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Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Pharmacological Manipulation

Phase 2
Not yet recruiting
Conditions
Anxiety Disorder
Depressive Disorder, Major
Interventions
Drug: Nociceptin Receptor Antagonist
Device: Aversive stimuli
Registration Number
NCT05232032
Lead Sponsor
Mclean Hospital
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
112
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonistNociceptin Receptor AntagonistAfter a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. Functional magnetic resonance imagining (fMRI) will begin 2 hours after the nociceptin receptor antagonist is administered.
Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonistAversive stimuliAfter a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. Functional magnetic resonance imagining (fMRI) will begin 2 hours after the nociceptin receptor antagonist is administered.
Participants with MDD or an anxiety disorder receiving the placeboAversive stimuliAfter a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered.
Healthy controls receiving the nociceptin receptor antagonistNociceptin Receptor AntagonistAfter a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive a nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the nociceptin receptor antagonist is administered.
Healthy controls receiving the nociceptin receptor antagonistAversive stimuliAfter a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive a nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the nociceptin receptor antagonist is administered.
Healthy controls receiving the placeboAversive stimuliAfter a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered.
Primary Outcome Measures
NameTimeMethod
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)Baseline

Diagnostic assessment

Magnetic Resonance ImaginingWithin 30 days of the clinical interview

Both structural and functional brain images

Approach/Avoidance TaskDuring the MRI scan

A novel behavioral task assessing approach/avoidance decision-making

Orphanin FQ/Nociceptin assays (using blood samples)On the day of the MRI scan

Measure of Orphanin FQ/Nociceptin

Secondary Outcome Measures
NameTimeMethod
Perceived Stress ScaleBaseline, 6-month follow-up, 12-month follow-up

14-item measure of stress appraisal; scores range from 0 to 56; higher scores indicate higher perceived stress

Medical Outcome Survey- Short FormBaseline, 6-month follow-up, 12-month follow-up

36-item measure of physical and social functioning; score range from 36 to 149; higher scores indicate higher physical and social functioning

Snaith Hamilton Pleasure ScaleBaseline, 6-month follow-up, 12-month follow-up

14-item measure of anhedonia; scores range from 14 to 56; higher scores indicate higher anhedonia

Hamilton Rating Scale for DepressionBaseline, 6-month follow-up, 12-month follow-up

17-item measure of depression severity; scores range from 0 to 34; higher scores indicate higher depression severity

Beck Depression Inventory-IIBaseline, 6-month follow-up, 12-month follow-up

21-item measure of depression severity; scores range from 0 to 63; higher scores indicate higher depression severity

Quality of Life Enjoyment and Satisfaction QuestionnaireBaseline, 6-month follow-up, 12-month follow-up

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

Temporal Experience of Pleasure ScaleBaseline, 6-month follow-up, 12-month follow-up

24-item measure of anticipatory and consummatory pleasure; scores range from 24 to 144; higher scores indicate higher anticipatory/consummatory pleasure

Life Events and Difficulties ScheduleBaseline, 6-month follow-up, 12-month follow-up

Measure of acute events, difficulties, stressors

Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987)6-month follow-up, 12-month follow-up

Retrospectively assesses different DSM-5 disorders, social and occupational functioning, and life satisfaction over the past 6 months

Columbia-Suicide Severity Rating ScaleBaseline, 6-month follow-up, 12-month follow-up

Suicide assessment

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