Relationship between VEGF-related gene polymorphisms and brain morphology in treatment-naïve patients with first-episode major depressive disorder

Vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder (MDD). Recently, a genome-wide association study has revealed that four VEGF-related single nucleotide polymorphisms (SNPs) (i.e., rs4416670, rs6921438, rs6993770 and rs10738760) were independently associated with circulating VEGF levels. The current study investigated the relationship between brain volume and these four SNPs in first-episode drug-naïve MDD patients. A total of 38 first-episode drug-naïve MDD patients and 39 healthy subjects (HS) were recruited and underwent high-resolution T1-weighted imaging. Blood samples were collected from all the participants for serum VEGF assays and VEGF-related SNPs genotyping. Genotype–diagnosis interactions related to whole-brain cortical thickness and hippocampal subfield volumes were evaluated for the four SNPs. The results revealed a genotype–diagnosis interaction only for rs6921438 (i.e., the MDD patients and HS with the G/G genotype versus the MDD patients and HS with A-carrier genotype) in the subiculum of the left hippocampus (p < 0.05), and not the other SNPs. There was a volume reduction in the left subiculum of G/G genotype patients compared with the other groups. The “hypochondriasis” scores of the HAMD-17 scale were significantly higher in the G/G genotype patients than the A-carrier genotype patients. The association was observed between VEGF-related SNP rs6921438 and subiculum atrophy in first-episode drug-naïve MDD patients.