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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство Aversive stimuli
  Electrotactile stimulation will be used as the aversive stimulus. 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 with previously MGH-approved IRB's (Milad et al., 2013).
• Препарат PET radiotracer
  A Nociceptin/Orphanin FQ ("N/OFQ") peptide tracer (\[11C\] NOP-1A) will be used as the PET radiotracer. Approximately 10 mCi of this tracer will be delivered intravenously as a slow bolus over 60 seconds with beginning of the PET imaging acquisition. Approximately 60 ml of blood will be drawn from an artery throughout the dynamic PET acquisition in order to measure the blood N/OFQ levels.

Первичные конечные точки

• Clinical Interview [Срок оценки: Baseline]
• Behavioral Performance on the Probabilistic Reward Task (PRT) [Срок оценки: Baseline]
• MRI Data [Срок оценки: within 30 days of Screening Visit]
• Salivary Cortisol [Срок оценки: Baseline]
• PET Data [Срок оценки: within 30 days of Screening Visit]
• Arterial blood data [Срок оценки: Baseline]
• Follow-up Clinical Interviews [Срок оценки: Change from Baseline at 6 months and 12 months after the PET visit]

Вторичные конечные точки (12)

• Beck Depression Inventory-II (BDI) [Срок оценки: Change from Baseline at 6 months and 12 months after the PET visit]
• Childhood Trauma Questionnaire (CTQ) [Срок оценки: Baseline]
• Medical Outcome Survey-Short form (SF-36) [Срок оценки: Change from Baseline at 6 months and 12 months after the PET visit]
• Perceived Stress Scale (PSS) [Срок оценки: Change from Baseline at 6 months and 12 months after the PET visit]
• Positive and Negative Affect Schedule (PANAS) [Срок оценки: Baseline]
• Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) [Срок оценки: Change from Baseline at 6 months and 12 months after the PET visit]
• Snaith Hamilton Pleasure Scale (SHAPS) [Срок оценки: Change from Baseline at 6 months and 12 months after the PET visit]
• Thought and Feeling Questionnaire (TFQ) [Срок оценки: Baseline]
• Defeat Scale (DS) [Срок оценки: Baseline]
• Questionnaire of Unpredictability in Childhood (QUIC) [Срок оценки: Change from Baseline at 6 months and 12 months after the PET visit]
• Mood and Anxiety Symptom Questionnaire (MASQ) [Срок оценки: Baseline]
• State-Trait Anxiety Inventory (STAI) [Срок оценки: Baseline]

Критерии участия

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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 1 центр

• McLean Hospital — Belmont

Идентификаторы

NCT: NCT05630963 · 2018P000318 · 4R37MH068376-17

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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