Role of Reward Dysregulation in the Association Between Depression and Obesity: A Systematical Review.

Zhang, Xuan; Han, Lin; Xiao, Yefei; Teopiz, Kayla M; McIntyre, Roger S; Gao, Xiao; Cao, Bing · Obes Rev · 2026

systematic_review · Level I

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Abstract

Depression and obesity represent major public health challenges, and their comorbidity suggests underlying shared mechanisms. A comprehensive understanding of the common cognitive-behavioral and neurobiological pathways, particularly those involving reward processing, is essential for developing effective clinical and public health interventions. This systematic review synthesizes evidence regarding the overlap of behavioral and neural substrates or correlates of reward processing and manifestations in depression and obesity. The findings indicate that comorbid depression and obesity are associated with reward-related behaviors, as well as functional and structural alterations in key reward-processing regions, such as the hippocampus, amygdala, and anterior cingulate cortex. These alterations correlate with increased severity of depressive symptoms and abnormal reward-related behaviors. Insulin resistance and dysregulation of serotonin pathways constitute significant mediators that exacerbate reward dysfunction in affected individuals. Additionally, early-life stress and genetic predispositions significantly shape both the structure and function of the brain's reward circuitry. This review highlights that the comorbidity of obesity and depression can be explained through complex behavioral and neural mechanisms, particularly those involving reward processing pathways. Further longitudinal and intervention studies are warranted to clarify causal relationships and underlying mechanisms.

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