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1. What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group.

Author

Ching CRK, Hibar DP, Gurholt TP, Nunes A, Thomopoulos SI, Abé C, Agartz I, Brouwer RM, Cannon DM, de Zwarte SMC, Eyler LT, Favre P, Hajek T, Haukvik UK, Houenou J, Landén M, Lett TA, McDonald C, Nabulsi L, Patel Y, Pauling ME, Paus T, Radua J, Soeiro-de-Souza MG, Tronchin G, van Haren NEM, Vieta E, Walter H, Zeng LL, Alda M, Almeida J, Alnaes D, Alonso-Lana S, Altimus C, Bauer M, Baune BT, Bearden CE, Bellani M, Benedetti F, Berk M, Bilderbeck AC, Blumberg HP, Bøen E, Bollettini I, Del Mar Bonnin C, Brambilla P, Canales-Rodríguez EJ, Caseras X, Dandash O, Dannlowski U, Delvecchio G, Díaz-Zuluaga AM, Dima D, Duchesnay É, Elvsåshagen T, Fears SC, Frangou S, Fullerton JM, Glahn DC, Goikolea JM, Green MJ, Grotegerd D, Gruber O, Haarman BCM, Henry C, Howells FM, Ives-Deliperi V, Jansen A, Kircher TTJ, Knöchel C, Kramer B, Lafer B, López-Jaramillo C, Machado-Vieira R, MacIntosh BJ, Melloni EMT, Mitchell PB, Nenadic I, Nery F, Nugent AC, Oertel V, Ophoff RA, Ota M, Overs BJ, Pham DL, Phillips ML, Pineda-Zapata JA, Poletti S, Polosan M, Pomarol-Clotet E, Pouchon A, Quidé Y, Rive MM, Roberts G, Ruhe HG, Salvador R, Sarró S, Satterthwaite TD, Schene AH, Sim K, Soares JC, Stäblein M, Stein DJ, Tamnes CK, Thomaidis GV, Upegui CV, Veltman DJ, Wessa M, Westlye LT, Whalley HC, Wolf DH, Wu MJ, Yatham LN, Zarate CA, Thompson PM, and Andreassen OA

Subjects
Humans, Meta-Analysis as Topic, Multicenter Studies as Topic, Bipolar Disorder diagnostic imaging, Bipolar Disorder pathology, Cerebral Cortex diagnostic imaging, Cerebral Cortex pathology, Magnetic Resonance Imaging, Neuroimaging
Abstract

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2022
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2. 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 UK, Gurholt TP, Nerland S, Elvsåshagen T, Akudjedu TN, Alda M, Alnaes D, Alonso-Lana S, Bauer J, Baune BT, Benedetti F, Berk M, Bettella F, Bøen E, Bonnín CM, Brambilla P, Canales-Rodríguez EJ, Cannon DM, Caseras X, Dandash O, Dannlowski U, Delvecchio G, Díaz-Zuluaga AM, van Erp TGM, Fatjó-Vilas M, Foley SF, Förster K, Fullerton JM, Goikolea JM, Grotegerd D, Gruber O, Haarman BCM, Haatveit B, Hajek T, Hallahan B, Harris M, Hawkins EL, Howells FM, Hülsmann C, Jahanshad N, Jørgensen KN, Kircher T, Krämer B, Krug A, Kuplicki R, Lagerberg TV, Lancaster TM, Lenroot RK, Lonning V, López-Jaramillo C, Malt UF, McDonald C, McIntosh AM, McPhilemy G, van der Meer D, Melle I, Melloni EMT, Mitchell PB, Nabulsi L, Nenadić I, Oertel V, Oldani L, Opel N, Otaduy MCG, Overs BJ, Pineda-Zapata JA, Pomarol-Clotet E, Radua J, Rauer L, Redlich R, Repple J, Rive MM, Roberts G, Ruhe HG, Salminen LE, Salvador R, Sarró S, Savitz J, Schene AH, Sim K, Soeiro-de-Souza MG, Stäblein M, Stein DJ, Stein F, Tamnes CK, Temmingh HS, Thomopoulos SI, Veltman DJ, Vieta E, Waltemate L, Westlye LT, Whalley HC, Sämann PG, Thompson PM, Ching CRK, Andreassen OA, and Agartz I

Subjects
Bipolar Disorder drug therapy, Genetics, Hippocampus drug effects, Humans, Bipolar Disorder diagnostic imaging, Bipolar Disorder pathology, Hippocampus diagnostic imaging, Hippocampus pathology, Magnetic Resonance Imaging, Neuroimaging
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., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2022
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3. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Author

