Stress Reactivity in Depression: The Role of Genetic and Cognitive Factors

描述(申请人提供)：严重抑郁障碍(MDD)是一种破坏性疾病，与自杀风险增加和包括心脏病和糖尿病在内的健康结局预后较差有关。此外，MDD占所有精神疾病经济成本的20%以上。鉴于MDD给个人和社会带来的高昂代价，确定导致抑郁发作的因素至关重要。抑郁症的素质-压力模型表明，抑郁发作风险的增加不是源于对应激源的最初反应的异常，而是由于调节随后的情感状态的困难(例如，Flynn&Rudolph，2007)。研究从压力中恢复的研究人员通常关注心理变化(通过自我报告来衡量)或生物变化(通过神经内分泌标记物来衡量)，但仍需要将两者结合起来的研究。这项拟议的研究将结合心理学和生物学方法，以检查阻碍易患MDD但从未经历过抑郁发作的人从压力中恢复的因素。这种脆弱性的一种定义方式是通过遗传易感性；5-羟色胺转运体基因(5-HTTLPR)的短等位基因与包括抑郁症在内的各种精神病理学有关。这项拟议的研究将是第一批考察5-HTTLPR与应激后长期负面影响之间联系的三种可能机制之一：对压力的生物高反应性，认知控制缺陷，以及不适应情绪调节策略的使用。这是至关重要的下一步，因为它可以确定可作为预防工作目标的风险因素。在完成诊断性访谈以确保没有当前或过去的精神病理之后，我将获取唾液样本进行基因分型，并要求参与者完成两项认知控制任务(一般工作记忆容量和抑制能力)。然后，参与者将接受一系列应激任务，我将在应激源之前、期间和之后评估神经内分泌功能。最后，我将要求参与者报告他们对沉思的使用情况，这是一种特别不适应的情绪调节策略，并对他们目前的情绪进行评级。这项拟议的研究从公共健康的角度来看很重要，因为这些发现可能会提高我们对导致抑郁症的风险因素的理解，抑郁症本身就是药物滥用、身体健康问题和其他情绪障碍的风险因素。与MDD相关的巨大的个人和社会成本强调了进行像我们这样的研究的重要性，以帮助阐明这种疾病的潜在风险的机制。

DESCRIPTION (provided by applicant): Major depressive disorder (MDD) is a devastating illness that is associated with an elevated risk of suicide and a poorer prognosis of health outcomes including heart disease and diabetes. Moreover, MDD accounts for over 20% of economic costs for all mental illness. Given the high personal and societal costs of MDD, it is critical to identify factors that contribute to the onset of a depressive episode. Diathesis-stress models of depression suggest that increased risk for depressive episodes stems not from abnormality in the initial response to a stressor, such as a negative life event, but rather from difficulties in regulating the ensuing affective state (e.g., Flynn & Rudolph, 2007)]. Researchers examining recovery from stress have typically focused on either psychological changes (measured via self-report) or biological changes (measured via neuroendocrine markers), yet studies are still needed that integrate the two. The proposed study will combine psychological and biological methods in order to examine factors that hinder recovery from stress among persons who are vulnerable to MDD but who have never experienced a depressive episode. One way that vulnerability has been defined is through a genetic predisposition; the short allele of the serotonin transporter gene (5-HTTLPR) has been linked to a variety of psychopathology, including depression. The proposed study will be among the first to examine three possible mechanisms that may underlie the association between 5-HTTLPR and prolonged negative affect following stress: biological hyperreactivity to stress, deficits in cognitive control, and the use of maladaptive emotion regulation strategies. This is a vital next step because it allows identification of risk factors that can be targeted in prevention efforts. After completing a diagnostic interview to ensure no current or past psychopathology, I will obtain saliva samples for genotyping and ask participants to complete two cognitive control tasks (general working memory capacity and inhibition). Participants then will undergo a series of stress tasks, and I will assess neuroendocrine functioning before, during, and following the stressor. Finally, I will ask participants to report on their use of rumination, a particularly maladaptive emotion regulation strategy, and rate their current affect. The proposed study is important from a public health perspective because these findings can potentially improve our understanding of risk factors that contribute to depression, a disorder which itself is a risk factor for substance abuse, physical health problems, and other emotional disorders. The significant personal and societal costs associated with MDD underscore the importance of conducting research like ours that helps elucidate the mechanisms that underlie risk for the disorder.