Great Expectations: A Critical Review of and Suggestions for the Study of Reward Processing as a Cause and Predictor of Depression

Abstract

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. Given the great promise of this research line, we scrutinized those findings and the theoretical claims that underlie them. To achieve this, we applied the framework provided by classical work on causality as well as contemporary approaches to prediction. We identified a number of conceptual, practical, and analytical challenges to this line of research and used a preregistered meta-analysis to quantify the longitudinal associations between reward processing abnormalities and depression. We also investigated the impact of measurement error on reported data. We found that reward processing abnormalities do not reach levels that would be useful for clinical prediction, yet the available evidence does not preclude a possible causal role in depression.

Reward sensitivity and internalizing symptoms during the transition to puberty: An examination of 9-and 10-year-olds in the ABCD Study

“…Reduced self-reported and task-measured reward sensitivity predict heightened internalizing symptoms (Alloy et al, 2016;Taubitz et al, 2015;Whitton et al, 2015), patterns that are mirrored by neuroimaging data (Luking et al, 2016). In particular, heightened internalizing symptoms have been associated with attenuated activity within the ventral and dorsal striatum (i.e., nucleus accumbens, caudate, and putamen) during reward anticipation and feedback (Auerbach et al, 2021;Pizzagalli et al, 2009a;Rappaport et al, 2020;Zhang et al, 2013) in adults and older adolescents (Auerbach et al, 2021;Forbes, 2011;Forbes et al, 2009Forbes et al, , 2010Luking et al, 2016;Morgan et al, 2013;Nielson et al, 2021). Similarly, reward-related activity within the orbitofrontal cortex (OFC) has been linked to negative emotion biases evident in internalizing disorders (Dichter et al, 2012b;Downar, 2019;McCabe et al, 2012;Rolls, 2016Rolls, , 2019Ubl et al, 2015).…”

Objective measures of reward sensitivity and motivation in people with high vs low anhedonia

“…First, most studies examine only one sub-component of reward (e.g., motivation) using one assay. However, a battery of tasks designed to probe different reward components (e.g., motivation, sensitivity) can demonstrate whether different components can be dissociated and whether anhedonia is related to a general reward deficit or specific to certain sub-components (Husain & Roiser, 2018;Nielson et al, 2020). Second, most studies compare people with MDD to healthy controls, with few directly measuring anhedonia using anhedonia questionnaires (McCabe, 2018).…”

Pleasure, reward value and prediction error in anhedonia

“…This pattern makes it difficult to ascertain whether they relate to reward valuation specifically or reflect a general alteration in reward processing. Second, because they used tasks not designed to capture behavioural differences, they were often not accompanied by differences in behaviour (here, the invigoration of responding with greater potential reward; Halahakoon et al, 2020;Nielson et al, 2021). This makes it difficult to interpret whether lower neural responses indicate impairment, compensation or relate to some group difference unrelated to reward processing .…”

“…Nearly all work on reward processing and anhedonia has been cross-sectional (Halahakoon et al 2020;Nielson et al 2021). More longitudinal studies would help ascertain whether the association between disruptions in reward processing and anhedonia is casual and could therefore be used as a risk marker and target for intervention, including prevention.…”