Dima D, Modabbernia A, Papachristou E, Doucet GE, Agartz I, Aghajani M, Akudjedu TN, Albajes-Eizagirre A, Alnaes D, Alpert KI, Andersson M, Andreasen NC, Andreassen OA, Asherson P, Banaschewski T, Bargallo N, Baumeister S, Baur-Streubel R, Bertolino A, Bonvino A, Boomsma DI, Borgwardt S, Bourque J, Brandeis D, Breier A, Brodaty H, Brouwer RM, Buitelaar JK, Busatto GF, Buckner RL, Calhoun V, Canales-Rodríguez EJ, Cannon DM, Caseras X, Castellanos FX, Cervenka S, Chaim-Avancini TM, Ching CRK, Chubar V, Clark VP, Conrod P, Conzelmann A, Crespo-Facorro B, Crivello F, Crone EA, Dannlowski U, Dale AM, Davey C, de Geus EJC, de Haan L, de Zubicaray GI, den Braber A, Dickie EW, Di Giorgio A, Doan NT, Dørum ES, Ehrlich S, Erk S, Espeseth T, Fatouros-Bergman H, Fisher SE, Fouche JP, Franke B, Frodl T, Fuentes-Claramonte P, Glahn DC, Gotlib IH, Grabe HJ, Grimm O, Groenewold NA, Grotegerd D, Gruber O, Gruner P, Gur RE, Gur RC, Hahn T, Harrison BJ, Hartman CA, Hatton SN, Heinz A, Heslenfeld DJ, Hibar DP, Hickie IB, Ho BC, Hoekstra PJ, Hohmann S, Holmes AJ, Hoogman M, Hosten N, Howells FM, Hulshoff Pol HE, Huyser C, Jahanshad N, James A, Jernigan TL, Jiang J, Jönsson EG, Joska JA, Kahn R, Kalnin A, Kanai R, Klein M, Klyushnik TP, Koenders L, Koops S, Krämer B, Kuntsi J, Lagopoulos J, Lázaro L, Lebedeva I, Lee WH, Lesch KP, Lochner C, Machielsen MWJ, Maingault S, Martin NG, Martínez-Zalacaín I, Mataix-Cols D, Mazoyer B, McDonald C, McDonald BC, McIntosh AM, McMahon KL, McPhilemy G, Meinert S, Menchón JM, Medland SE, Meyer-Lindenberg A, Naaijen J, Najt P, Nakao T, Nordvik JE, Nyberg L, Oosterlaan J, de la Foz VO, Paloyelis Y, Pauli P, Pergola G, Pomarol-Clotet E, Portella MJ, Potkin SG, Radua J, Reif A, Rinker DA, Roffman JL, Rosa PGP, Sacchet MD, Sachdev PS, Salvador R, Sánchez-Juan P, Sarró S, Satterthwaite TD, Saykin AJ, Serpa MH, Schmaal L, Schnell K, Schumann G, Sim K, Smoller JW, Sommer I, Soriano-Mas C, Stein DJ, Strike LT, Swagerman SC, Tamnes CK, Temmingh HS, Thomopoulos SI, Tomyshev AS, Tordesillas-Gutiérrez D, Trollor JN, Turner JA, Uhlmann A, van den Heuvel OA, van den Meer D, van der Wee NJA, van Haren NEM, Van't Ent D, van Erp TGM, Veer IM, Veltman DJ, Voineskos A, Völzke H, Walter H, Walton E, Wang L, Wang Y, Wassink TH, Weber B, Wen W, West JD, Westlye LT, Whalley H, Wierenga LM, Williams SCR, Wittfeld K, Wolf DH, Worker A, Wright MJ, Yang K, Yoncheva Y, Zanetti MV, Ziegler GC, Thompson PM, and Frangou S

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Young Adult, Amygdala anatomy & histology, Amygdala diagnostic imaging, Corpus Striatum anatomy & histology, Corpus Striatum diagnostic imaging, Hippocampus anatomy & histology, Hippocampus diagnostic imaging, Human Development physiology, Neuroimaging, Thalamus anatomy & histology, Thalamus diagnostic imaging
Abstract

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2022
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4. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Author

Frangou S, Modabbernia A, Williams SCR, Papachristou E, Doucet GE, Agartz I, Aghajani M, Akudjedu TN, Albajes-Eizagirre A, Alnaes D, Alpert KI, Andersson M, Andreasen NC, Andreassen OA, Asherson P, Banaschewski T, Bargallo N, Baumeister S, Baur-Streubel R, Bertolino A, Bonvino A, Boomsma DI, Borgwardt S, Bourque J, Brandeis D, Breier A, Brodaty H, Brouwer RM, Buitelaar JK, Busatto GF, Buckner RL, Calhoun V, Canales-Rodríguez EJ, Cannon DM, Caseras X, Castellanos FX, Cervenka S, Chaim-Avancini TM, Ching CRK, Chubar V, Clark VP, Conrod P, Conzelmann A, Crespo-Facorro B, Crivello F, Crone EA, Dale AM, Dannlowski U, Davey C, de Geus EJC, de Haan L, de Zubicaray GI, den Braber A, Dickie EW, Di Giorgio A, Doan NT, Dørum ES, Ehrlich S, Erk S, Espeseth T, Fatouros-Bergman H, Fisher SE, Fouche JP, Franke B, Frodl T, Fuentes-Claramonte P, Glahn DC, Gotlib IH, Grabe HJ, Grimm O, Groenewold NA, Grotegerd D, Gruber O, Gruner P, Gur RE, Gur RC, Hahn T, Harrison BJ, Hartman CA, Hatton SN, Heinz A, Heslenfeld DJ, Hibar DP, Hickie IB, Ho BC, Hoekstra PJ, Hohmann S, Holmes AJ, Hoogman M, Hosten N, Howells FM, Hulshoff Pol HE, Huyser C, Jahanshad N, James A, Jernigan TL, Jiang J, Jönsson EG, Joska JA, Kahn R, Kalnin A, Kanai R, Klein M, Klyushnik TP, Koenders L, Koops S, Krämer B, Kuntsi J, Lagopoulos J, Lázaro L, Lebedeva I, Lee WH, Lesch KP, Lochner C, Machielsen MWJ, Maingault S, Martin NG, Martínez-Zalacaín I, Mataix-Cols D, Mazoyer B, McDonald C, McDonald BC, McIntosh AM, McMahon KL, McPhilemy G, Meinert S, Menchón JM, Medland SE, Meyer-Lindenberg A, Naaijen J, Najt P, Nakao T, Nordvik JE, Nyberg L, Oosterlaan J, de la Foz VO, Paloyelis Y, Pauli P, Pergola G, Pomarol-Clotet E, Portella MJ, Potkin SG, Radua J, Reif A, Rinker DA, Roffman JL, Rosa PGP, Sacchet MD, Sachdev PS, Salvador R, Sánchez-Juan P, Sarró S, Satterthwaite TD, Saykin AJ, Serpa MH, Schmaal L, Schnell K, Schumann G, Sim K, Smoller JW, Sommer I, Soriano-Mas C, Stein DJ, Strike LT, Swagerman SC, Tamnes CK, Temmingh HS, Thomopoulos SI, Tomyshev AS, Tordesillas-Gutiérrez D, Trollor JN, Turner JA, Uhlmann A, van den Heuvel OA, van den Meer D, van der Wee NJA, van Haren NEM, van 't Ent D, van Erp TGM, Veer IM, Veltman DJ, Voineskos A, Völzke H, Walter H, Walton E, Wang L, Wang Y, Wassink TH, Weber B, Wen W, West JD, Westlye LT, Whalley H, Wierenga LM, Wittfeld K, Wolf DH, Worker A, Wright MJ, Yang K, Yoncheva Y, Zanetti MV, Ziegler GC, Thompson PM, and Dima D

