Melanopsin gene polymorphism and volumetric change in the left hippocampal dentate gyrus following light therapy in mood disorders: An exploratory study

Abstract

Introduction Bright light therapy (BLT) is an effective treatment for mood disorders. We previously reported that four weeks of bright light (BL) exposure in patients with mood disorders led to increased volume of the left dentate gyrus (DG). We propose a novel hypothesis that the extent of light-induced volumetric increase in the left DG may be influenced by individual genetic variation in the OPN4 gene, especially rs1079610. This exploratory study aimed to test this hypothesis. Methods We recontacted 21 patients with mood disorders who had previously participated in a 4-week, randomized controlled trial comparing BL (10,000 lux) and dim light (DL; 50 lux). All participants underwent magnetic resonance imaging and 18F-fluorodeoxyglucose (FDG) positron emission tomography at baseline and after 4 weeks of light exposure. Blood samples were collected for genotyping of two Single-Nucleotide Polymorphisms (SNPs) in OPN4 (rs1079610 and rs2675703), which are expressed in intrinsically photosensitive retinal ganglion cells. The primary outcome was the main effect of the rs1079610 genotype for percentage change volume (%ΔV) of the left DG. Analysis of covariance was conducted using a general linear model. Results The final sample size was 21 (BL group, n = 11; DL group, n = 10). A significant main effect of rs1079610 genotype (C allele carriers versus TT) was observed (F (1,17) = 7.16, P = 0.016, partial η2 = 0.3). Sensitivity analyses were performed with sequential adjustment for potential confounders. The association between rs1079610 genotype and %ΔV of the left DG remained statistically significant after adjustment for age, sex, baseline left DG volume, and diagnosis (F (1,13) = 4.8, P = 0.047, partial η2 = 0.27). Discussion The findings of this study suggest that rs1079610 in OPN4 might be a potential SNP that affects volumetric change in the left DG following light therapy in mood disorders.