Dichter GS, Kozink RV, McClernon FJ, Smoski MJ. Remitted major depression is characterized by reward network hyperactivation during reward anticipation and hypoactivation during reward outcomes. J Affect Disord 136: 1126-1134

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, United States.
Journal of Affective Disorders (Impact Factor: 3.38). 02/2012; 136(3):1126-34. DOI: 10.1016/j.jad.2011.09.048
Source: PubMed


Although functional brain imaging has established that individuals with unipolar major depressive disorder (MDD) are characterized by frontostriatal dysfunction during reward processing, no research to date has examined the chronometry of neural responses to rewards in euthymic individuals with a history of MDD.
A monetary incentive delay task was used during fMRI scanning to assess neural responses in frontostriatal reward regions during reward anticipation and outcomes in 19 participants with remitted major depressive disorder (rMDD) and in 19 matched control participants.
During the anticipation phase of the task, the rMDD group was characterized by relatively greater activation in bilateral anterior cingulate gyrus, in right midfrontal gyrus, and in the right cerebellum. During the outcome phase of the task, the rMDD group was characterized by relatively decreased activation in bilateral orbital frontal cortex, right frontal pole, left insular cortex, and left thalamus. Exploratory analyses indicated that activation within a right frontal pole cluster that differentiated groups during reward anticipation predicted the number of lifetime depressive episodes within the rMDD group.
Replication with larger samples is needed.
Results suggest a double dissociation between reward network reactivity and temporal phase of the reward response in rMDD, such that rMDD is generally characterized by reward network hyperactivation during reward anticipation and reward network hypoactivation during reward outcomes. More broadly, these data suggest that aberrant frontostriatal response to rewards may potentially represent a trait marker for MDD, though future research is needed to evaluate the prospective utility of this functional neural endophenotype as a marker of MDD risk.

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Available from: Francis Joseph McClernon, Oct 09, 2015
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    • "Taking this into consideration, there seems to be a change between acute and remitted states of depression from neural hypoactivation to hyperactivation in brain regions associated with reward processing. In our study, enhanced activity in rMDD might reflect increased neural efforts to activate greater neural resources which are needed to regulate rewarddirected behaviour during motivational reward processing (compare with Dichter et al. 2012). More precisely, the pattern of activation identified in this study can be interpreted as reflecting an increased effort to allocate neural activity in remitted depressed individuals for executive functioning, such as computational and attention-based processes, and for evaluative processes during anticipatory reward processing where uncertainty is high. "
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    ABSTRACT: Dysfunctional behavioural and neural processing of reward has been found in currently depressed individuals. However, little is known about altered reward processing in remitted depressed individuals. A total of 23 medication-free individuals with remitted major depressive disorder (rMDD) and 23 matched healthy controls (HCs) performed a reward task during functional magnetic resonance imaging. We also investigated reward dependence, novelty seeking and harm avoidance using the Tridimensional Personality Questionnaire and their association with neural responses of reward processing. Compared to HCs, individuals with rMDD exhibited enhanced responses to reward-predicting cues in the hippocampus, amygdala and superior frontal gyrus. When reward was delivered, rMDD subjects did not significantly differ from HCs. In both groups neural activity during reward anticipation was negatively correlated with harm avoidance. Our results show that rMDD is characterized by hyperactivation in fronto-limbic regions during reward anticipation. Alterations in neural activation during reward processing might reflect an increased effort in remitted depressed individuals to allocate neural activity for executive and evaluative processes during anticipatory reward processing.
    Psychological Medicine 08/2015; DOI:10.1017/S0033291715001452 · 5.94 Impact Factor
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    • "Negative mood state could have also affected the range of BIS/BAS scores. These results contrast previous research that has found disrupted reward-processing in remitted MDD (Dichter et al., 2012; Pechtel et al., 2013), as compared to healthy controls. We may have failed to find similar results due to the titration procedure, which could have helped r-MDD participants perform similarly to the HCs. "
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    ABSTRACT: Anhedonia, the diminished anticipation and pursuit of reward, is a core symptom of major depressive disorder (MDD). Trait behavioral activation (BA), as a proxy for anhedonia, and behavioral inhibition (BI) may moderate the relationship between MDD and reward-seeking. The present studies probed for reward learning deficits, potentially due to aberrant BA and/or BI, in active or remitted MDD individuals compared to healthy controls (HC). Active MDD (Study 1) and remitted MDD (Study 2) participants completed the modified monetary incentive delay task (mMIDT), a behavioral reward-seeking task whose response window parameters were individually titrated to theoretically elicit equivalent accuracy between groups. Participants completed the BI Scale and BA Reward-Responsiveness and Drive Scales. Despite individual titration, active MDD participants won significantly less money than HCs. Higher Reward-Responsiveness scores predicted more won; Drive and BI were not predictive. Remitted MDD participants' performance did not differ from controls', and trait BA and BI measures did not predict r-MDD performance. These results suggest that diminished reward-responsiveness may contribute to decreased motivation and reward pursuit during active MDD, but that reward learning is intact in remission. Understanding individual reward processing deficits in MDD may inform personalized intervention addressing anhedonia and motivation deficits in select MDD patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    08/2015; DOI:10.1016/j.psychres.2015.08.011
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    • "For example, it is not known whether decreased positive mood symptoms are generally more persistent than increased negative mood symptoms and whether low levels of decreased positive mood symptoms are more likely to be present between episodes of recurrent MDD. Interestingly, altered reward-network responsivity is found in individuals with a history of MDD but without significant current symptoms (Dichter et al., 2012b; McCabe et al., 2009). "
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    ABSTRACT: Restoration of positive mood, in addition to reducing negative mood, is an important treatment goal in the management of depression. The need to restore positive mood states in depressed patients is not adequately addressed by available treatments for major depressive disorder (MDD), suggesting that this mood dimension could be a useful target for drug development. However, for positive mood restoration to become a valid target for antidepressant drug development certain questions should be answered: are symptoms of decreased positive mood phenomenologically distinct from other symptoms of MDD? Should they be considered a distinct aspect of MDD in the diagnostic nomenclature? Is there evidence for differential responsiveness to treatment? Is the underlying pathophysiology understood and different from that of other MDD symptoms? Is low positive mood specific to depression or does it contribute to psychopathology in other disorders? Beyond these basic questions, this review identifies a number of design issues that need to be considered when conducting studies that target improving positive mood. These design issues include (1) what population to study, (2) what line of treatment to target, (3) the appropriateness and validation of methods and measures to evaluate positive mood and its restoration, (4) the role of functional outcome measures in determining success of the treatment, and (5) optimal designs for add-on therapy versus monotherapy agents.
    Journal of Psychopharmacology 05/2014; 28(6). DOI:10.1177/0269881114532857 · 3.59 Impact Factor
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