Assessment of Anhedonia in Adults With and Without Mental Illness: A Systematic Review and Meta-analysis

Importance Anhedonia, 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. Objective To generate and compare reference values for anhedonia levels in adults with and without mental illness. Data Sources Web 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 Selection Studies 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 Synthesis Random-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 Measures Self-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. Results In 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 Relevance The 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.


Introduction
Mental disorders are a major cause of disability, affecting 16% to 19% of the world's population or approximately 1 billion people every year. 1 The ability to experience pleasure is essential for well-being, 4 but is often reduced in mental illness. Anhedonia is defined as a reduced capacity for pleasure 5 and has been described in major depressive disorder (MDD), 6,7 bipolar disorder, 6 schizophrenia, 6,[8][9][10][11] substance use disorder (SUD), 12,13 chronic pain, 14,15 and Parkinson disease (PD). 16,17 Despite its presence across numerous psychiatric and neurologic disorders, anhedonia is rarely compared across conditions. Whether anhedonia differs in severity between diagnoses is therefore currently unknown.
Anhedonia is commonly measured using questionnaires, 18 such as the popular Snaith-Hamilton Pleasure Scale (SHAPS). 19 The SHAPS is considered "the gold standard for measuring anhedonia in depression," 18(p27) and is also frequently used to assess anhedonia in other patient groups. 13,17,[20][21][22][23][24][25][26][27][28][29][30][31][32][33] The SHAPS consists of 14 confirmatory statements about enjoyable situations typically encountered in daily life cross-culturally (food/drink, interests/pastimes, social interactions, and pleasurable sensory experiences). Respondents to the SHAPS indicate their level of agreement (definitely/strongly agree, agree, disagree, and strongly disagree) with each statement based on their recollection of the last few days. This time frame suggests that the SHAPS is meant to measure a relatively stable state of anhedonia. Responses are summed across items to yield a single anhedonia score.
Despite its popularity, reference values for the SHAPS are lacking and there is no standard scoring method for the questionnaire. Originally, disagreement with more than 2 statements served as a cutoff point between normal hedonic tone and anhedonia. 19 To compare anhedonia severity across disorders and estimate the threshold for healthy hedonic functioning, we conducted a set of meta-analyses of the numerous publications on studies in which anhedonia symptoms were assessed with the SHAPS. By calculating summary estimates of SHAPS scores (meta-analytic mean and 95% CI) for healthy adults and those with mental illness, we generated reference values for the SHAPS that may guide interpretation of anhedonia severity in future research and clinical settings.

Search Strategy and Selection Criteria
We limited the data material to all articles citing the original SHAPS report by Snaith et al, 19 identified through Web of Science, Scopus, PubMed, and Google Scholar, and made available between 1995 and 2019. Searches were conducted from April 5 to 11, 2018, and on July 2, 2019. We located the original SHAPS report within each database and used the built-in function of the databases to list and download all articles indexed as citing this report. We also included the original report. 19 We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting of systematic reviews. 34 A preregistration of this meta-analysis is available in the PROSPERO register. 35 (Figure 1). Disagreements at this stage were resolved through discussion between the 2 researchers.

Data Analysis
We did not prespecify which groups to include in the meta-analysis, but decided to evaluate all groups for whom data were available from a minimum of 4 separate samples using the same 2-or 4-point scoring method. 36 This threshold allowed us to generate nuanced and reliable reference values while keeping the meta-analysis exploratory.  To produce reliable and representative SHAPS reference values, we aimed to minimize missing data, verify that the questionnaire was sufficiently similar across samples, and ensure minimal diagnostic overlap between groups. The quality assessment therefore calculated (1) the number of samples as-

