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2. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author

Brouwer, Rachel M, Klein, Marieke, Grasby, Katrina L, Schnack, Hugo G, Jahanshad, Neda, Teeuw, Jalmar, Thomopoulos, Sophia I, Sprooten, Emma, Franz, Carol E, Gogtay, Nitin, Kremen, William S, Panizzon, Matthew S, Olde Loohuis, Loes M, Whelan, Christopher D, Aghajani, Moji, Alloza, Clara, Alnæs, Dag, Artiges, Eric, Ayesa-Arriola, Rosa, Barker, Gareth J, Bastin, Mark E, Blok, Elisabet, Bøen, Erlend, Breukelaar, Isabella A, Bright, Joanna K, Buimer, Elizabeth EL, Bülow, Robin, Cannon, Dara M, Ciufolini, Simone, Crossley, Nicolas A, Damatac, Christienne G, Dazzan, Paola, de Mol, Casper L, de Zwarte, Sonja MC, Desrivières, Sylvane, Díaz-Caneja, Covadonga M, Doan, Nhat Trung, Dohm, Katharina, Fröhner, Juliane H, Goltermann, Janik, Grigis, Antoine, Grotegerd, Dominik, Han, Laura KM, Harris, Mathew A, Hartman, Catharina A, Heany, Sarah J, Heindel, Walter, Heslenfeld, Dirk J, Hohmann, Sarah, Ittermann, Bernd, Jansen, Philip R, Janssen, Joost, Jia, Tianye, Jiang, Jiyang, Jockwitz, Christiane, Karali, Temmuz, Keeser, Daniel, Koevoets, Martijn GJC, Lenroot, Rhoshel K, Malchow, Berend, Mandl, René CW, Medel, Vicente, Meinert, Susanne, Morgan, Catherine A, Mühleisen, Thomas W, Nabulsi, Leila, Opel, Nils, de la Foz, Víctor Ortiz-García, Overs, Bronwyn J, Paillère Martinot, Marie-Laure, Redlich, Ronny, Marques, Tiago Reis, Repple, Jonathan, Roberts, Gloria, Roshchupkin, Gennady V, Setiaman, Nikita, Shumskaya, Elena, Stein, Frederike, Sudre, Gustavo, Takahashi, Shun, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, van der Lugt, Aad, van Haren, Neeltje EM, Wardlaw, Joanna M, Wen, Wei, Westeneng, Henk-Jan, Wittfeld, Katharina, Zhu, Alyssa H, Zugman, Andre, Armstrong, Nicola J, Bonfiglio, Gaia, Bralten, Janita, Dalvie, Shareefa, Davies, Gail, Di Forti, Marta, Ding, Linda, Donohoe, Gary, Forstner, Andreas J, and Gonzalez-Peñas, Javier

Subjects
Biological Psychology, Psychology, Neurosciences, Mental Illness, Human Genome, Genetics, Aging, Mental Health, Brain Disorders, 2.1 Biological and endogenous factors, Neurological, Mental health, Brain, Genome-Wide Association Study, Humans, Longevity, Magnetic Resonance Imaging, IMAGEN Consortium, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

Published
2022

3. Intelligence, educational attainment, and brain structure in those at familial high‐risk for schizophrenia or bipolar disorder

Author

Zwarte, Sonja MC, Brouwer, Rachel M, Agartz, Ingrid, Alda, Martin, Alonso‐Lana, Silvia, Bearden, Carrie E, Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth EL, Cahn, Wiepke, Canales‐Rodríguez, Erick J, Cannon, Dara M, Cannon, Tyrone D, Caseras, Xavier, Castro‐Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Bonnin, Caterina Mar, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E, Eker, Mehmet Cagdas, Erk, Susanne, Fatjó‐Vilas, Mar, Fears, Scott C, Foley, Sonya F, Frangou, Sophia, Fullerton, Janice M, Glahn, David C, Goghari, Vina M, Goikolea, Jose M, Goldman, Aaron L, Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L, Heinz, Andreas, Ongun, Ceren Hidiroglu, Hillegers, Manon HJ, Houenou, Josselin, Pol, Hilleke E Hulshoff, Hultman, Christina M, Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G, Kane, Fergus, Kempton, Matthew J, Koenis, Marinka MG, Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M, Lenroot, Rhoshel K, Marcelis, Machteld, Mattay, Venkata S, McDonald, Colm, Meyer‐Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B, Moreno, Dolores, Murray, Robin M, Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A, Os, Jim, Overs, Bronwyn J, Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M, Piguet, Camille, Pomarol‐Clotet, Edith, Radua, Joaquim, Ramsay, Ian S, Richter, Anja, Roberts, Gloria, Salvador, Raymond, Aydogan, Aybala Saricicek, Sarró, Salvador, Schofield, Peter R, Simsek, Esma M, Simsek, Fatma, Soares, Jair C, Sponheim, Scott R, Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R, Whalley, Heather C, Wu, Mon‐Ju, Yalin, Nefize, Andreassen, Ole A, Ching, Christopher RK, Thomopoulos, Sophia I, Erp, Theo GM, Jahanshad, Neda, and Thompson, Paul M

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Bipolar Disorder, Clinical Research, Serious Mental Illness, Neurosciences, Schizophrenia, Mental Health, Aetiology, 2.3 Psychological, social and economic factors, 2.1 Biological and endogenous factors, Mental health, Cognitive Dysfunction, Educational Status, Family, Genetic Predisposition to Disease, Humans, Intelligence, Magnetic Resonance Imaging, Neuroimaging, bipolar disorder, education, intelligence, neuroimaging, relatives, schizophrenia, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

Published
2022

4. In vivo hippocampal subfield volumes in bipolar disorder—A mega‐analysis from The Enhancing Neuro Imaging Genetics through Meta‐Analysis Bipolar Disorder Working Group

