Archival ReportSchizophrenia miR-137 Locus Risk Genotype Is Associated with Dorsolateral Prefrontal Cortex Hyperactivation
Section snippets
Participants
Forty-eight patients with schizophrenia (mean age ± SD = 37.0 ± 10.7, 35 male subjects) and 63 healthy volunteers (mean age ± SD = 37.6 ± 12.4, 39 male subjects) with similar mean age, sex, handedness, and race distributions, recruited from 9 sites part of the Function Biomedical Informatics Network Phase 2 study on multicenter functional imaging, participated in the study (Table 1). Study participants were between the ages of 18 and 70, had regular hearing levels (<25 db loss in either ear),
Results
Mixed-model regression analyses confirmed left DLPFC hyperactivation for SIRP load 3 probes in SZ patients compared with healthy volunteers (t100 = 1.91, p = .03). Individuals carrying the common miR-137 schizophrenia risk genotype (rs1625579 TT) showed hyperactivation compared with those carrying the less frequent GG/GT genotype (t100 = 2.17, p = .02; Figure 2). The analysis of additive effects of genotype and diagnoses showed significant effects of genotype (TT > GG/GT; t99 = 1.99, p = .03)
Discussion
The main finding of our study is that the rs1625579 TT (miR-137) schizophrenia risk genotype is associated with left DLPFC hyperactivation compared with the combined GG/GT genotype irrespective of diagnosis. Given equivalent working memory performance between rs1625579 TT and GG/GT carriers, we interpret the observed DLPFC hyperactivation in individuals with the rs1625579 TT genotype compared with those with the GG/GT genotypes as being consistent with neural inefficiency in rs1625579
References (65)
- et al.
Identifying gene regulatory networks in schizophrenia
Neuroimage
(2010) MicroRNAs: Genomics, biogenesis, mechanism, and function
Cell
(2004)- et al.
Genetic association study of the P300 endophenotype in schizophrenia
Schizophr Res
(2012) - et al.
Mood congruent psychotic symptoms and specific cognitive deficits in carriers of the novel schizophrenia risk variant at MIR-137
Neurosci Lett
(2013) The assessment and analysis of handedness: The Edinburgh inventory
Neuropsychologia
(1971)- et al.
The Schedule for the Deficit Syndrome: An instrument for research in schizophrenia
Psychiatry Res
(1989) - et al.
A depression rating scale for schizophrenics
Schizophr Res
(1990) - et al.
The InterSePT scale for suicidal thinking reliability and validity
Schizophr Res
(2003) AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages
Comput Biomed Res
(1996)- et al.
Reducing interscanner variability of activation in a multicenter fMRI study: Controlling for signal-to-fluctuation-noise-ratio (SFNR) differences
Neuroimage
(2006)
Improved optimization for the robust and accurate linear registration and motion correction of brain images
Neuroimage
An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets
Neuroimage
Precentral gyrus discrepancy in electronic versions of the Talairach atlas
Neuroimage
PLINK: A tool set for whole-genome association and population-based linkage analyses
Am J Hum Genet
Alterations of fronto-temporal connectivity during word encoding in schizophrenia
Psychiatry Res
MicroRNA dysregulation in schizophrenia
Neurobiol Dis
Experimental validation of candidate schizophrenia gene ZNF804A as target for hsa-miR-137
Schizophr Res
Autism spectrum disorders and childhood-onset schizophrenia: Clinical and biological contributions to a relation revisited
J Am Acad Child Adolesc Psychiatry
Is schizophrenia on the autism spectrum?
Brain Res
The association between early autistic traits and psychotic experiences in adolescence
Schizophr Res
Interactive effects of DAOA (G72) and catechol-O-methyltransferase on neurophysiology in prefrontal cortex
Biol Psychiatry
DISC1 is associated with cortical thickness and neural efficiency
Neuroimage
Quantifying the heritability of task-related brain activation and performance during the N-back working memory task: A twin fMRI study
Biol Psychol
The relationship between performance and fMRI signal during working memory in patients with schizophrenia, unaffected co-twins, and control subjects
Schizophr Res
Functional neuroimaging of working memory in schizophrenia: Task performance as a moderating variable
Neuropsychology
CNTRICS imaging biomarkers selection: Working memory
Schizophr Bull
Complexity of prefrontal cortical dysfunction in schizophrenia: More than up or down
Am J Psychiatry
Working memory and DLPFC inefficiency in schizophrenia: The FBIRN study
Schizophr Bull
A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype
Schizophr Bull
Gene discovery through imaging genetics: Identification of two novel genes associated with schizophrenia
Mol Psychiatry
Micro RNAs are complementary to 3' UTR sequence motifs that mediate negative post-transcriptional regulation
Nat Genet
microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder
Genome Biol
Cited by (64)
MicroRNA137-loaded lipid nanoparticles regulate synaptic proteins in the prefrontal cortex
2023, Molecular TherapyMicroRNA schizophrenia: Etiology, biomarkers and therapeutic targets
2023, Neuroscience and Biobehavioral ReviewsImaging genetics of schizophrenia in the post-GWAS era
2018, Progress in Neuro-Psychopharmacology and Biological PsychiatryPolymorphism in schizophrenia risk gene MIR137 is associated with the posterior cingulate Cortex's activation and functional and structural connectivity in healthy controls
2018, NeuroImage: ClinicalCitation Excerpt :This study examined the effects of the MIR137 rs1625579 genotype on neural correlates of working memory. Consistent with van Erp et al.'s (2014) fMRI study, we found that the risk allele homozygotes (TT) exhibited altered activation (less deactivation) at the PCC as compared to the GT heterozygotes during working memory. Less deactivation at the PCC when performing working memory tasks has been found in schizophrenia patients (Bittner et al., 2015; Fryer et al., 2013; Haatveit et al., 2016; Kim et al., 2009; Wu et al., 2014) and has been linked to poorer working memory performance (Eryilmaz et al., 2016; Pu et al., 2016; Zhou et al., 2016), which was replicated in the current study (See Supplementary Fig. S1).