Inclusion Criteria:
* 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
* Participants must have a level of understanding of the English language sufficient to provide informed consent and to agree to all tests and procedures, as well as the capacity and willingness to attend all study related visits and to comply with the study protocol
Exclusion Criteria:
Subjects will be excluded at the discretion of the PI/collaborating clinicians or for any of the following reasons:
* \<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
* Current or recent use (within last 8 wks) of medications that alter cardiovascular function or psychoactive or psychopharmacological drugs \[including (but not limited to) antidepressants, antipsychotics, benzodiazepines, mood stabilizers, sedatives/hypnotics, dopaminergic agents, stimulants, buspirone, and triptans\]
* Tobacco use (including electronic cigarettes)
* Females who are pregnant, breastfeeding, or planning to become pregnant; female subjects of child-bearing age must have a negative urine pregnancy test on the day of all experimental visits
* Current or past use of hormone replacement therapy
* Allergy to study drugs or pharmacological agents
