Examining the Relationships between Stress, Reward Processing, and Bipolar Disorder

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Examining the Relationships between Stress, Reward Processing, and Bipolar Disorder

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Title: Examining the Relationships between Stress, Reward Processing, and Bipolar Disorder
Author: Berghorst, Lisa Hinckley
Citation: Berghorst, Lisa Hinckley. 2012. Examining the Relationships between Stress, Reward Processing, and Bipolar Disorder. Doctoral dissertation, Harvard University.
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Abstract: Bipolar disorder (BD) is a prevalent illness associated with severe impairments in functioning and elusive etiological pathways. Although a strong link between negative life stress and the onset of mood episodes in BD has been documented, the mechanisms underlying this connection remain unclear. A dysregulated reward system may play a prominent role in bridging these phenomena given that anhedonia and hyperhedonia are often symptoms of BD. Furthermore, emerging research suggests that negative stress influences reward responsiveness and the neurobiological substrates that regulate this system. The overarching goal of this dissertation was to gain a more comprehensive understanding of the complex connections between negative stress, reward processing, and BD. The first aim was to closely examine the connection between negative stress and reward processing in psychiatrically healthy individuals by investigating the specificity of the effects of stress on sensitivity to reward versus punishment, and the role of perceived control over stress. This was implemented using a probabilistic stimulus selection task, an acute ('threat-of-shock') stressor, and three between-group conditions: 'controllable stress,' 'uncontrollable stress' and 'no-stress.' Consistent with hypotheses, individuals under stress exhibited reduced reward sensitivity relative to individuals not under stress, and these deficits were reward-specific. However, this effect emerged only when participants were re-grouped based on their cortisol reactivity, suggesting that the original experimental design (including manipulation of stress controllability) was only partially successful. The second aim was to examine the neural mechanisms underlying the relationships between stress, reward processing, and BD. To this end, euthymic individuals with BD and demographically-matched controls performed a Monetary Incentive Delay task while undergoing fMRI during no-stress and stress (negative psychosocial stressor) conditions. A significant between-group difference emerged in the no-stress condition: BD subjects had lower activation than controls in the dorsal ACC during reward anticipation. This finding may translate to an impaired ability to use reward-predicting cues to appropriately engage in goal-directed actions, thus highlighting a potential neural mechanism that could underlie dysfunctional reward processing in BD. Longitudinal studies using high-risk samples are needed to evaluate whether this finding reflects a vulnerability factor for BD or an effect of the illness.
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10382937
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