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The association between familial risk and brain abnormalities is disease-specific: an ENIGMA–Relatives study of schizophrenia and bipolar disorder

de Zwarte, Sonja M. C., Brouwer, Rachel M., Agartz, Ingrid, Alda, Martin, Aleman, André, Alpert, Kathryn I., Bearden, Carrie E., Bertolino, Alessandro, Bois, Catherine, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth E. L., Cahn, Wiepke, Cannon, Dara M., Cannon, Tyrone D., Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Di Giorgio, Annabella, Doucet, Gaelle E., Eker, Mehmet Cagdas, Fears, Scott C., Foley, Sonya F., Frangou, Sophia, Frankland, Andrew, Fullerton, Janice M., Glahn, David C., Goghari, Vina M., Gonul, Ali Saffet, Gruber, Oliver, de Haan, Lieuwe, Hajek, Tomas, Hawkins, Emma L., Heinz, Andreas, Hillegers, Manon H. J., Hulshoff Pol, Hilleke E., Hultman, Christina M., Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G., Kane, Fergus, Kempton, Matthew J., Koenis, Marinka M. G., Kopecek, Miloslav, Krabbendam, Lydia, Krämer, Bernd, Lawrie, Stephen M., Lenroot, Rhoshel K., Marcelis, Machteld, Marsman, Jan-Bernard C., Mattay, Venkata S., McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B., Moreno, Dolores, Murray, Robin M., Mwangi, Benson, Najt, Pablo, Neilson, Emma, Newport, Jason, Van Os, Jim, Overs, Bronwyn, Ozerdem, Aysegul, Picchioni, Marco M., Richter, Anja, Roberts, Gloria, Aydogan, Aybala Saricicek, Schofiels, Peter R., Simsek, Fatma, Soares, Jair C., Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Walter, Henrik, Wang, Lei, Weinberger, Daniel R., Whalley, Heather C., Yalin, Nefize, Andreassen, Ole A., Ching, Christopher R. K., van Erp, Theo G. M., Turner, Jessica A., Jahanshad, Neda, Thompson, Paul M., Kahn, Rene S. and van Haren, Neeltje E. M. 2019. The association between familial risk and brain abnormalities is disease-specific: an ENIGMA–Relatives study of schizophrenia and bipolar disorder. Biological Psychiatry 86 (7) , pp. 545-556. 10.1016/j.biopsych.2019.03.985

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

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
Publisher: Elsevier
ISSN: 0006-3223
Date of First Compliant Deposit: 8 October 2019
Date of Acceptance: 24 March 2019
Last Modified: 18 Jan 2021 11:30

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