Author

Haukvik, Unn K, Gurholt, Tiril P, Nerland, Stener, Elvsåshagen, Torbjørn, Akudjedu, Theophilus N, Alda, Martin, Alnæs, Dag, Alonso‐Lana, Silvia, Bauer, Jochen, Baune, Bernhard T, Benedetti, Francesco, Berk, Michael, Bettella, Francesco, Bøen, Erlend, Bonnín, Caterina M, Brambilla, Paolo, Canales‐Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Dandash, Orwa, Dannlowski, Udo, Delvecchio, Giuseppe, Díaz‐Zuluaga, Ana M, Erp, Theo GM, Fatjó‐Vilas, Mar, Foley, Sonya F, Förster, Katharina, Fullerton, Janice M, Goikolea, José M, Grotegerd, Dominik, Gruber, Oliver, Haarman, Bartholomeus CM, Haatveit, Beathe, Hajek, Tomas, Hallahan, Brian, Harris, Mathew, Hawkins, Emma L, Howells, Fleur M, Hülsmann, Carina, Jahanshad, Neda, Jørgensen, Kjetil N, Kircher, Tilo, Krämer, Bernd, Krug, Axel, Kuplicki, Rayus, Lagerberg, Trine V, Lancaster, Thomas M, Lenroot, Rhoshel K, Lonning, Vera, López‐Jaramillo, Carlos, Malt, Ulrik F, McDonald, Colm, McIntosh, Andrew M, McPhilemy, Genevieve, Meer, Dennis, Melle, Ingrid, Melloni, Elisa MT, Mitchell, Philip B, Nabulsi, Leila, Nenadić, Igor, Oertel, Viola, Oldani, Lucio, Opel, Nils, Otaduy, Maria CG, Overs, Bronwyn J, Pineda‐Zapata, Julian A, Pomarol‐Clotet, Edith, Radua, Joaquim, Rauer, Lisa, Redlich, Ronny, Repple, Jonathan, Rive, Maria M, Roberts, Gloria, Ruhe, Henricus G, Salminen, Lauren E, Salvador, Raymond, Sarró, Salvador, Savitz, Jonathan, Schene, Aart H, Sim, Kang, Soeiro‐de‐Souza, Marcio G, Stäblein, Michael, Stein, Dan J, Stein, Frederike, Tamnes, Christian K, Temmingh, Henk S, Thomopoulos, Sophia I, Veltman, Dick J, Vieta, Eduard, Waltemate, Lena, Westlye, Lars T, Whalley, Heather C, Sämann, Philipp G, Thompson, Paul M, Ching, Christopher RK, Andreassen, Ole A, Agartz, Ingrid, and Group, ENIGMA Bipolar Disorder Working

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Mental Health, Serious Mental Illness, Neurosciences, Biomedical Imaging, Bipolar Disorder, Mental health, Genetics, Hippocampus, Humans, Magnetic Resonance Imaging, Neuroimaging, ENIGMA Bipolar Disorder Working Group, bipolar disorder subtype, hippocampus, large-scale, lithium, psychosis, structural brain MRI, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

Published
2022

6. Using structural MRI to identify bipolar disorders – 13 site machine learning study in 3020 individuals from the ENIGMA Bipolar Disorders Working Group

Author

Nunes, Abraham, Schnack, Hugo G, Ching, Christopher RK, Agartz, Ingrid, Akudjedu, Theophilus N, Alda, Martin, Alnæs, Dag, Alonso-Lana, Silvia, Bauer, Jochen, Baune, Bernhard T, Bøen, Erlend, Bonnin, Caterina del Mar, Busatto, Geraldo F, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Chaim-Avancini, Tiffany M, Dannlowski, Udo, Díaz-Zuluaga, Ana M, Dietsche, Bruno, Doan, Nhat Trung, Duchesnay, Edouard, Elvsåshagen, Torbjørn, Emden, Daniel, Eyler, Lisa T, Fatjó-Vilas, Mar, Favre, Pauline, Foley, Sonya F, Fullerton, Janice M, Glahn, David C, Goikolea, Jose M, Grotegerd, Dominik, Hahn, Tim, Henry, Chantal, Hibar, Derrek P, Houenou, Josselin, Howells, Fleur M, Jahanshad, Neda, Kaufmann, Tobias, Kenney, Joanne, Kircher, Tilo TJ, Krug, Axel, Lagerberg, Trine V, Lenroot, Rhoshel K, López-Jaramillo, Carlos, Machado-Vieira, Rodrigo, Malt, Ulrik F, McDonald, Colm, Mitchell, Philip B, Mwangi, Benson, Nabulsi, Leila, Opel, Nils, Overs, Bronwyn J, Pineda-Zapata, Julian A, Pomarol-Clotet, Edith, Redlich, Ronny, Roberts, Gloria, Rosa, Pedro G, Salvador, Raymond, Satterthwaite, Theodore D, Soares, Jair C, Stein, Dan J, Temmingh, Henk S, Trappenberg, Thomas, Uhlmann, Anne, van Haren, Neeltje EM, Vieta, Eduard, Westlye, Lars T, Wolf, Daniel H, Yüksel, Dilara, Zanetti, Marcus V, Andreassen, Ole A, Thompson, Paul M, and Hajek, Tomas

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Biomedical Imaging, Neurosciences, Mental Health, Clinical Research, Mental health, Bipolar Disorder, Brain, Humans, Machine Learning, Magnetic Resonance Imaging, Neuroimaging, ENIGMA Bipolar Disorders Working Group, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70-60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen's Kappa = 0.83, 95% CI = 0.829-0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.

Published
2020

7. The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder

Author

de Zwarte, Sonja MC, Brouwer, Rachel M, Agartz, Ingrid, Alda, Martin, Aleman, André, Alpert, Kathryn I, Bearden, Carrie E, Bertolino, Alessandro, Bois, Catherine, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth EL, Cahn, Wiepke, Cannon, Dara M, Cannon, Tyrone D, Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Di Giorgio, Annabella, Doucet, Gaelle E, Eker, Mehmet Cagdas, Erk, Susanne, Fears, Scott C, Foley, Sonya F, Frangou, Sophia, Frankland, Andrew, Fullerton, Janice M, Glahn, David C, Goghari, Vina M, Goldman, Aaron L, Gonul, Ali Saffet, Gruber, Oliver, de Haan, Lieuwe, Hajek, Tomas, Hawkins, Emma L, Heinz, Andreas, Hillegers, Manon HJ, Pol, Hilleke E Hulshoff, Hultman, Christina M, Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G, Kane, Fergus, Kempton, Matthew J, Koenis, Marinka MG, Kopecek, Miloslav, Krabbendam, Lydia, Krämer, Bernd, Lawrie, Stephen M, Lenroot, Rhoshel K, Marcelis, Machteld, Marsman, Jan-Bernard C, Mattay, Venkata S, McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B, Moreno, Dolores, Murray, Robin M, Mwangi, Benson, Najt, Pablo, Neilson, Emma, Newport, Jason, van Os, Jim, Overs, Bronwyn, Ozerdem, Aysegul, Picchioni, Marco M, Richter, Anja, Roberts, Gloria, Aydogan, Aybala Saricicek, Schofield, Peter R, Simsek, Fatma, Soares, Jair C, Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Walter, Henrik, Wang, Lei, Weinberger, Daniel R, Whalley, Heather C, Yalin, Nefize, Andreassen, Ole A, Ching, Christopher RK, van Erp, Theo GM, Turner, Jessica A, Jahanshad, Neda, Thompson, Paul M, Kahn, René S, and van Haren, Neeltje EM

