Self-reported Anhedonia Research Articles

Investigating the role of mental imagery use in the assessment of anhedonia

ABSTRACT Anhedonia, or a deficit in the liking, wanting, and seeking of rewards, is typically assessed via self-reported “in-the-moment” emotional and motivational responses to reward stimuli and activities. Given that mental imagery is known to evoke emotion and motivational responses, we conducted two studies to investigate the relationship between mental imagery use and self-reported anhedonia. Using a novel Reward Response Scale (adapted from the Dimensional Anhedonia Rating Scale, DARS; Rizvi et al., 2015) modified to assess deliberate and spontaneous mental imagery use, Study 1 (N = 394) compared uninstructed and instructed mental imagery use, and Study 2 (N = 586) conducted a test of replication of uninstructed mental imagery use. Results showed that greater mental imagery use was associated with higher reward response scores (Study 1 & 2), and this relationship was not moderated by whether imagery use was uninstructed or instructed (Study 1). Importantly, mental imagery use moderated the convergence between reward response and depression scale measures of anhedonia, with lower convergence for those reporting higher mental imagery use (Study 1 & 2). Results suggest that higher spontaneous mental imagery use may increase self-reported reward response and reduce the convergence between reward response scale and depression questionnaire measures of anhedonia. [199 / 200 words]

A randomized proof-of-mechanism trial of TNF antagonism for motivational deficits and related corticostriatal circuitry in depressed patients with high inflammation.

Chronic, low-grade inflammation has been associated with motivational deficits in patients with major depression (MD). In turn, impaired motivation has been linked to poor quality of life across psychiatric disorders. We thus determined effects of the anti-inflammatory drug infliximab-a potent tumor necrosis factor (TNF) antagonist-on behavioral and neural measures of motivation in 42 medically stable, unmedicated MD patients with a C-reactive protein >3 mg/L. All patients underwent a double-blind, placebo-controlled, single-dose, randomized clinical trial with infliximab (5 mg/kg) versus placebo. Behavioral performance on an effort-based decision-making task, self-report questionnaires, and neural responses during event-related functional magnetic resonance imaging were assessed at baseline and 2 weeks following infusion. We found that relative to placebo, patients receiving infliximab were more willing to expend effort for rewards. Moreover, increase in effortful choices was associated with reduced TNF signaling as indexed by decreased soluble TNF receptor type 2 (sTNFR2). Changes in effort-based decision-making and sTNFR2 were also associated with changes in task-related activity in a network of brain areas, including dorsomedial prefrontal cortex (dmPFC), ventral striatum, and putamen, as well as the functional connectivity between these regions. Changes in sTNFR2 also mediated the relationships between drug condition and behavioral and neuroimaging measures. Finally, changes in self-reported anhedonia symptoms and effort-discounting behavior were associated with greater responses of an independently validated whole-brain predictive model (aka "neural signature") sensitive to monetary rewards. Taken together, these data support the use of anti-inflammatory treatment to improve effort-based decision-making and associated brain circuitry in depressed patients with high inflammation.

Development of a multivariate prediction model for antidepressant resistant depression using reward-related predictors.

Individuals with depression who do not respond to two or more courses of serotonergic antidepressants tend to have greater deficits in reward processing and greater internalizing symptoms, yet there is no validated self-report method to determine the likelihood of treatment resistance based on these symptom dimensions. This online case-control study leverages machine learning techniques to identify differences in self-reported anhedonia and internalizing symptom profiles of antidepressant non-responders compared to responders and healthy controls, as an initial proof-of-concept for relating these indicators to medication responsiveness. Random forest classifiers were used to identify a subset from a set of 24 reward predictors that distinguished among serotonergic medication resistant, non-resistant, and non-depressed individuals recruited online (N = 393). Feature selection was implemented to refine model prediction and improve interpretability. Accuracies for full predictor models ranged from .54 to .71, while feature selected models retained 3-5 predictors and generated accuracies of .42 to .70. Several models performed significantly above chance. Sensitivity for non-responders was greatest after feature selection when compared to only responders, reaching .82 with 3 predictors. The predictors retained from feature selection were then explored using factor analysis at the item level and cluster analysis of the full data to determine empirically driven data structures. Non-responders displayed 3 distinct symptom profiles along internalizing dimensions of anxiety, anhedonia, motivation, and cognitive function. Results should be replicated in a prospective cohort sample for predictive validity; however, this study demonstrates validity for using a limited anhedonia and internalizing self-report instrument for distinguishing between antidepressant resistant and responsive depression profiles.

