Striatal Dopamine Binding in Anhedonia: A Simultaneous [11C]Raclopride Positron Emission Tomography and Functional Magnetic Resonance Imaging Investigation

Background Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA binding, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample. Methods Participants with (n=25) and without (n=12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [ 11 C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors. Results Relative to controls, the anhedonia group exhibited increased [ 11 C]raclopride binding potential (ΔBP ND ) in response to rewards, interpreted as decreased task-related DA release, in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions (i.e., bilateral caudate, putamen, pallidum, medial prefrontal cortex, anterior cingulate cortex, and thalamus) in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC. We did not find evidence of associations between self-reported stress and striatal DA response to rewards, mesocorticolimbic fMRI activation or GFC in the anhedonic sample. Conclusions Results: provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.