Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Pharmacological Manipulation

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 (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).

Eligibility

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

Conditions4

Interventions1

Locations1 site

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