Modeling Hedonic Processing and Anhedonia in Depression

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DESCRIPTION (provided by applicant): Anhedonia, or the lack of positive emotion, is a critical component of depression that is represented in various ways in diagnostic criteria. All forms of depression may involve a lack of interest or pleasure in activities, particularly when depressed patients are contrasted against healthy controls. Melancholic depression specifically entails additional deficits in mood reactivity to pleasant events, in contrast to atypical depression, in which mood reactivity to pleasant events is present. Consistent with NIMH's Strategic Objective 1, this application seeks to assess anhedonia in a theoretically coherent way and address deficits in wanting, liking, and learning in depression, with tasks designed to assess the varieties of anhedonic processing in depression. In each task, postauricular reflex and zygomatic EMG magnitudes during pleasant vs. neutral conditions will be assessed as measures of positive emotional processing. Startle blink and corrugator EMG magnitudes will be assessed to examine whether depressed patients also differ in their levels of negative emotion, indicating an emotion context insensitivity in depression. Furthermore, multiple behavioral measures of positive emotion will be taken in each task to provide a comprehensive assessment of anhedonia across measurement domains. This project will also demonstrate which components and measures of depressive anhedonia are responsive to clinical intervention and which remain impaired, suggesting they may serve as endophenotypes for depression. We will recruit healthy controls and patients with melancholic, atypical, or non-subtyped depression. After completing psychodiagnostic interviews and self-reports of trait and state levels of hedonic processing, participants will complete three counterbalanced tasks. In one task, they will view emotional pictures and listen to emotional sounds, along with cues associated with each stimulus valence, to provide an experimental assessment of mood reactivity. Their ratings and bodies' reactions to the cues, pictures, and sounds will be recorded to assess their levels of liking the actual stimuli and wanting those stimuli (as measured by their reactions to the cues). Two additional tasks assess lack of pleasure (liking) or interest (wanting) in pleasant activities. One measures effort-based work for rewards and is an experimental assessment of participants' enjoyment (liking) and interest (wanting) during a rewarding activity. The other measures participants' ability to learn pleasant associations in an appetitive evaluative conditioning task, in which neutral words are paired with highly pleasant or neutral pictures. We will invite the same participants back to our laboratory three months after their initial session to examine which processes and measures of anhedonia are responsive to clinical improvement (particularly in anhedonic symptoms) and which remain impaired in remitted depressed participants. The latter make candidates for endophenotypes of depression, which can be used to identify people at risk for depression and intervene proactively before they become acutely depressed.