Reward processing in major depressive disorder and prediction of treatment response - Neuropharm study

Abstract

Major depressive disorder (MDD) is a prevalent brain disorder for which anhedonia is a core symptom, indicating aberrations in the neural processing of reward. The striatum, medial prefrontal cortex (mPFC) and anterior insula (AI) are core reward processing regions. Here we used a reward-related, card-guessing functional magnetic resonance imaging (fMRI) paradigm to assay brain responses to reward in 90 MDD individuals and 58 healthy controls. We evaluated group differences in task-responsive, reward-related striatal, mPFC, and AI reactivity and whether baseline reactivity predicted an eight-week escitalopram antidepressant treatment response in MDD individuals. Thirty-eight MDD individuals also completed the reward paradigm after treatment and we evaluated antidepressant effects on reward reactivity estimates. Multivariate statistical analysis of task-responsive striatum, mPFC and AI brain responses did not reveal statistically significant differences between MDD and HC individuals (p_uncorrected>0.23). Logistic regression models (five-fold cross-validation, statistical significance assessed with permutation testing) also did not support that baseline reward-related brain responses significantly predicted antidepressant treatment response (p_uncorrected>0.39). Finally, reward-related brain responses were not statistically significantly changed over the course of treatment (p_uncorrected>0.27). Our findings in a comparatively large MDD cohort do not support that these reward-related fMRI brain responses are informative biomarkers of MDD or antidepressant treatment response to escitalopram.

Keywords: Biomarker; Longitudinal clinical trial; Major depressive disorder; Reward; Ssri; fMRI.