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Mental Health, Brain Disorders, Serious Mental Illness, Schizophrenia, Genetics, Neurosciences, Clinical Research, Bipolar Disorder, 2.3 Psychological, social and economic factors, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adult, Brain, Cohort Studies, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Young Adult, Bipolar disorder, Familial risk, Imaging, Meta-analysis, Neurodevelopment, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundSchizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.MethodsWe performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.ResultsFDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d

Published
2019

8. Spatial dynamics within and between brain functional domains: A hierarchical approach to study time‐varying brain function

Author

Iraji, Armin, Fu, Zening, Damaraju, Eswar, DeRamus, Thomas P, Lewis, Noah, Bustillo, Juan R, Lenroot, Rhoshel K, Belger, Aysneil, Ford, Judith M, McEwen, Sarah, Mathalon, Daniel H, Mueller, Bryon A, Pearlson, Godfrey D, Potkin, Steven G, Preda, Adrian, Turner, Jessica A, Vaidya, Jatin G, Erp, Theo GM, and Calhoun, Vince D

Subjects
Neurosciences, Bioengineering, Neurological, Adolescent, Adult, Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Models, Neurological, Young Adult, brain dynamic, functional domain, functional module, high-order independent component analysis, intrinsic activity, resting state fMRI, schizophrenia, spatial domain state, spatial dynamics, Cognitive Sciences, Experimental Psychology
Abstract

The analysis of time-varying activity and connectivity patterns (i.e., the chronnectome) using resting-state magnetic resonance imaging has become an important part of ongoing neuroscience discussions. The majority of previous work has focused on variations of temporal coupling among fixed spatial nodes or transition of the dominant activity/connectivity pattern over time. Here, we introduce an approach to capture spatial dynamics within functional domains (FDs), as well as temporal dynamics within and between FDs. The approach models the brain as a hierarchical functional architecture with different levels of granularity, where lower levels have higher functional homogeneity and less dynamic behavior and higher levels have less homogeneity and more dynamic behavior. First, a high-order spatial independent component analysis is used to approximate functional units. A functional unit is a pattern of regions with very similar functional activity over time. Next, functional units are used to construct FDs. Finally, functional modules (FMs) are calculated from FDs, providing an overall view of brain dynamics. Results highlight the spatial fluidity within FDs, including a broad spectrum of changes in regional associations, from strong coupling to complete decoupling. Moreover, FMs capture the dynamic interplay between FDs. Patients with schizophrenia show transient reductions in functional activity and state connectivity across several FDs, particularly the subcortical domain. Activity and connectivity differences convey unique information in many cases (e.g., the default mode) highlighting their complementarity information. The proposed hierarchical model to capture FD spatiotemporal variations provides new insight into the macroscale chronnectome and identifies changes hidden from existing approaches.

Published
2019

9. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium.

Author

van Erp, Theo GM, Walton, Esther, Hibar, Derrek P, Schmaal, Lianne, Jiang, Wenhao, Glahn, David C, Pearlson, Godfrey D, Yao, Nailin, Fukunaga, Masaki, Hashimoto, Ryota, Okada, Naohiro, Yamamori, Hidenaga, Bustillo, Juan R, Clark, Vincent P, Agartz, Ingrid, Mueller, Bryon A, Cahn, Wiepke, de Zwarte, Sonja MC, Hulshoff Pol, Hilleke E, Kahn, René S, Ophoff, Roel A, van Haren, Neeltje EM, Andreassen, Ole A, Dale, Anders M, Doan, Nhat Trung, Gurholt, Tiril P, Hartberg, Cecilie B, Haukvik, Unn K, Jørgensen, Kjetil N, Lagerberg, Trine V, Melle, Ingrid, Westlye, Lars T, Gruber, Oliver, Kraemer, Bernd, Richter, Anja, Zilles, David, Calhoun, Vince D, Crespo-Facorro, Benedicto, Roiz-Santiañez, Roberto, Tordesillas-Gutiérrez, Diana, Loughland, Carmel, Carr, Vaughan J, Catts, Stanley, Cropley, Vanessa L, Fullerton, Janice M, Green, Melissa J, Henskens, Frans A, Jablensky, Assen, Lenroot, Rhoshel K, Mowry, Bryan J, Michie, Patricia T, Pantelis, Christos, Quidé, Yann, Schall, Ulrich, Scott, Rodney J, Cairns, Murray J, Seal, Marc, Tooney, Paul A, Rasser, Paul E, Cooper, Gavin, Shannon Weickert, Cynthia, Weickert, Thomas W, Morris, Derek W, Hong, Elliot, Kochunov, Peter, Beard, Lauren M, Gur, Raquel E, Gur, Ruben C, Satterthwaite, Theodore D, Wolf, Daniel H, Belger, Aysenil, Brown, Gregory G, Ford, Judith M, Macciardi, Fabio, Mathalon, Daniel H, O'Leary, Daniel S, Potkin, Steven G, Preda, Adrian, Voyvodic, James, Lim, Kelvin O, McEwen, Sarah, Yang, Fude, Tan, Yunlong, Tan, Shuping, Wang, Zhiren, Fan, Fengmei, Chen, Jingxu, Xiang, Hong, Tang, Shiyou, Guo, Hua, Wan, Ping, Wei, Dong, Bockholt, Henry J, Ehrlich, Stefan, Wolthusen, Rick PF, King, Margaret D, Shoemaker, Jody M, Sponheim, Scott R, De Haan, Lieuwe, and Koenders, Laura

