From Stress to Anhedonia: Molecular Processes through Functional Circuits.

Converging evidence across species highlights the contribution of environmental stress to anhedonia (loss of pleasure and/or motivation). However, despite a clear link between stress and the emergence of anhedonic-like behavior in both human and animal models, the underlying biological pathways remain elusive. Here, we synthesize recent findings across multiple levels, from molecular signaling pathways through whole-brain networks, to discuss mechanisms through which stress may influence anhedonia. Recent work suggests the involvement of diverse systems that converge on the mesolimbic reward pathway, including medial-prefrontal cortical circuitry, neuroendocrine stress responses, homeostatic energy regulation systems, and inflammation. We conclude by emphasizing the need to disentangle the influences of key dimensions of stress on specific aspects of reward processing, taking into account individual differences that could moderate this relationship.