Joelle LeMoult, Ph.D. - US grants

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.

DESCRIPTION (provided by applicant): Major Depressive Disorder (MDD) is one of the most common psychiatric illnesses, and is associated with substantial personal and societal costs. Difficulty removing negative information from working memory is a core cognitive feature of MDD. A growing body of research indicates that this cognitive difficulty is associated with the persistence of depressive symptoms and, in the face of negative events, with the tendency to repetitively ruminate about the negative aspects of such events. Rumination, in turn, is associated with impaired recovery from stress, both emotionally and biologically, which further contributes to symptom persistence. To date, research linking difficulty removing negative information from working memory with rumination, symptom persistence, and stress recovery has been limited by the use of correlational methodologies. Therefore, a major aim of the proposed study is to use established Cognitive Bias Modification methods to experimentally manipulate individuals' ability to remove negative information (RNI) from working memory. We propose to test the effects of RNI training on cognition, levels of rumination and depression, and emotional and biological recovery from stress. To achieve these aims, participants diagnosed with MDD will complete a laboratory- based pre-training session (Session 1), six at-home training sessions, and a second laboratory-based post- training session (Session 2). In Session 1, participants will complete a structured clinical interview, self-report measures of baseline rumination and depressive symptoms, and two computer-based cognitive tasks - one of which explicitly assesses their ability to remove negative information from working memory. Participants then will be randomly assigned to either Real RNI training or to a Sham RNI training condition. They will be taught how to perform the training tasks and will be provided with a laptop on which they will complete the training at home daily for the next six days. On the seventh day, participants will return to the laboratory for the post- training Session 2, during which they will complete the self-report measures and computer-based cognitive tasks that they completed in Session 1. In addition, participants will be exposed to a psychosocial stressor, during which we will measure stress-induced state rumination and assess psychological and biological recovery from the stressor. Compared to Sham RNI training, we expect that Real RNI training will a) increase participants' ability to remove negative information from working memory; b) decrease levels of depressive and ruminative symptoms from baseline; and c) decrease levels of stress-induced rumination, which we posit will, in turn, improve subsequent emotional and biological stress recovery. The results of this study will not only increase our understanding of the relations among cognition, rumination, and stress recovery, but will also provide insight into a novel and innovative treatment approach that has the potential to decrease rumination and improve psychological and biological responses to stress in MDD. Thus, we anticipate that the current study will contribute to both cognitive models of depression and clinical intervention efforts.