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 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 PET and study the role of the KOR in mediating the quality and severity of the depressive phenotype. This application is in response to the RDoC initiative of NIMH to clarify the role of the KOR in mediating fear, threat, and reward responsiveness.

Public Health Relevance

Better understanding of the interactive effects of the kappa opioid receptor (KOR) and glucocorticoid signaling has the potential to provide not only improved understanding of the neurobiology of aspects of the depressive phenotype, i.e. threat, fear and anhedonia, but may also lead to improving interventions and services for depressed individuals. We propose to recruit N=50 medication-free individuals across different diagnostic entities and with differing symptom severity and quality of the depressive syndrome, measure their [11C]LY2795050 volumes of distribution (VT), an equivalent of KOR availability using positron emission tomography (PET) and determine the role of the KOR and glucocorticoid signaling in mediating the heterogeneous components of the depressive phenotype.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH102566-01A1
Application #
8719701
Study Section
Pathophysiological Basis of Mental Disorders and Addictions Study Section (PMDA)
Program Officer
Rumsey, Judith M
Project Start
2014-06-01
Project End
2019-03-31
Budget Start
2014-06-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$438,003
Indirect Cost
$118,805
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Pietrzak, Robert H; Naganawa, Mika; Huang, Yiyun et al. (2014) Association of in vivo ?-opioid receptor availability and the transdiagnostic dimensional expression of trauma-related psychopathology. JAMA Psychiatry 71:1262-70
Pietrzak, Robert H; Huang, Yiyun; Corsi-Travali, Stefani et al. (2014) Cannabinoid type 1 receptor availability in the amygdala mediates threat processing in trauma survivors. Neuropsychopharmacology 39:2519-28