Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Pharmacological Manipulation
Purpose
The study will investigate whether a nociceptin receptor antagonist will normalize neural and behavioral processes of approach/avoidance decision-making in unmedicated individuals with major depressive disorder (MDD) and anxiety disorders. More specifically, the study aims to investigate dysregulation within (1) corticostriatal-midbrain circuitry and (2) nociceptin/orphanin FQ peptide and the nociceptin receptor (NOPR).
Conditions
- Depressive Disorder, Major
- Anxiety Disorder
Eligibility
- Eligible Ages
- Between 18 Years and 45 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
for MDD/anxiety disorder group: - DSM-5 diagnostic criteria for MDD, Generalized Anxiety Disorder, Social Phobia, Panic Disorder, Post Traumatic Stress (diagnosed using the SCID-5) - Written informed consent - For MDD subjects, a baseline Hamilton Depression Rating Scale score > 16 (17-item version) - Right-handed - Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment) - Absence of any psychotropic medications for at least 2 weeks (6 weeks for fluoxetine, 6 months for neuroleptics, 2 weeks for benzodiazepines, 2 weeks for any other antidepressants) Inclusion criteria for healthy controls: - Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse), as assessed by subject history and a structured clinical interview (diagnosed using the SCID-5) - Written informed consent - Right-handed - Absence of any medications for at least 3 weeks - Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
Exclusion Criteria
for all participants: - Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician - Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception - Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease - History of seizure disorder - History or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, obsessive-compulsive disorder, patients with mood congruent or mood incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse; which will lead to exclusion) - History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine) - History of use of dopaminergic drugs (including methylphenidate) - History or current diagnosis of dementia - 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 - Failure to meet standard magnetic resonance imaging safety requirements - Abnormal ECG and lab results - History of seizure disorder or currently on anticonvulsants
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Basic Science
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist |
After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. Functional magnetic resonance imagining (fMRI) will begin 2 hours after the nociceptin receptor antagonist is administered. |
|
Placebo Comparator Participants with MDD or an anxiety disorder receiving the placebo |
After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered. |
|
Experimental Healthy controls receiving the nociceptin receptor antagonist |
After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive a nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the nociceptin receptor antagonist is administered. |
|
Placebo Comparator Healthy controls receiving the placebo |
After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered. |
|
Recruiting Locations
More Details
- Status
- Recruiting
- Sponsor
- Mclean Hospital