Department of Psychiatry, Chonnam National University Medical School, 5 Hak-dong, Dong-gu, Gwangju 501-746, Republic of Korea.
Psychosom Med. 2012 Jan;74(1):8-15. doi: 10.1097/PSY.0b013e318241530c. Epub 2011 Dec 30.
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.
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 Mini-International Neuropsychiatric Interview and was classified into prevalent, persistent, and incident depression. Individual associations with 5-HTT gene-linked 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.
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 = 1.12-6.14) and persistent (odds ratio = 8.07, 95% confidence interval = 1.26-51.6) 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).
Our findings support a role of BDNF, not serotonin, in the etiology of depression occurring in women with breast cancer who received a mastectomy.
5-羟色胺转运体（5-HTT）和脑源性神经营养因子（BDNF）基因的多态性已被研究为发生在医学疾病中的抑郁症的候选基因。 5-羟色胺 2a 受体（5-HTR2a）基因已被研究为抑郁症的危险因素，但很少与医学条件结合研究。本研究旨在探讨 5-HTT、5-HTR2a 和 BDNF 基因中感兴趣的多态性是否与乳腺癌乳房切除术后的抑郁症相关。
309 例乳腺癌患者在乳房切除术后 1 周进行评估，244 例（79%）患者在 1 年后进行随访。根据 DSM-IV 标准使用 Mini-国际神经精神访谈对抑郁症（主要和轻度抑郁障碍）进行诊断，并将其分为现患、持续和新发抑郁症。使用逻辑回归模型估计 5-HTT 基因连接启动子区域、5-羟色胺转运体内含子 2 可变数串联重复、5-HTR2a 1438A/G、5-HTR2a 102T/C 和 BDNF Val66Met 多态性与个体的关联，并使用广义多因素维度减少方法研究基因-基因相互作用。
基线时，74 例（24%）患者被诊断为现患抑郁症，随访时，19 例（8%）和 25 例（10%）患者被诊断为持续性和新发抑郁症。BDNF Met/Met 基因型与现患（比值比=2.63，95%置信区间=1.12-6.14）和持续性（比值比=8.07，95%置信区间=1.26-51.6）抑郁症独立相关。未发现 5-HTT 和 5-HTR2a 基因的相关性（所有 p 值>.21），也未发现显著的基因-基因相互作用（所有 p 值>.36）。
我们的研究结果支持 BDNF 而非 5-羟色胺在接受乳房切除术的乳腺癌女性发生抑郁症的发病机制中的作用。