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Young Adult, Cross-Sectional Studies, Cerebral Cortex anatomy & histology, Cerebral Cortex diagnostic imaging, Human Development physiology, Neuroimaging
Abstract

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2022
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5. Greater male than female variability in regional brain structure across the lifespan.

Author

Wierenga LM, Doucet GE, Dima D, Agartz I, Aghajani M, Akudjedu TN, Albajes-Eizagirre A, Alnaes D, Alpert KI, Andreassen OA, Anticevic A, Asherson P, Banaschewski T, Bargallo N, Baumeister S, Baur-Streubel R, Bertolino A, Bonvino A, Boomsma DI, Borgwardt S, Bourque J, den Braber A, Brandeis D, Breier A, Brodaty H, Brouwer RM, Buitelaar JK, Busatto GF, Calhoun VD, Canales-Rodríguez EJ, Cannon DM, Caseras X, Castellanos FX, Chaim-Avancini TM, Ching CR, Clark VP, Conrod PJ, Conzelmann A, Crivello F, Davey CG, Dickie EW, Ehrlich S, Van't Ent D, Fisher SE, Fouche JP, Franke B, Fuentes-Claramonte P, de Geus EJ, Di Giorgio A, Glahn DC, Gotlib IH, Grabe HJ, Gruber O, Gruner P, Gur RE, Gur RC, Gurholt TP, de Haan L, Haatveit B, Harrison BJ, Hartman CA, Hatton SN, Heslenfeld DJ, van den Heuvel OA, Hickie IB, Hoekstra PJ, Hohmann S, Holmes AJ, Hoogman M, Hosten N, Howells FM, Hulshoff Pol HE, Huyser C, Jahanshad N, James AC, Jiang J, Jönsson EG, Joska JA, Kalnin AJ, Klein M, Koenders L, Kolskår KK, Krämer B, Kuntsi J, Lagopoulos J, Lazaro L, Lebedeva IS, Lee PH, Lochner C, Machielsen MW, Maingault S, Martin NG, Martínez-Zalacaín I, Mataix-Cols D, Mazoyer B, McDonald BC, McDonald C, McIntosh AM, McMahon KL, McPhilemy G, van der Meer D, Menchón JM, Naaijen J, Nyberg L, Oosterlaan J, Paloyelis Y, Pauli P, Pergola G, Pomarol-Clotet E, Portella MJ, Radua J, Reif A, Richard G, Roffman JL, Rosa PG, Sacchet MD, Sachdev PS, Salvador R, Sarró S, Satterthwaite TD, Saykin AJ, Serpa MH, Sim K, Simmons A, Smoller JW, Sommer IE, Soriano-Mas C, Stein DJ, Strike LT, Szeszko PR, Temmingh HS, Thomopoulos SI, Tomyshev AS, Trollor JN, Uhlmann A, Veer IM, Veltman DJ, Voineskos A, Völzke H, Walter H, Wang L, Wang Y, Weber B, Wen W, West JD, Westlye LT, Whalley HC, Williams SC, Wittfeld K, Wolf DH, Wright MJ, Yoncheva YN, Zanetti MV, Ziegler GC, de Zubicaray GI, Thompson PM, Crone EA, Frangou S, and Tamnes CK

Subjects
Female, Humans, Male, Brain Cortical Thickness, Cerebral Cortex anatomy & histology, Cerebral Cortex diagnostic imaging, Biological Variation, Population physiology, Brain anatomy & histology, Brain diagnostic imaging, Human Development physiology, Magnetic Resonance Imaging, Neuroimaging, Sex Characteristics
Abstract

