KOR Depression

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DESCRIPTION (provided by applicant): 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.