Reduced Caudate and Nucleus Accumbens Response to Rewards in Unmedicated Subjects with Major Depressive Disorder

By Diego A. Pizzagalli, Avram J. Holmes, Daniel G. Dillon, Elena Goetz, Jeffrey L. Birk, Ryan Bogdan, D. Dougherty, D. Iosifescu, Scott L. Rauch, Maurizio Fava. American Journal of Psychiatry, 2009

1,152 citations recorded by the source corpus.

Objective Major depressive disorder (MDD) 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 magnetic resonance imaging (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that MDD participants would show reduced reward-related responses in basal ganglia structures. Method A monetary incentive delay task was presented to 30 unmedicated MDD subjects 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, MDD participants showed significantly weaker responses to gains in the left nucleus accumbens and bilateral caudate. 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 MDD emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although MDD subjects showed reduced activation to reward cues in a small sector of the left posterior putamen. Among MDD subjects, anhedonic symptoms and depression severity were associated with reduced bilateral caudate volume. Conclusions These results indicate that basal ganglia dysfunction in MDD may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in MDD is related to caudate volume.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/45b8bf65fbe2e8899a84701a04da23c6e017feb9

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Citations in the corpus

Reconsidering Anhedonia in Depression: Lessons from Translational Neuroscience (2010, methodology): “…implicated in reward motivation, and has exhibited functional and structural abnormalities in patients with MDD. Structural MRI studies have reported reduced grey-matter volume within regions of the striatum (Kim et al., 2008; Matsuo et al., 2008; Pizzagalli et al., 2009; Wacker et al., 2009).”
A meta-analysis of neurofunctional imaging studies of emotion and cognition in major depression (2012, neutral): “Altered striatal (and anterior cingulate) activity has been discussed to be sensitively linked to impaired reward and punishment learning in MDD (Knutson et al., 2008; Pizzagalli et al., 2009).”
A Cybernetic Theory of Psychopathology (2018, background): “…is also possible, however, as being less sensitive to reward may be a particular risk for depression because lack of motivation to pursue goals can lead to hopelessness (Bress, Smith, Foti, Klein, & Hajcak, 2012; Pizzagalli et al., 2009; Pizzagalli, Iosifescu, Hallett, Ratner, & Fava, 2008).”
Effects of Early Life Stress on Cognitive and Affective Function: An Integrated Review of Human Literature (2010, background): “Blunted mesolimbic DA transmission has been postulated in depression, particularly in the presence of anhedonia, low energy, loss of libido, and apathy (Dunlop and Nemeroff 2007; Hasler et al. 2008; Pizzagalli et al. 2009a, b).”
Ventral striatal and medial prefrontal BOLD activation is correlated with reward-related electrocortical activity: A combined ERP and fMRI study (2011, background): “…the case of depression, behavioral findings (Pizzagalli et al., 2008), fMRI VS activation in adults (Epstein et al., 2006; Fitzgerald et al., 2008; Pizzagalli et al., 2009; but see Knutson et al., 2008 for alternative results) and children (Forbes et al., 2009, 2010), and FN ERP work (Foti and…”
Understanding resilience (2013, background): “Another study showed that DNA methyltransferase (DNMT) expression was altered in a region-specific manner in the brains of suicide victims compared to controls who died of causes other than suicide (Poulter et al., 2008).”
The Neurobiology of Anhedonia and Other Reward-Related Deficits (2011, background): “Further, selfreported anhedonia negatively correlated with ventral striatal gray matter and caudate volume [40, 54], but not with NAc volume in unmedicated MDD subjects [54].”
Reward processing dysfunction in major depression, bipolar disorder and schizophrenia (2015, background): “…in this circuitry might be hypothesized in MDD. Consistent with this notion, depressed adults showed reduced putamen activation during reward anticipation as well as reduced caudate, nucleus accumbens (NAcc), and dorsal anterior cingulate (ACC) activation to partially unpredictable rewards (10).”
Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans (2014, positive): “The anti-depression effect is consistent with the activation of the amygdala [60] and may be boosted by nucleus accumbens activation, as depression has been shown to decrease the response of the nucleus accumbens to reward [49].”