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

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

Author

de Zwarte SMC, Brouwer RM, Agartz I, Alda M, Alonso-Lana S, Bearden CE, Bertolino A, Bonvino A, Bramon E, Buimer EEL, Cahn W, Canales-Rodríguez EJ, Cannon DM, Cannon TD, Caseras X, Castro-Fornieles J, Chen Q, Chung Y, De la Serna E, Del Mar Bonnin C, Demro C, Di Giorgio A, Doucet GE, Eker MC, Erk S, Fatjó-Vilas M, Fears SC, Foley SF, Frangou S, Fullerton JM, Glahn DC, Goghari VM, Goikolea JM, Goldman AL, Gonul AS, Gruber O, Hajek T, Hawkins EL, Heinz A, Hidiroglu Ongun C, Hillegers MHJ, Houenou J, Hulshoff Pol HE, Hultman CM, Ingvar M, Johansson V, Jönsson EG, Kane F, Kempton MJ, Koenis MMG, Kopecek M, Krämer B, Lawrie SM, Lenroot RK, Marcelis M, Mattay VS, McDonald C, Meyer-Lindenberg A, Michielse S, Mitchell PB, Moreno D, Murray RM, Mwangi B, Nabulsi L, Newport J, Olman CA, van Os J, Overs BJ, Ozerdem A, Pergola G, Picchioni MM, Piguet C, Pomarol-Clotet E, Radua J, Ramsay IS, Richter A, Roberts G, Salvador R, Saricicek Aydogan A, Sarró S, Schofield PR, Simsek EM, Simsek F, Soares JC, Sponheim SR, Sugranyes G, Toulopoulou T, Tronchin G, Vieta E, Walter H, Weinberger DR, Whalley HC, Wu MJ, Yalin N, Andreassen OA, Ching CRK, Thomopoulos SI, van Erp TGM, Jahanshad N, Thompson PM, Kahn RS, and van Haren NEM

Subjects
Bipolar Disorder complications, Bipolar Disorder diagnostic imaging, Cognitive Dysfunction diagnostic imaging, Family, Humans, Magnetic Resonance Imaging, Schizophrenia complications, Schizophrenia diagnostic imaging, Schizophrenia etiology, Bipolar Disorder pathology, Cognitive Dysfunction pathology, Educational Status, Genetic Predisposition to Disease, Intelligence physiology, Neuroimaging, Schizophrenia pathology
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., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2022
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7. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data.

Author

Thompson PM, Stein JL, Medland SE, Hibar DP, Vasquez AA, Renteria ME, Toro R, Jahanshad N, Schumann G, Franke B, Wright MJ, Martin NG, Agartz I, Alda M, Alhusaini S, Almasy L, Almeida J, Alpert K, Andreasen NC, Andreassen OA, Apostolova LG, Appel K, Armstrong NJ, Aribisala B, Bastin ME, Bauer M, Bearden CE, Bergmann O, Binder EB, Blangero J, Bockholt HJ, Bøen E, Bois C, Boomsma DI, Booth T, Bowman IJ, Bralten J, Brouwer RM, Brunner HG, Brohawn DG, Buckner RL, Buitelaar J, Bulayeva K, Bustillo JR, Calhoun VD, Cannon DM, Cantor RM, Carless MA, Caseras X, Cavalleri GL, Chakravarty MM, Chang KD, Ching CR, Christoforou A, Cichon S, Clark VP, Conrod P, Coppola G, Crespo-Facorro B, Curran JE, Czisch M, Deary IJ, de Geus EJ, den Braber A, Delvecchio G, Depondt C, de Haan L, de Zubicaray GI, Dima D, Dimitrova R, Djurovic S, Dong H, Donohoe G, Duggirala R, Dyer TD, Ehrlich S, Ekman CJ, Elvsåshagen T, Emsell L, Erk S, Espeseth T, Fagerness J, Fears S, Fedko I, Fernández G, Fisher SE, Foroud T, Fox PT, Francks C, Frangou S, Frey EM, Frodl T, Frouin V, Garavan H, Giddaluru S, Glahn DC, Godlewska B, Goldstein RZ, Gollub RL, Grabe HJ, Grimm O, Gruber O, Guadalupe T, Gur RE, Gur RC, Göring HH, Hagenaars S, Hajek T, Hall GB, Hall J, Hardy J, Hartman CA, Hass J, Hatton SN, Haukvik UK, Hegenscheid K, Heinz A, Hickie IB, Ho BC, Hoehn D, Hoekstra PJ, Hollinshead M, Holmes AJ, Homuth G, Hoogman M, Hong LE, Hosten N, Hottenga JJ, Hulshoff Pol HE, Hwang KS, Jack CR Jr, Jenkinson M, Johnston C, Jönsson EG, Kahn RS, Kasperaviciute D, Kelly S, Kim S, Kochunov P, Koenders L, Krämer B, Kwok JB, Lagopoulos J, Laje G, Landen M, Landman BA, Lauriello J, Lawrie SM, Lee PH, Le Hellard S, Lemaître H, Leonardo CD, Li CS, Liberg B, Liewald DC, Liu X, Lopez LM, Loth E, Lourdusamy A, Luciano M, Macciardi F, Machielsen MW, Macqueen GM, Malt UF, Mandl R, Manoach DS, Martinot JL, Matarin M, Mather KA, Mattheisen M, Mattingsdal M, Meyer-Lindenberg A, McDonald C, McIntosh AM, McMahon FJ, McMahon KL, Meisenzahl E, Melle I, Milaneschi Y, Mohnke S, Montgomery GW, Morris DW, Moses EK, Mueller BA, Muñoz Maniega S, Mühleisen TW, Müller-Myhsok B, Mwangi B, Nauck M, Nho K, Nichols TE, Nilsson LG, Nugent AC, Nyberg L, Olvera RL, Oosterlaan J, Ophoff RA, Pandolfo M, Papalampropoulou-Tsiridou M, Papmeyer M, Paus T, Pausova Z, Pearlson GD, Penninx BW, Peterson CP, Pfennig A, Phillips M, Pike GB, Poline JB, Potkin SG, Pütz B, Ramasamy A, Rasmussen J, Rietschel M, Rijpkema M, Risacher SL, Roffman JL, Roiz-Santiañez R, Romanczuk-Seiferth N, Rose EJ, Royle NA, Rujescu D, Ryten M, Sachdev PS, Salami A, Satterthwaite TD, Savitz J, Saykin AJ, Scanlon C, Schmaal L, Schnack HG, Schork AJ, Schulz SC, Schür R, Seidman L, Shen L, Shoemaker JM, Simmons A, Sisodiya SM, Smith C, Smoller JW, Soares JC, Sponheim SR, Sprooten E, Starr JM, Steen VM, Strakowski S, Strike L, Sussmann J, Sämann PG, Teumer A, Toga AW, Tordesillas-Gutierrez D, Trabzuni D, Trost S, Turner J, Van den Heuvel M, van der Wee NJ, van Eijk K, van Erp TG, van Haren NE, van 't Ent D, van Tol MJ, Valdés Hernández MC, Veltman DJ, Versace A, Völzke H, Walker R, Walter H, Wang L, Wardlaw JM, Weale ME, Weiner MW, Wen W, Westlye LT, Whalley HC, Whelan CD, White T, Winkler AM, Wittfeld K, Woldehawariat G, Wolf C, Zilles D, Zwiers MP, Thalamuthu A, Schofield PR, Freimer NB, Lawrence NS, and Drevets W

