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Description: Both human and animal studies support the relationship between depression and reward processing abnormalities, giving rise to the expectation that neural signals of these processes may serve as biomarkers or mechanistic treatment targets. Here we present a number of conceptual, practical, and analytical challenges to this line of research, and use a pre-registered meta-analysis to quantify the longitudinal associations between reward processing aberrations and depression. We also investigate the impact of measurement error on reported data. We find that reward processing abnormalities are currently unsuited as a clinical prediction tool, yet the evidence thus far does not exclude their possible causal role in depression.