Affective Neuroscience Laboratory, Department of Psychology, Harvard University, Cambridge, MA, USA.
Neuropsychobiology. 2012;65(1):45-54. doi: 10.1159/000329105. Epub 2011 Nov 17.
Stressful life experiences frequently precede the onset of major depression; however, the mechanisms that underlie this link are poorly understood. Importantly, some individuals are more susceptible to the depressogenic effects of stress than others. Carriers of the S or LG allele of the 5-HTTLPR/rs25531 polymorphisms (S' participants) have been found to be more prone to developing depression under stress relative to L or LA homozygotes (L' participants). Moreover, emerging evidence indicates that stress-induced anhedonia may be a mechanism underlying links between stress and depression. Given these findings, we hypothesized that exposure to a naturalistic stressor (school final examinations) would disrupt reward responsiveness (a key behavioral component of anhedonia), and that this effect would be strongest in S' participants.
To objectively assess reward responsiveness, we administered a probabilistic reward task to 70 Bulgarian high school students over two sessions in the 6-month period preceding school finals. For each participant, the two sessions were designated as the 'stress' and 'control' conditions based on self-reported perceived stress.
A genotype×condition interaction emerged in males, with S' participants showing larger stress-related reduction in reward responsiveness relative to L' participants.
While in need of replication in a larger sample, our results indicate that stress associated with a real-life event is linked to reduced reward responsiveness, the susceptibility to which is modulated by 5-HTTLPR/rs25531 genotype. Although preliminary, these findings identify anhedonia as a promising mechanism linking 5-HTTLPR/rs25531 genotype and stress to depression.
压力生活经历常先于重度抑郁症发作;然而,其中的机制仍知之甚少。重要的是,一些个体比其他人更容易受到压力的抑郁影响。携带 5-HTTLPR/rs25531 多态性的 S 或 LG 等位基因(S'参与者)的个体比 L 或 LA 纯合子(L'参与者)更易在压力下发展为抑郁症。此外,新出现的证据表明,应激诱导的快感缺失可能是压力与抑郁之间联系的一种机制。鉴于这些发现,我们假设暴露于自然应激源(学校期末考试)会破坏奖赏反应性(快感缺失的关键行为成分),并且这种效应在 S'参与者中最强。
为了客观地评估奖赏反应性,我们在学校期末考试前的 6 个月内,通过两个阶段对 70 名保加利亚高中生进行了概率性奖赏任务。对于每个参与者,根据自我报告的感知压力,将两个阶段指定为“应激”和“对照”条件。
在男性中出现了基因型×条件的交互作用,S'参与者相对于 L'参与者表现出更大的与应激相关的奖赏反应性降低。
虽然需要在更大的样本中进行复制,但我们的结果表明,与现实生活事件相关的压力与奖赏反应性降低有关,而这种易感性受 5-HTTLPR/rs25531 基因型调节。虽然初步,但这些发现确定了快感缺失作为连接 5-HTTLPR/rs25531 基因型、压力和抑郁的有前途的机制。