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1. Brain charts for the human lifespan

Author: Bethlehem, RAI, Seidlitz, J, White, SR, Vogel, JW, Anderson, KM, Adamson, C, Adler, S, Alexopoulos, GS, Anagnostou, E, Areces-Gonzalez, A, Astle, DE, Auyeung, B, Ayub, M, Bae, J, Ball, G, Baron-Cohen, S, Beare, R, Bedford, SA, Benegal, V, Beyer, F, Blangero, J, Blesa Cábez, M, Boardman, JP, Borzage, M, Bosch-Bayard, JF, Bourke, N, Calhoun, VD, Chakravarty, MM, Chen, C, Chertavian, C, Chetelat, G, Chong, YS, Cole, JH, Corvin, A, Costantino, M, Courchesne, E, Crivello, F, Cropley, VL, Crosbie, J, Crossley, N, Delarue, M, Delorme, R, Desrivieres, S, Devenyi, GA, Di Biase, MA, Dolan, R, Donald, KA, Donohoe, G, Dunlop, K, Edwards, AD, Elison, JT, Ellis, CT, Elman, JA, Eyler, L, Fair, DA, Feczko, E, Fletcher, PC, Fonagy, P, Franz, CE, Galan-Garcia, L, Gholipour, A, Giedd, J, Gilmore, JH, Glahn, DC, Goodyer, IM, Grant, PE, Groenewold, NA, Gunning, FM, Gur, RE, Gur, RC, Hammill, CF, Hansson, O, Hedden, T, Heinz, A, Henson, RN, Heuer, K, Hoare, J, Holla, B, Holmes, AJ, Holt, R, Huang, H, Im, K, Ipser, J, Jack, CR, Jackowski, AP, Jia, T, Johnson, KA, Jones, PB, Jones, DT, Kahn, RS, Karlsson, H, Karlsson, L, Kawashima, R, Kelley, EA, Kern, S, Kim, KW, Kitzbichler, MG, Kremen, WS, Lalonde, F, and Landeau, B
Subjects: Biological Psychology, Psychology, Aging, Clinical Research, Neurosciences, Brain Disorders, Biomedical Imaging, Neurological, Mental health, Body Height, Brain, Humans, Longevity, Magnetic Resonance Imaging, Neuroimaging, 3R-BRAIN, AIBL, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s Disease Repository Without Borders Investigators, CALM Team, Cam-CAN, CCNP, COBRE, cVEDA, ENIGMA Developmental Brain Age Working Group, Developing Human Connectome Project, FinnBrain, Harvard Aging Brain Study, IMAGEN, KNE96, Mayo Clinic Study of Aging, NSPN, POND, PREVENT-AD Research Group, VETSA, General Science & Technology
Abstract: Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
Published: 2022

2. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author: Kelly, S, Jahanshad, N, Zalesky, A, Kochunov, P, Agartz, I, Alloza, C, Andreassen, OA, Arango, C, Banaj, N, Bouix, S, Bousman, CA, Brouwer, RM, Bruggemann, J, Bustillo, J, Cahn, W, Calhoun, V, Cannon, D, Carr, V, Catts, S, Chen, J, Chen, J-X, Chen, X, Chiapponi, C, Cho, Kl K, Ciullo, V, Corvin, AS, Crespo-Facorro, B, Cropley, V, De Rossi, P, Diaz-Caneja, CM, Dickie, EW, Ehrlich, S, Fan, F-M, Faskowitz, J, Fatouros-Bergman, H, Flyckt, L, Ford, JM, Fouche, J-P, Fukunaga, M, Gill, M, Glahn, DC, Gollub, R, Goudzwaard, ED, Guo, H, Gur, RE, Gur, RC, Gurholt, TP, Hashimoto, R, Hatton, SN, Henskens, FA, Hibar, DP, Hickie, IB, Hong, LE, Horacek, J, Howells, FM, Hulshoff Pol, HE, Hyde, CL, Isaev, D, Jablensky, A, Jansen, PR, Janssen, J, Jönsson, EG, Jung, LA, Kahn, RS, Kikinis, Z, Liu, K, Klauser, P, Knöchel, C, Kubicki, M, Lagopoulos, J, Langen, C, Lawrie, S, Lenroot, RK, Lim, KO, Lopez-Jaramillo, C, Lyall, A, Magnotta, V, Mandl, RCW, Mathalon, DH, McCarley, RW, McCarthy-Jones, S, McDonald, C, McEwen, S, McIntosh, A, Melicher, T, Mesholam-Gately, RI, Michie, PT, Mowry, B, Mueller, BA, Newell, DT, O'Donnell, P, Oertel-Knöchel, V, Oestreich, L, Paciga, SA, Pantelis, C, Pasternak, O, Pearlson, G, Pellicano, GR, Pereira, A, and Pineda Zapata, J
Subjects: Neurosciences, Brain Disorders, Mental Health, Serious Mental Illness, Biomedical Imaging, Schizophrenia, Clinical Research, Mental health, Adult, Aged, Aged, 80 and over, Brain, Cohort Studies, Corpus Callosum, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, White Matter, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
Published: 2018

3. Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Author: Hibar, DP, Westlye, LT, Doan, NT, Jahanshad, N, Cheung, JW, Ching, CRK, Versace, A, Bilderbeck, AC, Uhlmann, A, Mwangi, B, Krämer, B, Overs, B, Hartberg, CB, Abé, C, Dima, D, Grotegerd, D, Sprooten, E, Bøen, E, Jimenez, E, Howells, FM, Delvecchio, G, Temmingh, H, Starke, J, Almeida, JRC, Goikolea, JM, Houenou, J, Beard, LM, Rauer, L, Abramovic, L, Bonnin, M, Ponteduro, MF, Keil, M, Rive, MM, Yao, N, Yalin, N, Najt, P, Rosa, PG, Redlich, R, Trost, S, Hagenaars, S, Fears, SC, Alonso-Lana, S, van Erp, TGM, Nickson, T, Chaim-Avancini, TM, Meier, TB, Elvsåshagen, T, Haukvik, UK, Lee, WH, Schene, AH, Lloyd, AJ, Young, AH, Nugent, A, Dale, AM, Pfennig, A, McIntosh, AM, Lafer, B, Baune, BT, Ekman, CJ, Zarate, CA, Bearden, CE, Henry, C, Simhandl, C, McDonald, C, Bourne, C, Stein, DJ, Wolf, DH, Cannon, DM, Glahn, DC, Veltman, DJ, Pomarol-Clotet, E, Vieta, E, Canales-Rodriguez, EJ, Nery, FG, Duran, FLS, Busatto, GF, Roberts, G, Pearlson, GD, Goodwin, GM, Kugel, H, Whalley, HC, Ruhe, HG, Soares, JC, Fullerton, JM, Rybakowski, JK, Savitz, J, Chaim, KT, Fatjó-Vilas, M, Soeiro-de-Souza, MG, Boks, MP, Zanetti, MV, Otaduy, MCG, Schaufelberger, MS, Alda, M, Ingvar, M, Phillips, ML, Kempton, MJ, Bauer, M, Landén, M, and Lawrence, NS
Subjects: Brain, Cerebral Cortex, Frontal Lobe, Prefrontal Cortex, Temporal Lobe, Humans, Magnetic Resonance Imaging, Case-Control Studies, Bipolar Disorder, Psychotic Disorders, Age Factors, Sex Factors, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Neuroimaging, Gray Matter, Clinical Research, Serious Mental Illness, Biomedical Imaging, Brain Disorders, Mental Health, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Mental health, Neurological, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
Published: 2018

4. Erratum: GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium

Author: Trampush, JW, Yang, MLZ, Yu, J, Knowles, E, Davies, G, Liewald, DC, Starr, JM, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Horan, M, Chiba-Falek, O, Attix, DK, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Arking, DE, Smyrnis, N, Bilder, RM, Freimer, NA, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, ED, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Malhotra, AK, and Lencz, T
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical and Health Psychology, Clinical Sciences, Psychology, Genetics, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: This corrects the article DOI: 10.1038/mp.2016.244.
Published: 2017

5. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.

Author: Trampush, JW, Yang, MLZ, Yu, J, Knowles, E, Davies, G, Liewald, DC, Starr, JM, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Horan, M, Chiba-Falek, O, Attix, DK, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Arking, DE, Smyrnis, N, Bilder, RM, Freimer, NA, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, ED, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Malhotra, AK, and Lencz, T
Subjects: Psychiatry, Medical and Health Sciences, Biological Sciences, Psychology and Cognitive Sciences
Abstract: This corrects the article DOI: 10.1038/mp.2016.244.
Published: 2017

6. Subcortical volumetric abnormalities in bipolar disorder.

Author: Hibar, DP, Westlye, LT, van Erp, TGM, Rasmussen, J, Leonardo, CD, Faskowitz, J, Haukvik, UK, Hartberg, CB, Doan, NT, Agartz, I, Dale, AM, Gruber, O, Krämer, B, Trost, S, Liberg, B, Abé, C, Ekman, CJ, Ingvar, M, Landén, M, Fears, SC, Freimer, NB, Bearden, CE, Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes, Sprooten, E, Glahn, DC, Pearlson, GD, Emsell, L, Kenney, J, Scanlon, C, McDonald, C, Cannon, DM, Almeida, J, Versace, A, Caseras, X, Lawrence, NS, Phillips, ML, Dima, D, Delvecchio, G, Frangou, S, Satterthwaite, TD, Wolf, D, Houenou, J, Henry, C, Malt, UF, Bøen, E, Elvsåshagen, T, Young, AH, Lloyd, AJ, Goodwin, GM, Mackay, CE, Bourne, C, Bilderbeck, A, Abramovic, L, Boks, MP, van Haren, NEM, Ophoff, RA, Kahn, RS, Bauer, M, Pfennig, A, Alda, M, Hajek, T, Mwangi, B, Soares, JC, Nickson, T, Dimitrova, R, Sussmann, JE, Hagenaars, S, Whalley, HC, McIntosh, AM, Thompson, PM, and Andreassen, OA
Subjects: Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes, Brain, Humans, Magnetic Resonance Imaging, Organ Size, Case-Control Studies, Retrospective Studies, Bipolar Disorder, Adult, Middle Aged, Female, Male, Clinical Research, Mental Health, Brain Disorders, Serious Mental Illness, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Mental health, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.
Published: 2016

7. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium

Author: van Erp, TGM, Hibar, DP, Rasmussen, JM, Glahn, DC, Pearlson, GD, Andreassen, OA, Agartz, I, Westlye, LT, Haukvik, UK, Dale, AM, Melle, I, Hartberg, CB, Gruber, O, Kraemer, B, Zilles, D, Donohoe, G, Kelly, S, McDonald, C, Morris, DW, Cannon, DM, Corvin, A, Machielsen, MWJ, Koenders, L, de Haan, L, Veltman, DJ, Satterthwaite, TD, Wolf, DH, Gur, RC, Gur, RE, Potkin, SG, Mathalon, DH, Mueller, BA, Preda, A, Macciardi, F, Ehrlich, S, Walton, E, Hass, J, Calhoun, VD, Bockholt, HJ, Sponheim, SR, Shoemaker, JM, van Haren, NEM, Pol, HEH, Ophoff, RA, Kahn, RS, Roiz-Santiañez, R, Crespo-Facorro, B, Wang, L, Alpert, KI, Jönsson, EG, Dimitrova, R, Bois, C, Whalley, HC, McIntosh, AM, Lawrie, SM, Hashimoto, R, Thompson, PM, and Turner, JA
Subjects: Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Serious Mental Illness, Brain Disorders, Schizophrenia, Clinical Research, Neurosciences, Mental Health, Biomedical Imaging, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Adult, Brain, Brain Mapping, Case-Control Studies, Female, Functional Laterality, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Prospective Studies, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.
Published: 2016

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

Author: Schijven, D, Postema, MC, Fukunaga, M, Matsumoto, J, Miura, K, de Zwarte, SMC, van Haren, NEM, Cahn, W, Hulshoff Pol, HE, Kahn, RS, Ayesa-Arriola, R, Ortiz-García de la Foz, V, Tordesillas-Gutierrez, D, Vázquez-Bourgon, J, Crespo-Facorro, B, Alnæs, D, Dahl, A, Westlye, LT, Agartz, I, Andreassen, OA, Jönsson, EG, Kochunov, P, Bruggemann, JM, Catts, SV, Michie, PT, Mowry, BJ, Quidé, Y, Rasser, PE, Schall, U, Scott, RJ, Carr, VJ, Green, MJ, Henskens, FA, Loughland, CM, Pantelis, C, Weickert, CS, Weickert, TW, de Haan, L, Brosch, K, Pfarr, J-K, Ringwald, KG, Stein, F, Jansen, A, Kircher, TTJ, Nenadić, I, Krämer, B, Gruber, O, Satterthwaite, TD, Bustillo, J, Mathalon, DH, Preda, A, Calhoun, VD, Ford, JM, Potkin, SG, Chen, J, Tan, Y, Wang, Z, Xiang, H, Fan, F, Bernardoni, F, Ehrlich, S, Fuentes-Claramonte, P, Garcia-Leon, MA, Guerrero-Pedraza, A, Salvador, R, Sarró, S, Pomarol-Clotet, E, Ciullo, V, Piras, F, Vecchio, D, Banaj, N, Spalletta, G, Michielse, S, van Amelsvoort, T, Dickie, EW, Voineskos, AN, Sim, K, Ciufolini, S, Dazzan, P, Murray, RM, Kim, W-S, Chung, Y-C, Andreou, C, Schmidt, A, Borgwardt, S, McIntosh, AM, Whalley, HC, Lawrie, SM, du Plessis, S, Luckhoff, HK, Scheffler, F, Emsley, R, Grotegerd, D, Lencer, R, Dannlowski, U, Edmond, JT, Rootes-Murdy, K, Stephen, JM, Mayer, AR, Antonucci, LA, Fazio, L, Pergola, G, Bertolino, A, Díaz-Caneja, CM, Janssen, J, Lois, NG, Arango, C, Tomyshev, AS, Lebedeva, I, Cervenka, S, Sellgren, CM, Georgiadis, F, Kirschner, M, Kaiser, S, Hajek, T, Skoch, A, Spaniel, F, Kim, M, Kwak, YB, Oh, S, Kwon, JS, James, A, Bakker, G, Knöchel, C, Stäblein, M, Oertel, V, Uhlmann, A, Howells, FM, Stein, DJ, Temmingh, HS, Diaz-Zuluaga, AM, Pineda-Zapata, JA, López-Jaramillo, C, Homan, S, Ji, E, Surbeck, W, Homan, P, Fisher, SE, Franke, B, Glahn, DC, Gur, RC, Hashimoto, R, Jahanshad, N, Luders, E, Medland, SE, Thompson, PM, Turner, JA, van Erp, TGM, Francks, C, Schijven, D, Postema, MC, Fukunaga, M, Matsumoto, J, Miura, K, de Zwarte, SMC, van Haren, NEM, Cahn, W, Hulshoff Pol, HE, Kahn, RS, Ayesa-Arriola, R, Ortiz-García de la Foz, V, Tordesillas-Gutierrez, D, Vázquez-Bourgon, J, Crespo-Facorro, B, Alnæs, D, Dahl, A, Westlye, LT, Agartz, I, Andreassen, OA, Jönsson, EG, Kochunov, P, Bruggemann, JM, Catts, SV, Michie, PT, Mowry, BJ, Quidé, Y, Rasser, PE, Schall, U, Scott, RJ, Carr, VJ, Green, MJ, Henskens, FA, Loughland, CM, Pantelis, C, Weickert, CS, Weickert, TW, de Haan, L, Brosch, K, Pfarr, J-K, Ringwald, KG, Stein, F, Jansen, A, Kircher, TTJ, Nenadić, I, Krämer, B, Gruber, O, Satterthwaite, TD, Bustillo, J, Mathalon, DH, Preda, A, Calhoun, VD, Ford, JM, Potkin, SG, Chen, J, Tan, Y, Wang, Z, Xiang, H, Fan, F, Bernardoni, F, Ehrlich, S, Fuentes-Claramonte, P, Garcia-Leon, MA, Guerrero-Pedraza, A, Salvador, R, Sarró, S, Pomarol-Clotet, E, Ciullo, V, Piras, F, Vecchio, D, Banaj, N, Spalletta, G, Michielse, S, van Amelsvoort, T, Dickie, EW, Voineskos, AN, Sim, K, Ciufolini, S, Dazzan, P, Murray, RM, Kim, W-S, Chung, Y-C, Andreou, C, Schmidt, A, Borgwardt, S, McIntosh, AM, Whalley, HC, Lawrie, SM, du Plessis, S, Luckhoff, HK, Scheffler, F, Emsley, R, Grotegerd, D, Lencer, R, Dannlowski, U, Edmond, JT, Rootes-Murdy, K, Stephen, JM, Mayer, AR, Antonucci, LA, Fazio, L, Pergola, G, Bertolino, A, Díaz-Caneja, CM, Janssen, J, Lois, NG, Arango, C, Tomyshev, AS, Lebedeva, I, Cervenka, S, Sellgren, CM, Georgiadis, F, Kirschner, M, Kaiser, S, Hajek, T, Skoch, A, Spaniel, F, Kim, M, Kwak, YB, Oh, S, Kwon, JS, James, A, Bakker, G, Knöchel, C, Stäblein, M, Oertel, V, Uhlmann, A, Howells, FM, Stein, DJ, Temmingh, HS, Diaz-Zuluaga, AM, Pineda-Zapata, JA, López-Jaramillo, C, Homan, S, Ji, E, Surbeck, W, Homan, P, Fisher, SE, Franke, B, Glahn, DC, Gur, RC, Hashimoto, R, Jahanshad, N, Luders, E, Medland, SE, Thompson, PM, Turner, JA, van Erp, TGM, and Francks, C
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023

