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

Asuka Katsuki,1 Shingo Kakeda,2 Keita Watanabe,2 Ryohei Igata,1 Yuka Otsuka,1 Taro Kishi,3 LeHoa Nguyen,1 Issei Ueda,2 Nakao Iwata,3 Yukunori Korogi,2 Reiji Yoshimura11Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 8078555, Japan; 2Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 8078555, Japan; 3Department of Psychiatry, Fujita Health University, Toyoake, Aichi 4701192, JapanCorrespondence: Reiji YoshimuraDepartment of Psychiatry, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 8078555, JapanTel +81 93 691 7253Fax +81 93 692 4894Email yoshi621@med.uoeh-u.ac.jpObjective: Recently, 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).Methods: Forty-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.Results: Regarding 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.Conclusions: We 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.Keywords: single-nucleotide polymorphism, brain morphology, major depressive disorder, genome-wide association