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Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards.

ABSTRACT: Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during functional magnetic resonance imaging to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and 13 affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards.

SUBMITTER: Smoski MJ

PROVIDER: S-EPMC3225489 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards.

Smoski Moria J MJ Rittenberg Alison A Dichter Gabriel S GS

Psychiatry research 20111110 3

Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified M ...[more]

PMID: 22079658

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Project description:IntroductionReduced motivation is an important symptom of major depression, thought to impair recovery by reducing opportunities for rewarding experiences. We characterized motivation for monetary outcomes in depressed outpatients (N = 39, 22 female) and controls (N = 22, 11 female) in terms of their effectiveness in seeking rewards and avoiding losses. We assessed motivational function during learning of associations between stimuli and actions, as well as when learning was complete. We compared the activity within neural circuits underpinning these behaviors between depressed patients and controls.MethodsWe used a Go/No-Go task that assessed subjects' abilities in learning to emit or withhold actions to obtain monetary rewards or avoid losses. We derived motivation-relevant parameters of behavior (learning rate, Pavlovian bias, and motivational influence of gains and losses). After learning, participants performed the task during functional magnetic resonance imaging (fMRI). We compared neural activation during anticipation of action emission vs. action inhibition, and for actions performed to obtain rewards compared to actions that avoid losses.ResultsDepressed patients showed a similar Pavlovian bias to controls and were equivalent in terms of withholding action to gain rewards and emitting action to avoid losses, behaviors that conflict with well-described Pavlovian tendencies to approach rewards and avoid losses. Patients were not impaired in overall performance or learning and showed no abnormal neural responses, for example in bilateral midbrain or striatum. We conclude that basic mechanisms subserving motivated learning are thus intact in moderate depression.ImplicationsTherapeutically, the intact mechanisms identified here suggest that learning-based interventions may be particularly effective in encouraging recovery. Etiologically, our results suggest that the severe motivational deficits clinically observed in depression are likely to have complex origins, possibly related to an impairment in the representation of future states necessary for long-term planning.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:Peer victimization (or bullying) is a known risk factor for depression, especially among youth. However, the mechanisms connecting victimization experience to depression symptoms remains unknown. As depression is known to be associated with neural blunting to monetary rewards, aberrant responsiveness to social rewards may be a key deficit connecting socially stressful experiences with later depression. We, therefore, sought to determine whether adolescents' experiences with social stress would be related to their current response to social rewards over less socially relevant monetary rewards. Neural responses to monetary and social rewards were measured using event-related potentials (ERPs) to peer acceptance and rejection feedback (Island Getaway task) and to monetary reward and loss feedback (Doors task) in a sample of 56 late adolescents/emerging young adults followed longitudinally since preschool. In the Island Getaway task, participants voted whether to "keep" or "kick out" each co-player, providing an index of prosocial behavior, and then received feedback about how each player voted for the participant. Analyses tested whether early and recent peer victimization was related to response to rewards (peer acceptance or monetary gains), residualized for response to losses (peer rejection or monetary losses) using the reward positivity (RewP) component. Findings indicated that both experiencing greater early and greater recent peer victimization were significantly associated with participants casting fewer votes to keep other adolescents ("Keep" votes) and that greater early peer victimization was associated with reduced neural response to peer acceptance. Early and recent peer victimization were significantly more associated with neural response to social than monetary rewards. Together, these findings suggest that socially injurious experiences such as peer victimization, especially those occurring early in childhood, relate to two distinct but important findings: that early victimization is associated with later reduced response to peer acceptance, and is associated with later tendency to reject peers. Findings also suggest that there is evidence of specificity to reward processing of different types; thus, future research should expand studies of reward processing beyond monetary rewards to account for the possibility that individual differences may be related to other, more relevant, reward types.

Dataset Information

Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards.

Publications

Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards.

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