Stress and the Sympathetic Nervous System in Adults With Depression

To test our hypotheses, we will enroll healthy adults having no history of mood disorders and adults with major depressive disorder (MDD) having a broad range of depressive symptom severity. After screening, subjects will meet with the research coordinator or an investigator for a discussion, with opportunity for questions, before applicable consent forms are obtained. Daily stress processes will be assessed using an ecological momentary assessment approach for 8 consecutive days. On the last day of the daily stress assessment, we will directly measure muscle sympathetic nerve activity, blood pressure, and heart rate during acute laboratory-based cognitive, emotional, and physiological interventions to induce a stress response. A venous blood sample will be taken for measurements of metabolic and renal health and systemic inflammation. Aim 1: To examine the effect of daily psychosocial stressor exposure on acute sympathetic stress reactivity in MDD. Two stressor exposure indicators will be calculated: stressor frequency (i.e., percentage of interview days during which at least one stressor occurred) and total stress (i.e., total number of stressors reported across all interview days) and will be related to the magnitude of responsiveness to the acute stress interventions. We hypothesize that the slope of this relation will be steeper in adults with MDD compared to healthy non-depressed adults. Aim 2: To determine the relation between negative affective reactivity to daily psychosocial stressor exposure and acute sympathetic stress reactivity in MDD. Negative affective reactivity will be calculated as the change in affect on days when stressors occurred compared to one's typical affect on non-stressor days and will be related to the magnitude of responsiveness to the acute stress interventions. We hypothesize that the slope of this relation will be steeper in adults with MDD compared to healthy non-depressed adults.

Subjects will report cumulative exposure, perceived severity, and emotional responsiveness to commonly occurring everyday psychosocial stressors utilizing an ecological momentary assessment approach for 8 consecutive days.

Sympathetic nervous system activity and blood pressure will be measured before, during, and after several acute laboratory-based cognitive (Stroop Color Word Test), emotional (International Affective Picture System), and physiological (Cold Pressor Test) stressors.

change in muscle sympathetic nerve activity in response to acute stress (compared to resting baseline activity)

Inclusion Criteria: All participants will be 18-30 yrs. Healthy non-depressed men and women will have no history or evidence of psychiatric illness and will not have a family history of MDD or major psychiatric illness. Men and women with MDD will have symptomatic depression that meets diagnostic criteria and will be non-medicated. The capacity and willingness to provide written informed consent, 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 clinician or for any of the following reasons: psychiatric illness aside from MDD (including current or past psychotic disorders, bipolar disorder, schizophrenia or schizoaffective disorder, panic disorder, post-traumatic stress disorder, obsessive compulsive disorder) subthreshold depression current use of psychotropic medications (including major classes of antidepressants, anxiolytics, antipsychotics, mood stabilizers) active suicidal or homicidal ideation active substance dependence or eating disorders current use of any medications that could alter sympathetic reactivity diagnosed or suspected cardiovascular, renal, or metabolic disease (hypertension, heart disease, diabetes, hyperlipidemia) autonomic disorders tobacco use (including electronic cigarettes) obesity (body mass index > 30 kg/m2) breastfeeding or pregnancy <18 or >30 yrs

Per the data sharing policy of the National Institute of Mental Health (NIMH), we will deposit all phenotypic, psychosocial stress, and sympathetic reactivity data from this study to the NIMH Data Archive. We will use standard data dictionaries (NIH Toolbox Cognition Battery, NIH Toolbox Emotion Battery, PHQ-9) and will collect the data necessary to generate global unique identifiers for each study subject.