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: 3.71). 02/2012; 136(3):1126-34. DOI: 10.1016/j.jad.2011.09.048
Source: PubMed

ABSTRACT 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, Aug 21, 2015
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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 · 2.81 Impact Factor
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    • "A growing number of studies suggest that using functional neuroimaging in rMDD is a valid approach to investigating biological trait markers for future major depressive episodes ( Bhagwagar and Cowen, 2008 ; Dichter et al., 2012 ; Elliott et al., 2012 ; Nixon et al., 2014 ; Schiller et al., 2013 ; Pulcu et al., 2014 ). Studying remitted MDD has additional advantages such as mitigating the effects of current mood state and antidepressant medications ( Dichter et al., 2012 ; Schiller et al., 2013 ). Here, we investigated the following hypotheses, based on previous literature reviewed above: compared with controls, people with rMDD would exhibit 1) enhanced sgACC response to donation decisions relative to simple monetary rewards and 2) reduced responses to rewards in striatal regions (e.g. "
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    ABSTRACT: Background Major depressive disorder (MDD) is associated with functional abnormalities in fronto-meso-limbic networks contributing to decision-making, affective and reward processing impairments. Such functional disturbances may underlie a tendency for enhanced altruism driven by empathy-based guilt observed in some patients. However, despite the relevance of altruistic decisions to understanding vulnerability, as well as everyday psychosocial functioning, in MDD, their functional neuroanatomy is unknown. Methods Using a charitable donations experiment with fMRI, we compared 14 medication-free participants with fully remitted MDD and 15 demographically-matched control participants without MDD. Results Compared with the control group, the remitted MDD group exhibited enhanced BOLD response in a septal/subgenual cingulate cortex (sgACC) region for charitable donation relative to receiving simple rewards and higher striatum activation for both charitable donation and simple reward relative to a low level baseline. The groups did not differ in demographics, frequency of donations or response times, demonstrating only a difference in neural architecture. Conclusions We showed that altruistic decisions probe residual sgACC hypersensitivity in MDD even after symptoms are fully remitted. The sgACC has previously been shown to be associated with guilt which promotes altruistic decisions. In contrast, the striatum showed common activation to both simple and altruistic rewards and could be involved in the so-called “warm glow” of donation. Enhanced neural response in the depression group, in areas previously linked to altruistic decisions, supports the hypothesis of a possible association between hyper-altruism and depression vulnerability, as shown by recent epidemiological studies.
    Clinical neuroimaging 04/2014; 4:701–710. DOI:10.1016/j.nicl.2014.04.010 · 2.53 Impact Factor
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    • "However , these studies have yielded inconsistent results probably due to the differences in the tasks employed in the studies. Compared to healthy subjects, remitted patients with MDD showed decreased activity in the right frontal pole, left insula, left thalamus, and the OFC bilaterally during the outcome phase of the monetary incentive delay task (Dichter et al., 2012). When compared to healthy subjects, patients with MDD also showed increased activity in the left inferior frontal gyrus and thalamus bilaterally during the positive reward in outcome phase of the Wheel of Fortune task, but showed decreased activity in the medial frontal cortex, the right caudate, and auditory cortex combined with increased activity in the OFC, inferior frontal cortex, and middle frontal cortex during the negative reward in outcome phase (Smoski et al., 2009). "
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    ABSTRACT: Reduced motivation and blunted decision-making are key features of major depressive disorder (MDD). Patients with MDD show abnormal decision-making when given negative feedback regarding a reward. The brain mechanisms underpinning this behavior remain unclear. In the present study, we examined the association between rapid decision-making with negative feedback and brain volume in MDD. Thirty-six patients with MDD and 54 age-, sex- and IQ-matched healthy subjects were studied. Subjects performed a rapid decision-making monetary task in which participants could make high- or low-risk choices. We compared between the 2 groups the probability that a high-risk choice followed negative feedback. In addition, we used voxel-based morphometry (VBM) to compare between groups differences in gray matter volume, and the correlation between the probability for high-risk choices and brain volume. Compared to the healthy group, the MDD group showed significantly lower probabilities for high-risk choices following negative feedback. VBM analysis revealed the MDD group had less gray matter volume in the right medial prefrontal cortex and orbitofrontal cortex (OFC) compared to the healthy group. The right OFC volume was negatively correlated with the probability that a high-risk choice followed negative feedback in patients with MDD. We did not observe these trends in healthy subjects. Patients with MDD show reduced motivation for monetary incentives when they were required to make rapid decisions following negative feedback. We observed a correlation between this reduced motivation and gray matter volume in the medial and ventral prefrontal cortex, which suggests that these brain regions are likely involved in the pathophysiology of aberrant decision-making in MDD.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 09/2013; 48. DOI:10.1016/j.pnpbp.2013.09.011 · 4.03 Impact Factor
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