9. Publisher Correction: Brain charts for the human lifespan.

Author: Bethlehem, RAI, Seidlitz, J, White, SR, Vogel, JW, Anderson, KM, Adamson, C, Adler, S, Alexopoulos, GS, Anagnostou, E, Areces-Gonzalez, A, Astle, DE, Auyeung, B, Ayub, M, Bae, J, Ball, G, Baron-Cohen, S, Beare, R, Bedford, SA, Benegal, V, Beyer, F, Blangero, J, Blesa Cábez, M, Boardman, JP, Borzage, M, Bosch-Bayard, JF, Bourke, N, Calhoun, VD, Chakravarty, MM, Chen, C, Chertavian, C, Chetelat, G, Chong, YS, Cole, JH, Corvin, A, Costantino, M, Courchesne, E, Crivello, F, Cropley, VL, Crosbie, J, Crossley, N, Delarue, M, Delorme, R, Desrivieres, S, Devenyi, GA, Di Biase, MA, Dolan, R, Donald, KA, Donohoe, G, Dunlop, K, Edwards, AD, Elison, JT, Ellis, CT, Elman, JA, Eyler, L, Fair, DA, Feczko, E, Fletcher, PC, Fonagy, P, Franz, CE, Galan-Garcia, L, Gholipour, A, Giedd, J, Gilmore, JH, Glahn, DC, Goodyer, IM, Grant, PE, Groenewold, NA, Gunning, FM, Gur, RE, Gur, RC, Hammill, CF, Hansson, O, Hedden, T, Heinz, A, Henson, RN, Heuer, K, Hoare, J, Holla, B, Holmes, AJ, Holt, R, Huang, H, Im, K, Ipser, J, Jack, CR, Jackowski, AP, Jia, T, Johnson, KA, Jones, PB, Jones, DT, Kahn, RS, Karlsson, H, Karlsson, L, Kawashima, R, Kelley, EA, Kern, S, Kim, KW, Kitzbichler, MG, Kremen, WS, Lalonde, F, Landeau, B, Lee, S, Lerch, J, Lewis, JD, Li, J, Liao, W, Liston, C, Lombardo, MV, Lv, J, Lynch, C, Mallard, TT, Marcelis, M, Markello, RD, Mathias, SR, Mazoyer, B, McGuire, P, Meaney, MJ, Mechelli, A, Medic, N, Misic, B, Morgan, SE, Mothersill, D, Nigg, J, Ong, MQW, Ortinau, C, Ossenkoppele, R, Ouyang, M, Palaniyappan, L, Paly, L, Pan, PM, Pantelis, C, Park, MM, Paus, T, Pausova, Z, Paz-Linares, D, Pichet Binette, A, Pierce, K, Qian, X, Qiu, J, Qiu, A, Raznahan, A, Rittman, T, Rodrigue, A, Rollins, CK, Romero-Garcia, R, Ronan, L, Rosenberg, MD, Rowitch, DH, Salum, GA, Satterthwaite, TD, Schaare, HL, Schachar, RJ, Schultz, AP, Schumann, G, Schöll, M, Sharp, D, Shinohara, RT, Skoog, I, Smyser, CD, Sperling, RA, Stein, DJ, Stolicyn, A, Suckling, J, Sullivan, G, Taki, Y, Thyreau, B, Toro, R, Traut, N, Tsvetanov, KA, Turk-Browne, NB, Tuulari, JJ, Tzourio, C, Vachon-Presseau, É, Valdes-Sosa, MJ, Valdes-Sosa, PA, Valk, SL, van Amelsvoort, T, Vandekar, SN, Vasung, L, Victoria, LW, Villeneuve, S, Villringer, A, Vértes, PE, Wagstyl, K, Wang, YS, Warfield, SK, Warrier, V, Westman, E, Westwater, ML, Whalley, HC, Witte, AV, Yang, N, Yeo, B, Yun, H, Zalesky, A, Zar, HJ, Zettergren, A, Zhou, JH, Ziauddeen, H, Zugman, A, Zuo, XN, 3R-BRAIN, AIBL, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s Disease Repository Without Borders Investigators, CALM Team, Cam-CAN, CCNP, COBRE, cVEDA, ENIGMA Developmental Brain Age Working Group, Developing Human Connectome Project, FinnBrain, Harvard Aging Brain Study, IMAGEN, KNE96, Mayo Clinic Study of Aging, NSPN, POND, PREVENT-AD Research Group, VETSA, Bullmore, ET, Alexander-Bloch, AF, Bethlehem, RAI, Seidlitz, J, White, SR, Vogel, JW, Anderson, KM, Adamson, C, Adler, S, Alexopoulos, GS, Anagnostou, E, Areces-Gonzalez, A, Astle, DE, Auyeung, B, Ayub, M, Bae, J, Ball, G, Baron-Cohen, S, Beare, R, Bedford, SA, Benegal, V, Beyer, F, Blangero, J, Blesa Cábez, M, Boardman, JP, Borzage, M, Bosch-Bayard, JF, Bourke, N, Calhoun, VD, Chakravarty, MM, Chen, C, Chertavian, C, Chetelat, G, Chong, YS, Cole, JH, Corvin, A, Costantino, M, Courchesne, E, Crivello, F, Cropley, VL, Crosbie, J, Crossley, N, Delarue, M, Delorme, R, Desrivieres, S, Devenyi, GA, Di Biase, MA, Dolan, R, Donald, KA, Donohoe, G, Dunlop, K, Edwards, AD, Elison, JT, Ellis, CT, Elman, JA, Eyler, L, Fair, DA, Feczko, E, Fletcher, PC, Fonagy, P, Franz, CE, Galan-Garcia, L, Gholipour, A, Giedd, J, Gilmore, JH, Glahn, DC, Goodyer, IM, Grant, PE, Groenewold, NA, Gunning, FM, Gur, RE, Gur, RC, Hammill, CF, Hansson, O, Hedden, T, Heinz, A, Henson, RN, Heuer, K, Hoare, J, Holla, B, Holmes, AJ, Holt, R, Huang, H, Im, K, Ipser, J, Jack, CR, Jackowski, AP, Jia, T, Johnson, KA, Jones, PB, Jones, DT, Kahn, RS, Karlsson, H, Karlsson, L, Kawashima, R, Kelley, EA, Kern, S, Kim, KW, Kitzbichler, MG, Kremen, WS, Lalonde, F, Landeau, B, Lee, S, Lerch, J, Lewis, JD, Li, J, Liao, W, Liston, C, Lombardo, MV, Lv, J, Lynch, C, Mallard, TT, Marcelis, M, Markello, RD, Mathias, SR, Mazoyer, B, McGuire, P, Meaney, MJ, Mechelli, A, Medic, N, Misic, B, Morgan, SE, Mothersill, D, Nigg, J, Ong, MQW, Ortinau, C, Ossenkoppele, R, Ouyang, M, Palaniyappan, L, Paly, L, Pan, PM, Pantelis, C, Park, MM, Paus, T, Pausova, Z, Paz-Linares, D, Pichet Binette, A, Pierce, K, Qian, X, Qiu, J, Qiu, A, Raznahan, A, Rittman, T, Rodrigue, A, Rollins, CK, Romero-Garcia, R, Ronan, L, Rosenberg, MD, Rowitch, DH, Salum, GA, Satterthwaite, TD, Schaare, HL, Schachar, RJ, Schultz, AP, Schumann, G, Schöll, M, Sharp, D, Shinohara, RT, Skoog, I, Smyser, CD, Sperling, RA, Stein, DJ, Stolicyn, A, Suckling, J, Sullivan, G, Taki, Y, Thyreau, B, Toro, R, Traut, N, Tsvetanov, KA, Turk-Browne, NB, Tuulari, JJ, Tzourio, C, Vachon-Presseau, É, Valdes-Sosa, MJ, Valdes-Sosa, PA, Valk, SL, van Amelsvoort, T, Vandekar, SN, Vasung, L, Victoria, LW, Villeneuve, S, Villringer, A, Vértes, PE, Wagstyl, K, Wang, YS, Warfield, SK, Warrier, V, Westman, E, Westwater, ML, Whalley, HC, Witte, AV, Yang, N, Yeo, B, Yun, H, Zalesky, A, Zar, HJ, Zettergren, A, Zhou, JH, Ziauddeen, H, Zugman, A, Zuo, XN, 3R-BRAIN, AIBL, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s Disease Repository Without Borders Investigators, CALM Team, Cam-CAN, CCNP, COBRE, cVEDA, ENIGMA Developmental Brain Age Working Group, Developing Human Connectome Project, FinnBrain, Harvard Aging Brain Study, IMAGEN, KNE96, Mayo Clinic Study of Aging, NSPN, POND, PREVENT-AD Research Group, VETSA, Bullmore, ET, and Alexander-Bloch, AF
Published: 2022

10. Virtual histology of cortical thickness and shared neurobiology in 6 psychiatric disorders

Author: Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abé, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargalló, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, Del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bülow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodríguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjó-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, Silk, Timothy, Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abé, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargalló, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, Del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bülow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodríguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjó-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, and Silk, Timothy
Published: 2021

11. Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets

Author: Postema, MC, Hoogman, M, Ambrosino, S, Asherson, P, Banaschewski, T, Bandeira, CE, Baranov, A, Bau, CHD, Baumeister, S, Baur-Streubel, R, Bellgrove, MA, Biederman, J, Bralten, J, Brandeis, D, Brem, S, Buitelaar, JK, Busatto, GF, Castellanos, FX, Cercignani, M, Chaim-Avancini, TM, Chantiluke, KC, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, AI, Cupertino, RB, de Zeeuw, P, Doyle, AE, Durston, S, Earl, EA, Epstein, JN, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Frodl, T, Gabel, MC, Gogberashvili, T, Grevet, EH, Haavik, J, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hoekstra, PJ, Hohmann, S, Høvik, MF, Jernigan, TL, Kardatzki, B, Karkashadze, G, Kelly, C, Kohls, G, Konrad, K, Kuntsi, J, Lazaro, L, Lera-Miguel, S, Lesch, KP, Louza, MR, Lundervold, AJ, Malpas, CB, Mattos, P, McCarthy, H, Namazova-Baranova, L, Nicolau, R, Nigg, JT, Novotny, SE, Oberwelland Weiss, E, O'Gorman Tuura, RL, Oosterlaan, J, Oranje, B, Paloyelis, Y, Pauli, P, Picon, FA, Plessen, KJ, Ramos-Quiroga, JA, Reif, A, Reneman, L, Rosa, PGP, Rubia, K, Schrantee, A, Schweren, LJS, Seitz, J, Shaw, P, Silk, Tim, Skokauskas, N, Soliva Vila, JC, Stevens, MC, Sudre, G, Tamm, L, Tovar-Moll, F, van Erp, TGM, Vance, A, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Yoncheva, YN, Zanetti, MV, Ziegler, GC, Glahn, DC, Jahanshad, N, Postema, MC, Hoogman, M, Ambrosino, S, Asherson, P, Banaschewski, T, Bandeira, CE, Baranov, A, Bau, CHD, Baumeister, S, Baur-Streubel, R, Bellgrove, MA, Biederman, J, Bralten, J, Brandeis, D, Brem, S, Buitelaar, JK, Busatto, GF, Castellanos, FX, Cercignani, M, Chaim-Avancini, TM, Chantiluke, KC, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, AI, Cupertino, RB, de Zeeuw, P, Doyle, AE, Durston, S, Earl, EA, Epstein, JN, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Frodl, T, Gabel, MC, Gogberashvili, T, Grevet, EH, Haavik, J, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hoekstra, PJ, Hohmann, S, Høvik, MF, Jernigan, TL, Kardatzki, B, Karkashadze, G, Kelly, C, Kohls, G, Konrad, K, Kuntsi, J, Lazaro, L, Lera-Miguel, S, Lesch, KP, Louza, MR, Lundervold, AJ, Malpas, CB, Mattos, P, McCarthy, H, Namazova-Baranova, L, Nicolau, R, Nigg, JT, Novotny, SE, Oberwelland Weiss, E, O'Gorman Tuura, RL, Oosterlaan, J, Oranje, B, Paloyelis, Y, Pauli, P, Picon, FA, Plessen, KJ, Ramos-Quiroga, JA, Reif, A, Reneman, L, Rosa, PGP, Rubia, K, Schrantee, A, Schweren, LJS, Seitz, J, Shaw, P, Silk, Tim, Skokauskas, N, Soliva Vila, JC, Stevens, MC, Sudre, G, Tamm, L, Tovar-Moll, F, van Erp, TGM, Vance, A, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Yoncheva, YN, Zanetti, MV, Ziegler, GC, Glahn, DC, and Jahanshad, N
Published: 2021

12. Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Author: Velthorst, E, Mollon, J, Murray, RM, de Haan, L, Germeys, IM, Glahn, DC, Arango, C, van der Ven, E, Di Forti, M, Bernardo, M, Guloksuz, S, Delespaul, P, Mezquida, G, Amoretti, S, Bobes, J, Saiz, PA, Garcia-Portilla, MP, Santos, JL, Jimenez-Lopez, E, Sanjuan, J, Aguilar, EJ, Arrojo, M, Carracedo, A, Lopez, G, Gonzalez-Penas, J, Parellada, M, Atbasoglu, C, Saka, MC, Ucok, A, Alptekin, K, Akdede, B, Binbay, T, Altinyazar, V, Ulas, H, Yalincetin, B, Gumus-Akay, G, Beyaz, BC, Soygur, H, Cankurtaran, ES, Kaymak, SU, Maric, NP, Mihaljevic, MM, Petrovic, SA, Mirjanic, T, Del-Ben, CM, Ferraro, L, Gayer-Anderson, C, Jones, PB, Jongsma, HE, Kirkbride, JB, La Cascia, C, Lasalvia, A, Tosato, S, Llorca, P-M, Menezes, PR, Morgan, C, Quattrone, D, Menchetti, M, Selten, J-P, Szoke, A, Tarricone, I, Tortelli, A, McGuire, P, Valmaggia, L, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, McGorry, P, Pantelis, C, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, AA, Bruggeman, R, van Beveren, NJ, Luykx, JJ, Cahn, W, Simons, CJP, Kahn, RS, Schirmbeck, F, van Winkel, R, Reichenberg, A, Velthorst, E, Mollon, J, Murray, RM, de Haan, L, Germeys, IM, Glahn, DC, Arango, C, van der Ven, E, Di Forti, M, Bernardo, M, Guloksuz, S, Delespaul, P, Mezquida, G, Amoretti, S, Bobes, J, Saiz, PA, Garcia-Portilla, MP, Santos, JL, Jimenez-Lopez, E, Sanjuan, J, Aguilar, EJ, Arrojo, M, Carracedo, A, Lopez, G, Gonzalez-Penas, J, Parellada, M, Atbasoglu, C, Saka, MC, Ucok, A, Alptekin, K, Akdede, B, Binbay, T, Altinyazar, V, Ulas, H, Yalincetin, B, Gumus-Akay, G, Beyaz, BC, Soygur, H, Cankurtaran, ES, Kaymak, SU, Maric, NP, Mihaljevic, MM, Petrovic, SA, Mirjanic, T, Del-Ben, CM, Ferraro, L, Gayer-Anderson, C, Jones, PB, Jongsma, HE, Kirkbride, JB, La Cascia, C, Lasalvia, A, Tosato, S, Llorca, P-M, Menezes, PR, Morgan, C, Quattrone, D, Menchetti, M, Selten, J-P, Szoke, A, Tarricone, I, Tortelli, A, McGuire, P, Valmaggia, L, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, McGorry, P, Pantelis, C, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, AA, Bruggeman, R, van Beveren, NJ, Luykx, JJ, Cahn, W, Simons, CJP, Kahn, RS, Schirmbeck, F, van Winkel, R, and Reichenberg, A
Abstract: Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.
Published: 2021

13. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author: Sonderby, IE, van der Meer, D, Moreau, C, Kaufmann, T, Walters, GB, Ellegaard, M, Abdellaoui, A, Ames, D, Amunts, K, Andersson, M, Armstrong, NJ, Bernard, M, Blackburn, NB, Blangero, J, Boomsma, DI, Brodaty, H, Brouwer, RM, Buelow, R, Boen, R, Cahn, W, Calhoun, VD, Caspers, S, Ching, CRK, Cichon, S, Ciufolini, S, Crespo-Facorro, B, Curran, JE, Dale, AM, Dalvie, S, Dazzan, P, de Geus, EJC, de Zubicaray, GI, de Zwarte, SMC, Desrivieres, S, Doherty, JL, Donohoe, G, Draganski, B, Ehrlich, S, Eising, E, Espeseth, T, Fejgin, K, Fisher, SE, Fladby, T, Frei, O, Frouin, V, Fukunaga, M, Gareau, T, Ge, T, Glahn, DC, Grabe, HJ, Groenewold, NA, Gustafsson, O, Haavik, J, Haberg, AK, Hall, J, Hashimoto, R, Hehir-Kwa, JY, Hibar, DP, Hillegers, MHJ, Hoffmann, P, Holleran, L, Holmes, AJ, Homuth, G, Hottenga, J-J, Hulshoff Pol, HE, Ikeda, M, Jahanshad, N, Jockwitz, C, Johansson, S, Joensson, EG, Jorgensen, NR, Kikuchi, M, Knowles, EEM, Kumar, K, Le Hellard, S, Leu, C, Linden, DEJ, Liu, J, Lundervold, A, Lundervold, AJ, Maillard, AM, Martin, NG, Martin-Brevet, S, Mather, KA, Mathias, SR, McMahon, KL, McRae, AF, Medland, SE, Meyer-Lindenberg, A, Moberget, T, Modenato, C, Sanchez, JM, Morris, DW, Muehleisen, TW, Murray, RM, Nielsen, J, Nordvik, JE, Nyberg, L, Loohuis, LMO, Ophoff, RA, Owen, MJ, Paus, T, Pausova, Z, Peralta, JM, Pike, GB, Prieto, C, Quinlan, EB, Reinbold, CS, Marques, TR, Rucker, JJH, Sachdev, PS, Sando, SB, Schofield, PR, Schork, AJ, Schumann, G, Shin, J, Shumskaya, E, Silva, AI, Sisodiya, SM, Steen, VM, Stein, DJ, Strike, LT, Suzuki, IK, Tamnes, CK, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Uhlmann, A, Ulfarsson, MO, van 't Ent, D, van den Bree, MBM, Vanderhaeghen, P, Vassos, E, Wen, W, Wittfeld, K, Wright, MJ, Agartz, I, Djurovic, S, Westlye, LT, Stefansson, H, Stefansson, K, Jacquemont, S, Thompson, PM, Andreassen, OA, Sonderby, IE, van der Meer, D, Moreau, C, Kaufmann, T, Walters, GB, Ellegaard, M, Abdellaoui, A, Ames, D, Amunts, K, Andersson, M, Armstrong, NJ, Bernard, M, Blackburn, NB, Blangero, J, Boomsma, DI, Brodaty, H, Brouwer, RM, Buelow, R, Boen, R, Cahn, W, Calhoun, VD, Caspers, S, Ching, CRK, Cichon, S, Ciufolini, S, Crespo-Facorro, B, Curran, JE, Dale, AM, Dalvie, S, Dazzan, P, de Geus, EJC, de Zubicaray, GI, de Zwarte, SMC, Desrivieres, S, Doherty, JL, Donohoe, G, Draganski, B, Ehrlich, S, Eising, E, Espeseth, T, Fejgin, K, Fisher, SE, Fladby, T, Frei, O, Frouin, V, Fukunaga, M, Gareau, T, Ge, T, Glahn, DC, Grabe, HJ, Groenewold, NA, Gustafsson, O, Haavik, J, Haberg, AK, Hall, J, Hashimoto, R, Hehir-Kwa, JY, Hibar, DP, Hillegers, MHJ, Hoffmann, P, Holleran, L, Holmes, AJ, Homuth, G, Hottenga, J-J, Hulshoff Pol, HE, Ikeda, M, Jahanshad, N, Jockwitz, C, Johansson, S, Joensson, EG, Jorgensen, NR, Kikuchi, M, Knowles, EEM, Kumar, K, Le Hellard, S, Leu, C, Linden, DEJ, Liu, J, Lundervold, A, Lundervold, AJ, Maillard, AM, Martin, NG, Martin-Brevet, S, Mather, KA, Mathias, SR, McMahon, KL, McRae, AF, Medland, SE, Meyer-Lindenberg, A, Moberget, T, Modenato, C, Sanchez, JM, Morris, DW, Muehleisen, TW, Murray, RM, Nielsen, J, Nordvik, JE, Nyberg, L, Loohuis, LMO, Ophoff, RA, Owen, MJ, Paus, T, Pausova, Z, Peralta, JM, Pike, GB, Prieto, C, Quinlan, EB, Reinbold, CS, Marques, TR, Rucker, JJH, Sachdev, PS, Sando, SB, Schofield, PR, Schork, AJ, Schumann, G, Shin, J, Shumskaya, E, Silva, AI, Sisodiya, SM, Steen, VM, Stein, DJ, Strike, LT, Suzuki, IK, Tamnes, CK, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Uhlmann, A, Ulfarsson, MO, van 't Ent, D, van den Bree, MBM, Vanderhaeghen, P, Vassos, E, Wen, W, Wittfeld, K, Wright, MJ, Agartz, I, Djurovic, S, Westlye, LT, Stefansson, H, Stefansson, K, Jacquemont, S, Thompson, PM, and Andreassen, OA
Abstract: Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
Published: 2021

14. 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, K, Andersson, M, Andreasen, NC, Andreassen, OA, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Buckner, RL, Calhoun, V, Canales-Rodriguez, 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, Davey, C, de Geus, EJC, de Haan, L, de Zubicaray, G, den Braber, A, Dickie, EW, Di Giorgio, A, Nhat, TD, Dorum, ES, Ehrlich, S, Erk, S, Espeseth, T, Fatouros-Bergman, H, Fisher, SE, Fouche, J-P, Franke, B, Frodl, T, Fuentes-Claramonte, P, Glahn, DC, Gotlib, IH, Grabe, H-J, Grimm, O, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Harrison, BJ, Hartman, CA, Hatton, SN, Heinz, A, Heslenfeld, DJ, Hibar, DP, Hickie, IB, Ho, B-C, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, A, Jernigan, TL, Jiang, J, Jonsson, EG, Joska, JA, Kahn, R, Kalnin, A, Kanai, R, Klein, M, Klyushnik, TP, Koenders, L, Koops, S, Kraemer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, I, Lee, WH, Lesch, K-P, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, C, McDonald, BC, McIntosh, AM, McMahon, KL, McPhilemy, G, Menchon, JM, Medland, SE, Meyer-Lindenberg, A, Naaijen, J, Najt, P, Nakao, T, Nordvik, JE, Nyberg, L, Oosterlaan, J, Ortiz-Garcia De la Foz, V, 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, Sanchez-Juan, P, Sarro, 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, S, Tomyshev, AS, Tordesillas-Gutierrez, 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, Voelzke, 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, M, Ziegler, GC, Thompson, PM, Frangou, S, Dima, D, Modabbernia, A, Papachristou, E, Doucet, GE, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andersson, M, Andreasen, NC, Andreassen, OA, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Buckner, RL, Calhoun, V, Canales-Rodriguez, 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, Davey, C, de Geus, EJC, de Haan, L, de Zubicaray, G, den Braber, A, Dickie, EW, Di Giorgio, A, Nhat, TD, Dorum, ES, Ehrlich, S, Erk, S, Espeseth, T, Fatouros-Bergman, H, Fisher, SE, Fouche, J-P, Franke, B, Frodl, T, Fuentes-Claramonte, P, Glahn, DC, Gotlib, IH, Grabe, H-J, Grimm, O, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Harrison, BJ, Hartman, CA, Hatton, SN, Heinz, A, Heslenfeld, DJ, Hibar, DP, Hickie, IB, Ho, B-C, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, A, Jernigan, TL, Jiang, J, Jonsson, EG, Joska, JA, Kahn, R, Kalnin, A, Kanai, R, Klein, M, Klyushnik, TP, Koenders, L, Koops, S, Kraemer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, I, Lee, WH, Lesch, K-P, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, C, McDonald, BC, McIntosh, AM, McMahon, KL, McPhilemy, G, Menchon, JM, Medland, SE, Meyer-Lindenberg, A, Naaijen, J, Najt, P, Nakao, T, Nordvik, JE, Nyberg, L, Oosterlaan, J, Ortiz-Garcia De la Foz, V, 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, Sanchez-Juan, P, Sarro, 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, S, Tomyshev, AS, Tordesillas-Gutierrez, 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, Voelzke, 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, M, Ziegler, GC, Thompson, PM, and Frangou, S
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.
Published: 2021

15. 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, K, Andersson, M, Andreasen, NC, Andreassen, OA, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Buckner, RL, Calhoun, V, Canales-Rodriguez, 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, Davey, C, de Geus, EJC, de Haan, L, de Zubicaray, G, den Braber, A, Dickie, EW, Di Giorgio, A, Nhat, TD, Dorum, ES, Ehrlich, S, Erk, S, Espeseth, T, Fatouros-Bergman, H, Fisher, SE, Fouche, J-P, Franke, B, Frodl, T, Fuentes-Claramonte, P, Glahn, DC, Gotlib, IH, Grabe, H-J, Grimm, O, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Harrison, BJ, Hartman, CA, Hatton, SN, Heinz, A, Heslenfeld, DJ, Hibar, DP, Hickie, IB, Ho, B-C, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, A, Jernigan, TL, Jiang, J, Jonsson, EG, Joska, JA, Kahn, R, Kalnin, A, Kanai, R, Klein, M, Klyushnik, TP, Koenders, L, Koops, S, Kraemer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, I, Lee, WH, Lesch, K-P, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, C, McDonald, BC, McIntosh, AM, McMahon, KL, McPhilemy, G, Menchon, JM, Medland, SE, Meyer-Lindenberg, A, Naaijen, J, Najt, P, Nakao, T, Nordvik, JE, Nyberg, L, Oosterlaan, J, de la Foz, VO-G, 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, Sanchez-Juan, P, Sarro, 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, S, Tomyshev, AS, Tordesillas-Gutierrez, 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, Voelzke, 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, M, Ziegler, GC, Thompson, PM, Dima, D, Frangou, S, Modabbernia, A, Williams, SCR, Papachristou, E, Doucet, GE, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andersson, M, Andreasen, NC, Andreassen, OA, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Buckner, RL, Calhoun, V, Canales-Rodriguez, 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, Davey, C, de Geus, EJC, de Haan, L, de Zubicaray, G, den Braber, A, Dickie, EW, Di Giorgio, A, Nhat, TD, Dorum, ES, Ehrlich, S, Erk, S, Espeseth, T, Fatouros-Bergman, H, Fisher, SE, Fouche, J-P, Franke, B, Frodl, T, Fuentes-Claramonte, P, Glahn, DC, Gotlib, IH, Grabe, H-J, Grimm, O, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Harrison, BJ, Hartman, CA, Hatton, SN, Heinz, A, Heslenfeld, DJ, Hibar, DP, Hickie, IB, Ho, B-C, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, A, Jernigan, TL, Jiang, J, Jonsson, EG, Joska, JA, Kahn, R, Kalnin, A, Kanai, R, Klein, M, Klyushnik, TP, Koenders, L, Koops, S, Kraemer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, I, Lee, WH, Lesch, K-P, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, C, McDonald, BC, McIntosh, AM, McMahon, KL, McPhilemy, G, Menchon, JM, Medland, SE, Meyer-Lindenberg, A, Naaijen, J, Najt, P, Nakao, T, Nordvik, JE, Nyberg, L, Oosterlaan, J, de la Foz, VO-G, 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, Sanchez-Juan, P, Sarro, 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, S, Tomyshev, AS, Tordesillas-Gutierrez, 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, Voelzke, 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, M, Ziegler, GC, Thompson, PM, and Dima, D
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.
Published: 2021

16. Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics

Author: Lam, M, Chen, CY, Ge, T, Xia, Y, Hill, DW, Trampush, JW, Yu, J, Knowles, E, Davies, G, Stahl, EA, Huckins, L, Liewald, DC, Djurovic, S, Melle, I, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Hartmann, AM, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Chiba-Falek, O, Koltai, DC, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Smyrnis, N, Bilder, RM, Freimer, NB, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, ED, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Huang, H, Liu, C, Malhotra, AK, Lencz, T, Lam, M, Chen, CY, Ge, T, Xia, Y, Hill, DW, Trampush, JW, Yu, J, Knowles, E, Davies, G, Stahl, EA, Huckins, L, Liewald, DC, Djurovic, S, Melle, I, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Hartmann, AM, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Chiba-Falek, O, Koltai, DC, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Smyrnis, N, Bilder, RM, Freimer, NB, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, ED, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Huang, H, Liu, C, Malhotra, AK, and Lencz, T
Abstract: Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.
Published: 2021

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

Author: Nunes, A, Schnack, HG, Ching, CRK, Agartz, I, Akudjedu, TN, Alda, M, Alnæs, D, Alonso-Lana, S, Bauer, J, Baune, BT, Bøen, E, Bonnin, CDM, Busatto, GF, Canales-Rodríguez, EJ, Cannon, DM, Caseras, X, Chaim-Avancini, TM, Dannlowski, U, Díaz-Zuluaga, AM, Dietsche, B, Doan, NT, Duchesnay, E, Elvsåshagen, T, Emden, D, Eyler, LT, Fatjó-Vilas, M, Favre, P, Foley, SF, Fullerton, JM, Glahn, DC, Goikolea, JM, Grotegerd, D, Hahn, T, Henry, C, Hibar, DP, Houenou, J, Howells, FM, Jahanshad, N, Kaufmann, T, Kenney, J, Kircher, TTJ, Krug, A, Lagerberg, TV, Lenroot, RK, López-Jaramillo, C, Machado-Vieira, R, Malt, UF, McDonald, C, Mitchell, PB, Mwangi, B, Nabulsi, L, Opel, N, Overs, BJ, Pineda-Zapata, JA, Pomarol-Clotet, E, Redlich, R, Roberts, G, Rosa, PG, Salvador, R, Satterthwaite, TD, Soares, JC, Stein, DJ, Temmingh, HS, Trappenberg, T, Uhlmann, A, van Haren, NEM, Vieta, E, Westlye, LT, Wolf, DH, Yüksel, D, Zanetti, MV, Andreassen, OA, Thompson, PM, Hajek, T, Nunes, A, Schnack, HG, Ching, CRK, Agartz, I, Akudjedu, TN, Alda, M, Alnæs, D, Alonso-Lana, S, Bauer, J, Baune, BT, Bøen, E, Bonnin, CDM, Busatto, GF, Canales-Rodríguez, EJ, Cannon, DM, Caseras, X, Chaim-Avancini, TM, Dannlowski, U, Díaz-Zuluaga, AM, Dietsche, B, Doan, NT, Duchesnay, E, Elvsåshagen, T, Emden, D, Eyler, LT, Fatjó-Vilas, M, Favre, P, Foley, SF, Fullerton, JM, Glahn, DC, Goikolea, JM, Grotegerd, D, Hahn, T, Henry, C, Hibar, DP, Houenou, J, Howells, FM, Jahanshad, N, Kaufmann, T, Kenney, J, Kircher, TTJ, Krug, A, Lagerberg, TV, Lenroot, RK, López-Jaramillo, C, Machado-Vieira, R, Malt, UF, McDonald, C, Mitchell, PB, Mwangi, B, Nabulsi, L, Opel, N, Overs, BJ, Pineda-Zapata, JA, Pomarol-Clotet, E, Redlich, R, Roberts, G, Rosa, PG, Salvador, R, Satterthwaite, TD, Soares, JC, Stein, DJ, Temmingh, HS, Trappenberg, T, Uhlmann, A, van Haren, NEM, Vieta, E, Westlye, LT, Wolf, DH, Yüksel, D, Zanetti, MV, Andreassen, OA, Thompson, PM, and Hajek, T
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

18. 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, Alnæs, 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, 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, Alnæs, 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, and Sim, K
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.
Published: 2020

19. ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

Author: Thompson, PM, Jahanshad, N, Ching, CRK, Salminen, LE, Thomopoulos, SI, Bright, J, Baune, BT, Bertolin, S, Bralten, J, Bruin, WB, Buelow, R, Chen, J, Chye, Y, Dannlowski, U, de Kovel, CGF, Donohoe, G, Eyler, LT, Faraone, SV, Favre, P, Filippi, CA, Frodl, T, Garijo, D, Gil, Y, Grabe, HJ, Grasby, KL, Hajek, T, Han, LKM, Hatton, SN, Hilbert, K, Ho, TC, Holleran, L, Homuth, G, Hosten, N, Houenou, J, Ivanov, I, Jia, T, Kelly, S, Klein, M, Kwon, JS, Laansma, MA, Leerssen, J, Lueken, U, Nunes, A, Neill, JO, Opel, N, Piras, F, Postema, MC, Pozzi, E, Shatokhina, N, Soriano-Mas, C, Spalletta, G, Sun, D, Teumer, A, Tilot, AK, Tozzi, L, van der Merwe, C, Van Someren, EJW, van Wingen, GA, Voelzke, H, Walton, E, Wang, L, Winkler, AM, Wittfeld, K, Wright, MJ, Yun, J-Y, Zhang, G, Zhang-James, Y, Adhikari, BM, Agartz, I, Aghajani, M, Aleman, A, Althoff, RR, Altmann, A, Andreassen, OA, Baron, DA, Bartnik-Olson, BL, Bas-Hoogendam, J, Baskin-Sommers, AR, Bearden, CE, Berner, LA, Boedhoe, PSW, Brouwer, RM, Buitelaar, JK, Caeyenberghs, K, Cecil, CAM, Cohen, RA, Cole, JH, Conrod, PJ, De Brito, SA, de Zwarte, SMC, Dennis, EL, Desrivieres, S, Dima, D, Ehrlich, S, Esopenko, C, Fairchild, G, Fisher, SE, Fouche, J-P, Francks, C, Frangou, S, Franke, B, Garavan, HP, Glahn, DC, Groenewold, NA, Gurholt, TP, Gutman, BA, Hahn, T, Harding, IH, Hernaus, D, Hibar, DP, Hillary, FG, Hoogman, M, Pol, HE, Jalbrzikowski, M, Karkashadze, GA, Klapwijk, ET, Knickmeyer, RC, Kochunov, P, Koerte, IK, Kong, X-Z, Liew, S-L, Lin, AP, Logue, MW, Luders, E, Macciardi, F, Mackey, S, Mayer, AR, McDonald, CR, McMahon, AB, Medland, SE, Modinos, G, Morey, RA, Mueller, SC, Mukherjee, P, Namazova-Baranova, L, Nir, TM, Olsen, A, Paschou, P, Pine, DS, Pizzagalli, F, Renteria, ME, Rohrer, JD, Saemann, PG, Schmaal, L, Schumann, G, Shiroishi, MS, Sisodiya, SM, Smit, DJA, Sonderby, IE, Stein, DJ, Stein, JL, Tahmasian, M, Tate, DF, Turner, JA, van den Heuvel, OA, van der Wee, NJA, van der Werf, YD, van Erp, TGM, van Haren, NEM, van Rooij, D, van Velzen, LS, Veer, IM, Veltman, DJ, Villalon-Reina, JE, Walter, H, Whelan, CD, Wilde, EA, Zarei, M, Zelman, V, Thompson, PM, Jahanshad, N, Ching, CRK, Salminen, LE, Thomopoulos, SI, Bright, J, Baune, BT, Bertolin, S, Bralten, J, Bruin, WB, Buelow, R, Chen, J, Chye, Y, Dannlowski, U, de Kovel, CGF, Donohoe, G, Eyler, LT, Faraone, SV, Favre, P, Filippi, CA, Frodl, T, Garijo, D, Gil, Y, Grabe, HJ, Grasby, KL, Hajek, T, Han, LKM, Hatton, SN, Hilbert, K, Ho, TC, Holleran, L, Homuth, G, Hosten, N, Houenou, J, Ivanov, I, Jia, T, Kelly, S, Klein, M, Kwon, JS, Laansma, MA, Leerssen, J, Lueken, U, Nunes, A, Neill, JO, Opel, N, Piras, F, Postema, MC, Pozzi, E, Shatokhina, N, Soriano-Mas, C, Spalletta, G, Sun, D, Teumer, A, Tilot, AK, Tozzi, L, van der Merwe, C, Van Someren, EJW, van Wingen, GA, Voelzke, H, Walton, E, Wang, L, Winkler, AM, Wittfeld, K, Wright, MJ, Yun, J-Y, Zhang, G, Zhang-James, Y, Adhikari, BM, Agartz, I, Aghajani, M, Aleman, A, Althoff, RR, Altmann, A, Andreassen, OA, Baron, DA, Bartnik-Olson, BL, Bas-Hoogendam, J, Baskin-Sommers, AR, Bearden, CE, Berner, LA, Boedhoe, PSW, Brouwer, RM, Buitelaar, JK, Caeyenberghs, K, Cecil, CAM, Cohen, RA, Cole, JH, Conrod, PJ, De Brito, SA, de Zwarte, SMC, Dennis, EL, Desrivieres, S, Dima, D, Ehrlich, S, Esopenko, C, Fairchild, G, Fisher, SE, Fouche, J-P, Francks, C, Frangou, S, Franke, B, Garavan, HP, Glahn, DC, Groenewold, NA, Gurholt, TP, Gutman, BA, Hahn, T, Harding, IH, Hernaus, D, Hibar, DP, Hillary, FG, Hoogman, M, Pol, HE, Jalbrzikowski, M, Karkashadze, GA, Klapwijk, ET, Knickmeyer, RC, Kochunov, P, Koerte, IK, Kong, X-Z, Liew, S-L, Lin, AP, Logue, MW, Luders, E, Macciardi, F, Mackey, S, Mayer, AR, McDonald, CR, McMahon, AB, Medland, SE, Modinos, G, Morey, RA, Mueller, SC, Mukherjee, P, Namazova-Baranova, L, Nir, TM, Olsen, A, Paschou, P, Pine, DS, Pizzagalli, F, Renteria, ME, Rohrer, JD, Saemann, PG, Schmaal, L, Schumann, G, Shiroishi, MS, Sisodiya, SM, Smit, DJA, Sonderby, IE, Stein, DJ, Stein, JL, Tahmasian, M, Tate, DF, Turner, JA, van den Heuvel, OA, van der Wee, NJA, van der Werf, YD, van Erp, TGM, van Haren, NEM, van Rooij, D, van Velzen, LS, Veer, IM, Veltman, DJ, Villalon-Reina, JE, Walter, H, Whelan, CD, Wilde, EA, Zarei, M, and Zelman, V
Abstract: This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
Published: 2020

20. How do substance use disorders compare to other psychiatric conditions on structural brain abnormalities? A cross-disorder meta-analytic comparison using theENIGMAconsortium findings

Author: Navarri, X, Afzali, MH, Lavoie, J, Sinha, R, Stein, DJ, Momenan, R, Veltman, DJ, Korucuoglu, O, Sjoerds, Z, van Holst, RJ, Hester, R, Orr, C, Cousijn, J, Yucel, M, Lorenzetti, V, Wiers, R, Jahanshad, N, Glahn, DC, Thompson, PM, Mackey, S, Conrod, PJ, Navarri, X, Afzali, MH, Lavoie, J, Sinha, R, Stein, DJ, Momenan, R, Veltman, DJ, Korucuoglu, O, Sjoerds, Z, van Holst, RJ, Hester, R, Orr, C, Cousijn, J, Yucel, M, Lorenzetti, V, Wiers, R, Jahanshad, N, Glahn, DC, Thompson, PM, Mackey, S, and Conrod, PJ
Abstract: Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto-cerebellar and meso-cortico-limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large-scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case-control differences and to compare brain-correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta-analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age- and sex-matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case-control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co-variates . After correcting for multiple comparisons, AUD case-control meta-analysis of subcortical regions indicated significant differences in the thalamus, hippocampus, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta-analysis of CUD
Published: 2020

21. What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from theENIGMABipolar Disorder Working Group

Author: Ching, CRK, Hibar, DP, Gurholt, TP, Nunes, A, Thomopoulos, SI, Abe, C, Agartz, I, Brouwer, RM, Cannon, DM, de Zwarte, SMC, Eyler, LT, Favre, P, Hajek, T, Haukvik, UK, Houenou, J, Landen, 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, L-L, 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, Boen, E, Bollettini, I, del Mar Bonnin, C, Brambilla, P, Canales-Rodriguez, EJ, Caseras, X, Dandash, O, Dannlowski, U, Delvecchio, G, Diaz-Zuluaga, AM, Dima, D, Duchesnay, E, Elvsashagen, 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, Knoechel, C, Kramer, B, Lafer, B, Lopez-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, Quide, Y, Rive, MM, Roberts, G, Ruhe, HG, Salvador, R, Sarro, S, Satterthwaite, TD, Schene, AH, Sim, K, Soares, JC, Staeblein, M, Stein, DJ, Tamnes, CK, Thomaidis, GV, Upegui, CV, Veltman, DJ, Wessa, M, Westlye, LT, Whalley, HC, Wolf, DH, Wu, M-J, Yatham, LN, Zarate, CA, Thompson, PM, Andreassen, OA, Ching, CRK, Hibar, DP, Gurholt, TP, Nunes, A, Thomopoulos, SI, Abe, C, Agartz, I, Brouwer, RM, Cannon, DM, de Zwarte, SMC, Eyler, LT, Favre, P, Hajek, T, Haukvik, UK, Houenou, J, Landen, 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, L-L, 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, Boen, E, Bollettini, I, del Mar Bonnin, C, Brambilla, P, Canales-Rodriguez, EJ, Caseras, X, Dandash, O, Dannlowski, U, Delvecchio, G, Diaz-Zuluaga, AM, Dima, D, Duchesnay, E, Elvsashagen, 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, Knoechel, C, Kramer, B, Lafer, B, Lopez-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, Quide, Y, Rive, MM, Roberts, G, Ruhe, HG, Salvador, R, Sarro, S, Satterthwaite, TD, Schene, AH, Sim, K, Soares, JC, Staeblein, M, Stein, DJ, Tamnes, CK, Thomaidis, GV, Upegui, CV, Veltman, DJ, Wessa, M, Westlye, LT, Whalley, HC, Wolf, DH, Wu, M-J, Yatham, LN, Zarate, CA, Thompson, PM, and Andreassen, OA
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.
Published: 2020

22. Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Author: Kong, X-Z, Boedhoe, PSW, Abe, Y, Alonso, P, Ameis, SH, Arnold, PD, Assogna, F, Baker, JT, Batistuzzo, MC, Benedetti, F, Beucke, JC, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, J, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, J, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Glahn, DC, Gruner, P, Gursel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Lazaro, L, Liu, Y, Lochner, C, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Medland, SE, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Pittenger, C, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Tsuchiyagaito, A, van Rooij, D, van Wingen, GA, Venkatasubramanian, G, Wang, Z, Yun, J-Y, Thompson, PM, Stein, DJ, van den Heuvel, OA, Francks, C, Kong, X-Z, Boedhoe, PSW, Abe, Y, Alonso, P, Ameis, SH, Arnold, PD, Assogna, F, Baker, JT, Batistuzzo, MC, Benedetti, F, Beucke, JC, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, J, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, J, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Glahn, DC, Gruner, P, Gursel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Lazaro, L, Liu, Y, Lochner, C, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Medland, SE, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Pittenger, C, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Tsuchiyagaito, A, van Rooij, D, van Wingen, GA, Venkatasubramanian, G, Wang, Z, Yun, J-Y, Thompson, PM, Stein, DJ, van den Heuvel, OA, and Francks, C
Abstract: BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.
Published: 2020

23. 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, K, Andreassen, OA, Anticevic, A, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, den Braber, A, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Calhoun, VD, Canales-Rodriguez, EJ, Cannon, DM, Caseras, X, Castellanos, FX, Chaim-Avancini, TM, Ching, CRK, Clark, VP, Conrod, PJ, Conzelmann, A, Crivello, F, Davey, CG, Dickie, EW, Ehrlich, S, Van't Ent, D, Fisher, SE, Fouche, J-P, Franke, B, Fuentes-Claramonte, P, de Geus, EJC, 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, Pol, HEH, Huyser, C, Jahanshad, N, James, AC, Jiang, J, Jonsson, EG, Joska, JA, Kalnin, AJ, Klein, M, Koenders, L, Kolskar, KK, Kramer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, IS, Lee, PH, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, BC, McDonald, C, McIntosh, AM, McMahon, KL, McPhilemy, G, van der Meer, D, Menchon, 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, PGP, Sacchet, MD, Sachdev, PS, Salvador, R, Sarro, 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, S, Tomyshev, AS, Trollor, JN, Uhlmann, A, Veer, IM, Veltman, DJ, Voineskos, A, Volzke, H, Walter, H, Wang, L, Wang, Y, Weber, B, Wen, W, West, JD, Westlye, LT, Whalley, HC, Williams, SCR, Wittfeld, K, Wolf, DH, Wright, MJ, Yoncheva, YN, Zanetti, M, Ziegler, GC, de Zubicaray, G, Thompson, PM, Crone, EA, Frangou, S, Tamnes, CK, Wierenga, LM, Doucet, GE, Dima, D, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andreassen, OA, Anticevic, A, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, den Braber, A, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Calhoun, VD, Canales-Rodriguez, EJ, Cannon, DM, Caseras, X, Castellanos, FX, Chaim-Avancini, TM, Ching, CRK, Clark, VP, Conrod, PJ, Conzelmann, A, Crivello, F, Davey, CG, Dickie, EW, Ehrlich, S, Van't Ent, D, Fisher, SE, Fouche, J-P, Franke, B, Fuentes-Claramonte, P, de Geus, EJC, 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, Pol, HEH, Huyser, C, Jahanshad, N, James, AC, Jiang, J, Jonsson, EG, Joska, JA, Kalnin, AJ, Klein, M, Koenders, L, Kolskar, KK, Kramer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, IS, Lee, PH, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, BC, McDonald, C, McIntosh, AM, McMahon, KL, McPhilemy, G, van der Meer, D, Menchon, 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, PGP, Sacchet, MD, Sachdev, PS, Salvador, R, Sarro, 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, S, Tomyshev, AS, Trollor, JN, Uhlmann, A, Veer, IM, Veltman, DJ, Voineskos, A, Volzke, H, Walter, H, Wang, L, Wang, Y, Weber, B, Wen, W, West, JD, Westlye, LT, Whalley, HC, Williams, SCR, Wittfeld, K, Wolf, DH, Wright, MJ, Yoncheva, YN, Zanetti, M, Ziegler, GC, de Zubicaray, G, Thompson, PM, Crone, EA, Frangou, S, and Tamnes, CK
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.
Published: 2020

