DISC1 and SLC12A2 interaction affects human hippocampal function and connectivity

被引：25

作者：

Callicott, Joseph H. ^{[1
]}

Feighery, Emer L. ^{[1
]}

Mattay, Venkata S. ^{[1
,2
]}

White, Michael G. ^{[1
]}

Chen, Qiang ^{[1
,2
]}

Baranger, David A. A. ^{[1
]}

Berman, Karen F. ^{[1
]}

Lu, Bai ^{[3
]}

Song, Hongjun ^{[4
,5
]}

Ming, Guo-li ^{[4
,5
]}

Weinberger, Daniel R. ^{[1
,2
,6
,7
,8
,9
]}

机构：

[1] NIMH, Clin Brain Disorders Branch, Div Intramural Programs, NIH, Bethesda, MD 20892 USA

[2] Lieber Inst Brain Dev, Baltimore, MD USA

[3] GlaxoSmithKline, R&D China, Shanghai, Peoples R China

[4] Johns Hopkins Univ, Sch Med, Dept Neurol, Inst Cell Engn, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Neurosci, Inst Cell Engn, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[8] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[9] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2013年 / 123卷 / 07期

关键词：

SCHIZOPHRENIA; RISK; ASSOCIATION; DYSFUNCTION; MEMORY; MICE;

D O I：

10.1172/JCI67510

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Hippocampal development is coordinated by both extracellular factors like GABA neurotransmission and intracellular components like DISCI. 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.

引用

页码：2961 / 2964

页数：4

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