Investigating the Nociceptin/Orphanin FQ receptor's role in major depression

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

Observational Mclean Hospital · NCT05630963

This study looks at how a specific brain receptor might affect decision-making and stress in people with major depression to see if it can help predict future symptoms.

Quick facts

Study typeObservational
Enrollment228 (estimated)
Ages18 Years to 45 Years
SexAll
SponsorMclean Hospital Academic / other
Locations1 site (Belmont, Massachusetts)
Trial IDNCT05630963 on ClinicalTrials.gov

What this trial studies

This observational study explores the Nociceptin/Orphanin FQ receptor system in individuals with current or past major depressive disorder (MDD). It aims to understand how these individuals make decisions and the brain regions involved, utilizing advanced imaging techniques like fMRI and PET scans. The research will also assess stress-induced inflammation and identify neural markers that could predict future depressive symptoms. Data will be collected through MRI, PET, biospecimens, and behavioral tasks.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 18-45 with a history of major depressive disorder, either currently experiencing symptoms or in remission.

Not a fit: Patients with active suicidal ideation or those currently on psychotropic medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to better understanding and prediction of depressive symptoms, potentially improving treatment strategies for patients with MDD.

How similar studies have performed: While the specific approach of examining the Nociceptin/Orphanin FQ receptor in MDD is novel, similar studies have shown promise in understanding the neurobiological underpinnings of depression.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria for all participants:

* All genders, races, and ethnic origins, aged between 18 and 45
* Capable of providing written informed consent, and fluent in English
* Right-handed
* Absence of any psychotropic medications for at least 2 weeks
* Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)

Inclusion Criteria for "Remitted MDD" group:

* Meets inclusion criteria for all subjects, plus:
* History of MDD as defined by DSM-5
* Absence of anxiety disorder for the past two months

Inclusion Criteria for "Current MDD" group:

* Meets inclusion criteria for all subjects, plus:
* Presence of MDD as defined by DSM-5
* Absence of anxiety disorder for the past two months

Exclusion Criteria for all participants:

* Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment
* Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, or partner with vasectomy)
* Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
* History of seizure disorder
* History of psychiatric illnesses, other than depression or anxiety disorders among the Current MDD and Remitted MDD groups
* History of substance use disorder or alcohol use disorder (as these terms are defined by DSM-5); except depressed subjects may have a history of 'Mild' substance/alcohol use disorder only if it ended as least 12 months ago
* History of cocaine or stimulant use or dopaminergic drugs
* History or current diagnosis of dementia, or a score of \< 26 on the Mini Mental State Examination at the screening visit;
* Patients with mood congruent or mood incongruent psychotic features
* Current use of other psychotropic drugs
* Clinical or laboratory evidence of hypothyroidism
* Patients with a lifetime history of electroconvulsive therapy (ECT)
* Failure to meet standard MRI safety requirements
* Abnormal ECG and lab results
* History of seizure disorder
* Contraindications for arterial line (e.g., abnormal result on Allen test, Raynaud's syndrome, history of anemia or bleeding disorder, history of fainting from blood draws).

Where this trial is running

Belmont, Massachusetts

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Major Depressive Disorder
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.