Blunted reward responsiveness in remitted depression.

Major depressive disorder has been associated with blunted responsiveness to rewards, but inconsistencies exist whether such abnormalities persist after complete remission. To address this issue, across two independent studies, 47 adults with remitted major depressive disorder (rMDD) and 37 healthy controls completed a Probabilistic Reward Task, which used a differential reinforcement schedule of social or monetary feedback to examine reward responsiveness (i.e., ability to modulate behavior as a function of reinforcement history). Relative to controls, adults with rMDD showed blunted reward responsiveness. Importantly, a history of depression predicted reduced reward learning above and beyond residual depressive (including anhedonic) symptoms and perceived stress. Findings indicate that blunted reward responsiveness endures even when adults are in remission and might be a trait-related abnormality in MDD. More research is warranted to investigate if blunted reward responsiveness may predict future depressive episodes and whether targeting reward-related deficits may prevent the re-occurrence of the disorder.

Genetic moderation of the association between regulatory focus and reward responsiveness: a proof-of-concept study.

BACKGROUND: Recent studies implicate individual differences in regulatory focus as contributing to self-regulatory dysfunction, particularly not responding to positive outcomes. How such individual differences emerge, however, is unclear. We conducted a proof-of-concept study to examine the moderating effects of genetically driven variation in dopamine signaling, a key modulator of neural reward circuits, on the association between regulatory focus and reward cue responsiveness. METHOD: Healthy Caucasians (N=59) completed a measure of chronic regulatory focus and a probabilistic reward task. A common functional genetic polymorphism impacting prefrontal dopamine signaling (COMT rs4680) was evaluated. RESULTS: Response bias, the participants' propensity to modulate behavior as a function of reward, was predicted by an interaction of regulatory focus and COMT genotype. Specifically, self-perceived success at achieving promotion goals predicted total response bias, but only for individuals with the COMT genotype (Val/Val) associated with relatively increased phasic dopamine signaling and cognitive flexibility. CONCLUSIONS: The combination of success in promotion goal pursuit and Val/Val genotype appears to facilitate responding to reward opportunities in the environment. This study is among the first to integrate an assessment of self-regulatory style with an examination of genetic variability that underlies responsiveness to positive outcomes in goal pursuit.

Self-regulation and mechanisms of action in psychotherapy: a theory-based translational perspective.

Psychotherapy is a complex, multilayered process with the potential to bring about changes at multiple levels of functioning, from the neurobiology of the brain to the individual's role in the social world. Although studies of the mechanisms by which psychotherapy leads to change continue to appear, there remains much to be learned about how psychological interventions work. To guide explorations of how and for whom particular treatment approaches lead to change, researchers can rely on theory to identify potential loci for change and on translational research methods to integrate basic behavioral science and neuroscience with clinical science. In this article, we describe research linking individual differences in the self-regulation of personal goal pursuit with the etiology and treatment of mood disorders. The research draws upon regulatory focus theory as a model of self-regulation and on microintervention designs-controlled laboratory investigations of a specific therapeutic technique-to generate and test hypotheses about how psychological interventions can help to reverse maladaptive self-regulatory processes.

Neural responses to negative feedback are related to negative emotionality in healthy adults.

Prior neuroimaging and electrophysiological evidence suggests that potentiated responses in the anterior cingulate cortex (ACC), particularly the rostral ACC, may contribute to abnormal responses to negative feedback in individuals with elevated negative affect and depressive symptoms. The feedback-related negativity (FRN) represents an electrophysiological index of ACC-related activation in response to performance feedback. The purpose of the present study was to examine the FRN and underlying ACC activation using low resolution electromagnetic tomography source estimation techniques in relation to negative emotionality (a composite index including negative affect and subclinical depressive symptoms). To this end, 29 healthy adults performed a monetary incentive delay task while 128-channel event-related potentials were recorded. We found that enhanced FRNs and increased rostral ACC activation in response to negative--but not positive--feedback was related to greater negative emotionality. These results indicate that individual differences in negative emotionality--a putative risk factor for emotional disorders--modulate ACC-related processes critically implicated in assessing the motivational impact and/or salience of environmental feedback.

What shall I be, what must I be: neural correlates of personal goal activation.

How is the brain engaged when people are thinking about their hopes, dreams, and obligations? Regulatory focus theory postulates two classes of personal goals and motivational systems for pursuing them. Ideal goals, such as hopes and aspirations, are pursued via the promotion system through "making good things happen." Ought goals, such as obligations or responsibilities, are pursued via the prevention system through "keeping bad things from happening." This study investigated the neural correlates of ideal and ought goal priming using an event-related fMRI design with rapid masked stimulus presentations. We exposed participants to their self-identified ideal and ought goals, yoked-control words and non-words. We also examined correlations between goal-related activation and measures of regulatory focus, behavioral activation/inhibition, and negative affect. Ideal priming led to activation in frontal and occipital regions as well as caudate and thalamus, whereas prevention goal priming was associated with activation in precuneus and posterior cingulate cortex. Individual differences in dysphoric/anxious affect and regulatory focus, but not differences in BAS/BIS strength, were predictive of differential activation in response to goal priming. The regions activated in response to ideal and ought goal priming broadly map onto the cortical midline network that has been shown to index processing of self-referential stimuli. Individual differences in regulatory focus and negative affect impact this network and appeared to influence the strength and accessibility of the promotion and prevention systems. The results support a fundamental distinction between promotion and prevention and extend our understanding of how personal goals influence behavior.

Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder.

OBJECTIVE: Major depressive disorder is characterized by impaired reward processing, possibly due to dysfunction in the basal ganglia. However, few neuroimaging studies of depression have distinguished between anticipatory and consummatory phases of reward processing. Using functional MRI (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that individuals with major depression would show reduced reward-related responses in basal ganglia structures. METHOD: A monetary incentive delay task was presented to 30 unmedicated individuals with major depressive disorder and 31 healthy comparison subjects during fMRI scanning. Whole-brain analyses focused on neural responses to reward-predicting cues and rewarding outcomes (i.e., monetary gains). Secondary analyses focused on the relationship between anhedonic symptoms and basal ganglia volumes. RESULTS: Relative to comparison subjects, participants with major depression showed significantly weaker responses to gains in the left nucleus accumbens and the caudate bilaterally. Group differences in these regions were specific to rewarding outcomes and did not generalize to neutral or negative outcomes, although relatively reduced responses to monetary penalties in the major depression group emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although participants with major depression showed reduced activation to reward cues in a small sector of the left posterior putamen. In the major depression group, anhedonic symptoms and depression severity were associated with reduced caudate volume bilaterally. CONCLUSIONS: These results suggest that basal ganglia dysfunction in major depression may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in major depression is related to caudate volume.