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

5P50MH119467-02

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).

2024-08-01

2025-03-31

2025-03-31

Not yet recruiting

Early phase I

112

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 112, 'type': 'ESTIMATED'}}

2024-05-13