Subjects
Karolinska Schizophrenia Project, Brain, Frontal Lobe, Prefrontal Cortex, Temporal Lobe, Humans, Magnetic Resonance Imaging, Severity of Illness Index, Linear Models, Case-Control Studies, Schizophrenia, Age of Onset, Adolescent, Adult, Aged, Middle Aged, Child, Female, Male, Young Adult, Neuroimaging, Cortical, Imaging, Meta-analysis, Surface area, Thickness, Serious Mental Illness, Biomedical Imaging, Mental Health, Clinical Research, Neurosciences, Brain Disorders, Mental health, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundThe profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.MethodsThe study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide.ResultsCompared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.ConclusionsThe findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Published
2018

10. Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group

Author

Abé, Christoph, Ching, Christopher R.K., Liberg, Benny, Lebedev, Alexander V., Agartz, Ingrid, Akudjedu, Theophilus N., Alda, Martin, Alnæs, Dag, Alonso-Lana, Silvia, Benedetti, Francesco, Berk, Michael, Bøen, Erlend, Bonnin, Caterina del Mar, Breuer, Fabian, Brosch, Katharina, Brouwer, Rachel M., Canales-Rodríguez, Erick J., Cannon, Dara M., Chye, Yann, Dahl, Andreas, Dandash, Orwa, Dannlowski, Udo, Dohm, Katharina, Elvsåshagen, Torbjørn, Fisch, Lukas, Fullerton, Janice M., Goikolea, Jose M., Grotegerd, Dominik, Haatveit, Beathe, Hahn, Tim, Hajek, Tomas, Heindel, Walter, Ingvar, Martin, Sim, Kang, Kircher, Tilo T.J., Lenroot, Rhoshel K., Malt, Ulrik F., McDonald, Colm, McWhinney, Sean R., Melle, Ingrid, Meller, Tina, Melloni, Elisa M.T., Mitchell, Philip B., Nabulsi, Leila, Nenadić, Igor, Opel, Nils, Overs, Bronwyn J., Panicalli, Francesco, Pfarr, Julia-Katharina, Poletti, Sara, Pomarol-Clotet, Edith, Radua, Joaquim, Repple, Jonathan, Ringwald, Kai G., Roberts, Gloria, Rodriguez-Cano, Elena, Salvador, Raymond, Sarink, Kelvin, Sarró, Salvador, Schmitt, Simon, Stein, Frederike, Suo, Chao, Thomopoulos, Sophia I., Tronchin, Giulia, Vieta, Eduard, Westlye, Lars T., White, Adam G., Yatham, Lakshmi N., Zak, Nathalia, Thompson, Paul M., Andreassen, Ole A., and Landén, Mikael

Published
2022
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15. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

Author

Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Piehl, Fredrik, Agartz, Ingrid, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, van Erp, Theo G.M., Walton, Esther, Hibar, Derrek P., Schmaal, Lianne, Jiang, Wenhao, Glahn, David C., Pearlson, Godfrey D., Yao, Nailin, Fukunaga, Masaki, Hashimoto, Ryota, Okada, Naohiro, Yamamori, Hidenaga, Bustillo, Juan R., Clark, Vincent P., Mueller, Bryon A., Cahn, Wiepke, de Zwarte, Sonja M.C., Hulshoff Pol, Hilleke E., Kahn, René S., Ophoff, Roel A., van Haren, Neeltje E.M., Andreassen, Ole A., Dale, Anders M., Doan, Nhat Trung, Gurholt, Tiril P., Hartberg, Cecilie B., Haukvik, Unn K., Jørgensen, Kjetil N., Lagerberg, Trine V., Melle, Ingrid, Westlye, Lars T., Gruber, Oliver, Kraemer, Bernd, Richter, Anja, Zilles, David, Calhoun, Vince D., Crespo-Facorro, Benedicto, Roiz-Santiañez, Roberto, Tordesillas-Gutiérrez, Diana, Loughland, Carmel, Carr, Vaughan J., Catts, Stanley, Cropley, Vanessa L., Fullerton, Janice M., Green, Melissa J., Henskens, Frans A., Jablensky, Assen, Lenroot, Rhoshel K., Mowry, Bryan J., Michie, Patricia T., Pantelis, Christos, Quidé, Yann, Schall, Ulrich, Scott, Rodney J., Cairns, Murray J., Seal, Marc, Tooney, Paul A., Rasser, Paul E., Cooper, Gavin, Shannon Weickert, Cynthia, Weickert, Thomas W., Morris, Derek W., Hong, Elliot, Kochunov, Peter, Beard, Lauren M., Gur, Raquel E., Gur, Ruben C., Satterthwaite, Theodore D., Wolf, Daniel H., Belger, Aysenil, Brown, Gregory G., Ford, Judith M., Macciardi, Fabio, Mathalon, Daniel H., O’Leary, Daniel S., Potkin, Steven G., Preda, Adrian, Voyvodic, James, Lim, Kelvin O., McEwen, Sarah, Yang, Fude, Tan, Yunlong, Tan, Shuping, Wang, Zhiren, Fan, Fengmei, Chen, Jingxu, Xiang, Hong, Tang, Shiyou, Guo, Hua, Wan, Ping, Wei, Dong, Bockholt, Henry J., Ehrlich, Stefan, Wolthusen, Rick P.F., King, Margaret D., Shoemaker, Jody M., Sponheim, Scott R., De Haan, Lieuwe, Koenders, Laura, Machielsen, Marise W., van Amelsvoort, Therese, Veltman, Dick J., Assogna, Francesca, Banaj, Nerisa, de Rossi, Pietro, Iorio, Mariangela, Piras, Fabrizio, Spalletta, Gianfranco, McKenna, Peter J., Pomarol-Clotet, Edith, Salvador, Raymond, Corvin, Aiden, Donohoe, Gary, Kelly, Sinead, Whelan, Christopher D., Dickie, Erin W., Rotenberg, David, Voineskos, Aristotle N., Ciufolini, Simone, Radua, Joaquim, Dazzan, Paola, Murray, Robin, Reis Marques, Tiago, Simmons, Andrew, Borgwardt, Stefan, Egloff, Laura, Harrisberger, Fabienne, Riecher-Rössler, Anita, Smieskova, Renata, Alpert, Kathryn I., Wang, Lei, Jönsson, Erik G., Koops, Sanne, Sommer, Iris E.C., Bertolino, Alessandro, Bonvino, Aurora, Di Giorgio, Annabella, Neilson, Emma, Mayer, Andrew R., Stephen, Julia M., Kwon, Jun Soo, Yun, Je-Yeon, Cannon, Dara M., McDonald, Colm, Lebedeva, Irina, Tomyshev, Alexander S., Akhadov, Tolibjohn, Kaleda, Vasily, Busatto, Geraldo F., Rosa, Pedro G.P., Serpa, Mauricio H., Zanetti, Marcus V., Hoschl, Cyril, Skoch, Antonin, Spaniel, Filip, Tomecek, David, Hagenaars, Saskia P., McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., Knöchel, Christian, Oertel-Knöchel, Viola, Stäblein, Michael, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Uhlmann, Anne, Lopez-Jaramillo, Carlos, Dima, Danai, McMahon, Agnes, Faskowitz, Joshua I., Gutman, Boris A., Jahanshad, Neda, Thompson, Paul M., and Turner, Jessica A.

Published
2018
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18. Trauma exposure and disclosure in Hispanic youth at clinical high risk for psychosis: A retrospective review study.

Author

Barans, Samuel, Friedman, Bess, Lardier, David T., Saavedra, Justine L., Bustillo, Juan R., Halperin, Dawn, Lenroot, Rhoshel K., Tohen, Mauricio, Winger, Sarah, and Crisanti, Annette S.

Subjects
HISPANIC American youth, PSYCHOSES, DISCLOSURE, SELF-evaluation, INTEGRATED health care delivery
Abstract

Aim: This exploratory study aimed to examine differences in rates of self and clinician‐reports of trauma in youth at clinical high risk for psychosis (CHR) and whether rates of reporting differed by ethnicity. Methods: Self‐reported history of trauma was collected at intake amongst youth at CHR enrolled in Coordinated Specialty Care (CSC) services (N = 52). A structured chart review was conducted for the same sample to identify clinician‐reported history of trauma throughout treatment in CSC. Results: For all patients, frequency of self‐reported trauma at intake to CSC (56%) was lower compared to clinician‐reports of trauma throughout treatment (85%). Hispanic patients self‐reported trauma at intake (35%) less frequently than non‐Hispanics (69%) (p =.02). No differences were found in clinician reported exposure to trauma by ethnicity throughout treatment. Conclusion: Whilst further research is needed, these findings suggest the need for formalised, repeated, and culturally appropriate assessments of trauma within CSC. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Birth Outcomes and Academic Achievement in Childhood: A Population Record Linkage Study

Author

Moore, Elizabeth A., Harris, Felicity, Laurens, Kristin R., Green, Melissa J., Brinkman, Sally, Lenroot, Rhoshel K., and Carr, Vaughan J.

Abstract

Poor academic performance during childhood predicts later adverse outcomes, and could be targeted for improvement if detected early. This study used population-based record linkage to examine the association between early life risk factors and academic achievement at two different stages of development using two different cohorts: a kindergarten (~age 5 years) and a grade 3 cohort (~age 8 years). Similar factors were predictive of academic performance in both age groups, including positive effects of increasing maternal age and lack of maternal prenatal smoking. Female sex was associated with higher scores for literacy. The results suggest that children with less developed academic skills can be identified earlier, with effective programmes to enhance academic skills needed during the first year of school to enhance subsequent results.

Published
2014
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22. Annual Research Review: Developmental Considerations of Gene by Environment Interactions

Author

Lenroot, Rhoshel K. and Giedd, Jay N.

Abstract

Biological development is driven by a complex dance between nurture and nature, determined not only by the specific features of the interacting genetic and environmental influences but also by the timing of their rendezvous. The initiation of large-scale longitudinal studies, ever-expanding knowledge of genetics, and increasing availability of neuroimaging data to provide endophenotypic bridges between molecules and behavior are beginning to provide some insight into interactions of developmental stage, genes, and the environment, although daunting challenges remain. Prominent amongst these challenges are difficulties in identifying and quantifying relevant environmental factors, discerning the relative contributions to multiply determined outcomes, and the likelihood that brain development is a non-linear dynamic process in which small initial differences may yield large later effects. Age-sensitive mechanisms include developmental changes in gene expression, epigenetic modifications, synaptic arborization/pruning, and maturational improvements in our capacity to seek out environments of our choosing. Greater understanding of how genetic and environmental factors interact differently across ages is an important step toward elucidating the mechanisms by which phenotypes are created--and how they may differ in health and disease. This knowledge may also provide clues to guide the type and timing of interventions to maximize outcomes.

Published
2011
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23. Sex Differences in the Adolescent Brain

Author

Lenroot, Rhoshel K. and Giedd, Jay N.

Abstract

Adolescence is a time of increased divergence between males and females in physical characteristics, behavior, and risk for psychopathology. Here we will review data regarding sex differences in brain structure and function during this period of the lifespan. The most consistent sex difference in brain morphometry is the 9-12% larger brain size that has been reported in males. Individual brain regions that have most consistently been reported as different in males and females include the basal ganglia, hippocampus, and amygdala. Diffusion tensor imaging and magnetization transfer imaging studies have also shown sex differences in white matter development during adolescence. Functional imaging studies have shown different patterns of activation without differences in performance, suggesting male and female brains may use slightly different strategies for achieving similar cognitive abilities. Longitudinal studies have shown sex differences in the trajectory of brain development, with females reaching peak values of brain volumes earlier than males. Although compelling, these sex differences are present as group averages and should not be taken as indicative of relative capacities of males or females. (Contains 1 figure.)

Published
2010
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25. Effects of Sex Chromosome Aneuploidies on Brain Development: Evidence from Neuroimaging Studies

Author

Lenroot, Rhoshel K., Lee, Nancy Raitano, and Giedd, Jay N.

Abstract

Variation in the number of sex chromosomes is a relatively common genetic condition, affecting as many as 1/400 individuals. The sex chromosome aneuploidies (SCAs) are associated with characteristic behavioral and cognitive phenotypes, although the degree to which specific individuals are affected can fall within a wide range. Understanding the effects of different dosages of sex chromosome genes on brain development may help to understand the basis for functional differences in affected individuals. It may also be informative regarding how sex chromosomes contribute to typical sexual differentiation. Studies of 47,XXY males make up the bulk of the current literature of neuroimaging studies in individuals with supernumerary sex chromosomes, with a few small studies or case reports of the other SCAs. Findings in 47,XXY males typically include decreased gray and white matter volumes, with most pronounced effects in the frontal and temporal lobes. Functional studies have shown evidence of decreased lateralization. Although the hypogonadism typically found in 47,XXY males may contribute to the decreased brain volume, the observation that 47,XXX females also show decreased brain volume in the presence of normal pubertal maturation suggests a possible direct dosage effect of X chromosome genes. Additional X chromosomes, such as in 49,XXXXY males, are associated with more markedly decreased brain volume and increased incidence of white matter hyperintensities. The limited data regarding effects of having two Y chromosomes (47,XYY) do not find significant differences in brain volume, although there are some reports of increased head size. (Contains 1 table and 1 figure.)

