<p>A single-nucleotide polymorphism influences brain morphology in drug-naïve patients with major depressive disorder</p>

Abstract

ObjectiveRecently, a genome-wide association study successfully identified genetic variants associated with major depressive disorder (MDD). The study identified 17 independent single-nucleotide polymorphisms (SNPs) significantly associated with diagnosis of MDD. These SNPs were predicted to be enriched in genes that are expressed in the central nervous system and function in transcriptional regulation associated with neurodevelopment. The study aimed to investigate associations between 17 SNPs and brain morphometry using magnetic resonance imaging (MRI) in drug-naïve patients with MDD and healthy controls (HCs).MethodsForty-seven patients with MDD and 42 HCs were included. All participants underwent T1-weighted structural MRI and genotyping. The genotype–diagnosis interactions associated with regional cortical thicknesses were evaluated using voxel-based morphometry for the 17 SNPs.ResultsRegarding rs301806, an SNP in the RERE genomic regions, we found a significant difference in a genotype effect in the right-lateral orbitofrontal and postcentral lobes between diagnosis groups. After testing every possible diagnostic comparison, the genotype–diagnosis interaction in these areas revealed that the cortical thickness reductions in the MDD group relative to those in the HC group were significantly larger in T/T individuals than in C-carrier ones. For the other SNPs, no brain area was noted where a genotype effect significantly differed between the two groups.ConclusionsWe found that a RERE gene SNP was associated with cortical thickness reductions in the right-lateral orbitofrontal and postcentral lobes in drug-naïve patients with MDD. The effects of RERE gene polymorphism and gene–environment interactions may exist in brain structures of patients with MDD.

Prefrontal Interneuron Genes Underlie Neurobiological Processes Shared Between Psychiatric Disorders

“…2A). Finally, the intersection between genes comprised in C3, SCZ, and MDD top risk loci identi ed two genes: NEGR1, a neuronal growth regulator whose variants have been previously associated with MDD 10 , and RERE, a SCZ risk gene 11 encoding a member of the atrophin family of arginine-glutamic acid (RE) dipeptide repeat-containing proteins that have been associated with cortical thickness reductions in patients with MDD 30 and whose expression was higher in patients with SCZ 11 (Fig. 2B).…”

Alcohol drinking, DNA methylation and psychiatric disorders: A multi‐omics Mendelian randomization study to investigate causal pathways

“…The potential mechanism may be that the upregulation of RERE gene expression disrupts cognitive performance and increases the risk of schizophrenia [51]. Genetic loci at RERE have also been reported to be associated with the risk of MDD [52,53].…”

“…The potential mechanism may be that the upregulation of RERE gene expression disrupts cognitive performance and increases the risk of schizophrenia [51]. Genetic loci at RERE have also been reported to be associated with the risk of MDD [52, 53]. Clinical data has shown that the mutations in RERE lead to an autosomal‐dominant genetic syndrome characterized by neurodevelopmental defects, hypotonia, seizures, behavioral issues and structural central nervous system anomalies [54].…”