| Major Depressive Disorder (MDD) is a debilitating psychiatric illness that involves a complex interplay of neurobiological dysfunction. At present, the majority of MDD patients fail to remit with current antidepressants that target the serotonin and norepinephrine systems, resulting in a high prevalence of treatment resistant depression (TRD). In the last several years, emerging evidence has pointed to the role of anhedonia in predicting non-response to pharmacologic treatment. However, anhedonia scales, as measured in MDD, reflect consummatory pleasure, despite findings supporting a broader definition including interest, motivation and pleasure. Furthermore, the link between anhedonia and dopamine has not been clearly elucidated in a human MDD sample, nor has either been evaluated as a predictor of therapy in TRD. The goal of the present studies was to refine the measurement of anhedonia, explore its association with dopamine, and evaluate anhedonia and dopamine as potential biomarkers of response to Deep Brain Stimulation (DBS), a neurosurgery for TRD with putative dopaminergic effects. From the present studies it has been shown that refinement in anhedonia measurement in the Dimensional Anhedonia Rating Scale (DARS) by including interest, motivation, effort and consummatory pleasure provides additional utility over the gold standard scale, and may be able to identify MDD subtypes (i.e. TRD). Furthermore, the first preliminary evidence was provided for a direct link between self-reported anhedonia in MDD and dopamine D2/D3 receptor binding in the anterior cingulate cortex and dorsolateral prefrontal cortex, two regions implicated in reward response and depression. Finally, preliminary evidence suggests that D2/D3 binding potential in the orbitofrontal cortex, additional prefrontal regions, insula and temporal cortex can predict outcome to antidepressant therapy with DBS, representing a potential biomarker of response. |
