Beyond Monoamines: The Role of the Nociceptin/Orphanin FQ Receptor in Major Depression

Recruiting

• Conditions: Major Depressive Disorder
• Interventions: Device: Aversive stimuli; Drug: PET radiotracer

• Registration Number: NCT05630963
• Lead Sponsor: Mclean Hospital

Brief Summary

This study looks at the role of the Nociceptin/Orphanin FQ receptor system in the brain of individuals with current or past major depressive disorder (MDD). It also examines how individuals with a history of depression make certain decisions and which brain regions are involved in such decisions. Information collected through MRI, PET, biospecimens (i.e., blood, saliva) and behavioral tasks will be used to predict depressive symptoms in the future.

Detailed Description

The overarching goals of this research are to investigate: (1) the activity of the Nociceptin/Orphanin FQ receptor system among individuals with current or remitted MDD; (2) neural foundations of approach/avoidance behaviors in current or remitted MDDs; (3) stress-induced inflammation in individuals with remitted MDD; (4) neural markers that predict future disease course.

This will be achieved through an innovative method of using functional magnetic resonance imaging (fMRI) during an approach/avoidance decision-making task, in addition to a resting positron emission tomography (PET) scan.

Study Timeline

• Study Start: 2021-12-29
• Study First Submitted: 2022-11-16
• Study First Submitted QC: 2022-11-18
• Study First Posted: 2022-11-30
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-07
• Primary Completion: 2026-10-28
• Study Completion: 2027-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 228

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
MDD subjects	Aversive stimuli	Subjects diagnosed with Major Depression Disorder
MDD subjects	PET radiotracer	Subjects diagnosed with Major Depression Disorder
Remitted MDD subjects	PET radiotracer	Subjects with a history of major depressive disorder episode in the past
Control subjects	PET radiotracer	Subjects with no history of known neurological and psychiatric illness.
Remitted MDD subjects	Aversive stimuli	Subjects with a history of major depressive disorder episode in the past
Control subjects	Aversive stimuli	Subjects with no history of known neurological and psychiatric illness.

Primary Outcome Measures

Name	Time	Method
Behavioral Performance on the Probabilistic Reward Task (PRT)	Baseline	the PRT assesses individuals' ability to learn from rewards
Arterial blood data	Baseline	for PET modeling and assessing Nociceptin/Orphanin FQ levels in bloodstream
Salivary Cortisol	Baseline	For assessing stress level
Clinical Interview	Baseline	For assessing psychological state
MRI Data	within 30 days of Screening Visit	For testing the neural correlates of approach-avoidance decision making behaviors
PET Data	within 30 days of Screening Visit	For assessing the Nociceptin/Oprhanin FQ receptor system activity
Follow-up Clinical Interviews	Change from Baseline at 6 months and 12 months after the PET visit	To assess psychological state changes

Secondary Outcome Measures

Name	Time	Method
Defeat Scale (DS)	Baseline	self-report measure of perception of defeat
Hamilton-Depression Rating Scale (HAMD-17)	Change from Baseline at 6 months and 12 months after the PET visit	clinical measure of depression severity
Childhood Trauma Questionnaire (CTQ)	Baseline	self-report measure of childhood trauma
Medical Outcome Survey-Short form (SF-36)	Change from Baseline at 6 months and 12 months after the PET visit	self-report with subscales measuring physical functioning, physical role functioning, social functioning, etc.
Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)	Change from Baseline at 6 months and 12 months after the PET visit	self-report measure of satisfaction and enjoyment across domains (e.g., work, leisure, social relations)
Snaith Hamilton Pleasure Scale (SHAPS)	Change from Baseline at 6 months and 12 months after the PET visit	self-report measure of pleasure
Thought and Feeling Questionnaire (TFQ)	Baseline	self-report measure of perception of being stuck in difficult situations
Temporal Experience of Pleasure Scale (TEPS)	Change from Baseline at 6 months and 12 months after the PET visit	self-report measure of ability to want and enjoy rewards
Stress and Adversity Inventory (STRAIN)	Change from Baseline at 12 months after the PET visit	self-report measure of lifetime exposure to acute and chronic stress that may affect mental and physical health
Perceived Stress Scale (PSS)	Change from Baseline at 6 months and 12 months after the PET visit	self-report measure of stress levels
PRT Post-task Questionnaire	Baseline	self-report measure of participants' thoughts regarding the PRT task stimuli
Columbia-Suicide Severity Rating Scale (C-SSRS)	Baseline	clinical measure of suicidality
Positive and Negative Affect Schedule (PANAS)	Baseline	self-report measure of positive and negative affect
Beck Depression Inventory-II (BDI)	Change from Baseline at 6 months and 12 months after the PET visit	self-report measure of depressive symptoms
Mood and Anxiety Symptom Questionnaire (MASQ)	Baseline	self-report measure of mood symptom severity including 4 subscales related to depression and anxiety
Cognitive-Behavioral Avoidance Scale (CBAS)	Baseline	self-report measure of trait avoidance
Questionnaire of Unpredictability in Childhood (QUIC)	Change from Baseline at 6 months and 12 months after the PET visit	self-report measure of unpredictability of parental environment growing up
State-Trait Anxiety Inventory (STAI)	Baseline	Measures and differentiates between anxiety
Quick Inventory of Depressive Symptomatology (QIDS)	Change from Baseline at 6 months and 12 months after the PET visit	clinical measure of depression severity

Trial Locations

Locations (1)

McLean Hospital; 🇺🇸 Belmont, Massachusetts, United States