Subjects
Cooperative Behavior, Humans, Meta-Analysis as Topic, Brain Mapping methods, Genome-Wide Association Study methods, Neuroimaging methods
Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

Published
2014
Full Text
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8. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Author

Thompson, P.M., Stein, J.L., Medland, S.E., Hibar, D.P., Arias Vasquez, A., Renteria, M.E., Toro, R., Jahanshad, N., Schumann, G., Franke, B., Wright, M.J., Martin, N.G., Agartz, I., Alda, M., Alhusaini, S., Almasy, L., Almeida, J., Alpert, K., Andreasen, N.C., Andreassen, O.A., Apostolova, L.G., Appel, K., Armstrong, N.J., Aribisala, B., Bastin, M.E., Bauer, M., Bearden, C.E., Bergmann, O., Binder, E.B., Blangero, J., Bockholt, H.J., Boen, E., Bois, C., Boomsma, D.I., Booth, T., Bowman, I.J., Bralten, J., Brouwer, R.M., Brunner, H.G., Brohawn, D.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K., Bustillo, J.R., Calhoun, V.D., Cannon, D.M., Cantor, R.M., Carless, M.A., Caseras, X., Cavalleri, G.L., Chakravarty, M.M., Chang, K.D., Ching, C.R., Christoforou, A., Cichon, S., Clark, V.P., Conrod, P., Coppola, G., Crespo-Facorro, B., Curran, J.E., Czisch, M., Deary, I.J., Geus, E.J. de, Braber, A., Delvecchio, G., Depondt, C., Haan, L. de, Zubicaray, G.I. de, Dima, D., Dimitrova, R., Djurovic, S., Dong, H., Donohoe, G., Duggirala, R., Dyer, T.D., Ehrlich, S., Ekman, C.J., Elvsashagen, T., Emsell, L., Erk, S., Espeseth, T., Fagerness, J., Fears, S., Fedko, I., Fernandez, G.S.E., Fisher, S.E., Foroud, T., Fox, P.T., Francks, C., Frangou, S., Frey, E.M., Frodl, T., Frouin, V., Garavan, H., Giddaluru, S., Glahn, D.C., Godlewska, B., Goldstein, R.Z., Gollub, R.L., and Grabe, H.J.

Subjects
Neuroinformatics, endocrine system, Multi-site, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Neuroimaging, Medical and Health Sciences, Meta-Analysis as Topic, Clinical Research, 130 000 Cognitive Neurology & Memory, Saguenay Youth Study (SYS) Group, Genetics, Humans, 2.1 Biological and endogenous factors, GWAS, Cooperative Behavior, Aetiology, IMAGEN Consortium, Brain Mapping, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], EPIGEN Consortium, 120 000 Neuronal Coherence, Psychology and Cognitive Sciences, Neurosciences, Experimental Psychology, Alzheimer’s Disease Neuroimaging Initiative, Brain Disorders, Meta-analysis, Mental Health, Good Health and Well Being, Neurological, Schizophrenia, Biomedical Imaging, Consortium, Genome-Wide Association Study, MRI
Abstract

Contains fulltext : 127593.pdf (Publisher’s version ) (Open Access) The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. 30 p.

