Person:

Pizzagalli, Diego

Stress may promote the onset of psychopathology by disrupting reward processing. However, the extent to which stress impairs reward processing, rather than incentive processing more generally, is unclear. To evaluate the specificity of stress-induced reward processing disruption, 100 psychiatrically healthy females were administered a probabilistic stimulus selection task (PSST) that enabled comparison of sensitivity to reward-driven (Go) and punishment-driven (NoGo) learning under either “no stress” or “stress” (threat-of-shock) conditions. Cortisol samples and self-report measures were collected. Contrary to hypotheses, the groups did not differ significantly in task performance or cortisol reactivity. However, further analyses focusing only on individuals under “stress” who were high responders with regard to both cortisol reactivity and self-reported negative affect revealed reduced reward sensitivity relative to individuals tested in the “no stress” condition; importantly, these deficits were reward-specific. Overall, findings provide preliminary evidence that stress-reactive individuals show diminished sensitivity to reward, but not punishment, under stress. While such results highlight the possibility that stress-induced anhedonia might be an important mechanism linking stress to affective disorders, future studies are necessary to confirm this conjecture.

Background: Childhood adversity increases the risk of psychopathology, but the neurobiological mechanisms underlying this vulnerability are not well-understood. In animal models, early adversity is associated with dysfunction in basal ganglia regions involved in reward processing, but this relationship has not been established in humans. Methods: Functional magnetic resonance imaging was used to examine basal ganglia responses to (a) cues signaling possible monetary rewards and losses, and (b) delivery of monetary gains and penalties, in 13 young adults who experienced maltreatment before age 14 and 31 non-maltreated controls. Results: Relative to controls, individuals exposed to childhood adversity reported elevated symptoms of anhedonia and depression, rated reward cues less positively, and displayed a weaker response to reward cues in the left globus pallidus. There were no group differences in right hemisphere basal ganglia response to reward cues, or in basal ganglia response to loss cues, no-incentive cues, gains, or penalties. Conclusions: Results indicate that childhood adversity in humans is associated with blunted subjective responses to reward-predicting cues as well as dysfunction in left basal ganglia regions implicated in reward-related learning and motivation. This dysfunction may serve as a diathesis that contributes to the multiple negative outcomes and psychopathologies associated with childhood adversity. The findings suggest that interventions that target motivation and goal-directed action may be useful for reducing the negative consequences of childhood adversity.

Background: Bipolar disorder (BPD) features cycling mood states ranging from depression to mania with intermittent phases of euthymia. Bipolar disorder subjects often show excessive goal-directed and pleasure-seeking behavior during manic episodes and reduced hedonic capacity during depressive episodes, indicating that BPD might involve altered reward processing. Our goal was to test the hypothesis that BPD is characterized by impairments in adjusting behavior as a function of prior reinforcement history, particularly in the presence of residual anhedonic symptoms. Methods: Eighteen medicated BPD subjects and 25 demographically matched comparison subjects performed a probabilistic reward task. To identify putative dysfunctions in reward processing irrespective of mood state, primary analyses focused on euthymic BPD subjects (n = 13). With signal-detection methodologies, response bias toward a more frequently rewarded stimulus was used to objectively assess the participants' propensity to modulate behavior as a function of reinforcement history. Results: Relative to comparison subjects, euthymic BPD subjects showed a reduced and delayed acquisition of response bias toward the more frequently rewarded stimulus, which was partially due to increased sensitivity to single rewards of the disadvantageous stimulus. Analyses considering the entire BPD sample revealed that reduced reward learning correlated with self-reported anhedonic symptoms, even after adjusting for residual manic and anxious symptoms and general distress. Conclusions: The present study provides preliminary evidence indicating that BPD, even during euthymic states, is characterized by dysfunctional reward learning in situations requiring integration of reinforcement information over time and thus offers initial insights about the potential source of dysfunctional reward processing in this disorder.

Objective:

Anhedonia, the lack of reactivity to pleasurable stimuli, is a cardinal feature of depression that has received renewed interest as a potential endophenotype of this debilitating disease. The goal of the present study was to test the hypothesis that individuals with major depression are characterized by blunted reward responsiveness, particularly when anhedonic symptoms are prominent. Methods:

A probabilistic reward task rooted within signal-detection theory was utilized to objectively assess hedonic capacity in 23 unmedicated subjects meeting DSM-IV criteria for major depressive disorder (MDD) and 25 matched control subjects recruited from the community. Hedonic capacity was defined as reward responsiveness – i.e., the participants’ propensity to modulate behavior as a function of reward. Results:

Compared to controls, MDD subjects showed significantly reduced reward responsiveness. Trial-by-trial probability analyses revealed that MDD subjects, while responsive to delivery of single rewards, were impaired at integrating reinforcement history over time and expressing a response bias toward a more frequently rewarded cue in the absence of immediate reward. This selective impairment correlated with self-reported anhedonic symptoms, even after considering anxiety symptoms and general distress. Conclusions:

These findings indicate that MDD is characterized by an impaired tendency to modulate behavior as a function of prior reinforcements, and provides initial clues about which aspects of hedonic processing might be dysfunctional in depression.

