[Anhedonia: from clinical practice to biomarkers].

Anhedonia involves reduced pleasure, motivation, and reward learning, and while traditionally linked to dopamine, recent evidence indicates that immune-inflammatory changes in psychiatric disorders also contribute. Inflammation affects dopamine, glutamate, and opioid pathways, plus cellular immune responses like mTOR signaling, disrupting reward and motor circuits in the brain. This leads to anhedonia and psychomotor slowing. Animal models confirm that chronic inflammation lowers motivation, modeling anhedonia. These disruptions occur across psychotic, mood, and neurodevelopmental disorders, not just one condition. This shared dimension suggests targeted treatments may include dopaminergic drugs, glutamatergic agents like ketamine, anti-inflammatory therapies, and novel molecules.

Study at a glance

Abstract

Anhedonia, a complex symptom, is characterized by a decrease in experience of pleasure, reduced motivation, and/or impaired reward learning. Although these aspects are often linked to dopaminergic pathways, recent research shows that immuno-inflammatory alterations present in psychiatric disorders may also play a role, affecting dopaminergic, glutamatergic, and opioid pathways, as well as cellular immune responses (such as the mTOR pathway). These perturbations, through inflammation in the central nervous system, affect reward and motor circuits, contributing to the anhedonia and the psychomotor slowing that are often-associated. Animal models show that chronic inflammation can reduce motivation, providing a preclinical model for anhedonia. This dysfunction is not specific to a single pathology but is common to a variety ofpsychiatric disorders, including psychotic, mood, and neurodevelopmental disorders. These common dimensions of anhedonia across different pathologies open up perspects for targeted treatments, including dopaminergic treatments, glutamatergic treatments (such as ketamine), anti-inflammatory therapies, and the development of new molecules.