Learning to want [electronic resource] : incentive salience attribution and motivation in major depressive disorder

Major Depressive Disorder (MDD) is characterized by a pervasive decrease in motivation and a pattern of disengagement from the environment. Traditionally, this motivational deficit has been attributed to anhedonia, the reduced ability to experience pleasure. Although this explanation is appealingly intuitive, recent advances in translational neuroscience have revealed a more nuanced story in which the enjoyment of something (i.e., 'liking') does not always go hand-in-hand with the desire or energy to pursue it (i.e., 'wanting'). Indeed, though typically tightly coupled, reward 'liking' and 'wanting' are supported by partially overlapping, but separable, brain systems. These preclinical studies have further demonstrated that dopamine, previously considered a "pleasure molecule" implicated in the pathophysiology of depression, is involved more strongly in processes related to incentive salience and anticipatory affect than to consummatory pleasure. In such a framework, it is possible for MDD to be re-conceptualized as a disorder of incentive salience and goal attribution in which motivational processes are disrupted independent of any potential alteration in hedonic tone. The research in this dissertation was designed to disentangle reward 'liking, ' 'wanting, ' and incentive salience attribution in order to achieve a finer-grained understanding of the reward-related dysfunctions in MDD. In Study 1, we used an effort-based decision-making task to test the hypothesis that 'liking' and 'wanting' would be decoupled in MDD. The findings revealed that, although depressed and nondepressed participants did not differ in their overall levels of reward 'liking, ' this 'liking' predicted motivation to exert effort for the rewards only in nondepressed participants; in depressed participants, 'liking' and 'wanting' were indeed dissociated. To further probe aberrations in incentive salience, Study 1 also tested the hypothesis that MDD would be associated with impairments in incentive salience attribution. The results indicated that, whereas nondepressed participants formed positive affective associations with reward cues, depressed participants formed relatively weak affective associations, suggesting a failure to attribute reward cues with incentive salience. Study 2 was designed to build upon this preliminary evidence of aberrant incentive salience attribution and to rule out alternative hypotheses that failure to form positive affective associations with reward cues could be a simple offshoot of impaired reward learning or decreased reward liking. Despite exhibiting no difficulty in learning the predictive value of the reward cues, for depressed participants, this explicit learning did not translate into the formation of more implicit affective associations with the reward cues, as reflected by physiological reactivity. Further, for depressed participants who did form positive affective associations with the cues, these associations were comparatively weaker and more susceptible to extinction. Together, the findings in this dissertation contribute to a growing literature examining the motivational features of anhedonia and suggest that incentive salience and incentive salience attribution may play a critical role in the pathology of MDD.

Keywords: Psychology.
Advisor: Gotlib Ian H.
Gross James
Knutson Brian advisor. Thesis advisor