The impact of genome wide supported microRNA-137 (MIR137) risk variants on frontal and striatal white matter integrity, neurocognitive functioning, and negative symptoms in schizophrenia.
Although genome wide association studies have highlighted MicroRNA 137 (MIR137) as a novel susceptibility gene for schizophrenia, the mechanisms by which MIR137 risk variants mediate the neurobiology of schizophrenia are not clear. Based on extant data linking MIR 137 gene with structural brain anomalies and functional brain activations in schizophrenia, we hypothesized that MIR137 risk variants rs1625579 and rs1198588 would be associated with reduced fractional anisotropy in frontostriatal brain regions, impaired neurocognitive functioning and worse psychotic symptoms in schizophrenia patients compared with healthy controls. A total of 147 Chinese participants (84 patients with DSM-IV diagnosis of schizophrenia (SCZ) and 63 healthy controls (HC)) were genotyped using blood samples and underwent diffusion tensor imaging. Neurocognitive domains and psychotic symptoms were assessed using The Brief Assessment of Cognition Battery for Schizophrenia and Positive and Negative Syndrome Scale respectively. We found significant diagnosis-genotype interactions in the right orbitofrontal regions (rs1625579: F = 5.44, P = 0.021; rs1198599: F = 7.55, P = 0.005), left striatum (rs1625579: F = 8.09, P=0.007; rs1198599: F=9.56, P = 0.002), and negative symptoms (rs1625579: t = 2.45, P = 0.016; rs1198588: t = 2.29, P = 0.024). Specifically, SCZ carrying the risk TT genotype had worse negative symptoms and decreased FA in the fronto-striatal regions compared to G and A allele carriers for rs1625579 and rs1198588 respectively, and worse attention and processing speed compared with G-allele for rs1625579. Our findings suggested that the MI137 risk variants were associated with decreased fronto-striatal brain white matter integrity which may underlie poorer attention, processing speed, and greater negative symptoms in schizophrenia.
Research Division, Institute of Mental Health, Singapore.
Carissa Nadia
CN
Kuswanto
Research Division, Institute of Mental Health, Singapore.
Min Yi
MY
Sum
Department of Bioengineering, National University of Singapore, Singapore.
Anqi
A
Qiu
Department of Neuroradiology, National Neuroscience Institute, Singapore.
Yih-Yian
YY
Sitoh
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
Jianjun
J
Liu
Research Division, Institute of Mental Health, Singapore.|Department of General Psychiatry, Institute of Mental Health, Singapore.
Kang
K
Sim
D000328:Adult; D044466:Asian People / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011618:Psychotic Disorders / Q000235:genetics; D012306:Risk; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D066127:White Matter / Q000378:metabolism*; D055815:Young Adult
C545567:MIRN137 microRNA, human; D035683:MicroRNAs
diffusion tensor imaging; microRNA; negative symptoms; neurocognitive deficits; schizophrenia