Zwarte, S. M. C.Brouwer, R. M.Agartz, I.Alda, M.Aleman, A.Alpert, K. I.Bearden, C. E.Bertolino, A.Bois, C.Bonvino, A.Bramon, E.Buimer, E.Cahn, W.Cannon, D. M.Cannon, T. D.Caseras, X.Castro-Fornieles, J.Chen, Q.Serna, E.Giorgio, A. D.Doucet, G.Eker, M. C.Erk, S.Fears, S.Foley, S.Frangou, S.Frankland, A.Fullerton, J.Glahn, D.Goghari, V.Goldman, A.Gonul, A.Gruber, O.Haan, L.Hajek, T.Hawkins, E.Heinz, A.Hillegers, M.Pol, H.Hultman, C.Ingvar, M.Johansson, V.Jönsson, E.Kane, K.Kempton, M.Koenis, M.Kopecek, M.Krabbendam, L.Krämer, B.Lawrie, S.Lenroot, R.Marcelis, M.Marsman, J-BMattay, V.McDonald, C.Meyer-Lindenberg, A.Michielse, S.Mitchell, P.Moreno, D.Murray, R.Mwangi, B.Najt, P.Neilson, E.Newport, J.Os, J.Overs, B.Özerdem, A.Picchioni, M.Richter, A.Roberts, G.Aydoğan, A. S.Schofield, P.Şimşek, F.Soares, J.Sugranyes, G.Toulopoulou, TimotheaTronchin, G.Walter, H.Wang, L.Weinberger, D.Whalley, H.Yalın, N.Andreassen, O.Ching, C.Erp, T.Turner, J.Jahanshad, N.Thompson, P.Kahn, R.Haren, N.2020-01-272020-01-2720190006-3223http://hdl.handle.net/11693/52842Abstract 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.EnglishBipolar disorderFamilial riskImagingMeta-analysisNeurodevelopmentSchizophreniaReport10.1016/j.biopsych.2019.03.985