Individualized Functional Brain System Topologies and Major Depression: Relationships Among Patch Sizes and Clinical Profiles and Behavior

BackgroundNeuroimaging studies of major depression have typically been conducted using group-level approaches. However, given interindividual differences in brain systems, there is a need for individualized approaches to brain systems mapping and putative links toward diagnosis, symptoms, and behavior. MethodsWe used an iterative parcellation approach to map individualized brain systems in 328 participants from a multisite, placebo-controlled clinical trial. We hypothesized that participants with depression would show abnormalities in salience, control, default, and affective systems, which would be associated with higher levels of self-reported anhedonia, anxious arousal, and worse cognitive performance. Within hypothesized brain systems, we compared patch sizes (number of vertices) between depressed and healthy control groups. Within depressed groups, abnormal patches were correlated with hypothesized clinical and behavioral measures. ResultsSignificant group differences emerged in hypothesized patches of 1) the lateral salience system (parietal operculum; t326 = −3.11, p = .002) and 2) the control system (left medial posterior prefrontal cortex region; z = −3.63, p < .001), with significantly smaller patches in these regions in participants with depression than in healthy control participants. Results suggest that participants with depression with significantly smaller patch sizes in the lateral salience system and control system regions experience greater anxious arousal and cognitive deficits. ConclusionsThe findings imply that neural features mapped at the individual level may relate meaningfully to diagnosis, symptoms, and behavior. There is strong clinical relevance in taking an individualized brain systems approach to mapping neural functional connectivity because these associated region patch sizes may help advance our understanding of neural features linked to psychopathology and foster future patient-specific clinical decision making.

Social support mediates the effects of childhood unpredictability on anhedonia: A retrospective investigation in an online adult community sample

Increasingly, research is highlighting the implications of exposure to unpredictable environments during childhood (i.e., “childhood unpredictability”) on outcomes in adulthood. Converging evidence from preclinical and clinical studies has implicated childhood unpredictability in disrupted reward processing and anhedonia. From the stress generation literature, altered social support has emerged as a possible mechanism by which this effect may occur. In the current study, our goal was to understand whether the pathway from childhood unpredictability to anhedonia occurs through reduced perceptions of social support. Toward this end, we recruited an online community sample of adults in the US (N = 242) to complete surveys assessing childhood unpredictability, depressive symptoms, anhedonia, and social support, as well as a novel online version of the Probabilistic Reward Task. We found that childhood unpredictability was associated with increased depressive symptoms and anhedonia (but not objective measure of anhedonia), and reduced perceptions of social support in adulthood. Mediation analyses revealed a significant indirect effect of perceived social support on the association between childhood unpredictability and anhedonia, controlling for age, sex, and non-anhedonic depressive symptoms. Unexpectedly, measures of reward responsiveness from the behavioral task were not related to childhood unpredictability. The current findings replicate previous reports linking childhood unpredictability and self-reported anhedonia, and extend them to incorporate the potential mediating pathway of reduced social support. Implications for treatment for anhedonia are discussed.

Effectiveness of a blended school-based mindfulness program for the prevention of co-rumination and internalizing problems in Dutch secondary school girls: a cluster randomized controlled trial

BackgroundA growing body of literature indicates that adolescent girls who talk with close friends about interpersonal problems or worries in an excessive, speculative way, and with an intense focus on distress (i.e., co-rumination) are at heightened risk for developing internalizing symptoms and disorders as well as reduced friendship quality. However, to date, there are no prevention programs available that target high levels of co-rumination between adolescent girls. As such, we developed the blended school-based mindfulness prevention program Happy Friends, Positive Minds (HFPM) that targets co-rumination at the dyadic level, i.e., between two close female friends. The aim of this trial is to evaluate the effectiveness of HFPM to reduce co-rumination and internalizing problems and to enhance wellbeing and social-emotional behavior in Dutch adolescent girls.MethodsA cluster Randomized Controlled Trial (cRCT) will be conducted to evaluate HFPM effectiveness. We will recruit 160 female friendship dyads (n = 320 girls) aged 13 to 15 years who will be characterized by high levels of self-reported co-rumination. The cRCT has two arms: (1) an intervention condition in which 160 girls (80 friendship dyads) will receive the 14-week HFPM program in two consecutive cohorts (cohort 1 in academic year 2023/2024 and cohort 2 in academic year 2024/2025, and (2) a control condition in which 160 girls (80 dyads) will receive care-as-usual (CAU) in two consecutive cohorts (cohort 1 in academic year 2023/2024 and cohort 2 in academic year 2024/2025). Data will be collected at baseline (T0), during the program (T1;T2; T3), immediately after the program (T4), and at 1-year follow-up (T5). Participant-level self-reported risk for (early onset) depression and anxiety, self-reported and observed co-rumination, self- and friend-reported friendship quality, self-reported positive and negative affect, self-reported interpersonal responses to positive affect, and self-reported anhedonia symptoms will be the outcome variables.DiscussionThis study will provide insights into the short-term and long-term effects of the HFPM program on girls’ internalizing problems, wellbeing, and social-emotional behavior.Trial registrationInternational Standard Randomized Controlled Trials, identifier: ISRCTN54246670. Registered on 27 February 2023.

