Neural Indicators of Anhedonia: Predictors and Mechanisms of Treatment Change in a Randomized Clinical Trial in Early Childhood Depression

Abstract

Background: Early childhood depression is associated with anhedonia and reduced event-related potential (ERP) responses to rewarding or pleasant stimuli. Whether these neural measures are indicators of target engagement or treatment outcome is not yet known.

Methods: We measured ERP responses to win and loss feedback in a guessing task and to pleasant versus neutral pictures in young (4.0-6.9 years of age) depressed children before and after randomization to either 18 weeks of Parent-Child Interaction Therapy-Emotion Development (PCIT-ED) treatment or waitlist (WL) control condition.

Results: Analyses included reward positivity (RewP) data from 118 children randomized to PCIT-ED treatment (n = 60) or WL control condition (n = 58) at baseline and late positive potential (LPP) data from 99 children (44 PCIT-ED treatment vs. 55 WL control condition) at baseline. Children in the PCIT-ED group showed a greater reduction in anhedonia (F_1,103 = 10.32, p = .002, partial η² = .09). RewP reward responses increased more (F_1,87 = 5.45, p = .02, partial η² = .06) for PCIT-ED and a greater change in RewP was associated with a greater reduction in major depressive disorder symptoms (r = -.24, p = .05). Baseline RewP did not predict treatment change. LPPs to positive pictures did not change across treatment, but greater baseline LPPs to positive pictures predicted a higher likelihood of remission from major depressive disorder in the PCIT-ED group (B = 0.14; SE = 0.07; odds ratio = 1.15; p = .03).

Conclusions: The ERP reward response improved in young children with depression during a treatment designed to enhance emotion development, providing evidence of target engagement of the neural systems associated with reward. Further, greater baseline LPP responses to positive pictures were associated with a greater reduction in depression, suggesting that this ERP measure can predict which children are most likely to respond to treatment.

Keywords: Anhedonia; Clinical trial; Depression; ERP; Preschool; Reward.

Figure 1.. Reward Positivity at Baseline and Post Treatment:

ERP waveforms at Pz to win outcomes at baseline (graph on the left) and post treatment (graph on the right). The blue lines are responses in the PCIT-ED treatment condition and the red lines are responses in the Wait List Control condition. Voltages are plotted with the more negative values at the top of the graph, as is the frequent convention in ERP reports.

Figure 2.. Association Between Change in Depression Symptoms and Change in Reward Positivity:

Graph illustrating the relationship between change in Reward Positivity (RewP) at Pz and change in Depression. The RewP score is the difference between Post Treatment Win_resid and Baseline Win_resid and the MDD score is the difference between Post Treatment and Baseline MDD symptom scores.

Figure 3.. Baseline Late Positive Potential and Remission:

ERP waveforms at the average of O1, Oz, and O2 to pleasant pictures at Baseline in children who did not remit from depression (blue lines) and those who did remit from depression (red lines). Voltages are plotted with the more negative values at the top of the graph, as is the frequent convention in ERP reports.