Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Study 1.1. (Pharmacological Manipulation)

• Status: Not yet recruiting
• Trial end date: 2025-03-31
• Target enrollment: 0
• Participant gender: All

Summary

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 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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Mclean Hospital
• Collaborators: Brown University; Massachusetts General Hospital; Massachusetts Institute of Technology; National Institute of Mental Health (NIMH); University of Washington
• Treatments: Nociceptin

Criteria

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)

• Written informed consent

• For MDD subjects, a baseline HRSD score (Hamilton 1960) > 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)

• 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, OCD, 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 MRI safety requirements

• Abnormal ECG and lab results

• History of seizure disorder or currently on anticonvulsants