Background: Difficulties in defining and characterizing phenotypes has hindered progress in psychiatric genetics and clinical neuroscience. Decreased approach-related behavior and anhedonia (lack of responsiveness to pleasure) are considered cardinal features of depression, but few studies have used laboratory-based measures to objectively characterize these constructs. Methods: To assess hedonic capacity in relation to depressive, particularly anhedonic, symptoms, 62 participants completed a signal-detection task based on a differential reinforcement schedule. Anhedonia was operationalized as decreased reward responsiveness. Results: Unequal frequency of reward between two correct responses produced a response bias (i.e., a systematic preference to identify the stimulus paired with the more frequent reward). Subjects with elevated depressive symptoms (Beck Depression Inventory scores ≥ 16) failed to show a response bias. Impaired reward responsiveness predicted higher anhedonic symptoms 1 month later, after controlling for general negative affectivity. Conclusions: Impaired tendency to modulate behavior as a function of prior reinforcement might underline diminished hedonic capacity in depression. When applied to a clinical population, objective assessments of participants’ propensity to modulate behavior as a function of reward might provide a powerful tool for improving the phenotypic definition of depression and thus offer a reliable behavioral screening approach for neuroscience studies of depression.

Background: Tobacco smoking, driven by the addictive properties of nicotine, is the most prevalent preventable cause of death in the Western world. Accumulated evidence suggests that nicotine may increase appetitive responding for nondrug incentives in the environment. Methods: To test this hypothesis, we conducted a randomized, double-blind, placebo-controlled, crossover study of the effect of a single dose of transdermal nicotine on reward responsiveness in 30 psychiatrically healthy nonsmokers. A novel signal detection task in which correct responses were differentially rewarded in a 3:1 ratio was used to assess the extent to which participants modulated their behavior as a function of reward. Results: Despite expected adverse effects such as nausea, nicotine significantly increased response bias toward the more frequently rewarded condition, at the expense of accuracy, independent of effects on attention or overall vigilance. Additionally, response bias on placebo was greater in participants who received nicotine in the first session, indicating that an effect of nicotine on reward responsiveness or reward-based learning persisted for at least 1 week. Conclusions: These findings suggest that a single dose of nicotine enhances response to non-drug-related rewards in the environment, with lasting effects. This effect may contribute to reinforcement of early smoking behavior and development of nicotine dependence.

Anhedonia, the reduced propensity to experience pleasure, is a promising endo-- phenotype and vulnerability factor for several psychiatric disorders, including depression and schizophrenia. In the present study, we used resting electroencephalography, functional magnetic resonance imaging, and volumetric analyses to probe putative associations between anhedonia and individual differences in key nodes of the brain's reward system in a non-clinical sample. We found that anhedonia, but not other symptoms of depression or anxiety, was correlated with reduced nucleus accumbens (NAcc) responses to rewards (gains in a monetary incentive delay task), reduced NAcc volume, and increased resting delta current density (i.e., decreased resting activity) in the rostral anterior cingulate cortex (rACC), an area previously implicated in positive subjective experience. In addition, NAcc reward responses were inversely associated with rACC resting delta activity, supporting the hypothesis that delta might be lawfully related to activity within the brain's reward circuit. Taken together, these results help elucidate the neural basis of anhedonia and strengthen the argument for anhedonia as an endophenotype for depression.

Preclinical studies suggest that stress exerts depressogenic effects by impairing hedonic capacity, in humans, however, the precise mechanisms linking stress and depression are largely unknown. As an initial step towards better understanding the association between stress and anhedonia, the present study tested, in two independent samples, whether individuals reporting elevated stress exhibit decreased hedonic capacity. The Perceived Stress Scale (PSS) measured the decree to which participants appraised their daily life as unpredictable, uncontrollable, and overwhelming. Hedonic capacity was objectively assessed using a signal-detection task based on a differential reinforcement schedule. Decreased reward responsiveness (i.e., the participants propensity to modulate behavior as a function of reward) was used as an operational measure of hedonic capacity. In both Study 1 (n = 88) and Study 2 (n = 80), participants with high PSS scores displayed blunted reward responsiveness and reported elevated anhedonic symptoms. Additionally, PSS scores predicted reduced reward responsiveness even after controlling for general distress and anxiety symptoms. These findings are consistent with preclinical data highlighting links between stress and anhedonia, and offer promising insights into potential mechanisms linking stress to depression.