Project Summary/Abstract Stressful life events can increase risk for atherosclerotic cardiovascular disease (CVD), a leading cause of mortality in the US and globally. However, knowledge of who is at highest risk of developing CVD following stress exposure remains limited. Evidence from behavioral and neuroscientific studies suggest that affective patterns, a construct encompassing features of emotions and moods, may partly explain individual differences in stress- related CVD risk. Negative affective patterns, in particular, are associated with CVD-related morbidity and mortality and subclinical biomarkers of CVD risk, including atherosclerotic progression, the metabolic syndrome, and systemic inflammation. However, the ability to regulate negative affect by cognitive reappraisal, which involves changing one’s construal of an emotional stimulus, may be cardio-protective in the context of stressor exposure. Brain systems for affective processing and regulation may play a role in these protective effects. Hence, amygdala and anterior cingulate cortex activity during affect processing or cognitive reappraisal covary with atherosclerotic progression and systemic inflammation in adults. A major knowledge gap concerns the extent to which brain and behavioral measures of affective processing and regulation modify stress-related changes in subclinical precursors to clinical CVD. Research question and design: The present study thus tests whether the relationship between stressful life events and subclinical biomarkers of CVD risk depends on individual differences in brain and behavioral measures of negative affect and cognitive reappraisal. Using deidentified data on 656 healthy adults (mean age: 42.15 yrs) from the Sponsor’s NHLBI Program Project, the applicant will examine the cross-sectional and longitudinal relationship between (1) stressful life events, negative affect (a. self-report, b. neural representation of negative affect), and subclinical biomarkers of CVD risk (i.e., carotid intima media thickness, systemic inflammation, metabolic syndrome index) and (2) stressful life events, cognitive reappraisal (a. self-report, b. neural representation of cognitive reappraisal), and subclinical biomarkers of CVD risk. Health-Related Impact: Identifying brain-based and biobehavioral affective processing and regulation patterns that index vulnerability to preclinical CVD progression may help inform early prevention and prediction efforts directed toward stress-related CVD risk. Training plan: This fellowship will prepare the applicant for a research career aimed at using neuroscience and psychoneuroimmunology to understand biopsychosocial mechanisms linking stress to CVD and related comorbid diseases. In addition, the applicant will 1) complete didactics in CVD pathophysiology, computational modeling of functional neuroimaging data, and statistics, 2) gain experience conducting immunoassays, calculating atherosclerotic progression, and building predictive...