Prefrontal cortical response to natural rewards and self-reported anhedonia are associated with greater craving among recently withdrawn patients in residential treatment for opioid use disorder

Both anhedonia and craving are common among patients with opioid use disorder (OUD), and are associated with vulnerability to relapse. Although these constructs are theoretically linked relatively few studies have examined them together. In the current study, recently withdrawn patients (N = 71) in residential treatment for prescription OUD underwent a cue reactivity paradigm while being monitored with functional near-infrared spectroscopy (fNIRS). Patients also self-reported symptoms of anhedonia via the Snaith-Hamilton Pleasure Scale (SHAPS), while smartphone-based ecological momentary assessments (EMA) were used to measure craving levels. On average, lower right prefrontal cortex (PFC) activity in response to positive social stimuli was associated with higher craving (β = − 2.87; S.E. = 1.23; p = 0.02). Self-reported anhedonia moderated the association between PFC activity and craving (β = − 1.02; S.E. = 0.48; p = 0.04), such that patients with two or more anhedonic symptoms had a significant and stronger negative association between PFC activation to hedonically positive images and craving, compared to patients with fewer than two anhedonic symptoms, among whom the association was not significant. This finding provides evidence that higher levels of anhedonia among patients in residential treatment for OUD are associated with a stronger link between lower PFC response to positive social experiences and higher levels of craving, potentially increasing overall vulnerability to relapse.

Enhancing the Psychometric Properties of the Iowa Gambling Task Using Full Generative Modeling.

Poor psychometrics, particularly low test-retest reliability, pose a major challenge for using behavioral tasks in individual differences research. Here, we demonstrate that full generative modeling of the Iowa Gambling Task (IGT) substantially improves test-retest reliability and may also enhance the IGT's validity for use in characterizing internalizing pathology, compared to the traditional analytic approach. IGT data was collected across two sessions, one month apart. Our full generative model incorporated (1) the Outcome Representation Learning (ORL) computational model at the person-level and (2) a group-level model that explicitly modeled test-retest reliability, along with other group-level effects. Compared to the traditional 'summary score' (proportion good decks selected), the ORL model provides a theoretically rich set of performance metrics (Reward Learning Rate , Punishment Learning Rate , Win Frequency Sensitivity , Perseveration Tendency , Memory Decay ), capturing distinct psychological processes. While test-retest reliability for the traditional summary score was only moderate (, BCa 95% CI [.04, .63]), test-retest reliabilities for ORL performance metrics produced by the full generative model were substantially improved, with test-retest correlations ranging between for the five ORL parameters. Further, while summary scores showed no substantial associations with internalizing symptoms, ORL parameters were significantly associated with internalizing symptoms. Specifically, Punishment Learning Rate was associated with higher self-reported depression and Perseveration Tendency was associated with lower self-reported anhedonia. Generative modeling offers promise for advancing individual differences research using the IGT, and behavioral tasks more generally, through enhancing task psychometrics.

Multi-modal assessment of reward functioning in adolescent anhedonia.

