IMPORTANCE Dysfunctional reward processing is a leading candidate mechanism for the development of certain depressive symptoms, such as anhedonia. However, to our knowledge, there has not yet been a systematic assessment of whether and to what extent depression is associated with impairments on behavioral reward-processing tasks. OBJECTIVE To determine whether depression is associated with impairments in reward-processing behavior. DATA SOURCES The MEDLINE/PubMed, Embase, and PsycInfo databases were searched for studies that investigated reward processing using performance on behavioral tasks by individuals with depression and nondepressed control groups, published between January 1, 1946, and August 16, 2019. STUDY SELECTION Studies that contained data regarding performance by depressed and healthy control groups on reward-processing tasks were included in the systematic review and meta-analysis. DATA EXTRACTION AND SYNTHESIS Summary statistics comparing performance between depressed and healthy groups on reward-processing tasks were converted to standardized mean difference (SMD) scores, from which summary effect sizes for overall impairment in reward processing and 4 subcomponent categories were calculated. Study quality, heterogeneity, replicability-index, and publication bias were also assessed. MAIN OUTCOME AND MEASURES Performance on reward-processing tasks. RESULTS The final data set comprised 48 case-control studies (1387 healthy control individuals and 1767 individuals with major depressive disorder). The mean age was 37.85 years and 58% of the participants were women. These studies used tasks assessing option valuation (n = 9), reward bias (n = 6), reward response vigor (n = 12), reinforcement learning (n = 20), and grip force (n = 1). Across all tasks, depression was associated with small to medium impairments in reward-processing behavior (SMD = 0.345; 95% CI, 0.209-0.480). When examining reward-processing subcomponent categories, impairment was associated with tasks assessing option valuation (SMD = 0.309; 95% CI, 0.147-0.471), reward bias (SMD = 0.644; 95% CI, 0.270-1.017), and reinforcement learning (SMD = 0.352; 95% CI, 0.115-0.588) but not reward response vigor (SMD = 0.083; 95% CI, −0.144 to 0.309). The medication status of the major depressive disorder sample did not explain any of the variance in the overall effect size. There was significant between-study heterogeneity overall and in all subcomponent categories other than option valuation. Significant publication bias was identified overall and in the reinforcement learning category. CONCLUSIONS AND RELEVANCE Relative to healthy control individuals, individuals with depression exhibit reward-processing impairments, particularly for tests of reward bias, option valuation, and reinforcement learning. Understanding the neural mechanisms driving these associations may assist in designing novel interventions.

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Depression is reliably associated with cognitive impairment, but the causal nature of this relationship remains unclear. This is important because if cognitive impairment drives the development of depressive symptoms, boosting cognition may help to treat or even prevent depression. In this issue of JAMA Psychiatry, MacKenzie and colleagues 1 address this issue, performing a systematic review and meta-analysis of cognition in individuals with a first-degree relative with depression.The association between depression and cognitive impairment is well established 2 with meta-analytic estimates of effect sizes derived from case-control studies lying in the range Cohen d (standardized mean difference) of 0.4 to 0.5. This is consistent with criterion 8 for a major depressive episode in the DSM-5: "Diminished ability to think or concentrate, or indecisiveness." 3 However, it remains unclear whether cognitive impairment in depression is best characterized as an etiologic factor, an epiphenomenon arising from symptoms, or a consequence of confounding, with some shared risk factors causing both independently. Contemporary theoretical accounts, such as the cognitive neuropsychological model of depression, 4 propose a causal role, with cognitive impairment mediating the process by which low-level negative emotional biases are transformed into the high-level dysfunctional negative schemata that drive and maintain symptoms. Consistent with this view, cognitive impairment is present during depressive episodes and remission. 2 However, other factors complicate the interpretation of those findings; for example, depressive symptoms that commonly persist during remission, such as anhedonia and poor sleep, may impair cognition. 4,5 Another approach to address this question is to compare cognitive performance in individuals who have never had depression with and without a close relative with depression, as those with a family history are known to be at elevated risk. MacKenzie and colleagues 1 have conducted the first metaanalysis of this body of work to our knowledge, comprising a total sample of 8468 individuals (3246 first-degree relatives and 5222 controls) from 54 studies. Their analysis provides robust evidence of cognitive impairment in first-degree relatives of individuals with depression, although to a varying degree across different measures (IQ: d = 0.19-0.29; academic performance: d = 0.4; standardized neuropsychological assessment: d = 0.14-0.22; language: d = 0.29). Effect sizes were generally lower than estimates derived from case-control studies of patients with depression, which is expected as some of the relatives will never have depression.