Beyond Monoamines: The Role of the Nociceptin/Orphanin FQ Receptor in Major Depression

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).