Imaging Depression in Parkinson's Disease

Inclusion Criteria

• Age 40-80.
• For women of reproductive potential, a negative pregnancy test at screening and scanning
• For PD patients, clinical diagnosis of PD, able to consent and tolerate PET procedures
• For PD depression patients - at least moderate symptom severity as determined by at least 15 on the MADRS, which has shown maximum discrimination between depressed and non-depressed PD patients.
• For dPD patients undergoing ketamine, abstinence from drugs of abuse, other than alcohol, cannabis, nicotine and caffeine for the duration of the study. Patients with substance use disorders as defined by the DSM-5 will be excluded.

Exclusion Criteria

• Dementia (Montreal Cognitive Assessment (MoCA) score \<21)
• A significant primary DSM-5 psychiatric disorder except for MDD
• A history of or current significant medical (e.g. cardiovascular, renal), or neurological (e.g. cerebrovascular, seizure, traumatic brain injury) illness other than PD that is unstable and significantly increase their risk and/or might affect the study objectives, as determined by study physicians.
• Prior radiation exposure for research purposes within such that participation in this study would place them over FDA limits for annual radiation exposure
• Medications affecting SV2A availability (e.g. levetiracetam)
• For dPD patients receiving ketamine, uncontrolled hypertension, defined as average blood pressure greater than or equal to 140 mmHg or an average diastolic blood pressure greater than or equal to 90 mmHg among those patients who have hypertension.
• Contraindications to MRI.
• For patients undergoing arterial sampling for the PET scan: Iodine allergy, bleeding disorder and/or use of blood thinning medication
• Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.