Common and disorder-specific aberrant activation during reward and loss processing in major depressive disorder and addiction: a meta-analysis of fMRI studies.

Accumulating evidence has demonstrated that dysfunction in the brain reward circuit plays a pivotal role in the pathogenesis of both major depressive disorder (MDD) and addictive disorders (substance use and behavioral addictions). However, it remains unclear whether the neural dysfunctions during reward processing are shared or distinct between these disorders. To address this, we employed the Seed-based d Mapping (SDM) toolbox to explore shared and distinct task-based fMRI findings in MDD and addictive disorders during the processing of reward (anticipation and outcome) and loss (outcome). The electronic databases PubMed, EMBASE, Scopus, Web of Science, and PsycINFO were searched from their inception until September 20, 2025. Studies were included if they used fMRI to compare brain responses during reward/loss tasks between patients (with MDD or addictive disorders) and healthy controls, and reported whole-brain coordinates (in Talairach or MNI space). The analysis included 76 articles, including 45 articles with 1212 addiction patients, 31 articles with 1211 MDD patients, and 2126 healthy controls aggregated from the 76 articles. Conjunction analysis revealed no significant common hypo- or hyper-activated brain regions between patients with addictive disorders and those with MDD (addiction & MDD) relative to healthy controls across all experimental conditions. Differential analysis showed addiction patients had greater left striatum activation (vs. MDD) during reward anticipation, and greater right putamen and left striatum activation (vs. MDD) during reward outcome. No significant differences were found under the loss outcome. Our findings indicate that during reward processing, the striatum is a common functionally abnormal brain region in both MDD and addictive disorders, but the activation directions of the two disorders in this region show opposite trends. The striatum can serve as a transdiagnostic common abnormal marker for MDD and addictive disorders. Our results provide potential targets for future research on neuromodulatory, pharmacological, and clinical interventions in patients with MDD alone, addictive disorders alone, and comorbid patients of the two disorders.