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).
Males and females aged 18-55 yrs
Non-depressed health adults (HA) will have no evidence of current or lifetime history of major psychiatric illness, assessed by the MINI and self-report and confirmed by a Licensed Clinical Psychologist
Adults with major depressive disorder (MDD) must meet the DSM-5 criteria for MDD and be currently symptomatic, assessed by the MINI and confirmed by a Licensed Clinical Psychologist; participants with co-morbid anxiety, stress, and trauma-related disorders will be included
Absence of unstable or chronic clinical disease, including cardiovascular, metabolic, renal, hepatic, autonomic, autoimmune, or dermatological disease, as determined by medical history, physical examination, blood chemistries, and 12-lead resting electrocardiogram; however, to ensure a more generalizable sample, adults with elevated systolic BP (<130mmHg), direct low-density lipoprotein (<160mg/dl), and glucose (HbA1c <5.7%) will be included
<18 or >55 yrs
Lifetime or current co-morbid neuropsychiatric disease (bipolar disorder, psychotic disorders, schizophrenia, eating disorders, obsessive-compulsive disorder, alcohol or substance use disorders)
Serious and imminent active suicidal/homicidal ideation with intent, plans, or behaviors, determined by the Licensed Clinical Psychologist or other clinical study team staff
Diagnosed chronic clinical disease, including cardiovascular, metabolic, renal, hepatic, autonomic, autoimmune, or dermatological disease, as determined by medical history, physical examination (resting systolic BP ≥130mmHg, body mass index ≥35 kg/m2), clinically significant abnormal blood chemistries (direct low-density lipoprotein ≥160mg/dl, HbA1c≥5.7%), and clinically significant abnormal 12-lead resting ECG
Parallel
NG-nitro-L-arginine methyl ester (L-NAME)
Other interventionAcute local perfusion of L-NAME (15 mM) directly to the microvasculature will be used to inhibit NO synthase.
Nitric 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.
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.
Click on the lead sponsor to view all of their trials.
University of Delaware
Lead sponsor
National Institute of General Medical Sciences (NIGMS)
Collaborator
