The Neural Correlates of Anhedonia in Major Depressive Disorder

Section of Neuroscience and Emotion, Department of Psychological Medicine, Institute of Psychiatry, Decrespigny Park, London, United Kingdom.
Biological Psychiatry (Impact Factor: 10.26). 01/2006; 58(11):843-53. DOI: 10.1016/j.biopsych.2005.05.019
Source: PubMed

ABSTRACT

Anhedonia is a relative lack of pleasure in response to formerly rewarding stimuli. It is an important diagnostic feature of major depressive disorder (MDD), and predicts antidepressant efficacy. Understanding its neurobiological basis may help to target new treatments and predict treatment outcomes. Using a novel paradigm, we aimed to explore the correlations between anhedonia severity and magnitude of neural responses to happy and sad stimuli in regions previously implicated in studies of human reward processing and depressive anhedonia.
Neural responses to happy and sad emotional stimuli (autobiographical prompts and mood congruent facial expressions) were measured using blood oxygen level dependent (BOLD) functional magnetic resonance imaging in twelve MDD individuals with varying degrees of anhedonia.
In response to happy stimuli, anhedonia, but not depression severity per se, was positively and negatively correlated with ventromedial prefrontal cortex (VMPFC) and amygdala/ventral striatal activity, respectively. State anxiety independently contributed to a VMPFC-subcortical dissociation of response to happy (but not sad) stimuli, which was similar, but different, to anhedonia.
These findings suggest that anhedonia and state anxiety are associated with dysfunction within neural systems underlying the response to, and assessment of, the rewarding potential of emotive stimuli in MDD, and highlight the importance of employing a symptom-dimension-based approach in the examination of the neurobiology of depression.

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    • "Disrupted reward processing also predicts the future development of depressive symptoms (Forbes et al., 2007; Pizzagalli et al., 2005; Vrieze et al., 2013). In addition, neuroimaging studies have consistently shown that anhedonic symptoms, but not depressive symptoms per se, are negatively correlated with ventral striatal activation in patients with MDD (Dowd and Barch, 2010; Epstein et al., 2006; Harvey et al., 2010; Keedwell et al., 2005; Wacker et al., 2009), with a similar pattern observed in nonclinical samples (Chentsova-Dutton and Hanley, 2010; Harvey et al., 2007). "
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    ABSTRACT: Background: Anhedonia is a cardinal feature of major depression and is hypothesized to be driven by low motivation, in particular blunted reward sensitivity. It has been suggested to be a marker that represents a genetic predisposition to this disorder. However, little is known about the mechanisms underlying this heightened risk in unaffected first-degree relatives of patients with major depression. We previously demonstrated abnormal reward biases in acutely depressed patients. The present study aimed to examine the development of reward bias in first-degree relatives of patients with major depression. Methods: Forty-seven first-degree relatives of patients with major depression (26 females, age 18-52) and 60 healthy controls with no family history of depression (34 females, age 21-48) were recruited. A probabilistically rewarded difficult visual discrimination task, in which participants were instructed about the contingencies, was used to assess blunted reward sensitivity. A response bias towards the more frequently rewarded stimulus (termed "reward bias") was the primary outcome variable in this study. Participants also completed self-reported measures of anhedonia and depressive symptoms. Results: Compared with the control group, relatives of patients with major depression with sub-clinical depressive symptoms displayed a blunted reward bias. Relatives without symptoms displayed largely intact motivational processing on both self-report and experimental measures. The degree of anhedonia was associated with attenuated reward bias in first-degree relatives of patients with major depression, especially in those with sub-clinical symptoms. Limitations: The study did not include a depressed patient group, which restricted our ability to interpret the observed group differences. Conclusions: Blunted reward sensitivity may be largely manifested in a subgroup of relatives with high levels of depressive symptoms.
    No preview · Article · Nov 2015 · Journal of Affective Disorders
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    • "Such high rates of occurrence nationally and globally demonstrate the critical need for continuing research into the etiology and treatment of this disorder . Anhedonia, the reduced anticipation of pleasurable stimuli and blunted responsiveness to reward, is one of the core symptoms of major depressive disorder (MDD) in the DSM-5 (American Psychiatric Association, 2013) and has been shown to be a predictor of antidepressant efficacy (Keedwell et al., 2005). Anhedonia contributes to reward-processing deficits in depression (Treadway et al., 2009) and can be studied using paradigms that assess both anticipatory and consummatory processes. "
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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.
    Full-text · Article · Aug 2015
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    • "This is in keeping with mood induction fMRI findings in patients with depression, who show an opposite direction of effects compared with healthy controls . For instance, in adults with MDD, severity of depressive symptoms correlated negatively with activation in the following areas following happy, but not sad mood induction: left putamen, bilateral caudate, left nucleus accumbens , and left amygdala (Keedwell et al. 2005b). Furthermore , decreased ventral striatum activity when processing positive words in depressed versus healthy adults correlated with symptoms of anhedonia (Epstein et al. 2006), consistent with abnormalities in the reward processing system in depression. "
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    ABSTRACT: Introduction: Little is known about the neural correlates of mood states and the specific physiological changes associated with their valence and duration, especially in young people. Arterial spin labeling (ASL) imaging is particularly well-suited to study sustained cerebral states in young people, due to its robustness to low-frequency drift, excellent interscan reliability, and noninvasiveness. Yet, it has so far been underutilized for understanding the neural mechanisms underlying mood states in youth. Methods: In this exploratory study, 21 healthy adolescents aged 16 to 18 took part in a mood induction experiment. Neutral, sad, and happy mood states were induced using film clips and explicit instructions. An ASL scan was obtained following presentation of each film clip. Results: Mood induction led to robust changes in self-reported mood ratings. Compared to neutral, sad mood was associated with increased regional cerebral blood flow (rCBF) in the left middle frontal gyrus and anterior prefrontal cortex, and decreased rCBF in the right middle frontal gyrus and the inferior parietal lobule. A decrease in self-reported mood from neutral to sad condition was associated with increased rCBF in the precuneus. Happy mood was associated with increased rCBF in medial frontal and cingulate gyri, the subgenual anterior cingulate cortex, and ventral striatum, and decreased rCBF in the inferior parietal lobule. The level of current self-reported depressive symptoms was negatively associated with rCBF change in the cerebellum and lingual gyrus following both sad and happy mood inductions. Conclusions: Arterial spin labeling is sensitive to experimentally induced mood changes in healthy young people. The effects of happy mood on rCBF patterns were generally stronger than the effects of sad mood.
    Full-text · Article · Jun 2015 · Brain and Behavior
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