The objective of this proposal is to determine whether heightened negative affective responsivity (NA-R) to daily stressors is related to blunted nitric oxide (NO)-mediated endothelium-dependent dilation (EDD) in working age adults and the extent to which this association is impacted by major depressive disorder (MDD).
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. Working age non-depressed healthy adults (HA) and adults with MDD (unmedicated) will participate. 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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
18
Acute local perfusion of L-NAME (15 mM) directly to the microvasculature will be used to inhibit NO synthase.
University of Delaware
Newark, Delaware, United States
RECRUITINGNitric oxide (NO)-mediated endothelium-dependent dilation (EDD)
A standard local heating protocol will be used to elicit EDD and the NO-dependent portion of this response will be determined pharmacologically (local perfusion of L-NAME). Vascular conductance will be calculated (CVC=flux/mean arterial pressure) and normalized to the site-specific maximum. NO-mediated EDD will be calculated as the percent change from the local heating-induced plateau to the post-L-NAME plateau.
Time frame: immediately before and after the 14-day testing cycle
Negative affective responsivity (NA-R) to daily stressors
NA-R to daily stressors will be operationalized as the within-person slope of the change in negative affect on stressor days compared to stressor-free days and calculated using multilevel modeling. The models for computing NA-R slopes will use maximum likelihood estimation (MLE), which accounts for participants potentially providing different numbers of diary days, and will include stressor exposure.
Time frame: immediately after the 14-day testing cycle
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.