Serotonergic and BDNF Genes Associated With Depression 1 Week and 1 Year After Mastectomy for Breast Cancer

Objective: Polymorphisms of serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) genes have been investigated as candidate genes for depression occurring in medical disorders. The serotonin 2a receptor (5-HTR2a) genes have been investigated as risk factors for depression but rarely in combination with medical conditions. This study aimed to investigate whether polymorphisms of interest in 5-HTT, 5-HTR2a, and BDNF genes are associated with depression after mastectomy for breast cancer. Methods: A total of 309 patients with breast cancer were evaluated 1 week after mastectomy, and 244 patients (79%) were followed up 1 year later. Depression (major and minor depressive disorders) was diagnosed according to DSM-IV criteria using the MiniInternational Neuropsychiatric Interview and was classified into prevalent, persistent, and incident depression. Individual associations with 5-HTT geneYlinked promoter region, serotonin transporter intron 2 variable number tandem repeat, 5-HTR2a 1438A/G, 5-HTR2a 102T/C, and BDNF Val66Met polymorphisms were estimated using logistic regression models, and gene-gene interactions were investigated using the generalized multifactor dimensionality reduction method. Results: At baseline, 74 patients (24%) were classified with prevalent depression, and at follow-up, 19 patients (8%) and 25 patients (10%) were classified with persistent and incident depression, respectively. The BDNF Met/Met genotype was independently associated with prevalent (odds ratio = 2.63, 95% confidence interval = 1.12Y6.14) and persistent (odds ratio = 8.07, 95% confidence interval = 1.26Y51.6) depression. No associations with 5-HTT and 5-HTR2a genes (all p values > .21) were found, and no significant gene-gene interactions were identified (all p values > .36). Conclusions: Our findings support a role of BDNF, not serotonin, in the etiology of depression occurring in women with breast cancer who received a mastectomy.