Major Depressive Disorder
Conditions
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.
Interventions
DEVICEAversive 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).
DRUGPET 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.
Sponsors
National Institute of Mental Health (NIMH)
Mclean Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Interview | Baseline | For assessing psychological state |
| Behavioral Performance on the Probabilistic Reward Task (PRT) | Baseline | the PRT assesses individuals' ability to learn from rewards |
| MRI Data | within 30 days of Screening Visit | For testing the neural correlates of approach-avoidance decision making behaviors |
| Salivary Cortisol | Baseline | For assessing stress level |
| PET Data | within 30 days of Screening Visit | For assessing the Nociceptin/Oprhanin FQ receptor system activity |
| Arterial blood data | Baseline | for PET modeling and assessing Nociceptin/Orphanin FQ levels in bloodstream |
| Follow-up Clinical Interviews | Change from Baseline at 6 months and 12 months after the PET visit | To assess psychological state changes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Thought and Feeling Questionnaire (TFQ) | Baseline | self-report measure of perception of being stuck in difficult situations |
| Defeat Scale (DS) | Baseline | self-report measure of perception of defeat |
| 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 |
| Mood and Anxiety Symptom Questionnaire (MASQ) | Baseline | self-report measure of mood symptom severity including 4 subscales related to depression and anxiety |
| State-Trait Anxiety Inventory (STAI) | Baseline | Measures and differentiates between anxiety |
| PRT Post-task Questionnaire | Baseline | self-report measure of participants' thoughts regarding the PRT task stimuli |
| Beck Depression Inventory-II (BDI) | Change from Baseline at 6 months and 12 months after the PET visit | self-report measure of depressive symptoms |
| Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline | clinical measure of suicidality |
| Hamilton-Depression Rating Scale (HAMD-17) | Change from Baseline at 6 months and 12 months after the PET visit | clinical measure of depression severity |
| Quick Inventory of Depressive Symptomatology (QIDS) | Change from Baseline at 6 months and 12 months after the PET visit | clinical measure of depression severity |
| Cognitive-Behavioral Avoidance Scale (CBAS) | Baseline | self-report measure of trait avoidance |
| 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 |
| 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 |
| 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. |
| Perceived Stress Scale (PSS) | Change from Baseline at 6 months and 12 months after the PET visit | self-report measure of stress levels |
| Positive and Negative Affect Schedule (PANAS) | Baseline | self-report measure of positive and negative affect |
| 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 |
Countries
United States
Contacts
Primary ContactTracy Lam, BS
Backup ContactDavid Crowley, ALM
Outcome results
None listed