%O Copyright © 2019 Society of Biological Psychiatry. This is an open access article under theCC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). %A SMC de Zwarte %A RM Brouwer %A I Agartz %A M Alda %A A Aleman %A KI Alpert %A CE Bearden %A A Bertolino %A C Bois %A A Bonvino %A E Bramon %A EEL Buimer %A W Cahn %A DM Cannon %A TD Cannon %A X Caseras %A J Castro-Fornieles %A Q Chen %A Y Chung %A E De la Serna %A A Di Giorgio %A GE Doucet %A MC Eker %A S Erk %A SC Fears %A SF Foley %A S Frangou %A A Frankland %A JM Fullerton %A DC Glahn %A VM Goghari %A AL Goldman %A AS Gonul %A O Gruber %A L de Haan %A T Hajek %A EL Hawkins %A A Heinz %A MHJ Hillegers %A HEH Pol %A CM Hultman %A M Ingvar %A V Johansson %A EG Jonsson %A F Kane %A MJ Kempton %A MMG Koenis %A M Kopecek %A L Krabbendam %A B Kraemer %A SM Lawrie %A RK Lenroot %A M Marcelis %A J-BC Marsman %A VS Mattay %A C McDonald %A A Meyer-Lindenberg %A S Michielse %A PB Mitchell %A D Moreno %A RM Murray %A B Mwangi %A P Najt %A E Neilson %A J Newport %A J van Os %A B Overs %A A Ozerdem %A MM Picchioni %A A Richter %A G Roberts %A AS Aydogan %A PR Schofield %A F Simsek %A JC Soares %A G Sugranyes %A T Toulopoulou %A G Tronchin %A H Walter %A L Wang %A DR Weinberger %A HC Whalley %A N Yalin %A OA Andreassen %A CRK Ching %A TGM van Erp %A JA Turner %A N Jahanshad %A PM Thompson %A RS Kahn %A NEM van Haren %J Biological Psychiatry %L discovery10091739 %I ELSEVIER SCIENCE INC %X 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 = 10.16, q , .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = 20.12, 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 , 20.09, q , .05 corrected); and third ventricle was larger (d = 10.15, 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. %K Bipolar disorder, Familial risk, Imaging, Meta-analysis, Neurodevelopment, Schizophrenia %T The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder %N 7 %D 2019 %P 545-556 %V 86