Stress to inflammation and anhedonia: Mechanistic insights from preclinical and clinical models

Anhedonia, as evidenced by impaired pleasurable response to reward, reduced reward motivation, and/or deficits in reward-related learning, is a common feature of depression. Such deficits in reward processing are also an important clinical target as a risk factor for depression onset. Unfortunately, reward-related deficits remain difficult to treat. To address this gap and inform the development of effective prevention and treatment strategies, it is critical to understand the mechanisms that drive impairments in reward function. Stress-induced inflammation is a plausible mechanism of reward deficits. The purpose of this paper is to review evidence for two components of this psychobiological pathway: 1) the effects of stress on reward function; and 2) the effects of inflammation on reward function. Within these two areas, we draw upon preclinical and clinical models, distinguish between acute and chronic effects of stress and inflammation, and address specific domains of reward dysregulation. By addressing these contextual factors, the review reveals a nuanced literature which might be targeted for additional scientific inquiry to inform the development of precise interventions.

Automated summary

Anhedonia, a common feature of depression, is characterized by impaired pleasurable response to reward, reduced reward motivation, and/or deficits in reward-related learning. Stress-induced inflammation may be a plausible mechanism for these reward deficits. This paper reviews evidence for the effects of stress and inflammation on reward function and highlights the need for further scientific inquiry to inform the development of precise interventions.