra, Teresi, Giana L., Valk, Sofie L., Van Someren, Eus, Vandewalle, Gilles, Van Egroo, Maxime, Völzke, Henry, Walter, Martin, Wassing, Rick, Weber, Frederik D., Weihs, Antoine, Westlye, Lars Tjelta, Wright, Margaret J., Wu, Mon-Ju, Zak, Nathalia, and Zarei, Mojtaba
Abstract: Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
Published: 2021
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50. White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric Moderate to Severe Traumatic Brain Injury.

Author: Dennis, Emily L, Dennis, Emily L, Caeyenberghs, Karen, Hoskinson, Kristen R, Merkley, Tricia L, Suskauer, Stacy J, Asarnow, Robert F, Babikian, Talin, Bartnik-Olson, Brenda, Bickart, Kevin, Bigler, Erin D, Ewing-Cobbs, Linda, Figaji, Anthony, Giza, Christopher C, Goodrich-Hunsaker, Naomi J, Hodges, Cooper B, Hovenden Aa, Elizabeth S, Irimia, Andrei, Königs, Marsh, Levin, Harvey S, Lindsey, Hannah M, Max, Jeffrey E, Newsome, Mary R, Olsen, Alexander, Ryan, Nicholas P, Schmidt, Adam T, Spruiell, Matthew S, Wade, Benjamin Sc, Ware, Ashley L, Watson, Christopher G, Wheeler, Anne L, Yeates, Keith Owen, Zielinski, Brandon A, Kochunov, Peter, Jahanshad, Neda, Thompson, Paul M, Tate, David F, Wilde, Elisabeth A, Dennis, Emily L, Dennis, Emily L, Caeyenberghs, Karen, Hoskinson, Kristen R, Merkley, Tricia L, Suskauer, Stacy J, Asarnow, Robert F, Babikian, Talin, Bartnik-Olson, Brenda, Bickart, Kevin, Bigler, Erin D, Ewing-Cobbs, Linda, Figaji, Anthony, Giza, Christopher C, Goodrich-Hunsaker, Naomi J, Hodges, Cooper B, Hovenden Aa, Elizabeth S, Irimia, Andrei, Königs, Marsh, Levin, Harvey S, Lindsey, Hannah M, Max, Jeffrey E, Newsome, Mary R, Olsen, Alexander, Ryan, Nicholas P, Schmidt, Adam T, Spruiell, Matthew S, Wade, Benjamin Sc, Ware, Ashley L, Watson, Christopher G, Wheeler, Anne L, Yeates, Keith Owen, Zielinski, Brandon A, Kochunov, Peter, Jahanshad, Neda, Thompson, Paul M, Tate, David F, and Wilde, Elisabeth A
Abstract: ObjectiveOur study addressed aims: (1) test the hypothesis that moderate-severe TBI in pediatric patients is associated with widespread white matter (WM) disruption; (2) test the hypothesis that age and sex impact WM organization after injury; and (3) examine associations between WM organization and neurobehavioral outcomes.MethodsData from ten previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric msTBI working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline.ResultsFive hundred and seven children and adolescents (244 with complicated mild to severe TBI [msTBI] and 263 controls) were included. Patients were clustered into three post-injury intervals: acute/subacute - <2 months, post-acute - 2-6 months, chronic - 6+ months. Outcomes were dMRI metrics and post-injury behavioral problems as indexed by the Child Behavior Checklist (CBCL). Our analyses revealed altered WM diffusion metrics across multiple tracts and all post-injury intervals (effect sizes ranging between d=-0.5 to -1.3). Injury severity is a significant contributor to the extent of WM alterations but explained less variance in dMRI measures with increasing time post-injury. We observed a sex-by-group interaction: females with TBI had significantly lower fractional anisotropy in the uncinate fasciculus than controls (?=0.043), which coincided with more parent-reported behavioral problems (?=-0.0027).ConclusionsWM disruption after msTBI is widespread, persistent, and influenced by demographic and clinical variables. Future work will test techniques for harmonizing neurocognitive data, enabling more advanced analyses to identify symptom clusters and clinically-meaningful patient subtypes.
Published: 2021

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