Linking affective dynamics in response to daily stress to peripheral vascular function in working age adults

University Of Delaware, Newark DE

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Abstract

Convincing evidence indicates that the deleterious impacts of psychosocial stress on emotional well-being and behavioral health are likely major contributors to excessive cardiovascular disease (CVD) risk in middle-aged and younger adults. In line with this, heightened negative affective (i.e., emotional) responsivity (NA-R) to daily stressors predicts CVD morbidity and mortality. Importantly, NA-R to daily stressors—the naturally occurring but unexpected hassles and challenges that arise out of routine everyday life (e.g., argument with a partner, pressing work deadline)—is most pronounced in ‘working age adults’ (18-55 yrs). Unfortunately, these effects appear further compounded in adults with major depressive disorder (MDD), an increasingly prevalent mood disorder whose core pathology is characterized by dysregulated affective dynamics. However, the physiological mechanisms linking dysregulated daily stress-related affective dynamics to poorer long-term cardiovascular health trajectories in working age adults remain incompletely understood. Our global hypothesis that affective dysregulation in response to daily stressors contributes to worsening endothelial health in working age adults, the effects of which are exacerbated in adults with MDD. To test this premise, we propose an innovative, multi-pronged, interdisciplinary approach utilizing techniques across the clinical-translational spectrum. Working age non-depressed healthy adults (HA) and adults with MDD (unmedicated) will complete two testing cycles separated by ~3-6 months. During each testing cycle, multiple dynamic aspects of affective regulation and daily stress processes will be assessed during routine everyday life for 14 consecutive days (mobile app). On the days immediately before and after these ambulatory assessments, the mechanistic regulation of microvascular endothelial function will be assessed (in vivo; physiological and pharmacological approaches). Aim 1 will determine the stability and temporal patterning of the dynamic coupling between daily stressor events and the ensuing affective response within an individual (within and between testing cycles); Aim 2 will determine whether NA-R to daily stressors impacts peripheral endothelial function and the extent to which these effects are impacted by MDD. This project addresses several clinically relevant gaps in knowledge and will fundamentally advance our understanding of the mechanisms linking affective dysregulation in response to daily stressors to increased CVD risk in working age adults. The anticipated outcomes will identify multiple novel mechanistic targets for therapeutic intervention strategies to preserve cardiovascular health in those who are most emotionally vulnerable to daily stressors.