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

Steven G. Potkin, Theo G M Van Erp, Ilaria Guella, Marquis P. Vawter, Jessica Turner, Gregory G. Brown, Gregory McCarthy, Douglas N. Greve, Gary H. Glover, Vince D. Calhoun, Kelvin O. Lim, Juan R. Bustillo, Aysenil Belger, Judith M. Ford, Daniel H. Mathalon, Michele Diaz, Adrian Preda, Dana Nguyen, Fabio Macciardi

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65 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)398-405
Number of pages8
JournalBiological psychiatry
Issue number5
StatePublished - Mar 1 2014

Bibliographical note

Funding Information:
This work was supported by the National Center for Research Resources at the National Institutes of Health (NIH; Grant Nos.: NIH 1 U24 RR021992 , Function Biomedical Informatics Research Network ; NIH 1 U24 RR025736-01 , Biomedical Informatics Research Network Coordinating Center; ), the William Lion Penzner Foundation (University of California, Irvine, Department of Psychiatry and Human Behavior), and the National Institutes of Mental Health (Grant No. R01MH085801 to MVP).


  • Genes
  • imaging
  • mir137
  • rs1625579
  • schizophrenia
  • working memory


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