Anhedonia is a core symptom of depression that predicts worse treatment outcomes. Dysfunction in neural reward circuits is thought to contribute to anhedonia. However, whether laboratory-based assessments of anhedonia and reward-related neural function translate to adolescents' subjective affective experiences in real-world contexts remains unclear. We recruited a sample of adolescents (n = 82; ages 12-18; mean = 15.83) who varied in anhedonia and measured the relationships among clinician-rated and self-reported anhedonia, behaviorally assessed reward learning ability, neural response to monetary reward and loss (as assessed with functional magnetic resonance imaging), and repeated ecological momentary assessment (EMA) of positive affect (PA) and negative affect (NA) in daily life. Anhedonia was associated with lower mean PA and higher mean NA across the 5-day EMA period. Anhedonia was not related to impaired behavioral reward learning, but low PA was associated with reduced nucleus accumbens response during reward anticipation and reduced medial prefrontal cortex (mPFC) response during reward outcome. Greater mean NA was associated with increased mPFC response to loss outcome. Traditional laboratory-based measures of anhedonia were associated with lower subjective PA and higher subjective NA in youths' daily lives. Lower subjective PA and higher subjective NA were associated with decreased reward-related striatal functioning. Higher NA was also related to increased mPFC activity to loss. Collectively, these findings demonstrate that laboratory-based measures of anhedonia translate to real-world contexts and that subjective ratings of PA and NA may be associated with neural response to reward and loss.

Associations between different facets of anhedonia and neural response to monetary, social, and food reward in emerging adults

Anhedonia is present in diverse psychiatric disorders and has been linked to reduced neural responses to reward. However, most studies of anhedonia have used monetary reward, making it unclear whether previously-observed deficits represent broad domain-general impairments, or whether associations with anhedonia might vary across incentive types. The present study (N = 120) investigated associations between multiple measures of self-reported anhedonia and reward responsiveness and the reward positivity (RewP), a neural index of reward processing, following monetary, social, and food reward. Greater social anhedonia was associated with a smaller RewP following positive social feedback, whereas reduced consummatory pleasure was associated with a smaller RewP following food reward. Associations among both self-report and neural measures of reward sensitivity were generally modest. Our findings suggest that neither anhedonia nor neural reward sensitivity are unidimensional constructs, and that category-specific reward deficits might better capture specific problems in hedonic functioning.

Trait Anhedonia in Schizophrenia: A Systematic Review and Comparative Meta-analysis.

Anhedonia, the reduced capacity to experience pleasure, has long been considered a prominent feature of schizophrenia spectrum disorders. Many domain-specific conceptualizations of anhedonia and pleasure capacity have been developed, and there currently exist a variety of self-report assessment tools that purport to assess these various domains. The current systematic review and meta-analysis (PROSPERO: CRD42020156169) aimed to quantify overall and domain-specific self-reported anhedonia in people with schizophrenia compared to nonpsychiatric controls. We performed a literature search of PsycINFO, MEDLINE, and Embase databases for dissertations and peer-reviewed articles published in English prior to June 2021. Studies employing a psychometrically validated self-report measure of anhedonia, pleasure experience or affect in people with schizophrenia, schizoaffective, or schizophreniform disorders; studies utilizing at least one clearly defined healthy or community control group for comparison; and studies providing sufficient data to calculate effect sizes were included in this review. Random and mixed effects meta-analyses, meta-regressions, and subgroup comparisons were run across domains of anhedonia to explore weighted mean effect sizes and their associated moderators. In total, 146 studies met inclusion criteria, yielding 390 Hedges' g effect sizes from the included comparisons. People with schizophrenia reported moderate-to-large elevations in overall and domain-specific anhedonia. A sensitivity analysis accounting for high risk of bias studies did not significantly impact results. Lastly, patient sex, education, negative symptom severity, antipsychotic class, and trait negative affect differentially moderated effect sizes across domains of anhedonia. Despite the heterogeneity inherent in schizophrenia spectrum disorders, self-reported anhedonia is ubiquitously reported across self-report measures in this population.

Anhedonia in eating disorders: A meta-analysis and systematic review.

Anhedonia, or loss of pleasure, is related to deficits in reward processing across a variety of psychiatric disorders. In light of research suggesting abnormal reward processing in eating disorders (EDs), the study of anhedonia in EDs may yield important insights into the role of reward in eating pathology. This meta-analysis and review aimed to provide both a quantitative and qualitative synthesis of the existing literature on this topic. We conducted this research (or these meta-analyses) according to PRISMA guidelines. We searched four databases for both peer-reviewed and unpublished literature, and included studies only if a self-report or clinical interview measure of anhedonia was administered to a sample with an ED diagnosis. We included 21 studies in the systematic review, and 10 studies in two meta-analyses that compared anhedonia between ED and control samples (n= 9 studies) and within different ED diagnoses (n= 5 studies). Meta-analyses revealed that anhedonia was significantly higher in ED groups compared to healthy controls, but there was no significant difference in anhedonia between ED diagnostic groups. A qualitative review of the literature also suggested that anhedonia may be correlated with increased ED symptom severity. Findings indicated that anhedonia is elevated in EDs and may be a relevant treatment target. Future research should examine how self-reported anhedonia may correlate with components of reward processing in EDs in order to improve theoretical models as well as targeted interventions.