24. The genetic architecture of the human cerebral cortex

Author: Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Nhat, TD, Dohm, K, Ehrlich, S, Engelbrecht, H-R, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, J-J, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Kramer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Mirza-Schreiber, N, Moreira, JCV, Muhleisen, TW, Mueller-Myhsok, B, Najt, P, Nakahara, S, Nho, K, Loohuis, LMO, Orfanos, DP, Pearson, JF, Pitcher, TL, Putz, B, Quide, Y, Ragothaman, A, Rashid, FM, Reay, WR, Redlich, R, Reinbold, CS, Repple, J, Richard, G, Riedel, BC, Risacher, SL, Rocha, CS, Mota, NR, Salminen, L, Saremi, A, Saykin, AJ, Schlag, F, Schmaal, L, Schofield, PR, Secolin, R, Shapland, CY, Shen, L, Shin, J, Shumskaya, E, Sonderby, IE, Sprooten, E, Tansey, KE, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, JA, Uhlmann, A, Vallerga, CL, van der Meer, D, van Donkelaar, MMJ, van Eijk, L, van Erp, TGM, van Haren, NEM, van Rooij, D, van Tol, M-J, Veldink, JH, Verhoef, E, Walton, E, Wang, M, Wang, Y, Wardlaw, JM, Wen, W, Westlye, LT, Whelan, CD, Witt, SH, Wittfeld, K, Wolf, C, Wolfers, T, Wu, JQ, Yasuda, CL, Zaremba, D, Zhang, Z, Zwiers, MP, Artiges, E, Assareh, AA, Ayesa-Arriola, R, Belger, A, Brandt, CL, Brown, GG, Cichon, S, Curran, JE, Davies, GE, Degenhardt, F, Dennis, MF, Dietsche, B, Djurovic, S, Doherty, CP, Espiritu, R, Garijo, D, Gil, Y, Gowland, PA, Green, RC, Hausler, AN, Heindel, W, Ho, B-C, Hoffmann, WU, Holsboer, F, Homuth, G, Hosten, N, Jack, CR, Jang, M, Jansen, A, Kimbrel, NA, Kolskar, K, Koops, S, Krug, A, Lim, KO, Luykx, JJ, Mathalon, DH, Mather, KA, Mattay, VS, Matthews, S, Van Son, JM, McEwen, SC, Melle, I, Morris, DW, Mueller, BA, Nauck, M, Nordvik, JE, Noethen, MM, O'Leary, DS, Opel, N, Martinot, M-LP, Pike, GB, Preda, A, Quinlan, EB, Rasser, PE, Ratnakar, V, Reppermund, S, Steen, VM, Tooney, PA, Torres, FR, Veltman, DJ, Voyvodic, JT, Whelan, R, White, T, Yamamori, H, Adams, HHH, Bis, JC, Debette, S, Decarli, C, Fornage, M, Gudnason, V, Hofer, E, Ikram, MA, Launer, L, Longstreth, WT, Lopez, OL, Mazoyer, B, Mosley, TH, Roshchupkin, GV, Satizabal, CL, Schmidt, R, Seshadri, S, Yang, Q, Alvim, MKM, Ames, D, Anderson, TJ, Andreassen, OA, Arias-Vasquez, A, Bastin, ME, Baune, BT, Beckham, JC, Blangero, J, Boomsma, DI, Brodaty, H, Brunner, HG, Buckner, RL, Buitelaar, JK, Bustillo, JR, Cahn, W, Cairns, MJ, Calhoun, V, Carr, VJ, Caseras, X, Caspers, S, Cavalleri, GL, Cendes, F, Corvin, A, Crespo-Facorro, B, Dalrymple-Alford, JC, Dannlowski, U, de Geus, EJC, Deary, IJ, Delanty, N, Depondt, C, Desrivieres, S, Donohoe, G, Espeseth, T, Fernandez, G, Fisher, SE, Flor, H, Forstner, AJ, Francks, C, Franke, B, Glahn, DC, Gollub, RL, Grabe, HJ, Gruber, O, Haberg, AK, Hariri, AR, Hartman, CA, Hashimoto, R, Heinz, A, Henskens, FA, Hillegers, MHJ, Hoekstra, PJ, Holmes, AJ, Hong, LE, Hopkins, WD, Pol, HEH, Jernigan, TL, Jonsson, EG, Kahn, RS, Kennedy, MA, Kircher, TTJ, Kochunov, P, Kwok, JBJ, Le Hellard, S, Loughland, CM, Martin, NG, Martinot, J-L, McDonald, C, McMahon, KL, Meyer-Lindenberg, A, Michie, PT, Morey, RA, Mowry, B, Nyberg, L, Oosterlaan, J, Ophoff, RA, Pantelis, C, Paus, T, Pausova, Z, Penninx, BWJH, Polderman, TJC, Posthuma, D, Rietschel, M, Roffman, JL, Rowland, LM, Sachdev, PS, Samann, PG, Schall, U, Schumann, G, Scott, RJ, Sim, K, Sisodiya, SM, Smoller, JW, Sommer, IE, St Pourcain, B, Stein, DJ, Toga, AW, Trollor, JN, Van der Wee, NJA, van't Ent, D, Volzke, H, Walter, H, Weber, B, Weinberger, DR, Wright, MJ, Zhou, J, Stein, JL, Thompson, PM, Medland, SE, Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Nhat, TD, Dohm, K, Ehrlich, S, Engelbrecht, H-R, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, J-J, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Kramer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Mirza-Schreiber, N, Moreira, JCV, Muhleisen, TW, Mueller-Myhsok, B, Najt, P, Nakahara, S, Nho, K, Loohuis, LMO, Orfanos, DP, Pearson, JF, Pitcher, TL, Putz, B, Quide, Y, Ragothaman, A, Rashid, FM, Reay, WR, Redlich, R, Reinbold, CS, Repple, J, Richard, G, Riedel, BC, Risacher, SL, Rocha, CS, Mota, NR, Salminen, L, Saremi, A, Saykin, AJ, Schlag, F, Schmaal, L, Schofield, PR, Secolin, R, Shapland, CY, Shen, L, Shin, J, Shumskaya, E, Sonderby, IE, Sprooten, E, Tansey, KE, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, JA, Uhlmann, A, Vallerga, CL, van der Meer, D, van Donkelaar, MMJ, van Eijk, L, van Erp, TGM, van Haren, NEM, van Rooij, D, van Tol, M-J, Veldink, JH, Verhoef, E, Walton, E, Wang, M, Wang, Y, Wardlaw, JM, Wen, W, Westlye, LT, Whelan, CD, Witt, SH, Wittfeld, K, Wolf, C, Wolfers, T, Wu, JQ, Yasuda, CL, Zaremba, D, Zhang, Z, Zwiers, MP, Artiges, E, Assareh, AA, Ayesa-Arriola, R, Belger, A, Brandt, CL, Brown, GG, Cichon, S, Curran, JE, Davies, GE, Degenhardt, F, Dennis, MF, Dietsche, B, Djurovic, S, Doherty, CP, Espiritu, R, Garijo, D, Gil, Y, Gowland, PA, Green, RC, Hausler, AN, Heindel, W, Ho, B-C, Hoffmann, WU, Holsboer, F, Homuth, G, Hosten, N, Jack, CR, Jang, M, Jansen, A, Kimbrel, NA, Kolskar, K, Koops, S, Krug, A, Lim, KO, Luykx, JJ, Mathalon, DH, Mather, KA, Mattay, VS, Matthews, S, Van Son, JM, McEwen, SC, Melle, I, Morris, DW, Mueller, BA, Nauck, M, Nordvik, JE, Noethen, MM, O'Leary, DS, Opel, N, Martinot, M-LP, Pike, GB, Preda, A, Quinlan, EB, Rasser, PE, Ratnakar, V, Reppermund, S, Steen, VM, Tooney, PA, Torres, FR, Veltman, DJ, Voyvodic, JT, Whelan, R, White, T, Yamamori, H, Adams, HHH, Bis, JC, Debette, S, Decarli, C, Fornage, M, Gudnason, V, Hofer, E, Ikram, MA, Launer, L, Longstreth, WT, Lopez, OL, Mazoyer, B, Mosley, TH, Roshchupkin, GV, Satizabal, CL, Schmidt, R, Seshadri, S, Yang, Q, Alvim, MKM, Ames, D, Anderson, TJ, Andreassen, OA, Arias-Vasquez, A, Bastin, ME, Baune, BT, Beckham, JC, Blangero, J, Boomsma, DI, Brodaty, H, Brunner, HG, Buckner, RL, Buitelaar, JK, Bustillo, JR, Cahn, W, Cairns, MJ, Calhoun, V, Carr, VJ, Caseras, X, Caspers, S, Cavalleri, GL, Cendes, F, Corvin, A, Crespo-Facorro, B, Dalrymple-Alford, JC, Dannlowski, U, de Geus, EJC, Deary, IJ, Delanty, N, Depondt, C, Desrivieres, S, Donohoe, G, Espeseth, T, Fernandez, G, Fisher, SE, Flor, H, Forstner, AJ, Francks, C, Franke, B, Glahn, DC, Gollub, RL, Grabe, HJ, Gruber, O, Haberg, AK, Hariri, AR, Hartman, CA, Hashimoto, R, Heinz, A, Henskens, FA, Hillegers, MHJ, Hoekstra, PJ, Holmes, AJ, Hong, LE, Hopkins, WD, Pol, HEH, Jernigan, TL, Jonsson, EG, Kahn, RS, Kennedy, MA, Kircher, TTJ, Kochunov, P, Kwok, JBJ, Le Hellard, S, Loughland, CM, Martin, NG, Martinot, J-L, McDonald, C, McMahon, KL, Meyer-Lindenberg, A, Michie, PT, Morey, RA, Mowry, B, Nyberg, L, Oosterlaan, J, Ophoff, RA, Pantelis, C, Paus, T, Pausova, Z, Penninx, BWJH, Polderman, TJC, Posthuma, D, Rietschel, M, Roffman, JL, Rowland, LM, Sachdev, PS, Samann, PG, Schall, U, Schumann, G, Scott, RJ, Sim, K, Sisodiya, SM, Smoller, JW, Sommer, IE, St Pourcain, B, Stein, DJ, Toga, AW, Trollor, JN, Van der Wee, NJA, van't Ent, D, Volzke, H, Walter, H, Weber, B, Weinberger, DR, Wright, MJ, Zhou, J, Stein, JL, Thompson, PM, and Medland, SE
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020

25. Mapping brain asymmetry in health and disease through the ENIGMA consortium

Author: Kong, X-Z, Postema, MC, Guadalupe, T, de Kovel, C, Boedhoe, PSW, Hoogman, M, Mathias, SR, van Rooij, D, Schijven, D, Glahn, DC, Medland, SE, Jahanshad, N, Thomopoulos, S, Turner, JA, Buitelaar, J, van Erp, TGM, Franke, B, Fisher, SE, van den Heuvel, OA, Schmaal, L, Thompson, PM, Francks, C, Kong, X-Z, Postema, MC, Guadalupe, T, de Kovel, C, Boedhoe, PSW, Hoogman, M, Mathias, SR, van Rooij, D, Schijven, D, Glahn, DC, Medland, SE, Jahanshad, N, Thomopoulos, S, Turner, JA, Buitelaar, J, van Erp, TGM, Franke, B, Fisher, SE, van den Heuvel, OA, Schmaal, L, Thompson, PM, and Francks, C
Abstract: Left-right asymmetry of the human brain is one of its cardinal features, and also a complex, multivariate trait. Decades of research have suggested that brain asymmetry may be altered in psychiatric disorders. However, findings have been inconsistent and often based on small sample sizes. There are also open questions surrounding which structures are asymmetrical on average in the healthy population, and how variability in brain asymmetry relates to basic biological variables such as age and sex. Over the last 4 years, the ENIGMA-Laterality Working Group has published six studies of gray matter morphological asymmetry based on total sample sizes from roughly 3,500 to 17,000 individuals, which were between one and two orders of magnitude larger than those published in previous decades. A population-level mapping of average asymmetry was achieved, including an intriguing fronto-occipital gradient of cortical thickness asymmetry in healthy brains. ENIGMA's multi-dataset approach also supported an empirical illustration of reproducibility of hemispheric differences across datasets. Effect sizes were estimated for gray matter asymmetry based on large, international, samples in relation to age, sex, handedness, and brain volume, as well as for three psychiatric disorders: autism spectrum disorder was associated with subtly reduced asymmetry of cortical thickness at regions spread widely over the cortex; pediatric obsessive-compulsive disorder was associated with altered subcortical asymmetry; major depressive disorder was not significantly associated with changes of asymmetry. Ongoing studies are examining brain asymmetry in other disorders. Moreover, a groundwork has been laid for possibly identifying shared genetic contributions to brain asymmetry and disorders.
Published: 2020

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

Author: Kochunov, P, Hong, LE, Dennis, EL, Morey, RA, Tate, DF, Wilde, EA, Logue, M, Kelly, S, Donohoe, G, Favre, P, Houenou, J, Ching, CRK, Holleran, L, Andreassen, OA, van Velzen, LS, Schmaal, L, Villalon-Reina, JE, Bearden, CE, Piras, F, Spalletta, G, van den Heuvel, OA, Veltman, DJ, Stein, DJ, Ryan, MC, Tan, Y, van Erp, TGM, Turner, JA, Haddad, L, Nir, TM, Glahn, DC, Thompson, PM, Jahanshad, N, Kochunov, P, Hong, LE, Dennis, EL, Morey, RA, Tate, DF, Wilde, EA, Logue, M, Kelly, S, Donohoe, G, Favre, P, Houenou, J, Ching, CRK, Holleran, L, Andreassen, OA, van Velzen, LS, Schmaal, L, Villalon-Reina, JE, Bearden, CE, Piras, F, Spalletta, G, van den Heuvel, OA, Veltman, DJ, Stein, DJ, Ryan, MC, Tan, Y, van Erp, TGM, Turner, JA, Haddad, L, Nir, TM, Glahn, DC, Thompson, PM, and Jahanshad, N
Abstract: The ENIGMA-DTI (diffusion tensor imaging) workgroup supports analyses that examine the effects of psychiatric, neurological, and developmental disorders on the white matter pathways of the human brain, as well as the effects of normal variation and its genetic associations. The seven ENIGMA disorder-oriented working groups used the ENIGMA-DTI workflow to derive patterns of deficits using coherent and coordinated analyses that model the disease effects across cohorts worldwide. This yielded the largest studies detailing patterns of white matter deficits in schizophrenia spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and 22q11 deletion syndrome. These deficit patterns are informative of the underlying neurobiology and reproducible in independent cohorts. We reviewed these findings, demonstrated their reproducibility in independent cohorts, and compared the deficit patterns across illnesses. We discussed translating ENIGMA-defined deficit patterns on the level of individual subjects using a metric called the regional vulnerability index (RVI), a correlation of an individual's brain metrics with the expected pattern for a disorder. We discussed the similarity in white matter deficit patterns among SSD, BD, MDD, and OCD and provided a rationale for using this index in cross-diagnostic neuropsychiatric research. We also discussed the difference in deficit patterns between idiopathic schizophrenia and 22q11 deletion syndrome, which is used as a developmental and genetic model of schizophrenia. Together, these findings highlight the importance of collaborative large-scale research to provide robust and reproducible effects that offer insights into individual vulnerability and cross-diagnosis features.
Published: 2020

27. Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes

Author: Carless, MA, Glahn, DC, Johnson, MP, Curran, JE, Bozaoglu, K, Dyer, TD, Winkler, AM, Cole, SA, Almasy, L, MacCluer, JW, Duggirala, R, Moses, EK, Göring, HHH, and Blangero, J
Published: 2011
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28. Dissecting the functions of DISC1

Author: Carless, MA, Glahn, DC, Winkler, AM, and Blangero, J
Published: 2011
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29. 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, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Bustillo, JR, Clark, VP, Agartz, I, Mueller, BA, Cahn, W, de Zwarte, SMC, Hulshoff Pol, HE, Kahn, RS, Ophoff, RA, van Haren, NEM, Andreassen, OA, Dale, AM, Doan, NT, Gurholt, TP, Hartberg, CB, Haukvik, UK, Jørgensen, KN, Lagerberg, TV, Melle, I, Westlye, LT, Gruber, O, Kraemer, B, Richter, A, Zilles, D, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Carr, VJ, Catts, S, Cropley, VL, Fullerton, JM, Green, MJ, Henskens, FA, Jablensky, A, Lenroot, RK, Mowry, BJ, Michie, PT, Pantelis, C, Quidé, Y, Schall, U, and Scott, RJ
Abstract: © 2018 Society of Biological Psychiatry Background: The 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. Methods: The 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. Results: Compared 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. Conclusions: The 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

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

Author: de Zwarte, SMC, Brouwer, RM, Agartz, I, Alda, M, Aleman, A, Alpert, KI, Bearden, CE, Bertolino, A, Bois, C, Bonvino, A, Bramon, E, Buimer, EEL, Cahn, W, Cannon, DM, Cannon, TD, Caseras, X, Castro-Fornieles, J, Chen, Q, Chung, Y, De la Serna, E, Di Giorgio, A, Doucet, GE, Eker, MC, Erk, S, Fears, SC, Foley, SF, Frangou, S, Frankland, A, Fullerton, JM, Glahn, DC, Goghari, VM, Goldman, AL, Gonul, AS, Gruber, O, de Haan, L, Hajek, T, Hawkins, EL, Heinz, A, Hillegers, MHJ, Hulshoff Pol, HE, Hultman, CM, Ingvar, M, Johansson, V, Jönsson, EG, Kane, F, Kempton, MJ, Koenis, MMG, Kopecek, M, Krabbendam, L, Krämer, B, Lawrie, SM, Lenroot, RK, Marcelis, M, Marsman, JBC, Mattay, VS, McDonald, C, Meyer-Lindenberg, A, Michielse, S, Mitchell, PB, Moreno, D, Murray, RM, Mwangi, B, Najt, P, Neilson, E, Newport, J, van Os, J, Overs, B, Ozerdem, A, Picchioni, MM, Richter, A, Roberts, G, Aydogan, AS, Schofield, PR, Simsek, F, Soares, JC, Sugranyes, G, Toulopoulou, T, Tronchin, G, Walter, H, Wang, L, Weinberger, DR, Whalley, HC, Yalin, N, Andreassen, OA, Ching, CRK, van Erp, TGM, Turner, JA, Jahanshad, N, Thompson, PM, Kahn, RS, van Haren, NEM, de Zwarte, SMC, Brouwer, RM, Agartz, I, Alda, M, Aleman, A, Alpert, KI, Bearden, CE, Bertolino, A, Bois, C, Bonvino, A, Bramon, E, Buimer, EEL, Cahn, W, Cannon, DM, Cannon, TD, Caseras, X, Castro-Fornieles, J, Chen, Q, Chung, Y, De la Serna, E, Di Giorgio, A, Doucet, GE, Eker, MC, Erk, S, Fears, SC, Foley, SF, Frangou, S, Frankland, A, Fullerton, JM, Glahn, DC, Goghari, VM, Goldman, AL, Gonul, AS, Gruber, O, de Haan, L, Hajek, T, Hawkins, EL, Heinz, A, Hillegers, MHJ, Hulshoff Pol, HE, Hultman, CM, Ingvar, M, Johansson, V, Jönsson, EG, Kane, F, Kempton, MJ, Koenis, MMG, Kopecek, M, Krabbendam, L, Krämer, B, Lawrie, SM, Lenroot, RK, Marcelis, M, Marsman, JBC, Mattay, VS, McDonald, C, Meyer-Lindenberg, A, Michielse, S, Mitchell, PB, Moreno, D, Murray, RM, Mwangi, B, Najt, P, Neilson, E, Newport, J, van Os, J, Overs, B, Ozerdem, A, Picchioni, MM, Richter, A, Roberts, G, Aydogan, AS, Schofield, PR, Simsek, F, Soares, JC, Sugranyes, G, Toulopoulou, T, Tronchin, G, Walter, H, Wang, L, Weinberger, DR, Whalley, HC, Yalin, N, Andreassen, OA, Ching, CRK, van Erp, TGM, Turner, JA, Jahanshad, N, Thompson, PM, Kahn, RS, and van Haren, NEM
Abstract: Background: Schizophrenia 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. Methods: We 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. Results: FDRs-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 < −0.09, q <.05 corrected); and third ventricle was larger (d = +0.15, q <.05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. Conclusions: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
Published: 2019

31. Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

Author: van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Clark, VP, Mueller, BA, de Zwarte, SMC, Ophoff, RA, van Haren, NEM, Andreassen, OA, Gurholt, TP, Gruber, O, Kraemer, B, Richter, A, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Catts, S, Fullerton, JM, Green, MJ, Henskens, F, Jablensky, A, Mowry, BJ, Pantelis, C, Quidé, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Shannon Weickert, C, Weickert, TW, Hong, E, Kochunov, P, Gur, RE, Gur, RC, Ford, JM, Macciardi, F, Mathalon, DH, Potkin, SG, Preda, A, Fan, F, Ehrlich, S, King, MD, De Haan, L, Veltman, DJ, Assogna, F, Banaj, N, de Rossi, P, Iorio, M, Piras, F, Spalletta, G, Pomarol-Clotet, E, Kelly, S, Ciufolini, S, Radua, J, Murray, R, Marques, TR, Simmons, A, Borgwardt, S, Schönborn-Harrisberger, F, Riecher-Rössler, A, Smieskova, R, Alpert, KI, Bertolino, A, Bonvino, A, Di Giorgio, A, Neilson, E, Mayer, AR, Yun, JY, Cannon, DM, Lebedeva, I, Tomyshev, AS, Akhadov, T, Kaleda, V, Fatouros-Bergman, H, Flyckt, L, Farde, L, Cervenka, S, Agartz, I, Collste, K, Victorsson, P, Engberg, G, Erhardt, S, Schwieler, L, Malmqvist, A, Hedberg, M, Orhan, F, van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Clark, VP, Mueller, BA, de Zwarte, SMC, Ophoff, RA, van Haren, NEM, Andreassen, OA, Gurholt, TP, Gruber, O, Kraemer, B, Richter, A, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Catts, S, Fullerton, JM, Green, MJ, Henskens, F, Jablensky, A, Mowry, BJ, Pantelis, C, Quidé, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Shannon Weickert, C, Weickert, TW, Hong, E, Kochunov, P, Gur, RE, Gur, RC, Ford, JM, Macciardi, F, Mathalon, DH, Potkin, SG, Preda, A, Fan, F, Ehrlich, S, King, MD, De Haan, L, Veltman, DJ, Assogna, F, Banaj, N, de Rossi, P, Iorio, M, Piras, F, Spalletta, G, Pomarol-Clotet, E, Kelly, S, Ciufolini, S, Radua, J, Murray, R, Marques, TR, Simmons, A, Borgwardt, S, Schönborn-Harrisberger, F, Riecher-Rössler, A, Smieskova, R, Alpert, KI, Bertolino, A, Bonvino, A, Di Giorgio, A, Neilson, E, Mayer, AR, Yun, JY, Cannon, DM, Lebedeva, I, Tomyshev, AS, Akhadov, T, Kaleda, V, Fatouros-Bergman, H, Flyckt, L, Farde, L, Cervenka, S, Agartz, I, Collste, K, Victorsson, P, Engberg, G, Erhardt, S, Schwieler, L, Malmqvist, A, Hedberg, M, and Orhan, F
Published: 2019

32. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, DeRosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A, Trompet, S, van der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Boehmer, AC, Boyle, PA, Brodaty, H, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kahonen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Knopman, DS, Kochan, NA, Konte, B, Kwok, JB, Le Hellard, S, Lee, T, Lehtimaki, T, Li, S-C, Liu, T, Koini, M, London, E, Longstreth, WT, Lopez, OL, Loukola, A, Luck, T, Lundervold, AJ, Lundquist, A, Lyytikainen, L-P, Martin, NG, Montgomery, GW, Murray, AD, Need, AC, Noordam, R, Nyberg, L, Ollier, W, Papenberg, G, Pattie, A, Polasek, O, Poldrack, RA, Psaty, BM, Reppermund, S, Riedel-Heller, SG, Rose, RJ, Rotter, JI, Roussos, P, Rovio, SP, Saba, Y, Sabb, FW, Sachdev, PS, Satizabal, CL, Schmid, M, Scott, RJ, Scult, MA, Simino, J, Slagboom, PE, Smyrnis, N, Soumare, A, Stefanis, NC, Stott, DJ, Straub, RE, Sundet, K, Taylor, AM, Taylor, KD, Tzoulaki, I, Tzourio, C, Uitterlinden, A, Vitart, V, Voineskos, AN, Kaprio, J, Wagner, M, Wagner, H, Weinhold, L, Wen, KH, Widen, E, Yang, Q, Zhao, W, Adams, HHH, Arking, DE, Bilder, RM, Bitsios, P, Boerwinkle, E, Chiba-Falek, O, Corvin, A, De Jager, PL, Debette, S, Donohoe, G, Elliott, P, Fitzpatrick, AL, Gill, M, Glahn, DC, Hagg, S, Hansell, NK, Hariri, AR, Ikram, MK, Jukema, JW, Vuoksimaa, E, Keller, MC, Kremen, WS, Launer, L, Lindenberger, U, Palotie, A, Pedersen, NL, Pendleton, N, Porteous, DJ, Raikkonen, K, Raitakari, OT, Ramirez, A, Reinvang, I, Rudan, I, Rujescu, D, Schmidt, R, Schmidt, H, Schofield, PW, Schofield, PR, Starr, JM, Steen, VM, Trollor, JN, Turner, ST, Van Duijn, CM, Villringer, A, Weinberger, DR, Weir, DR, Wilson, JF, Malhotra, A, McIntosh, AM, Gale, CR, Seshadri, S, Mosley, TH, Bressler, J, Lencz, T, Deary, IJ, Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, DeRosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A, Trompet, S, van der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Boehmer, AC, Boyle, PA, Brodaty, H, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kahonen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Knopman, DS, Kochan, NA, Konte, B, Kwok, JB, Le Hellard, S, Lee, T, Lehtimaki, T, Li, S-C, Liu, T, Koini, M, London, E, Longstreth, WT, Lopez, OL, Loukola, A, Luck, T, Lundervold, AJ, Lundquist, A, Lyytikainen, L-P, Martin, NG, Montgomery, GW, Murray, AD, Need, AC, Noordam, R, Nyberg, L, Ollier, W, Papenberg, G, Pattie, A, Polasek, O, Poldrack, RA, Psaty, BM, Reppermund, S, Riedel-Heller, SG, Rose, RJ, Rotter, JI, Roussos, P, Rovio, SP, Saba, Y, Sabb, FW, Sachdev, PS, Satizabal, CL, Schmid, M, Scott, RJ, Scult, MA, Simino, J, Slagboom, PE, Smyrnis, N, Soumare, A, Stefanis, NC, Stott, DJ, Straub, RE, Sundet, K, Taylor, AM, Taylor, KD, Tzoulaki, I, Tzourio, C, Uitterlinden, A, Vitart, V, Voineskos, AN, Kaprio, J, Wagner, M, Wagner, H, Weinhold, L, Wen, KH, Widen, E, Yang, Q, Zhao, W, Adams, HHH, Arking, DE, Bilder, RM, Bitsios, P, Boerwinkle, E, Chiba-Falek, O, Corvin, A, De Jager, PL, Debette, S, Donohoe, G, Elliott, P, Fitzpatrick, AL, Gill, M, Glahn, DC, Hagg, S, Hansell, NK, Hariri, AR, Ikram, MK, Jukema, JW, Vuoksimaa, E, Keller, MC, Kremen, WS, Launer, L, Lindenberger, U, Palotie, A, Pedersen, NL, Pendleton, N, Porteous, DJ, Raikkonen, K, Raitakari, OT, Ramirez, A, Reinvang, I, Rudan, I, Rujescu, D, Schmidt, R, Schmidt, H, Schofield, PW, Schofield, PR, Starr, JM, Steen, VM, Trollor, JN, Turner, ST, Van Duijn, CM, Villringer, A, Weinberger, DR, Weir, DR, Wilson, JF, Malhotra, A, McIntosh, AM, Gale, CR, Seshadri, S, Mosley, TH, Bressler, J, Lencz, T, and Deary, IJ
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
Published: 2018

33. GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium (vol 22, pg 336, 2017)

Author: Trampush, JW, Yang, MLZ, Yu, J, Knowles, E, Davies, G, Liewald, DC, Starr, JM, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Raikkonen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Horan, M, Chiba-Falek, O, Attix, DK, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Arking, DE, Smyrnis, N, Bilder, RM, Freimer, NA, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, ED, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Malhotra, AK, and Lencz, T
Subjects: Psychiatry, 17 Psychology And Cognitive Sciences, Biochemistry & Molecular Biology, Science & Technology, Neurosciences, Neurosciences & Neurology, 11 Medical And Health Sciences, 06 Biological Sciences, Life Sciences & Biomedicine
Published: 2017

34. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

Author: Guadalupe, T, Mathias, SR, vanErp, TGM, Whelan, CD, Zwiers, MP, Abe, Y, Abramovic, L, Agartz, I, Andreassen, OA, Arias-Vásquez, A, Aribisala, BS, Armstrong, NJ, Arolt, V, Artiges, E, Ayesa-Arriola, R, Baboyan, VG, Banaschewski, T, Barker, G, Bastin, ME, Baune, BT, Blangero, J, Bokde, ALW, Boedhoe, PSW, Bose, A, Brem, S, Brodaty, H, Bromberg, U, Brooks, S, Büchel, C, Buitelaar, J, Calhoun, VD, Cannon, DM, Cattrell, A, Cheng, Y, Conrod, PJ, Conzelmann, A, Corvin, A, Crespo-Facorro, B, Crivello, F, Dannlowski, U, de Zubicaray, GI, de Zwarte, SMC, Deary, IJ, Desrivières, S, Doan, NT, Donohoe, G, Dørum, ES, Ehrlich, S, Espeseth, T, Fernández, G, Flor, H, Fouche, J-P, Frouin, V, Fukunaga, M, Gallinat, J, Garavan, H, Gill, M, Suarez, AG, Gowland, P, Grabe, HJ, Grotegerd, D, Gruber, O, Hagenaars, S, Hashimoto, R, Hauser, TU, Heinz, A, Hibar, DP, Hoekstra, PJ, Hoogman, M, Howells, FM, Hu, H, Hulshoff Pol, HE, Huyser, C, Ittermann, B, Jahanshad, N, Jönsson, EG, Jurk, S, Kahn, RS, Kelly, S, Kraemer, B, Kugel, H, Kwon, JS, Lemaitre, H, Lesch, K-P, Lochner, C, Luciano, M, Marquand, AF, Martin, NG, Martínez-Zalacaín, I, Martinot, J-L, Mataix-Cols, D, Mather, K, McDonald, C, McMahon, KL, Medland, SE, Menchón, JM, Morris, DW, Mothersill, O, Maniega, SM, Mwangi, B, Nakamae, T, Nakao, T, Narayanaswaamy, JC, Nees, F, Nordvik, JE, Onnink, AMH, Opel, N, Ophoff, R, Paillère Martinot, M-L, Papadopoulos Orfanos, D, Pauli, P, Paus, T, Poustka, L, Reddy, JY, Renteria, ME, Roiz-Santiáñez, R, Roos, A, Royle, NA, Sachdev, P, Sánchez-Juan, P, Schmaal, L, Schumann, G, Shumskaya, E, Smolka, MN, Soares, JC, Soriano-Mas, C, Stein, DJ, Strike, LT, Toro, R, Turner, JA, Tzourio-Mazoyer, N, Uhlmann, A, Hernández, MV, van den Heuvel, OA, van der Meer, D, van Haren, NEM, Veltman, DJ, Venkatasubramanian, G, Vetter, NC, Vuletic, D, Walitza, S, Walter, H, Walton, E, Wang, Z, Wardlaw, J, Wen, W, Westlye, LT, Whelan, R, Wittfeld, K, Wolfers, T, Wright, MJ, Xu, J, Xu, X, Yun, J-Y, Zhao, J, Franke, B, Thompson, PM, Glahn, DC, Mazoyer, B, Fisher, SE, Francks, C, Guadalupe, T, Mathias, SR, vanErp, TGM, Whelan, CD, Zwiers, MP, Abe, Y, Abramovic, L, Agartz, I, Andreassen, OA, Arias-Vásquez, A, Aribisala, BS, Armstrong, NJ, Arolt, V, Artiges, E, Ayesa-Arriola, R, Baboyan, VG, Banaschewski, T, Barker, G, Bastin, ME, Baune, BT, Blangero, J, Bokde, ALW, Boedhoe, PSW, Bose, A, Brem, S, Brodaty, H, Bromberg, U, Brooks, S, Büchel, C, Buitelaar, J, Calhoun, VD, Cannon, DM, Cattrell, A, Cheng, Y, Conrod, PJ, Conzelmann, A, Corvin, A, Crespo-Facorro, B, Crivello, F, Dannlowski, U, de Zubicaray, GI, de Zwarte, SMC, Deary, IJ, Desrivières, S, Doan, NT, Donohoe, G, Dørum, ES, Ehrlich, S, Espeseth, T, Fernández, G, Flor, H, Fouche, J-P, Frouin, V, Fukunaga, M, Gallinat, J, Garavan, H, Gill, M, Suarez, AG, Gowland, P, Grabe, HJ, Grotegerd, D, Gruber, O, Hagenaars, S, Hashimoto, R, Hauser, TU, Heinz, A, Hibar, DP, Hoekstra, PJ, Hoogman, M, Howells, FM, Hu, H, Hulshoff Pol, HE, Huyser, C, Ittermann, B, Jahanshad, N, Jönsson, EG, Jurk, S, Kahn, RS, Kelly, S, Kraemer, B, Kugel, H, Kwon, JS, Lemaitre, H, Lesch, K-P, Lochner, C, Luciano, M, Marquand, AF, Martin, NG, Martínez-Zalacaín, I, Martinot, J-L, Mataix-Cols, D, Mather, K, McDonald, C, McMahon, KL, Medland, SE, Menchón, JM, Morris, DW, Mothersill, O, Maniega, SM, Mwangi, B, Nakamae, T, Nakao, T, Narayanaswaamy, JC, Nees, F, Nordvik, JE, Onnink, AMH, Opel, N, Ophoff, R, Paillère Martinot, M-L, Papadopoulos Orfanos, D, Pauli, P, Paus, T, Poustka, L, Reddy, JY, Renteria, ME, Roiz-Santiáñez, R, Roos, A, Royle, NA, Sachdev, P, Sánchez-Juan, P, Schmaal, L, Schumann, G, Shumskaya, E, Smolka, MN, Soares, JC, Soriano-Mas, C, Stein, DJ, Strike, LT, Toro, R, Turner, JA, Tzourio-Mazoyer, N, Uhlmann, A, Hernández, MV, van den Heuvel, OA, van der Meer, D, van Haren, NEM, Veltman, DJ, Venkatasubramanian, G, Vetter, NC, Vuletic, D, Walitza, S, Walter, H, Walton, E, Wang, Z, Wardlaw, J, Wen, W, Westlye, LT, Whelan, R, Wittfeld, K, Wolfers, T, Wright, MJ, Xu, J, Xu, X, Yun, J-Y, Zhao, J, Franke, B, Thompson, PM, Glahn, DC, Mazoyer, B, Fisher, SE, and Francks, C
Abstract: The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.
Published: 2017

35. Novel genetic loci associated with hippocampal volume

Author: Hibar, DP, Adams, HHH, Jahanshad, N, Chauhan, G, Stein, JL, Hofer, E, Renteria, ME, Bis, JC, Arias-Vasquez, A, Ikram, MK, Desrivieres, S, Vernooij, MW, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beecham, AH, Beiser, A, Bernard, M, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chen, Q, Ching, CRK, Chouraki, V, Cuellar-Partida, G, Crivello, F, Den Braber, A, Nhat, TD, Ehrlich, S, Giddaluru, S, Goldman, AL, Gottesman, RF, Grimm, O, Griswold, ME, Guadalupe, T, Gutman, BA, Hass, J, Haukvik, UK, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Jorgensen, KN, Karbalai, N, Kasperaviciute, D, Kim, S, Klein, M, Kraemer, B, Lee, PH, Liewald, DCM, Lopez, LM, Luciano, M, Macare, C, Marquand, AF, Matarin, M, Mather, KA, Mattheisen, M, McKay, DR, Milaneschi, Y, Maniega, SM, Nho, K, Nugent, AC, Nyquist, P, Loohuis, LMO, Oosterlaan, J, Papmeyer, M, Pirpamer, L, Puetz, B, Ramasamy, A, Richards, JS, Risacher, SL, Roiz-Santianez, R, Rommelse, N, Ropele, S, Rose, EJ, Royle, NA, Rundek, T, Saemann, PG, Saremi, A, Satizabal, CL, Schmaal, L, Schork, AJ, Shen, L, Shin, J, Shumskaya, E, Smith, AV, Sprooten, E, Strike, LT, Teumer, A, Tordesillas-Gutierrez, D, Toro, R, Trabzuni, D, Trompet, S, Vaidya, D, Van der Grond, J, Van der Lee, SJ, Van der Meer, D, Van Donkelaar, MMJ, Van Eijk, KR, Van Erp, TGM, Van Rooij, D, Walton, E, Westlye, LT, Whelan, CD, Windham, BG, Winkler, AM, Wittfeld, K, Woldehawariat, G, Wolf, C, Wolfers, T, Yanek, LR, Yang, J, Zijdenbos, A, Zwiers, MP, Agartz, I, Almasy, L, Ames, D, Amouyel, P, Andreassen, OA, Arepalli, S, Assareh, AA, Barral, S, Bastin, ME, Becker, DM, Becker, JT, Bennett, DA, Blangero, J, van Bokhoven, H, Boomsma, DI, Brodaty, H, Brouwer, RM, Brunner, HG, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cahn, W, Calhoun, VD, Cannon, DM, Cavalleri, GL, Cheng, C-Y, Cichon, S, Cookson, MR, Corvin, A, Crespo-Facorro, B, Curran, JE, Czisch, M, Dale, AM, Davies, GE, De Craen, AJM, De Geus, EJC, De Jager, PL, De Zubicaray, GI, Deary, IJ, Debette, S, DeCarli, C, Delanty, N, Depondt, C, DeStefano, A, Dillman, A, Djurovic, S, Donohoe, G, Drevets, WC, Duggirala, R, Dyer, TD, Enzinger, C, Erk, S, Espeseth, T, Fedko, IO, Fernandez, G, Ferrucci, L, Fisher, SE, Fleischman, DA, Ford, I, Fornage, M, Foroud, TM, Fox, PT, Francks, C, Fukunaga, M, Gibbs, JR, Glahn, DC, Gollub, RL, Goring, HHH, Green, RC, Gruber, O, Gudnason, V, Guelfi, S, Haberg, AK, Hansell, NK, Hardy, J, Hartman, CA, Hashimoto, R, Hegenscheid, K, Heinz, A, Le Hellard, S, Hernandez, DG, Heslenfeld, DJ, Ho, B-C, Hoekstra, PJ, Hoffmann, W, Hofman, A, Holsboer, F, Homuth, G, Hosten, N, Hottenga, J-J, Huentelman, M, Pol, HEH, Ikeda, M, Jack, CR, Jenkinson, M, Johnson, R, Joensson, EG, Jukema, JW, Kahn, RS, Kanai, R, Kloszewska, I, Knopman, DS, Kochunov, P, Kwok, JB, Lawrie, SM, Lemaitre, H, Liu, X, Longo, DL, Lopez, OL, Lovestone, S, Martinez, O, Martinot, J-L, Mattay, VS, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Mecocci, P, Melle, I, Meyer-Lindenberg, A, Mohnke, S, Montgomery, GW, Morris, DW, Mosley, TH, Muhleisen, TW, Mueller-Myhsok, B, Nalls, MA, Nauck, M, Nichols, TE, Niessen, WJ, Nothen, MM, Nyberg, L, Ohi, K, Olvera, RL, Ophoff, RA, Pandolfo, M, Paus, T, Pausova, Z, Penninx, BWJH, Pike, GB, Potkin, SG, Psaty, BM, Reppermund, S, Rietschel, M, Roffman, JL, Romanczuk-Seiferth, N, Rotter, JI, Ryten, M, Sacco, RL, Sachdev, PS, Saykin, AJ, Schmidt, R, Schmidt, H, Schofield, PR, Sigursson, S, Simmons, A, Singleton, A, Sisodiya, SM, Smith, C, Smoller, JW, Soininen, H, Steen, VM, Stott, DJ, Sussmann, JE, Thalamuthu, A, Toga, AW, Traynor, BJ, Troncoso, J, Tsolaki, M, Tzourio, C, Uitterlinden, AG, Hernandez, MCV, Van der Brug, M, van der Lugt, A, van der Wee, NJA, Van Haren, NEM, van't Ent, D, Van Tol, M-J, Vardarajan, BN, Vellas, B, Veltman, DJ, Voelzke, H, Walter, H, Wardlaw, JM, Wassink, TH, Weale, ME, Weinberger, DR, Weiner, MW, Wen, W, Westman, E, White, T, Wong, TY, Wright, CB, Zielke, RH, Zonderman, AB, Martin, NG, Van Duijn, CM, Wright, MJ, Longstreth, WT, Schumann, G, Grabe, HJ, Franke, B, Launer, LJ, Medland, SE, Seshadri, S, Thompson, PM, Ikram, MA, Hibar, DP, Adams, HHH, Jahanshad, N, Chauhan, G, Stein, JL, Hofer, E, Renteria, ME, Bis, JC, Arias-Vasquez, A, Ikram, MK, Desrivieres, S, Vernooij, MW, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beecham, AH, Beiser, A, Bernard, M, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chen, Q, Ching, CRK, Chouraki, V, Cuellar-Partida, G, Crivello, F, Den Braber, A, Nhat, TD, Ehrlich, S, Giddaluru, S, Goldman, AL, Gottesman, RF, Grimm, O, Griswold, ME, Guadalupe, T, Gutman, BA, Hass, J, Haukvik, UK, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Jorgensen, KN, Karbalai, N, Kasperaviciute, D, Kim, S, Klein, M, Kraemer, B, Lee, PH, Liewald, DCM, Lopez, LM, Luciano, M, Macare, C, Marquand, AF, Matarin, M, Mather, KA, Mattheisen, M, McKay, DR, Milaneschi, Y, Maniega, SM, Nho, K, Nugent, AC, Nyquist, P, Loohuis, LMO, Oosterlaan, J, Papmeyer, M, Pirpamer, L, Puetz, B, Ramasamy, A, Richards, JS, Risacher, SL, Roiz-Santianez, R, Rommelse, N, Ropele, S, Rose, EJ, Royle, NA, Rundek, T, Saemann, PG, Saremi, A, Satizabal, CL, Schmaal, L, Schork, AJ, Shen, L, Shin, J, Shumskaya, E, Smith, AV, Sprooten, E, Strike, LT, Teumer, A, Tordesillas-Gutierrez, D, Toro, R, Trabzuni, D, Trompet, S, Vaidya, D, Van der Grond, J, Van der Lee, SJ, Van der Meer, D, Van Donkelaar, MMJ, Van Eijk, KR, Van Erp, TGM, Van Rooij, D, Walton, E, Westlye, LT, Whelan, CD, Windham, BG, Winkler, AM, Wittfeld, K, Woldehawariat, G, Wolf, C, Wolfers, T, Yanek, LR, Yang, J, Zijdenbos, A, Zwiers, MP, Agartz, I, Almasy, L, Ames, D, Amouyel, P, Andreassen, OA, Arepalli, S, Assareh, AA, Barral, S, Bastin, ME, Becker, DM, Becker, JT, Bennett, DA, Blangero, J, van Bokhoven, H, Boomsma, DI, Brodaty, H, Brouwer, RM, Brunner, HG, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cahn, W, Calhoun, VD, Cannon, DM, Cavalleri, GL, Cheng, C-Y, Cichon, S, Cookson, MR, Corvin, A, Crespo-Facorro, B, Curran, JE, Czisch, M, Dale, AM, Davies, GE, De Craen, AJM, De Geus, EJC, De Jager, PL, De Zubicaray, GI, Deary, IJ, Debette, S, DeCarli, C, Delanty, N, Depondt, C, DeStefano, A, Dillman, A, Djurovic, S, Donohoe, G, Drevets, WC, Duggirala, R, Dyer, TD, Enzinger, C, Erk, S, Espeseth, T, Fedko, IO, Fernandez, G, Ferrucci, L, Fisher, SE, Fleischman, DA, Ford, I, Fornage, M, Foroud, TM, Fox, PT, Francks, C, Fukunaga, M, Gibbs, JR, Glahn, DC, Gollub, RL, Goring, HHH, Green, RC, Gruber, O, Gudnason, V, Guelfi, S, Haberg, AK, Hansell, NK, Hardy, J, Hartman, CA, Hashimoto, R, Hegenscheid, K, Heinz, A, Le Hellard, S, Hernandez, DG, Heslenfeld, DJ, Ho, B-C, Hoekstra, PJ, Hoffmann, W, Hofman, A, Holsboer, F, Homuth, G, Hosten, N, Hottenga, J-J, Huentelman, M, Pol, HEH, Ikeda, M, Jack, CR, Jenkinson, M, Johnson, R, Joensson, EG, Jukema, JW, Kahn, RS, Kanai, R, Kloszewska, I, Knopman, DS, Kochunov, P, Kwok, JB, Lawrie, SM, Lemaitre, H, Liu, X, Longo, DL, Lopez, OL, Lovestone, S, Martinez, O, Martinot, J-L, Mattay, VS, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Mecocci, P, Melle, I, Meyer-Lindenberg, A, Mohnke, S, Montgomery, GW, Morris, DW, Mosley, TH, Muhleisen, TW, Mueller-Myhsok, B, Nalls, MA, Nauck, M, Nichols, TE, Niessen, WJ, Nothen, MM, Nyberg, L, Ohi, K, Olvera, RL, Ophoff, RA, Pandolfo, M, Paus, T, Pausova, Z, Penninx, BWJH, Pike, GB, Potkin, SG, Psaty, BM, Reppermund, S, Rietschel, M, Roffman, JL, Romanczuk-Seiferth, N, Rotter, JI, Ryten, M, Sacco, RL, Sachdev, PS, Saykin, AJ, Schmidt, R, Schmidt, H, Schofield, PR, Sigursson, S, Simmons, A, Singleton, A, Sisodiya, SM, Smith, C, Smoller, JW, Soininen, H, Steen, VM, Stott, DJ, Sussmann, JE, Thalamuthu, A, Toga, AW, Traynor, BJ, Troncoso, J, Tsolaki, M, Tzourio, C, Uitterlinden, AG, Hernandez, MCV, Van der Brug, M, van der Lugt, A, van der Wee, NJA, Van Haren, NEM, van't Ent, D, Van Tol, M-J, Vardarajan, BN, Vellas, B, Veltman, DJ, Voelzke, H, Walter, H, Wardlaw, JM, Wassink, TH, Weale, ME, Weinberger, DR, Weiner, MW, Wen, W, Westman, E, White, T, Wong, TY, Wright, CB, Zielke, RH, Zonderman, AB, Martin, NG, Van Duijn, CM, Wright, MJ, Longstreth, WT, Schumann, G, Grabe, HJ, Franke, B, Launer, LJ, Medland, SE, Seshadri, S, Thompson, PM, and Ikram, MA
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017

36. ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide

Author: Thompson, PM, Andreassen, OA, Arias-Vasquez, A, Bearden, CE, Boedhoe, PS, Brouwer, RM, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cannon, DM, Cohen, RA, Conrod, PJ, Dale, AM, Deary, IJ, Dennis, EL, de Reus, MA, Desrivieres, S, Dima, D, Donohoe, G, Fisher, SE, Fouche, J-P, Francks, C, Frangou, S, Franke, B, Ganjgahi, H, Garavan, H, Glahn, DC, Grabe, HJ, Guadalupe, T, Gutman, BA, Hashimoto, R, Hibar, DP, Holland, D, Hoogman, M, Pol, HEH, Hosten, N, Jahanshad, N, Kelly, S, Kochunov, P, Kremen, WS, Lee, PH, Mackey, S, Martin, NG, Mazoyer, B, McDonald, C, Medland, SE, Morey, RA, Nichols, TE, Paus, T, Pausova, Z, Schmaal, L, Schumann, G, Shen, L, Sisodiya, SM, Smit, DJA, Smoller, JW, Stein, DJ, Stein, JL, Toro, R, Turner, JA, van den Heuvel, MP, van den Heuvel, OL, van Erp, TGM, van Rooij, D, Veltman, DJ, Walter, H, Wang, Y, Wardlaw, JM, Whelan, CD, Wright, MJ, Ye, J, Thompson, PM, Andreassen, OA, Arias-Vasquez, A, Bearden, CE, Boedhoe, PS, Brouwer, RM, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cannon, DM, Cohen, RA, Conrod, PJ, Dale, AM, Deary, IJ, Dennis, EL, de Reus, MA, Desrivieres, S, Dima, D, Donohoe, G, Fisher, SE, Fouche, J-P, Francks, C, Frangou, S, Franke, B, Ganjgahi, H, Garavan, H, Glahn, DC, Grabe, HJ, Guadalupe, T, Gutman, BA, Hashimoto, R, Hibar, DP, Holland, D, Hoogman, M, Pol, HEH, Hosten, N, Jahanshad, N, Kelly, S, Kochunov, P, Kremen, WS, Lee, PH, Mackey, S, Martin, NG, Mazoyer, B, McDonald, C, Medland, SE, Morey, RA, Nichols, TE, Paus, T, Pausova, Z, Schmaal, L, Schumann, G, Shen, L, Sisodiya, SM, Smit, DJA, Smoller, JW, Stein, DJ, Stein, JL, Toro, R, Turner, JA, van den Heuvel, MP, van den Heuvel, OL, van Erp, TGM, van Rooij, D, Veltman, DJ, Walter, H, Wang, Y, Wardlaw, JM, Whelan, CD, Wright, MJ, and Ye, J
Abstract: In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others1, ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.
Published: 2017

37. Erratum: Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium (Molecular Psychiatry (2015) DOI:10.1038/mp.2015.63)

Author: Van Erp, TGM, Hibar, DP, Rasmussen, JM, Glahn, DC, Pearlson, GD, Andreassen, OA, Agartz, I, Westlye, LT, Haukvik, UK, Dale, AM, Melle, I, Hartberg, CB, Gruber, O, Kraemer, B, Zilles, D, Donohoe, G, Kelly, S, Mcdonald, C, Morris, DW, Cannon, DM, Corvin, A, Machielsen, MWJ, Koenders, L, De Haan, L, Veltman, DJ, Satterthwaite, TD, Wolf, DH, Gur, RC, Gur, RE, Potkin, SG, Mathalon, DH, Mueller, BA, Preda, A, Macciardi, F, Ehrlich, S, Walton, E, Hass, J, Calhoun, VD, Bockholt, HJ, Sponheim, SR, Shoemaker, JM, Van Haren, NEM, Pol, HEH, Ophoff, RA, Kahn, RS, Roiz-Santiañez, R, Crespo-Facorro, B, Wang, L, Alpert, KI, Jönsson, EG, Dimitrova, R, Bois, C, Whalley, HC, Mcintosh, AM, Lawrie, SM, Hashimoto, R, Thompson, PM, and Turner, JA
Published: 2016

38. Lipidomic risk score independently and cost-effectively predicts risk of future type 2 diabetes: results from diverse cohorts

Author: Mamtani, M, Kulkarni, H, Wong, G, Weir, JM, Barlow, CK, Dyer, TD, Almasy, L, Mahaney, MC, Comuzzie, AG, Glahn, DC, Magliano, DJ, Zimmet, P, Shaw, J, Williams-Blangero, S, Duggirala, R, Blangero, J, Meikle, PJ, Curran, JE, Mamtani, M, Kulkarni, H, Wong, G, Weir, JM, Barlow, CK, Dyer, TD, Almasy, L, Mahaney, MC, Comuzzie, AG, Glahn, DC, Magliano, DJ, Zimmet, P, Shaw, J, Williams-Blangero, S, Duggirala, R, Blangero, J, Meikle, PJ, and Curran, JE
Abstract: BACKGROUND: Detection of type 2 diabetes (T2D) is routinely based on the presence of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the potential of plasma lipidomics as a biomarker of future T2D is unknown. Our objective was to develop and validate a plasma lipidomic risk score (LRS) as a biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for T2D screening. METHODS: Plasma LRS, based on significantly associated lipid species from an array of 319 lipid species, was developed in a cohort of initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS). The LRS derived from SAFHS as well as its recalibrated version were validated in an independent cohort from Australia--the AusDiab cohort. The participants were T2D-free at baseline and followed for 9197 person-years in the SAFHS cohort (n = 771) and 5930 person-years in the AusDiab cohort (n = 644). Statistically and clinically improved T2D prediction was evaluated with established statistical parameters in both cohorts. Modeling studies were conducted to determine whether the use of LRS would be cost-effective for T2D screening. The main outcome measures included accuracy and incremental value of the LRS over routinely used clinical predictors of T2D risk; validation of these results in an independent cohort and cost-effectiveness of including LRS in screening/intervention programs for T2D. RESULTS: The LRS was based on plasma concentration of dihydroceramide 18:0, lysoalkylphosphatidylcholine 22:1 and triacyglycerol 16:0/18:0/18:1. The score predicted future T2D independently of prediabetes with an accuracy of 76%. Even in the subset of initially euglycemic individuals, the LRS improved T2D prediction. In the AusDiab cohort, the LRS continued to predict T2D significantly and independently. When combined with risk-stratification methods currently used in clinical practice, the LRS significantly improved the model fit (p < 0.001), information content (p
Published: 2016

39. Abnormal ventral and dorsal attention network activity during single and dual target detection in schizophrenia

Author: Jimenez, AM, Jimenez, AM, Lee, J, Wynn, JK, Cohen, MS, Engel, SA, Glahn, DC, Nuechterlein, KH, Reavis, EA, Green, MF, Jimenez, AM, Jimenez, AM, Lee, J, Wynn, JK, Cohen, MS, Engel, SA, Glahn, DC, Nuechterlein, KH, Reavis, EA, and Green, MF
Abstract: Early visual perception and attention are impaired in schizophrenia, and these deficits can be observed on target detection tasks. These tasks activate distinct ventral and dorsal brain networks which support stimulus-driven and goal-directed attention, respectively. We used single and dual target rapid serial visual presentation (RSVP) tasks during fMRI with an ROI approach to examine regions within these networks associated with target detection and the attentional blink (AB) in 21 schizophrenia outpatients and 25 healthy controls. In both tasks, letters were targets and numbers were distractors. For the dual target task, the second target (T2) was presented at three different lags after the first target (T1) (lag1 = 100 ms, lag3 = 300 ms, lag7 = 700ms). For both single and dual target tasks, patients identified fewer targets than controls. For the dual target task, both groups showed the expected AB effect with poorer performance at lag 3 than at lags 1 or 7, and there was no group by lag interaction. During the single target task, patients showed abnormally increased deactivation of the temporo-parietal junction (TPJ), a key region of the ventral network. When attention demands were increased during the dual target task, patients showed overactivation of the posterior intraparietal cortex, a key dorsal network region, along with failure to deactivate TPJ. Results suggest inefficient and faulty suppression of salience-oriented processing regions, resulting in increased sensitivity to stimuli in general, and difficulty distinguishing targets from non-targets.
Published: 2016

40. 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, Boen, 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, CRK, Christoforou, A, Cichon, S, Clark, VP, Conrod, P, Coppola, G, Crespo-Facorro, B, Curran, JE, Czisch, M, Deary, IJ, de Geus, EJC, 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, Elvsashagen, T, Emsell, L, Erk, S, Espeseth, T, Fagerness, J, Fears, S, Fedko, I, Fernandez, 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, Goering, HHH, 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, B-C, Hoehn, D, Hoekstra, PJ, Hollinshead, M, Holmes, AJ, Homuth, G, Hoogman, M, Hong, LE, Hosten, N, Hottenga, J-J, Pol, HEH, Hwang, KS, Jack, CR, Jenkinson, M, Johnston, C, Joensson, EG, Kahn, RS, Kasperaviciute, D, Kelly, S, Kim, S, Kochunov, P, Koenders, L, Kraemer, B, Kwok, JBJ, Lagopoulos, J, Laje, G, Landen, M, Landman, BA, Lauriello, J, Lawrie, SM, Lee, PH, Le Hellard, S, Lemaitre, H, Leonardo, CD, Li, C-S, Liberg, B, Liewald, DC, Liu, X, Lopez, LM, Loth, E, Lourdusamy, A, Luciano, M, Macciardi, F, Machielsen, MWJ, MacQueen, GM, Malt, UF, Mandl, R, Manoach, DS, Martinot, J-L, 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, Munoz Maniega, S, Muehleisen, TW, Mueller-Myhsok, B, Mwangi, B, Nauck, M, Nho, K, Nichols, TE, Nilsson, L-G, 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, J-B, Potkin, SG, Puetz, B, Ramasamy, A, Rasmussen, J, Rietschel, M, Rijpkema, M, Risacher, SL, Roffman, JL, Roiz-Santianez, 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, Schuer, 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, Saemann, 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, TGM, van Haren, NEM, van 't Ent, D, van Tol, M-J, Hernandez, MCV, Veltman, DJ, Versace, A, Voelzke, 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, Drevets, W, 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, Boen, 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, CRK, Christoforou, A, Cichon, S, Clark, VP, Conrod, P, Coppola, G, Crespo-Facorro, B, Curran, JE, Czisch, M, Deary, IJ, de Geus, EJC, 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, Elvsashagen, T, Emsell, L, Erk, S, Espeseth, T, Fagerness, J, Fears, S, Fedko, I, Fernandez, 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, Goering, HHH, 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, B-C, Hoehn, D, Hoekstra, PJ, Hollinshead, M, Holmes, AJ, Homuth, G, Hoogman, M, Hong, LE, Hosten, N, Hottenga, J-J, Pol, HEH, Hwang, KS, Jack, CR, Jenkinson, M, Johnston, C, Joensson, EG, Kahn, RS, Kasperaviciute, D, Kelly, S, Kim, S, Kochunov, P, Koenders, L, Kraemer, B, Kwok, JBJ, Lagopoulos, J, Laje, G, Landen, M, Landman, BA, Lauriello, J, Lawrie, SM, Lee, PH, Le Hellard, S, Lemaitre, H, Leonardo, CD, Li, C-S, Liberg, B, Liewald, DC, Liu, X, Lopez, LM, Loth, E, Lourdusamy, A, Luciano, M, Macciardi, F, Machielsen, MWJ, MacQueen, GM, Malt, UF, Mandl, R, Manoach, DS, Martinot, J-L, 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, Munoz Maniega, S, Muehleisen, TW, Mueller-Myhsok, B, Mwangi, B, Nauck, M, Nho, K, Nichols, TE, Nilsson, L-G, 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, J-B, Potkin, SG, Puetz, B, Ramasamy, A, Rasmussen, J, Rietschel, M, Rijpkema, M, Risacher, SL, Roffman, JL, Roiz-Santianez, 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, Schuer, 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, Saemann, 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, TGM, van Haren, NEM, van 't Ent, D, van Tol, M-J, Hernandez, MCV, Veltman, DJ, Versace, A, Voelzke, 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
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

41. Amygdala enlargement and shape distortion in bipolar disorder

Author: Glahn, Dc, Jenkinson, M., Monkul, Es, Robinson, Jl, Bearden, Ce, Escamilla, Ma, Peter Fox, Smith, S., and Patenaude, B.
Published: 2008

42. Three-dimensional mapping of hippocampal anatomy in unmedicated and lithium-treated patients with bipolar disorder

Author: Bearden, Ce, Thompson, Pm, Dutton, Ra, Frey, Bn, Peluso, Ma, Nicoletti, M., Diershke, N., Hayashi, Km, Klunder, Ad, Glahn, Dc, paolo brambilla, Sassi, Rb, Mallinger, Ag, and Soares, Jc
Published: 2008

43. Orbitofrontal cortex gray matter volume is inversely associated with impulsivity in healthy individuals: A voxel-based morphometry study

Author: Nemoto, K, Nicoletti, M, Matsuo, K, Soares, JC, Glahn, DC, Nery, FG, Peluso, MAM, Vipraio, GA, Caetano, SC, Najt, P, Silva, LP, Sanches, M, and Monkul, ES
Published: 2006

44. Right amygdala hyperactivation in untreated depressed individuals

Author: Lancaster, J, Fox, P, Gao, JH, Soares, JC, Zamarripa, F, Najt, P, Li, J, Peluso, MAM, Glahn, DC, and Monkul, S
Published: 2005

45. Declarative memory impairment in pediatric bipolar disorder

Author: Pliszka, S, Olvera, RL, Soares, JC, Caetano, SC, Beardene, CE, Glahn, DC, Fonseca, M, Najt, P, and Hunter, K
Published: 2005

46. Sources of declarative memory impairment in bipolar disorder

Author: Glahn, DC, Bearden, CE, Soares, JC, Monkul, S, Barrette, J, Najit, P, Sanches, M, Villarreal, V, and Bowden, C
Published: 2005

47. Temperament and character in symptomatic bipolar patients

Author: Fonseca, M, Soares, JC, Cloninger, CR, Bowden, C, Kaur, S, Najt, P, Monkul, S, Nicoletti, M, Glahn, DC, Hatch, JP, and Nery, FG
Published: 2005

48. Heritability of Volume, Surface Area and Thickness for Anatomically Defined Cortical Brain Regions Estimated in a Large Extended Pedigree

Author: Winkler, AM, primary, Kochunov, P, additional, Fox, PT, additional, Duggirala, R, additional, Almasy, L, additional, Blangero, J, additional, and Glahn, DC, additional
Published: 2009
Full Text: View/download PDF

49. An Automatic Segmentation Tool for White Matter Hyperintensities using FLAIR and T1-Weighted Images

Author: Winkler, AM, primary, Kochunov, P, additional, Dierschke, NA, additional, Lancaster, JL, additional, Fox, PT, additional, and Glahn, DC, additional
Published: 2009
Full Text: View/download PDF

50. BrainVISA Plug-In for Measurements of Sulcal Span

Author: Kochunov, PK, primary, Rogers, B, additional, Lancaster, JL, additional, Glahn, DC, additional, Blangero, J, additional, and Fox, PT, additional
Published: 2009
Full Text: View/download PDF

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