title: Schizophrenia miR-137 locus risk genotype is associated with dorsolateral prefrontal cortex hyperactivation.
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.
authors.affiliation: Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California Irvine, Irvine, California.
authors.forename: Theo G M
authors.initials: TG
authors.lastname: van Erp
authors.affiliation: 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.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guella
authors.affiliation: Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California Irvine, Irvine, California.
authors.forename: Marquis P
authors.initials: MP
authors.lastname: Vawter
authors.affiliation: Mind Research Network, University of New Mexico, Albuquerque, New Mexico; Departments of Psychiatry & Neuroscience, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Jessica
authors.initials: J
authors.lastname: Turner
authors.affiliation: VA San Diego Healthcare System and Department of Psychiatry, University of California, San Diego, San Diego, California.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Brown
authors.affiliation: Department of Psychology, Yale University, New Haven, Connecticut.
authors.forename: Gregory
authors.initials: G
authors.lastname: McCarthy
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
authors.affiliation: Department of Radiology, Stanford University, Stanford, California.
authors.forename: Gary H
authors.initials: GH
authors.lastname: Glover
authors.affiliation: Mind Research Network, University of New Mexico, Albuquerque, New Mexico; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Kelvin O
authors.initials: KO
authors.lastname: Lim
authors.affiliation: Departments of Psychiatry & Neuroscience, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Bustillo
authors.affiliation: Department of Psychiatry and Psychology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Aysenil
authors.initials: A
authors.lastname: Belger
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, California.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Ford
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, California.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Mathalon
authors.affiliation: Brain Imaging and Analysis Center, Duke University Medical Center, Durham, North Carolina.
authors.forename: Michele
authors.initials: M
authors.lastname: Diaz
authors.affiliation: Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California Irvine, Irvine, California.
authors.forename: Adrian
authors.initials: A
authors.lastname: Preda
authors.affiliation: Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California Irvine, Irvine, California.
authors.forename: Dana
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California Irvine, Irvine, California.
authors.forename: Fabio
authors.initials: F
authors.lastname: Macciardi
authors.affiliation: Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California Irvine, Irvine, California. Electronic address: sgpotkin@uci.edu.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000473:pathology; D012044:Regression Analysis; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs
keywords: Genes; imaging; mir137; rs1625579; schizophrenia; working memory
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