Statistical Analysis
All analyses were performed using random-effects models implemented in the metafor package 39 in R statistical software, version 3.5.2. 40 We used the DerSimonian-Laird method 41 for estimating the between-studies variance component (T 2 ) in each random-effects model and calculated 95% CIs using the critical z value at α = .05. Results were considered statistically significant if P < .05, as determined with 2-tailed, unpaired testing. Multiple testing is common yet seldom addressed in meta-analyses, 42,43 and consensus on how to account for multiple testing is lacking. 44,45 Results are reported herein without adjustments for multiple testing.
The primary set of meta-analyses produced and compared point estimates of the mean SHAPS scores for each included group. Separate random-effects models were computed for each included group using SHAPS scores of individual samples as input. These meta-analyses were performed separately for studies using 4-point and 2-point SHAPS scoring formats. We used meta-regression to compare groups.
The second set of meta-analyses consisted of traditional effect size meta-analyses of standardized differences in SHAPS scores between healthy groups and those with mental illness. We used Hedges g 46 as the effect size measure and meta-regression to compare effect sizes between groups.
We performed additional meta-regressions to assess the importance of age, sex, general depression severity, medication status (current MDD, schizophrenia, and PD only), and drug use status (SUD only) for SHAPS scores. eAppendix 1 in the Supplement provides more details and analytic considerations, including sensitivity analyses (eTables 1-6 in the Supplement) and a smallscale meta-analysis of individual SHAPS items.

Results
The final data material contained 168 studies assessing SHAPS scores in 246 samples ( male; 1138 [7%] missing accurate sex data; and age range, 13-72 years). eTable 8 in the Supplement provides group characteristics. Data on anxiety-related and eating disorders were not included in the meta-analysis owing to limited availability but are presented in eTable 9 in the Supplement.

Quality Assessment
Risk of bias owing to modifications of the SHAPS was low, as the questionnaire was largely invariant across studies. Fifty-three samples (21%) used non-English translations of the SHAPS. Other minimal modifications occurred in only 4 samples (2%) [47][48][49] (eAppendix 2 in the Supplement).
Before we contacted authors, necessary SHAPS data were available for only 13% to 80% (mean, 33%) of the identified samples for each included group (Figure 1; eTable 10 in the Supplement). After obtaining missing data, we were able to include 70% to 100% (mean, 75%) of the identified samples.
This addition reduced the risk of publication bias and bias due to selective reporting of SHAPS scores.
There was little diagnostic overlap between the MDD, schizophrenia, and SUD groups (eTable 11 in the Supplement). Information about co-occurring psychiatric disorders was often lacking for PD samples, and comorbidity with anxiety disorders was rarely reported for any group. The low comorbidity allowed us to largely isolate the anhedonia severity associated with each diagnosis.
Meta-analyses of effect sizes ( Figure 2C) were conducted on studies using either scoring method and including data from both patients and healthy controls. Again, SHAPS scores for patients with current MDD were significantly above levels in healthy individuals (Hedges g, 2.2; 95% CI, SHAPS scores were significantly higher in current MDD compared with any other group (Table 1).
Although no formal subgroup analyses could be performed for the bipolar disorder group, data from

Discussion
To our knowledge, it has not been possible previously to compare the degree of anhedonia symptom load across diagnoses, despite the extensive data available in the literature. We used a metaanalytic approach to generate suggested reference values for the level of anhedonia in adults with and without mental illness based on SHAPS scores from 16 494 people. While anhedonia scores were significantly increased in current but not remitted MDD, schizophrenia, SUD, PD, and chronic pain compared with healthy participants, we found evidence for substantially higher anhedonia in ongoing MDD compared with other types of illness. This pattern replicated across scoring methods for the SHAPS and was consistent across point-estimate and effect size analyses.
Our findings apparently support the clinical association between anhedonia and schizophrenia, SUD, PD, and chronic pain. 6,7,12,17 The observed variability in anhedonia severity across conditions is     To test whether patients with a specific mental health diagnosis typically experience anhedonia for the same subset of pleasures, we conducted an exploratory meta-analysis of raw, item-level data from 376 healthy volunteers, 64 patients with major depression, and 487 chronic pain patients (for details, see eAppendix 1 in the Supplement). Item-level data for other groups were not available to us at the time of writing. Diamonds indicate mean and 95% CI. SHAPS indicates Snaith-Hamilton Pleasure Scale. An item-level meta-analysis of available data from individuals with MDD, chronic pain, and healthy volunteers showed that this pattern appears to be consistent (Figure 3), with modest increases in anhedonia for all items in chronic pain. Similarly, patients with MDD scored consistently higher on every SHAPS item. Thus, at the group level, we found no support for the notion that anhedonia in patients with chronic pain or MDD is associated with specific impairments, such as anosmia. Instead, MDD and chronic pain may uniformly dampen people's enjoyment of life.

