Clinical trial NCT05630963: Beyond Monoamines: The Role of the Nociceptin/Orphanin FQ Receptor in Major Depression
Official title: Beyond Monoamines: The Role of the Nociceptin/Orphanin FQ Receptor in Major Depression
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Major Depressive Disorder
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2022-11-30
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The subjects for this research will be 228 participants recruited from the community by the Center for Depression, Anxiety and Stress Research (Director: Dr. Diego Pizzagalli, Ph.D.). Demographically-matched participants will include: (1) 38 participants with current MDD; (2) 38 participants with past MDD; and (3) 38 healthy controls.

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.

Eligibility 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).

Primary outcomes:
measure: Clinical Interview
timeFrame: Baseline
measure: Behavioral Performance on the Probabilistic Reward Task (PRT)
timeFrame: Baseline
measure: MRI Data
timeFrame: within 30 days of Screening Visit
measure: Salivary Cortisol
timeFrame: Baseline
measure: PET Data
timeFrame: within 30 days of Screening Visit
measure: Arterial blood data
timeFrame: Baseline
measure: Follow-up Clinical Interviews
timeFrame: Change from Baseline at 6 months and 12 months after the PET visit
Secondary outcomes:
measure: Beck Depression Inventory-II (BDI)
timeFrame: Change from Baseline at 6 months and 12 months after the PET visit
measure: Childhood Trauma Questionnaire (CTQ)
timeFrame: Baseline
measure: Medical Outcome Survey-Short form (SF-36)
timeFrame: Change from Baseline at 6 months and 12 months after the PET visit
measure: Perceived Stress Scale (PSS)
timeFrame: Change from Baseline at 6 months and 12 months after the PET visit
measure: Positive and Negative Affect Schedule (PANAS)
timeFrame: Baseline
measure: Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)
timeFrame: Change from Baseline at 6 months and 12 months after the PET visit
measure: Snaith Hamilton Pleasure Scale (SHAPS)
timeFrame: Change from Baseline at 6 months and 12 months after the PET visit
measure: Thought and Feeling Questionnaire (TFQ)
timeFrame: Baseline
measure: Defeat Scale (DS)
timeFrame: Baseline
measure: Questionnaire of Unpredictability in Childhood (QUIC)
timeFrame: Change from Baseline at 6 months and 12 months after the PET visit
measure: Mood and Anxiety Symptom Questionnaire (MASQ)
timeFrame: Baseline
measure: State-Trait Anxiety Inventory (STAI)
timeFrame: Baseline
measure: PRT Post-task Questionnaire
timeFrame: Baseline
measure: Temporal Experience of Pleasure Scale (TEPS)
timeFrame: Change from Baseline at 6 months and 12 months after the PET visit
measure: Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline
measure: Hamilton-Depression Rating Scale (HAMD-17)
timeFrame: Change from Baseline at 6 months and 12 months after the PET visit
measure: Quick Inventory of Depressive Symptomatology (QIDS)
timeFrame: Change from Baseline at 6 months and 12 months after the PET visit
measure: Cognitive-Behavioral Avoidance Scale (CBAS)
timeFrame: Baseline
measure: Stress and Adversity Inventory (STRAIN)
timeFrame: Change from Baseline at 12 months after the PET visit
Other outcomes:
Locations:
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
Study officials:
affiliation: Mclean Hospital
name: Diego Pizzagalli, PhD
role: PRINCIPAL_INVESTIGATOR
References: