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.
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.
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