Kappa Opioid Receptor Imaging in Depression (KOR Depression)

The purpose of this study is to use positron emission tomography (PET) imaging to measure the activity of the kappa opioid receptor (KOR) in the brains of depressed and non-depressed individuals.

The kappa opioid receptor (KOR) has been implicated in the etiology of fear, threat, and anhedonia in animal models of human depression psychopathology. Herein, we propose to study the KOR in vivo using positron emission tomography, and we will also measure the activity of the hypothalamic-pituitary-adrenal (HPA)-axis in all study participants. We propose to recruit up to N=50 medication-free individuals using a transdiagnostic approach, measure their KOR-selective radioligand \[11C\]LY2795050 volumes of distribution (VT), an equivalent of KOR availability using positron emission tomography (PET) and study the role of the KOR in mediating the quality and severity of the depressive phenotype.

Eligibility Criteria:
Inclusion Criteria:

1. Inclusion criteria for all subjects include a willingness to participate in a psychiatric evaluation, collection of behavioral ratings and neuroendocrine assessments, and imaging studies including 1 positron emission tomography (PET) scan and 1 mantic resonance imaging (MRI) scan.
2. We propose to use a transdiagnostic approach where participants will be stratified according to their symptom severity to have a full representation of different depressive severities and components of the depressive phenotype in the cohort. To ensure recruitment of participants from each level of this phenotype, we will employ a stratified sampling approach to recruit 12 participants who are asymptomatic (i.e., Montgomery-Asberg Depression Rating Scale (MADRS) score=0-6); 12 who are mildly symptomatic (i.e., MADRS score=7-19; 12 who are moderately symptomatic (i.e., MADRS sore=20-34); and 12 who are severely symptomatic (i.e., MADRS score\>34).

Exclusion Criteria:

1. any major medical (including HIV due to possible neuropsychiatric affects; and asthma or heart disease which may limit the interpretation of the imaging results, for example due to changes in tracer delivery in hypertensive patients or significant weight change in prior 12 weeks prior to the study) and neurological illness or injury (i.e. head trauma with loss of consciousness);
2. any current or prior clinically significant substance use disorder (abuse and dependence within a year from imaging studies) as determined by Structured Clinical Interview for Diagnostic and Statistical Manual Disorders (SCID) interview;
3. acute or chronic suicidality as determined by the SCID interview;
4. presence of any legal or illegal psychoactive substances determined with urine toxicology, urine cotinine, carbon monoxide (CO) monitoring, and breathalyzer;
5. intelligence quotient (IQ) \<70 based on past intelligence testing;
6. any metal in body that would pose a risk with MRI;
7. claustrophobia that would interfere with MRI or PET imaging;
8. pregnancy or nursing for women;
9. women with estrogen and/or progesterone levels outside the normal range, on birth control pills, peri- and post- menopausal women, and those with ovarectomies;
10. obesity as defined by a body mass index (BMI) of \> 35;
11. use of psychoactive medications including regular use of benzodiazepines;
12. having an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participation in the study;
13. life-time history of use and abuse of opioids; and
14. presence of psychotic symptoms in patients with mood and anxiety disorders, schizophrenia or schizoaffective disorders; and
15. blood donation within 8 weeks prior to the study.