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What is the impact of genome-wide supported risk variants for schizophrenia and bipolar disorder on brain structure and function? A systematic review

Published online by Cambridge University Press:  10 April 2015

R. Gurung  and
D. P. Prata
R. Gurung
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK
D. P. Prata*
Affiliation:
Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, UK Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
*
*Address for correspondence: D. P. Prata, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal. (Email: diana.prata@kcl.ac.uk)
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Abstract

The powerful genome-wide association studies (GWAS) revealed common mutations that increase susceptibility for schizophrenia (SZ) and bipolar disorder (BD), but the vast majority were not known to be functional or associated with these illnesses. To help fill this gap, their impact on human brain structure and function has been examined. We systematically discuss this output to facilitate its timely integration in the psychosis research field; and encourage reflection for future research. Irrespective of imaging modality, studies addressing the effect of SZ/BD GWAS risk genes (ANK3, CACNA1C, MHC, TCF4, NRGN, DGKH, PBRM1, NCAN and ZNF804A) were included. Most GWAS risk variations were reported to affect neuroimaging phenotypes implicated in SZ/BD: white-matter integrity (ANK3 and ZNF804A), volume (CACNA1C and ZNF804A) and density (ZNF804A); grey-matter (CACNA1C, NRGN, TCF4 and ZNF804A) and ventricular (TCF4) volume; cortical folding (NCAN) and thickness (ZNF804A); regional activation during executive tasks (ANK3, CACNA1C, DGKH, NRGN and ZNF804A) and functional connectivity during executive tasks (CACNA1C and ZNF804A), facial affect recognition (CACNA1C and ZNF804A) and theory-of-mind (ZNF804A); but inconsistencies and non-replications also exist. Further efforts such as standardizing reporting and exploring complementary designs, are warranted to test the reproducibility of these early findings.

Keywords

ANK3bipolar disorderCACNA1CDGKHDTIgenome-wide associationimaging geneticsintermediate phenotypesMRIreviewNCANneuroimagingNRGNpsychosisschizophreniaTCF4ZNF804A
Type
Review Article
Information
Psychological Medicine , Volume 45 , Issue 12 , September 2015 , pp. 2461 - 2480
Copyright
Copyright © Cambridge University Press 2015 

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