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Biol Psychiatry. 2014 Mar 1;75(5):398-405. doi: 10.1016/j.biopsych.2013.06.016. Epub 2013 Aug 1.

Schizophrenia miR-137 locus risk genotype is associated with dorsolateral prefrontal cortex hyperactivation.

Author information

1
Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California Irvine, Irvine, California.
2
Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California Irvine, Irvine, California; Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California Irvine, Irvine, California.
3
Mind Research Network, University of New Mexico, Albuquerque, New Mexico; Departments of Psychiatry & Neuroscience, University of New Mexico, Albuquerque, New Mexico.
4
VA San Diego Healthcare System and Department of Psychiatry, University of California, San Diego, San Diego, California.
5
Department of Psychology, Yale University, New Haven, Connecticut.
6
Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
7
Department of Radiology, Stanford University, Stanford, California.
8
Mind Research Network, University of New Mexico, Albuquerque, New Mexico; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, New Mexico.
9
Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.
10
Departments of Psychiatry & Neuroscience, University of New Mexico, Albuquerque, New Mexico.
11
Department of Psychiatry and Psychology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
12
Department of Psychiatry, University of California, San Francisco, San Francisco, California.
13
Brain Imaging and Analysis Center, Duke University Medical Center, Durham, North Carolina.
14
Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California Irvine, Irvine, California. Electronic address: sgpotkin@uci.edu.

Abstract

BACKGROUND:

miR-137 dysregulation has been implicated in the etiology of schizophrenia, but its functional role remains to be determined.

METHODS:

Functional magnetic resonance imaging scans were acquired on 48 schizophrenia patients and 63 healthy volunteers (total sample size N = 111 subjects), with similar mean age and sex distribution, while subjects performed a Sternberg Item Response Paradigm with memory loads of one, three, and five numbers. Dorsolateral prefrontal cortex (DLPFC) retrieval activation for the working memory load of three numbers, for which hyperactivation had been shown in schizophrenia patients compared with control subjects, was extracted. The genome-wide association study confirmed schizophrenia risk single nucleotide polymorphism rs1625579 (miR-137 locus) was genotyped (schizophrenia: GG n = 0, GT n = 9, TT n = 39; healthy volunteers: GG = 2, GT n = 15, and TT n = 46). Fisher's exact test examined the effect of diagnosis on rs1625579 allele frequency distribution (p = nonsignificant). Mixed model regression analyses examined the effects of diagnosis and genotype on working memory performance measures and DLPFC activation.

RESULTS:

Patients showed significantly higher left DLPFC retrieval activation on working memory load 3, lower working memory performance, and longer response times compared with controls. There was no effect of genotype on working memory performance or response times in either group. However, individuals with the rs1625579 TT genotype had significantly higher left DLPFC activation than those with the GG/GT genotypes.

CONCLUSIONS:

Our study suggests that the rs1625579 TT (miR-137 locus) schizophrenia risk genotype is associated with the schizophrenia risk phenotype DLPFC hyperactivation commonly considered a measure of brain inefficiency.

KEYWORDS:

Genes; imaging; mir137; rs1625579; schizophrenia; working memory

PMID:
23910899
PMCID:
PMC4428556
DOI:
10.1016/j.biopsych.2013.06.016
[Indexed for MEDLINE]
Free PMC Article

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