JAMA Network Open | Psychiatry
Despite reported behavioral and neural reward impairments in remitted MDD, 50 Anhedonia is a key symptom thought to differentiate depression from anxiety disorders. 61 While there were insufficient data to include anxiety disorders in the current meta-analyses, the 3 available studies on posttraumatic stress disorder reported SHAPS scores comparable to severe anhedonia levels in current MDD. [62][63][64] Only modest anhedonia as measured by the SHAPS has been reported in individuals with obsessive-compulsive disorder. 65,66 Despite theoretical interest in the role of anhedonia and reward functioning for eating disorders, 67-69 we could retrieve SHAPS scores from only 2 studies. These scores were consistent with mild anhedonia in anorexia nervosa. 70,71 Dysfunction in the mesolimbic dopamine system and its interactions with the endogenous opioid system have been proposed as a central mechanism underlying anhedonia. 12,72 Recent evidence suggests that there are similarities in the genetic and neural underpinnings of anhedonia across multiple disorders. 73 It is unclear whether differences in anhedonia severity across conditions observed herein with the SHAPS reflect different physiologic pathways or distinct levels of disruption of the same underlying mechanisms.

Limitations
This study has limitations. The SHAPS literature consists primarily of smaller-scale studies of patients without comorbidities and is therefore likely not representative of the entire patient populations.
Accordingly, bias in representativeness was not formally assessed. 74 Conversely, these reference values may be more indicative of the levels of anhedonia specifically associated with each disorder in isolation, and therefore useful in improving discriminant validity of psychiatric taxa in taxometric investigations and future nosologic efforts. Large-scale epidemiologic studies are needed to produce anhedonia severity estimates that generalize to the larger patient populations in which diagnostic comorbidity is more common. This meta-analysis operationalized anhedonia as scores on the SHAPS and results may not generalize to other anhedonia questionnaires or other facets of reward processing outlined in the Research Domain Criteria framework.

JAMA Network Open | Psychiatry
Reference values for some of the smaller groups (eg, schizophrenia, SUD, and PD) may be less reliable than those for the larger groups (healthy and current MDD). However, the similar pattern of results found across the independent samples scored with the 2-and 4-point formats speaks to the stability, generalizability, and statistical coherence of the present results.
Smoking is common in patients with mental illness 75 and has bidirectional associations with anhedonia. 76,77 Owing to limited data and inconsistent reporting across studies, we were unable to evaluate potential moderating effects of smoking behavior on SHAPS scores. For the same reason, we were able to assess the effect of medication status on anhedonia only in MDD, schizophrenia, or PD and not the effects of specific drugs. Moderating effects of age and sex were estimated as modest.

Conclusions
The results of this meta-analysis suggest that anhedonia, as measured by the SHAPS, differs quantitatively across conditions typically associated with this symptom. While modest anhedonia was seen in patients with schizophrenia, SUD, PD, and chronic pain, studies have consistently reported more severe anhedonia in patients with current MDD. We recommend that, for clarity and ease of comparison across samples, researchers and clinicians report SHAPS scores using both the 2-and 4-point scoring methods applied here, taking care to ensure that higher scores indicate anhedonia.