Published
2014

9. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Author

Pm, Thompson, Jl, Stein, Se, Medland, Dp, Hibar, Aa, Vasquez, Me, Renteria, Toro R, Jahanshad N, Schumann G, Franke B, Mj, Wright, Ng, Martin, Agartz I, Alda M, Alhusaini S, Almasy L, Almeida J, Alpert K, Nc, Andreasen, Oa, Andreassen, Lg, Apostolova, Appel K, Nj, Armstrong, Aribisala B, Me, Bastin, Bauer M, Ce, Bearden, Bergmann O, Eb, Binder, Blangero J, Hj, Bockholt, Bøen E, Bois C, Di, Boomsma, Booth T, Ij, Bowman, Bralten J, Rm, Brouwer, Hg, Brunner, Dg, Brohawn, Rl, Buckner, Buitelaar J, Bulayeva K, Jr, Bustillo, Vd, Calhoun, Dm, Cannon, Rm, Cantor, Ma, Carless, Caseras X, Gl, Cavalleri, Mm, Chakravarty, Kd, Chang, Cr, Ching, Christoforou A, Cichon S, Vp, Clark, Conrod P, Coppola G, Crespo-Facorro B, Je, Curran, Czisch M, Ij, Deary, Ej, Geus, den Braber A, Delvecchio G, Depondt C, de Haan L, Gi, Zubicaray, Dima D, Dimitrova R, Djurovic S, Dong H, Donohoe G, Duggirala R, Td, Dyer, Ehrlich S, Cj, Ekman, Elvsåshagen T, Emsell L, Erk S, Espeseth T, Fagerness J, Fears S, Fedko I, Fernández G, Se, Fisher, Foroud T, Pt, Fox, Francks C, Frangou S, Em, Frey, Frodl T, Frouin V, Garavan H, Giddaluru S, Dc, Glahn, Godlewska B, Rz, Goldstein, Rl, Gollub, Hj, Grabe, Grimm O, Gruber O, Guadalupe T, Re, Gur, Rc, Gur, Hh, Göring, Hagenaars S, Hajek T, Gb, Hall, Hall J, Hardy J, Ca, Hartman, Hass J, Sn, Hatton, Uk, Haukvik, Hegenscheid K, Heinz A, Ib, Hickie, Bc, Ho, Hoehn D, Pj, Hoekstra, Hollinshead M, Aj, Holmes, Homuth G, Martine Hoogman, Le, Hong, Hosten N, Jj, Hottenga, He, Hulshoff Pol, Ks, Hwang, Cr, Jack Jr, Jenkinson M, Johnston C, Eg, Jönsson, Rs, Kahn, Kasperaviciute D, Kelly S, Kim S, Kochunov P, Koenders L, Krämer B, Jb, Kwok, Lagopoulos J, Laje G, Landen M, Ba, Landman, Lauriello J, Sm, Lawrie, Ph, Lee, Le Hellard S, Lemaître H, Cd, Leonardo, Cs, Li, Liberg B, Dc, Liewald, Liu X, Lm, Lopez, Loth E, Lourdusamy A, Luciano M, Macciardi F, Mw, Machielsen, Gm, Macqueen, Uf, Malt, Mandl R, Ds, Manoach, Jl, Martinot, Matarin M, Ka, Mather, Mattheisen M, Mattingsdal M, Meyer-Lindenberg A, McDonald C, Am, Mcintosh, Fj, Mcmahon, Kl, Mcmahon, Meisenzahl E, Melle I, Milaneschi Y, Mohnke S, Gw, Montgomery, Dw, Morris, Ek, Moses, Ba, Mueller, Muñoz Maniega S, Tw, Mühleisen, Müller-Myhsok B, Mwangi B, Nauck M, Nho K, Te, Nichols, Lg, Nilsson, Ac, Nugent, Nyberg L, Rl, Olvera, Oosterlaan J, Ra, Ophoff, Pandolfo M, Papalampropoulou-Tsiridou M, Papmeyer M, Paus T, Pausova Z, Gd, Pearlson, Bw, Penninx, Cp, Peterson, Pfennig A, Phillips M, Gb, Pike, Jb, Poline, Sg, Potkin, Pütz B, Ramasamy A, Rasmussen J, Rietschel M, Rijpkema M, Sl, Risacher, Jl, Roffman, Roiz-Santiañez R, Romanczuk-Seiferth N, Ej, Rose, Na, Royle, Rujescu D, Ryten M, Ps, Sachdev, Salami A, Td, Satterthwaite, Savitz J, Aj, Saykin, Scanlon C, Schmaal L, Hg, Schnack, Aj, Schork, Sc, Schulz, Schür R, Seidman L, Shen L, Jm, Shoemaker, Simmons A, Sm, Sisodiya, Smith C, Jw, Smoller, Jc, Soares, Sr, Sponheim, Sprooten E, Jm, Starr, Vm, Steen, Strakowski S, Strike L, Sussmann J, Pg, Sämann, Teumer A, Aw, Toga, Tordesillas-Gutierrez D, Trabzuni D, Trost S, Turner J, Van den Heuvel M, Nj, Wee, van Eijk K, Tg, Erp, Ne, Haren, van 't Ent D, Mj, Tol, Mc, Valdés Hernández, Dj, Veltman, Versace A, Völzke H, Walker R, Walter H, Wang L, Jm, Wardlaw, Me, Weale, Mw, Weiner, Wen W, Lt, Westlye, Hc, Whalley, Cd, Whelan, White T, Am, Winkler, Wittfeld K, Woldehawariat G, Wolf C, Zilles D, Mp, Zwiers, Thalamuthu A, Pr, Schofield, Nb, Freimer, Ns, Lawrence, Drevets W, The Alzheimer’s Disease Neuroimaging Initiative, Epigen Consortium, Laboratory of Neuro Imaging [Los Angeles] (LONI), University of California [Los Angeles] (UCLA), University of California-University of California, David Geffen School of Medicine [Los Angeles], Medstar Research Institute, Keck School of Medicine [Los Angeles], University of Southern California (USC), Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Department of Psychiatry, Donders Centre for Neuroscience, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], Genetic Epidemiology Lab [Brisbane], Queensland Institute of Medical Research, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Dalhousie University [Halifax], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Department of Genetics, Southwest Foundation for Biomedical Research, Departamento de Matemática Pura, Faculdade de Ciências (UNIVERSIDADE DO PORTO), Universidade do Porto = University of Porto, Department of Psychiatry and Psychotherapy, University of Edinburgh, Center for Sepsis Control & Care, Jena University Hospital, Division Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Texas Biomedical Research Institute [San Antonio, TX], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Radboud University Medical Center [Nijmegen], Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Department of Genomics, Douglas Mental Health University Institute, McGill University = Université McGill [Montréal, Canada], sans affiliation, Università degli Studi di Salermo, Università degli Studi di Salerno (UNISA), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), School of Psychology, University of Queensland, University of Queensland [Brisbane], Department of Hematology, 'Ion Chiricuta' Cancer Institute, University of Oslo (UiO), The University of Texas Health Science Center at Houston (UTHealth), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Department of Psychiatry, Division of Medical Psychology, Champalimaud Neuroscience Programme, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University System-Indiana University System, Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Division of Hemato-Oncology, Saint Anna Children's Hospital [Vienne] = St Anna Kinderspital (St. Anna Children's Hospital), Psychiatry and Psychotherapy, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Vermont [Burlington], Haukeland University Hospital, University of Bergen (UiB), Dpt of Psychiatry [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM), Laboratory of Molecular Neuropsychiatry, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Universität Heidelberg [Heidelberg], International Max Planck