The study will investigate whether a nociceptin receptor antagonist will normalize neural and behavioral processes of approach/avoidance decision-making in unmedicated individuals with major depressive disorder (MDD) and anxiety disorders. More specifically, the study aims to investigate dysregulation within (1) corticostriatal-midbrain circuitry and (2) nociceptin/orphanin FQ peptide and the nociceptin receptor (NOPR).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
112
Participants in the experimental arms will receive 40 mg of the nociceptin receptor antagonist. Peak concentrations are achieved 2-4 hours post-administration.
As part of the approach/avoidance task, electrotactile stimulation will be used. The aversive stimulus is delivered in the form of a mild half-second stimulation to the ankle, calibrated to a subjective threshold that is uncomfortable but not painful. This stimulation is delivered by Digitimer DS8R Constant Current Stimulator (Digitimer North America, LLC. Ft. Lauderdale, FL). Its previous model, DS71, has been safely implemented in studies within Massachusetts General Hospital (Milad et al., 2013).
Mclean Hospital
Belmont, Massachusetts, United States
RECRUITINGStructured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
Diagnostic assessment
Time frame: Baseline
Magnetic Resonance Imagining
Both structural and functional brain images
Time frame: Within 30 days of the clinical interview
Approach/Avoidance Task
A novel behavioral task assessing approach/avoidance decision-making
Time frame: During the MRI scan
Orphanin FQ/Nociceptin assays (using blood samples)
Measure of Orphanin FQ/Nociceptin
Time frame: On the day of the MRI scan
Beck Depression Inventory-II
21-item measure of depression severity; scores range from 0 to 63; higher scores indicate higher depression severity
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Hamilton Rating Scale for Depression
17-item measure of depression severity; scores range from 0 to 34; higher scores indicate higher depression severity
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Perceived Stress Scale
14-item measure of stress appraisal; scores range from 0 to 56; higher scores indicate higher perceived stress
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Snaith Hamilton Pleasure Scale
14-item measure of anhedonia; scores range from 14 to 56; higher scores indicate higher anhedonia
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Medical Outcome Survey- Short Form
36-item measure of physical and social functioning; score range from 36 to 149; higher scores indicate higher physical and social functioning
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Quality of Life Enjoyment and Satisfaction Questionnaire
16-item measure of satisfaction and enjoyment across domains (e.g., work, interpersonal); scores range from 16 to 80; higher scores indicate higher life enjoyment and satisfaction
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Temporal Experience of Pleasure Scale
24-item measure of anticipatory and consummatory pleasure; scores range from 24 to 144; higher scores indicate higher anticipatory/consummatory pleasure
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Life Events and Difficulties Schedule
Measure of acute events, difficulties, stressors
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987)
Retrospectively assesses different DSM-5 disorders, social and occupational functioning, and life satisfaction over the past 6 months
Time frame: 6-month follow-up, 12-month follow-up
Columbia-Suicide Severity Rating Scale
Suicide assessment
Time frame: Baseline, 6-month follow-up, 12-month follow-up
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