Published
2009
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27. Differential effect of disease-associated ST8SIA2 haplotype on cerebral white matter diffusion properties in schizophrenia and healthy controls

Author

Fullerton, Janice M., Klauser, Paul, Lenroot, Rhoshel K., Shaw, Alex D., Overs, Bronwyn, Heath, Anna, Cairns, Murray J., Atkins, Joshua, Scott, Rodney, The Australian Schizophrenia Research Bank, Schofield, Peter R., Weickert, Cyndi Shannon, Pantelis, Christos, Fornito, Alex, Whitford, Thomas J., Weickert, Thomas W., and Zalesky, Andrew

Published
2018
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28. Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder.

Author

de Zwarte, Sonja MC, de Zwarte, Sonja MC, Brouwer, Rachel M, Agartz, Ingrid, Alda, Martin, Alonso-Lana, Silvia, Bearden, Carrie E, Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth EL, Cahn, Wiepke, Canales-Rodríguez, Erick J, Cannon, Dara M, Cannon, Tyrone D, Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Del Mar Bonnin, Caterina, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E, Eker, Mehmet Cagdas, Erk, Susanne, Fatjó-Vilas, Mar, Fears, Scott C, Foley, Sonya F, Frangou, Sophia, Fullerton, Janice M, Glahn, David C, Goghari, Vina M, Goikolea, Jose M, Goldman, Aaron L, Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L, Heinz, Andreas, Hidiroglu Ongun, Ceren, Hillegers, Manon HJ, Houenou, Josselin, Hulshoff Pol, Hilleke E, Hultman, Christina M, Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G, Kane, Fergus, Kempton, Matthew J, Koenis, Marinka MG, Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M, Lenroot, Rhoshel K, Marcelis, Machteld, Mattay, Venkata S, McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B, Moreno, Dolores, Murray, Robin M, Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A, van Os, Jim, Overs, Bronwyn J, Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M, Piguet, Camille, Pomarol-Clotet, Edith, Radua, Joaquim, Ramsay, Ian S, Richter, Anja, Roberts, Gloria, Salvador, Raymond, Saricicek Aydogan, Aybala, Sarró, Salvador, Schofield, Peter R, Simsek, Esma M, Simsek, Fatma, Soares, Jair C, Sponheim, Scott R, Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R, Whalley, Heather C, Wu, Mon-Ju, Yalin, Nefize, Andreassen, Ole A, Ching, Christopher RK, Thomopoulos, Sophia I, van Erp, Theo GM, Jahanshad, Neda, Thompson, Paul M, de Zwarte, Sonja MC, de Zwarte, Sonja MC, Brouwer, Rachel M, Agartz, Ingrid, Alda, Martin, Alonso-Lana, Silvia, Bearden, Carrie E, Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth EL, Cahn, Wiepke, Canales-Rodríguez, Erick J, Cannon, Dara M, Cannon, Tyrone D, Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Del Mar Bonnin, Caterina, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E, Eker, Mehmet Cagdas, Erk, Susanne, Fatjó-Vilas, Mar, Fears, Scott C, Foley, Sonya F, Frangou, Sophia, Fullerton, Janice M, Glahn, David C, Goghari, Vina M, Goikolea, Jose M, Goldman, Aaron L, Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L, Heinz, Andreas, Hidiroglu Ongun, Ceren, Hillegers, Manon HJ, Houenou, Josselin, Hulshoff Pol, Hilleke E, Hultman, Christina M, Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G, Kane, Fergus, Kempton, Matthew J, Koenis, Marinka MG, Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M, Lenroot, Rhoshel K, Marcelis, Machteld, Mattay, Venkata S, McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B, Moreno, Dolores, Murray, Robin M, Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A, van Os, Jim, Overs, Bronwyn J, Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M, Piguet, Camille, Pomarol-Clotet, Edith, Radua, Joaquim, Ramsay, Ian S, Richter, Anja, Roberts, Gloria, Salvador, Raymond, Saricicek Aydogan, Aybala, Sarró, Salvador, Schofield, Peter R, Simsek, Esma M, Simsek, Fatma, Soares, Jair C, Sponheim, Scott R, Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R, Whalley, Heather C, Wu, Mon-Ju, Yalin, Nefize, Andreassen, Ole A, Ching, Christopher RK, Thomopoulos, Sophia I, van Erp, Theo GM, Jahanshad, Neda, and Thompson, Paul M