Research School for Language Sciences (IMPRS ), Lancaster University, Georgia Institute of Technology [Atlanta], Greifswald University Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Clinical Research Unit, Brain & Mind Research Institute-The University of Sydney, Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, University Medical Center Groningen [Groningen] (UMCG), Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Mental Health Sciences Unit, University College of London [London] (UCL), University Medical Center [Utrecht], Department of Radiology [Rochester], Mayo Clinic [Rochester], Department of Clinical Neurology [Oxford], University of Oxford [Oxford]-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], Centre for the Cellular Basis of Behavior, Bureau d'Économie Théorique et Appliquée (BETA), Institut National de la Recherche Agronomique (INRA)-Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Medicine, Imperial College London, MetaCase [Jyväskylä], Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, University of Maryland System, Sahlgrenska Academy at University of Gothenburg [Göteborg], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Université de Cergy Pontoise (UCP), Université Paris-Seine, National Institutes of Health [Bethesda] (NIH), Department of Forensic and Neurodevelopmental Sciences, University of California [Irvine] (UCI), University of California, Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Division of Mental Health and Addiction, Oslo University Hospital [Oslo], VU University Medical Center [Amsterdam], Metacohorts Consortium, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Indiana Alzheimer Disease Center, Department of Statistics [Warwick], University of Warwick [Coventry], Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Modelling brain structure, function and variability based on high-field MRI data (PARIETAL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden, University of Pennsylvania [Philadelphia], Department of Cognitive Sciences [San Diego], University of California [San Diego] (UC San Diego), Indiana University System, Natbrainlab, Department of Forensic and Neurodevelopmental Sciences, Institute of psychiatry-King‘s College London, Institute of Neurology [London], Laboratoire des symbioses tropicales et méditerranéennes (UMR LSTM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Stanley Center for Psychiatric Research, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], King Faisal Specialist Hospital and Research Centre, Georgia State University, University System of Georgia (USG), Department of Psychiatry and Human Behavior [Irvine], Leiden University Medical Center (LUMC), Institute for Community Medicine, School of Music and Music Education (UNSW), Science & Technology Information Institute, Shandong Academy of Agricultural Science, University of California [San Francisco] (UCSF), Department of Physics [Hong Kong University of Science and Technology], Hong Kong University of Science and Technology (HKUST), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Research Laboratory for Archaeology & the History of Art, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dundee Technopole, CXR Biosciences Ltd, Georg-August-University [Göttingen], Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Prince of Wales Medical Research Institute, Center for Neurobehavioral Genetics, Wales Institute of Cognitive Neuroscience, Cardiff University, Complutense University of Madrid (UCM), Universidade do Porto [Porto], Texas Biomedical Research Institute [San Antonio, Texas], Karakter Child and Adolescent Psychiatry University Centre, McGill University, Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), St. Anna Children's Hospital, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Bergen (UIB), Yale University School of Medicine, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), McGill University-McGill University, Technische Universität Dresden (TUD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Inria Saclay - Ile de France, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Physics [Kowloon], University of California (UC)-University of California (UC), QIMR Berghofer Medical Research Institute, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Department of Clinical Neurosciences, Neurology Division, Karolinska Institutet, Karolinska University Hospital [Stockholm], Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University [Chicago, Ill. USA], Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Ernst-Moritz-Arndt-Universität Greifswald, School of Mathematics and Statistics, Brain Research Imaging Centre, Imaging Sciences, University Hospital Carl Gustav Carus [Dresden, Germany], Semel Institute for Neuroscience and Human Behavior [Los Angeles, Ca], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Royal Hospital for Sick Children [Edinburgh], Department of General Practice/EMGO Institute, Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh-Medical Research Council (MRC), Radboud University [Nijmegen], Brain Centre Rudolf Magnus [Utrecht], Department of Human Genetics [Nijmegen], Psychiatric and Neurodevelopmental Genetics Unit, Harvard University, Russian Academy of Sciences [Moscow] (RAS), The University of New Mexico [Albuquerque], The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), National University of Ireland [Galway] (NUI Galway), University of California (UC), Institute of Psychological Medicine and Clinical Neurosciences, Centre for Addiction and Mental Health [Toronto] (CAMH), Institute of Biomaterials and Biomedical Engineering [Toronto, ON, Canada] (IBBME), University of Toronto, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Universität Bonn = University of Bonn, Jülich Research Centre, University of Basel (Unibas), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Fundación Marqués de Valdecilla-Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Centre for Cognitive Ageing and Cognitive Epidemiology, Trinity College Dublin, Department of Psychiatry Massachusetts General Hospital (MGH), South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, University Hospital