Interplay of Val66Met and BDNF methylation: effect on reward learning and cognitive performance in major depression

BackgroundThere is a growing interest in the role of brain-derived neurotrophic factor (BDNF) in major depressive disorder (MDD). BDNF potentially exhibits opposite effects in the pathways linked to anhedonia and reward learning on the one hand and cognitive performance, on the other hand. However, the epigenetic mechanisms behind this remain unknown. In the present study, we aimed to investigate the interplay of DNA methylation of different BDNF exons and the common Val66Met polymorphism on anhedonia, reward learning and cognitive performance in MDD.MethodsWe recruited 80 depressed patients and 58 age- and gender-matched healthy controls. Participants underwent clinical assessment including neuropsychological testing and a probabilistic reward task to assess reward learning. Val66Met polymorphism and DNA methylation of BDNF promoters I, IV and exon IX were assessed from whole blood derived DNA, using pyrosequencing.ResultsBDNF promoter I methylation was lower in MDD patients (p = 0.042) and was negatively associated with self-reported anhedonia. In depressed patients, both Val66Met polymorphism and DNA methylation of promoter I were significantly associated with reward bias (p < 0.050 and p = 0.040, respectively), without an interaction effect. On the other hand, methylation of exon IX had a negative impact on executive functioning (p = 0.002) and mediated the effect of Val66Met on this outcome in patients with MDD.ConclusionsOur results provide the first evidence of Val66Met susceptibility to differential epigenetic regulation of BDNF exons in reward learning and executive functioning in MDD, which needs to be further explored.

Residual Effects of Cannabis Use on Effort-Based Decision-Making.

Acute Δ9-tetrahydrocannabinol (THC) administration in humans (Lawn etal., 2016) and rats (Silveira, Adams, Morena, Hill, & Winstanley, 2016) has been associated with decreased effort allocation that may explain amotivation during acute cannabis intoxication. To date, however, whether residual effects of cannabis use on effort-based decision-making are present and observable in humans have not yet been determined. The goal of this study was to test whether prolonged cannabis use has residual effects on effort-based decision-making in 24-hr abstinent cannabis using adults. We evaluated performance on the Effort Expenditure for Reward Task (EEfRT) in 41 adult cannabis users (mean age = 24.63 years, 21 males) and 45 nonusers (mean age = 23.90 years, 19 males). A mixed 2x3x3 ANOVA with age as a covariate was performed to examine the effect of group, probability of winning, and reward amount on EEfRT performance. EEfRT performance was operationalized as % of trials for which the hard (vs. easy) condition was chosen. Pearson's correlations were conducted to test the relationship between EEfRT performance and measures of cannabis use, anhedonia and motivation. We found that cannabis users selected hard trials significantly more than nonusers regardless of win probability or reward level. Frequency of cannabis use was positively correlated with amount of % hard trials chosen. There were no significant correlations between % hard trials chosen, self-reported anhedonia, or motivation. These results suggest that unlike acute effects, residual effects of cannabis following 24 hrs of abstinence are associated with greater effort allocation during effort-based decision-making.

Virtual Reality Reward Training for Anhedonia: A Pilot Study.

Anhedonia is a risk factor for suicide and poor treatment response in depressed individuals. Most evidence-based psychological therapies target symptoms of heightened negative affect (e.g., negative inferential style) instead of deficits in positive affect (e.g., attenuated reward response) and typically show little benefit for anhedonia. Viewing positive scenes through virtual reality (VR) has been shown to increase positive affect and holds great promise for addressing anhedonic symptoms. In this pilot study, six participants with clinically significant depression completed 13 sessions of exposure to positive scenes in a controlled VR environment. Significant decreases were found in self-reported anhedonia, depression, anxiety, and impairments in functioning from baseline to 1-month follow-up. Negative affect decreased over all 13 sessions, and positive affect increased over sessions 8–13. Results suggest that positive experiences in VR may be a novel avenue for the treatment of anhedonia in depressed individuals.