Abstract

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

Published
2022

29. Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder

Author

de Zwarte, Sonja M. C., Brouwer, Rachel M., Agartz, Ingrid, Alda, Martin, Alonso-Lana, Silvia, Bearden, Carrie E., Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth E. L., Cahn, Wiepke, Canales-Rodríguez, Erick J., Cannon, Dara M., Cannon, Tyrone D., Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Del Mar Bonnin, Caterina, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E., Eker, Mehmet Cagdas, Erk, Susanne, Fatjó-Vilas, Mar, Fears, Scott C., Foley, Sonya F., Frangou, Sophia, Fullerton, Janice M., Glahn, David C., Goghari, Vina M., Goikolea, Jose M., Goldman, Aaron L., Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L., Heinz, Andreas, Hidiroglu Ongun, Ceren, Hillegers, Manon H.J., Houenou, Josselin, Hulshoff Pol, Hilleke E., Hultman, Christina M., Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G., Kane, Fergus, Kempton, Matthew J., Koenis, Marinka M. G., Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M., Lenroot, Rhoshel K., Marcelis, Machteld, Mattay, Venkata S., McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B., Moreno, Dolores, Murray, Robin M., Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A., van Os, Jim, Overs, Bronwyn J., Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M., Piguet, Camille, Pomarol-Clotet, Edith, Radua, Joaquim, Ramsay, Ian S., Richter, Anja, Roberts, Gloria, Salvador, Raymond, Saricicek Aydogan, Aybala, Sarró, Salvador, Schofield, Peter R., Simsek, Esma M., Simsek, Fatma, Soares, Jair C., Sponheim, Scott R., Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R., Whalley, Heather C., Wu, Mon-Ju, Yalin, Nefize, Andreassen, Ole A., Ching, Christopher R. K., Thomopoulos, Sophia I., van Erp, Theo G. M., Jahanshad, Neda, Thompson, Paul M., Kahn, René S., van Haren, Neeltje E. M., de Zwarte, Sonja M. C., Brouwer, Rachel M., Agartz, Ingrid, Alda, Martin, Alonso-Lana, Silvia, Bearden, Carrie E., Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth E. L., Cahn, Wiepke, Canales-Rodríguez, Erick J., Cannon, Dara M., Cannon, Tyrone D., Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Del Mar Bonnin, Caterina, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E., Eker, Mehmet Cagdas, Erk, Susanne, Fatjó-Vilas, Mar, Fears, Scott C., Foley, Sonya F., Frangou, Sophia, Fullerton, Janice M., Glahn, David C., Goghari, Vina M., Goikolea, Jose M., Goldman, Aaron L., Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L., Heinz, Andreas, Hidiroglu Ongun, Ceren, Hillegers, Manon H.J., Houenou, Josselin, Hulshoff Pol, Hilleke E., Hultman, Christina M., Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G., Kane, Fergus, Kempton, Matthew J., Koenis, Marinka M. G., Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M., Lenroot, Rhoshel K., Marcelis, Machteld, Mattay, Venkata S., McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B., Moreno, Dolores, Murray, Robin M., Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A., van Os, Jim, Overs, Bronwyn J., Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M., Piguet, Camille, Pomarol-Clotet, Edith, Radua, Joaquim, Ramsay, Ian S., Richter, Anja, Roberts, Gloria, Salvador, Raymond, Saricicek Aydogan, Aybala, Sarró, Salvador, Schofield, Peter R., Simsek, Esma M., Simsek, Fatma, Soares, Jair C., Sponheim, Scott R., Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R., Whalley, Heather C., Wu, Mon-Ju, Yalin, Nefize, Andreassen, Ole A., Ching, Christopher R. K., Thomopoulos, Sophia I., van Erp, Theo G. M., Jahanshad, Neda, Thompson, Paul M., Kahn, René S., and van Haren, Neeltje E. M.

Abstract

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

Published
2022
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30. Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder

Author

de Zwarte, Sonja M.C., Brouwer, Rachel M., Agartz, Ingrid, Alda, Martin, Alonso-Lana, Silvia, Bearden, Carrie E., Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth E.L., Cahn, Wiepke, Canales-Rodríguez, Erick J., Cannon, Dara M., Cannon, Tyrone D., Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, del Mar Bonnin, Caterina, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E., Eker, Mehmet Cagdas, Erk, Susanne, Fatjó-Vilas, Mar, Fears, Scott C., Foley, Sonya F., Frangou, Sophia, Fullerton, Janice M., Glahn, David C., Goghari, Vina M., Goikolea, Jose M., Goldman, Aaron L., Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L., Heinz, Andreas, Hidiroglu Ongun, Ceren, Hillegers, Manon H.J., Houenou, Josselin, Hulshoff Pol, Hilleke E., Hultman, Christina M., Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G., Kane, Fergus, Kempton, Matthew J., Koenis, Marinka M.G., Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M., Lenroot, Rhoshel K., Marcelis, Machteld, Mattay, Venkata S., McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B., Moreno, Dolores, Murray, Robin M., Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A., van Os, Jim, Overs, Bronwyn J., Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M., Piguet, Camille, Pomarol-Clotet, Edith, Radua, Joaquim, Ramsay, Ian S., Richter, Anja, Roberts, Gloria, Salvador, Raymond, Saricicek Aydogan, Aybala, Sarró, Salvador, Schofield, Peter R., Simsek, Esma M., Simsek, Fatma, Soares, Jair C., Sponheim, Scott R., Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R., Whalley, Heather C., Wu, Mon Ju, Yalin, Nefize, Andreassen, Ole A., Ching, Christopher R.K., Thomopoulos, Sophia I., van Erp, Theo G.M., Jahanshad, Neda, Thompson, Paul M., Kahn, René S., van Haren, Neeltje E.M., de Zwarte, Sonja M.C., Brouwer, Rachel M., Agartz, Ingrid, Alda, Martin, Alonso-Lana, Silvia, Bearden, Carrie E., Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth E.L., Cahn, Wiepke, Canales-Rodríguez, Erick J., Cannon, Dara M., Cannon, Tyrone D., Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, del Mar Bonnin, Caterina, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E., Eker, Mehmet Cagdas, Erk, Susanne, Fatjó-Vilas, Mar, Fears, Scott C., Foley, Sonya F., Frangou, Sophia, Fullerton, Janice M., Glahn, David C., Goghari, Vina M., Goikolea, Jose M., Goldman, Aaron L., Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L., Heinz, Andreas, Hidiroglu Ongun, Ceren, Hillegers, Manon H.J., Houenou, Josselin, Hulshoff Pol, Hilleke E., Hultman, Christina M., Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G., Kane, Fergus, Kempton, Matthew J., Koenis, Marinka M.G., Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M., Lenroot, Rhoshel K., Marcelis, Machteld, Mattay, Venkata S., McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B., Moreno, Dolores, Murray, Robin M., Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A., van Os, Jim, Overs, Bronwyn J., Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M., Piguet, Camille, Pomarol-Clotet, Edith, Radua, Joaquim, Ramsay, Ian S., Richter, Anja, Roberts, Gloria, Salvador, Raymond, Saricicek Aydogan, Aybala, Sarró, Salvador, Schofield, Peter R., Simsek, Esma M., Simsek, Fatma, Soares, Jair C., Sponheim, Scott R., Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R., Whalley, Heather C., Wu, Mon Ju, Yalin, Nefize, Andreassen, Ole A., Ching, Christopher R.K., Thomopoulos, Sophia I., van Erp, Theo G.M., Jahanshad, Neda, Thompson, Paul M., Kahn, René S., and van Haren, Neeltje E.M.

Abstract

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = −0.42, p = 3 × 10−5), with weak evidence of IQ reductions among BD-FDRs (d = −0.23, p =.045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

Published
2022

39. Anatomical brain magnetic resonance imaging of typically developing children and adolescents

Author

Giedd, Jay N., Lalonde, Francois M., Celano, Mark J., White, Samantha L., Wallace, Gregory L., Lee, Nancy R., and Lenroot, Rhoshel K.