Regensburg, Hartford Hospital, University of Oxford, HELIOS Klinikum Stralsund Hanseatic, University of Heidelberg, Medical Faculty, Georg-August-University = Georg-August-Universität Göttingen, University of Pennsylvania, McMaster University [Hamilton, Ontario], UCL, Institute of Neurology [London], Brain and Mind Research Institute, University of Technology Sydney (UTS), Diakonhjemmet Hospital, University of Maryland School of Medicine, Oakland University, University of Rochester School of Medicine, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), South London and Maudsley NHS Foundation Trust, Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Maryland [Baltimore], Neuroscience Research Australia (NeuRA), University of Gothenburg (GU), Karolinska Institutet [Stockholm], Vanderbilt University [Nashville], University of Missouri [Columbia] (Mizzou), University of Missouri System, Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neuroscience, Yale University School of Medicine, Columbia University Medical Center (CUMC), Columbia University [New York], University of Nottingham, UK (UON), University of California [Irvine] (UC Irvine), Università degli Studi di Milano = University of Milan (UNIMI), Hotchkiss Brain Institute, University of Calgary, Oslo and Akershus University College of Applied Sciences [Oslo] (HiOA), Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Aarhus University [Aarhus], Sorlandet Hospital HF, University Hospital Mannheim | Universitätsmedizin Mannheim, Centre for Advanced Imaging [Brisbane] (CAI), Ludwig Maximilian University [Munich] (LMU), Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, The University of Western Australia (UWA), University of Minnesota [Morris], University of Minnesota System, Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), The University of Texas Medical School at Houston, Indiana State University, Stockholm Brain Institute [Stockholm, Sweden], Stockholm University, Umeå University, University of Texas Health Science Center, Department of Clinical Neuropsychology, University of Amsterdam [Amsterdam] (UvA), Rotman Research Institute at the Baycrest Centre (RRI), The Hospital for sick children [Toronto] (SickKids), University of Pittsburgh (PITT), University of California [Berkeley] (UC Berkeley), King's College, Reta Lila Weston Institute, UCL Institute of Neurology, Department of Molecular Neuroscience, University College of London [London] (UCL)-Institute of Neurology, University of Cantabria, Santander, Research Triangle Institute International (RTI International), Martin-Luther-Universität Halle Wittenberg (MLU), Prince of Wales Hospital, Karolinska Institute, Laureate institute for brain research, Tulsa, University of Tulsa, Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), University of Minnesota Medical School, Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Maudsley NHS Foundation Trust and Institute of Psychiatry, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, Edinburgh Dementia Prevention & Centre for Clinical Brain Sciences, Center for Human Genetic Research, VA NY Harbor Health Care System, Alzheimer Scotland Dementia Research Centre, Department of Psychiatry and Behavioral Neuroscience [UC, Cincinnati], University of Cincinnati (UC), University of Cincinnati College of Medicine, Marqués de Valdecilla University Hospital [Santander], King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Psychiatry and Leiden Institute for Brain and Cognition, Universiteit Leiden-Universiteit Leiden, Universiteit Leiden, Department of Biological Psychology [Amsterdam], Vrije Universiteit Amsterdam [Amsterdam] (VU), The Centre for Regenerative Medicine, Berlin School of Mind and Brain [Berlin], Humboldt University Of Berlin, University of California [San Francisco] (UC San Francisco), School of Chemistry, University of Edinburgh, Department of Public Health, Erasmus University Medical Centre, Rotterdam, Erasmus University Medical Centre, Rotterdam, Department of Psychiatry and Biobehavioral Sciences, University of Exeter, Janssen Research & Development, A complete listing of ADNI investigators is available at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf The work reviewed here was funded by a large number of federal and private agencies worldwide, listed in Stein et al. (2012), the funding for listed consortia is also itemized in Stein et al. (2012)., Medical Oncology, Epidemiology, Clinical Chemistry, Cardiology, Neurosciences, Child and Adolescent Psychiatry / Psychology, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Universidade do Porto, FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital]-University of Oxford [Oxford], Université de Lorraine (UL)-Université de Strasbourg (UNISTRA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Service NEUROSPIN (NEUROSPIN), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Smoller, Jordan, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANS - Amsterdam Neuroscience, Adult Psychiatry, Other departments, University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-FMRIB Centre, and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
endocrine system, Multi-site, Cognitive Neuroscience, [SDV]Life Sciences [q-bio], body-mass index, Clinical Neurology, multivariate parallel ica, Neuroimaging, methods [Genome-Wide Association Study], human brain structure, methods [Brain Mapping], Behavioral Neuroscience, Cellular and Molecular Neuroscience, ddc:150, Meta-Analysis as Topic, cortical surface-area, Genetics, voxel-based morphometry, GWAS, Humans, Cooperative Behavior, disease risk variant, Brain Mapping, MRI, Consortium, Meta-analysis, white-matter microstructure, SI: Genetic Neuroimaging in Aging and Age-Related Diseases, Psychiatry and Mental health, Neurology, Radiology Nuclear Medicine and imaging, quantitative trait loci, RC0321, genome-wide association, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], tensor-based morphometry, methods [Neuroimaging], Genome-Wide Association Study
Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA’s first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

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