Department of Psychology, Harvard University, Cambridge, MA 02138, USA.
Genes Brain Behav. 2010 Aug;9(6):658-67. doi: 10.1111/j.1601-183X.2010.00600.x. Epub 2010 Jun 7.
Research suggests that stress disrupts reinforcement learning and induces anhedonia. The mineralocorticoid receptor (MR) determines the sensitivity of the stress response, and the missense iso/val polymorphism (Ile180Val, rs5522) of the MR gene (NR3C2) has been associated with enhanced physiological stress responses, elevated depressive symptoms and reduced cortisol-induced MR gene expression. The goal of these studies was to evaluate whether rs5522 genotype and stress independently and interactively influence reward learning. In study 1, participants (n = 174) completed a probabilistic reward task under baseline (i.e. no-stress) conditions. In study 2, participants (n = 53) completed the task during a stress (threat-of-shock) and no-stress condition. Reward learning, i.e. the ability to modulate behavior as a function of reinforcement history, was the main variable of interest. In study 1, in which participants were evaluated under no-stress conditions, reward learning was enhanced in val carriers. In study 2, participants developed a weaker response bias toward a more frequently rewarded stimulus under the stress relative to no-stress condition. Critically, stress-induced reward learning deficits were largest in val carriers. Although preliminary and in need of replication due to small sample size, findings indicate that psychiatrically healthy individuals carrying the MR val allele, gene, which has been recently linked to depression, showed a reduced ability to modulate behavior as a function of reward when facing an acute, uncontrollable stressor. Future studies are warranted to evaluate whether rs5522 genotype interacts with naturalistic stressors to increase the risk of depression and whether stress-induced anhedonia might moderate such risk.
研究表明，压力会破坏强化学习并导致快感缺失。盐皮质激素受体（MR）决定了应激反应的敏感性，而 MR 基因（NR3C2）的错义同工型/缬氨酸多态性（Ile180Val，rs5522）与增强的生理应激反应、升高的抑郁症状和降低的皮质醇诱导的 MR 基因表达有关。这些研究的目的是评估 rs5522 基因型和压力是否独立和交互地影响奖励学习。在研究 1 中，参与者（n=174）在基线（即无压力）条件下完成了概率奖励任务。在研究 2 中，参与者（n=53）在压力（电击威胁）和无压力条件下完成了任务。奖励学习，即根据强化历史调节行为的能力，是主要的感兴趣变量。在研究 1 中，在无压力条件下评估参与者，val 携带者的奖励学习得到增强。在研究 2 中，与无压力条件相比，参与者在压力下对更频繁奖励的刺激形成较弱的反应偏向。关键的是，在 val 携带者中，压力引起的奖励学习缺陷最大。尽管由于样本量小，这些发现初步且需要复制，但表明携带最近与抑郁症相关的 MR val 等位基因的精神健康个体在面对急性、不可控的应激源时，根据奖励调节行为的能力降低。需要进一步的研究来评估 rs5522 基因型是否与自然应激源相互作用，从而增加患抑郁症的风险，以及压力引起的快感缺失是否会调节这种风险。