Novel polygenic risk score as a translational tool linking depression-related changes in the corticolimbic transcriptome with neural face processing and anhedonic symptoms

Convergent data from imaging and postmortem brain transcriptome studies implicate corticolimbic circuit (CLC) dysregulation in the pathophysiology of depression. To more directly bridge these lines of work, we generated a novel transcriptome-based polygenic risk score (T-PRS), capturing subtle shifts toward depression-like gene expression patterns in key CLC regions, and mapped this T-PRS onto brain function and related depressive symptoms in a nonclinical sample of 478 young adults (225 men; age 19.79 +/− 1.24) from the Duke Neurogenetics Study. First, T-PRS was generated based on common functional SNPs shifting CLC gene expression toward a depression-like state. Next, we used multivariate partial least squares regression to map T-PRS onto whole-brain activity patterns during perceptual processing of social stimuli (i.e., human faces). For validation, we conducted a comparative analysis with a PRS summarizing depression risk variants identified by the Psychiatric Genomics Consortium (PGC-PRS). Sex was modeled as moderating factor. We showed that T-PRS was associated with widespread reductions in neural response to neutral faces in women and increases in neural response to emotional faces and shapes in men (multivariate p < 0.01). This female-specific reductions in neural response to neutral faces was also associated with PGC-PRS (multivariate p < 0.03). Reduced reactivity to neutral faces was further associated with increased self-reported anhedonia. We conclude that women with functional alleles mimicking the postmortem transcriptomic CLC signature of depression have blunted neural activity to social stimuli, which may be expressed as higher anhedonia.

Factor Structure and Measurement Invariance of the Chinese version of the Snaith-Hamilton Pleasure Scale (SHAPS) in Non-clinical and Clinical populations

BackgroundAnhedonia, a key symptom of depression and schizophrenia, has emerged as a potential endophenotype. The aim of this study was to evaluate the psychometric properties of a Chinese version of the Snaith-Hamilton Pleasure Scale(SHAPS), a self-report anhedonia scale, in a non-clinical sample and clinical sample inclusive of major depressive disorder (MDD), schizophrenia, or a personality disorder. MethodsA total of 4,722 undergraduate students and 352 clinical patients participated in this study. Internal consistency was assessed by calculating Cronbach's α and mean inter-item correlation (MIC) values. Test-retest reliability and convergent validity were assessed with Pearson r coefficients. The best fitting of six potential factor-structure models was determined by confirmatory factor analysis (CFA). Measurement invariance across genders and samples was determined by multi-group CFA. ResultsInternal consistency of the Chinese version of the SHAPS was acceptable in non-clinical (Cronbach's α = 0.90) and clinical (Cronbach's α = 0.91) samples. Four-week interval test-retest reliability was 0.60. Moreover, the Spanish four-factor structure had the best fit indexes in both samples. Scalar invariance was established across genders as well as across non-clinical sample and clinical sample. SHAPS was significantly related with the Temporal Experience of Pleasure Scale (TEPS) and Beck Depression Inventory (BDI). LimitationsThere was a restricted scope of convergent validity and the size of clinical sample is relatively small, psychometric properties in elderly sample is also required. ConclusionThe Chinese version of the SHAPS is a reliable, effective, simple and convenient tool for assessing and screening for anhedonia.

Diagnostic and dimensional evaluation of implicit reward learning in social anxiety disorder and major depression.

Increasing evidence supports the presence of an anhedonic endophenotype in major depressive disorder (MDD), characterized by impairments in various components of reward processing, particularly incentive motivation, effort-based decision making, and reward learning. In addition to its prominent role in MDD, reward processing dysregulation has been proposed as a transdiagnostic risk and/or maintenance factor for a range of other forms of psychopathology. Individuals with social anxiety disorder (SAD)-a condition that frequently co-occurs with MDD-demonstrate low trait positive affectivity and altered processing of rewards and positively valenced information. However, no studies to date have directly tested reward learning-the ability to modulate behavior in response to rewards-in this population. The current study evaluated reward learning in MDD, SAD, and healthy control subjects (N = 90) using a well-validated signal detection task. Given increasing data supporting transdiagnostic features of psychopathology, we also evaluated associations between anhedonia and task performance transdiagnostically in the patient sample. Contrary to expectations, results indicated no significant group differences in response bias in the full sample, suggesting no diagnostic differences in reward learning. However, dimensional analyses revealed that higher self-reported anhedonia (but not general distress or anxious arousal) was associated with worse reward learning in both the MDD and SAD groups explaining about 11% of the variance. Deficits in implicit reward learning are associated with anhedonia but not necessarily with major depressive disorder as a diagnosis, which supports the use of transdiagnostic approaches to understanding psychopathology.

