Cognitive Phenotype Neural Circuitry in Vivo In Mood Disorders and Suicidal Behavior

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SUMMARY – PROJECT 4 How we respond to negative events, regulate our responses to them, and later remember them – plays a central role in mood and/or anxiety disorders, such as depression, and can lead individuals to engage in self- destructive behaviors, including suicide. As such, a critical question for research is what psychological and neural mechanisms generate our initial response to an aversive event, encode that event into memory, and enable us to regulate our response to it. In the current funding period, we began addressing these issues by examining the relationship between MDD, suicide risk, and the generation and regulation of responses to normatively negative and positive stimuli. In this renewal, three factors guide our continued focus on negative emotional reactivity and regulation as well as a new focus on memory. First, in the current funding period we found that responses to aversive stimuli were most strongly related to clinically relevant variables collected in Ps 1, 3 and 5. Second, to capture idosyncratically self-relevant negative responses that may be relevant to suicide risk, we developed a novel variant of our emotion regulation task that involved recollecting unpleasant autobiographical memories and in pilot data found that it was sensitive to MDD vs. control differences in amygdala and hippocampal function. Third, chronic stress is known to impact structural integrity of the PFC and hippocampus via HPA axis activation and neuroinflammation, and postmortem P1 data has identified such changes in suicide decedents. Given these data, in this proposal we focus on studying how MDD and suicide risk are related to PFC, amygdala and hippocampal systems, in the context of: (Aim 1) recollecting and regulating responses to aversive autobiographical memories, (Aim 2) generating enduring negative emotional states that may carry over to subsequent neutral experiences and color memory for them, and understanding how individual differences in clinical and biological variables collected under Projects 3 and 5 relate to data collected under Aims 1 and 2.