Subjects
Magnetic resonance imaging -- Methods, Brain -- Observations, Brain -- Physiological aspects, Neuroanatomy -- Observations, Adolescence -- Physiological aspects, Family and marriage, Psychology and mental health
Abstract

Methodological issues relevant to magnetic resonance imaging studies of brain anatomy are discussed along with the findings on the neuroanatomic changes during childhood and adolescence. The development of the brain is also discussed.

Published
2009

48. Intelligence, educational attainment, and brain structure in those at familial high‐risk for schizophrenia or bipolar disorder

Author

Zwarte, Sonja M. C., primary, Brouwer, Rachel M., additional, Agartz, Ingrid, additional, Alda, Martin, additional, Alonso‐Lana, Silvia, additional, Bearden, Carrie E., additional, Bertolino, Alessandro, additional, Bonvino, Aurora, additional, Bramon, Elvira, additional, Buimer, Elizabeth E. L., additional, Cahn, Wiepke, additional, Canales‐Rodríguez, Erick J., additional, Cannon, Dara M., additional, Cannon, Tyrone D., additional, Caseras, Xavier, additional, Castro‐Fornieles, Josefina, additional, Chen, Qiang, additional, Chung, Yoonho, additional, De la Serna, Elena, additional, Mar Bonnin, Caterina, additional, Demro, Caroline, additional, Di Giorgio, Annabella, additional, Doucet, Gaelle E., additional, Eker, Mehmet Cagdas, additional, Erk, Susanne, additional, Fatjó‐Vilas, Mar, additional, Fears, Scott C., additional, Foley, Sonya F., additional, Frangou, Sophia, additional, Fullerton, Janice M., additional, Glahn, David C., additional, Goghari, Vina M., additional, Goikolea, Jose M., additional, Goldman, Aaron L., additional, Gonul, Ali Saffet, additional, Gruber, Oliver, additional, Hajek, Tomas, additional, Hawkins, Emma L., additional, Heinz, Andreas, additional, Hidiroglu Ongun, Ceren, additional, Hillegers, Manon H. J., additional, Houenou, Josselin, additional, Hulshoff Pol, Hilleke E., additional, Hultman, Christina M., additional, Ingvar, Martin, additional, Johansson, Viktoria, additional, Jönsson, Erik G., additional, Kane, Fergus, additional, Kempton, Matthew J., additional, Koenis, Marinka M. G., additional, Kopecek, Miloslav, additional, Krämer, Bernd, additional, Lawrie, Stephen M., additional, Lenroot, Rhoshel K., additional, Marcelis, Machteld, additional, Mattay, Venkata S., additional, McDonald, Colm, additional, Meyer‐Lindenberg, Andreas, additional, Michielse, Stijn, additional, Mitchell, Philip B., additional, Moreno, Dolores, additional, Murray, Robin M., additional, Mwangi, Benson, additional, Nabulsi, Leila, additional, Newport, Jason, additional, Olman, Cheryl A., additional, Os, Jim, additional, Overs, Bronwyn J., additional, Ozerdem, Aysegul, additional, Pergola, Giulio, additional, Picchioni, Marco M., additional, Piguet, Camille, additional, Pomarol‐Clotet, Edith, additional, Radua, Joaquim, additional, Ramsay, Ian S., additional, Richter, Anja, additional, Roberts, Gloria, additional, Salvador, Raymond, additional, Saricicek Aydogan, Aybala, additional, Sarró, Salvador, additional, Schofield, Peter R., additional, Simsek, Esma M., additional, Simsek, Fatma, additional, Soares, Jair C., additional, Sponheim, Scott R., additional, Sugranyes, Gisela, additional, Toulopoulou, Timothea, additional, Tronchin, Giulia, additional, Vieta, Eduard, additional, Walter, Henrik, additional, Weinberger, Daniel R., additional, Whalley, Heather C., additional, Wu, Mon‐Ju, additional, Yalin, Nefize, additional, Andreassen, Ole A., additional, Ching, Christopher R. K., additional, Thomopoulos, Sophia I., additional, Erp, Theo G. M., additional, Jahanshad, Neda, additional, Thompson, Paul M., additional, Kahn, René S., additional, and Haren, Neeltje E. M., additional

Published
2020
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50. Cognitive reserve attenuates age-related cognitive decline in the context of putatively accelerated brain ageing in schizophrenia-spectrum disorders

Author

Van Rheenen, Tamsyn E., Cropley, Vanessa, Fagerlund, Birgitte, Wannan, Cassandra, Bruggemann, Jason, Lenroot, Rhoshel K., Sundram, Suresh, Weickert, Cynthia Shannon, Weickert, Thomas W., Zalesky, Andrew, Bousman, Chad A., Pantelis, Christos, Van Rheenen, Tamsyn E., Cropley, Vanessa, Fagerlund, Birgitte, Wannan, Cassandra, Bruggemann, Jason, Lenroot, Rhoshel K., Sundram, Suresh, Weickert, Cynthia Shannon, Weickert, Thomas W., Zalesky, Andrew, Bousman, Chad A., and Pantelis, Christos

Abstract

BackgroundIn schizophrenia, relative stability in the magnitude of cognitive deficits across age and illness duration is inconsistent with the evidence of accelerated deterioration in brain regions known to support these functions. These discrepant brain-cognition outcomes may be explained by variability in cognitive reserve (CR), which in neurological disorders has been shown to buffer against brain pathology and minimize its impact on cognitive or clinical indicators of illness.MethodsAge-related change in fluid reasoning, working memory and frontal brain volume, area and thickness were mapped using regression analysis in 214 individuals with schizophrenia or schizoaffective disorder and 168 healthy controls. In patients, these changes were modelled as a function of CR.ResultsPatients showed exaggerated age-related decline in brain structure, but not fluid reasoning compared to controls. In the patient group, no moderation of age-related brain structural change by CR was evident. However, age-related cognitive change was moderated by CR, such that only patients with low CR showed evidence of exaggerated fluid reasoning decline that paralleled the exaggerated age-related deterioration of underpinning brain structures seen in all patients.ConclusionsIn schizophrenia-spectrum illness, CR may negate ageing effects on fluid reasoning by buffering against pathologically exaggerated structural brain deterioration through some form of compensation. CR may represent an important modifier that could explain inconsistencies in brain structure - cognition outcomes in the extant literature.

Published
2020

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