Assessment of Anhedonia in Adults With and Without Mental Illness

ImportanceAnhedonia, a reduced capacity for pleasure, is described for many psychiatric and neurologic conditions. However, a decade after the Research Domain Criteria launch, whether anhedonia severity differs between diagnoses is still unclear. Reference values for hedonic capacity in healthy humans are also needed.ObjectiveTo generate and compare reference values for anhedonia levels in adults with and without mental illness.Data SourcesWeb of Science, Scopus, PubMed, and Google Scholar were used to list all articles from January 1, 1995 to July 2, 2019, citing the scale development report of a widely used anhedonia questionnaire, the Snaith-Hamilton Pleasure Scale (SHAPS). Searches were conducted from April 5 to 11, 2018, and on July 2, 2019.Study SelectionStudies including healthy patients and those with a verified diagnosis, assessed at baseline or in a no-treatment condition with the complete 14-item SHAPS, were included in this preregistered meta-analysis.Data Extraction and SynthesisRandom-effects models were used to calculate mean SHAPS scores and 95% CIs separately for healthy participants and patients with current major depressive disorder (MDD), past/remitted MDD, bipolar disorder, schizophrenia, substance use disorders, Parkinson disease, and chronic pain. SHAPS scores were compared between groups using meta-regression, and traditional effect size meta-analyses were conducted to estimate differences in SHAPS scores between healthy and patient samples. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.Main Outcomes and MeasuresSelf-reported anhedonia as measured by 2 different formats of the SHAPS (possible ranges, 0-14 and 14-56 points), with higher values on both scales indicating greater anhedonia symptoms.ResultsIn the available literature (168 articles; 16 494 participants; 8058 [49%] female participants; aged 13-72 years), patients with current MDD, schizophrenia, substance use disorder, Parkinson disease, and chronic pain scored higher on the SHAPS than healthy participants. Within the patient groups, those with current MDD scored considerably higher than all other groups. Patients with remitted MDD scored within the healthy range (g = 0.1). This pattern replicated across SHAPS scoring methods and was consistent across point estimate and effect size analyses.Conclusions and RelevanceThe findings of this meta-analysis indicate that the severity of anhedonia may differ across disorders associated with anhedonia. Whereas anhedonia in MDD affects multiple pleasure domains, patients with other conditions may experience decreased enjoyment of only a minority of life’s many rewards. These findings have implications for psychiatric taxonomy development, where dimensional approaches are gaining attention. Moreover, the SHAPS reference values presented herein may be useful for researchers and clinicians assessing the efficacy of anhedonia treatments.

Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS).

Anhedonia remains a major clinical issue for which there is few effective interventions. Untreated or poorly controlled anhedonia has been linked to worse disease course and increased suicidal behavior across disorders. Taking a proof-of-mechanism approach under the auspices of the National Institute of Mental Health FAST-FAIL initiative, we were the first to show that, in a transdiagnostic sample screened for elevated self-reported anhedonia, 8 weeks of treatment with a kappa-opioid receptor (KOR) antagonist resulted in significantly higher reward-related activation in one of the core hubs of the brain reward system (the ventral striatum), better reward learning in the Probabilistic Reward Task (PRT), and lower anhedonic symptoms, relative to 8 weeks of placebo. Here, we performed secondary analyses of the PRT data to investigate the putative effects of KOR antagonism on anhedonic behavior with more precision by using trial-level model-based Bayesian computational modeling and probability analyses. We found that, relative to placebo, KOR antagonism resulted in significantly higher learning rate (i.e., ability to learn from reward feedback) and a more sustained preference toward the more frequently rewarded stimulus, but unaltered reward sensitivity (i.e., the hedonic response to reward feedback). Collectively, these findings provide novel evidence that in a transdiagnostic sample characterized by elevated anhedonia, KOR antagonism improved the ability to modulate behavior as a function of prior rewards. Together with confirmation of target engagement in the primary report (Krystal et al., Nat Med, 2020), the current findings suggest that further transdiagnostic investigation of KOR antagonism for anhedonia is warranted.