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J Clin Invest. 2013 Jul;123(7):2961-4. doi: 10.1172/JCI67510.

DISC1 and SLC12A2 interaction affects human hippocampal function and connectivity.

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  • 1Clinical Brain Disorders Branch, Division of Intramural Programs, National Institute of Mental Health, NIH, Bethesda, Maryland 20892-1379, USA. callicottj@mail.nih.gov

Abstract

Hippocampal development is coordinated by both extracellular factors like GABA neurotransmission and intracellular components like DISC1. We previously reported that SLC12A2-dependent GABA depolarization and DISC1 coregulate hippocampal neuronal development, and 2 SNPs in these genes linked to mRNA expression interactively increase schizophrenia risk. Using functional MRI, we now confirm this biological interaction in vivo by showing in 2 independent samples of healthy individuals (total N = 349) that subjects homozygous for both risk alleles evince dramatically decreased hippocampal area activation (Cohen's d = 0.78)and connectivity (d = 0.57) during a recognition memory task. These data highlight the importance of epistatic models in understanding genetic association with complex brain phenotypes.

PMID:
23921125
[PubMed - indexed for MEDLINE]
PMCID:
PMC3999052
Free PMC Article
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