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.