Major depressive disorder, as a common neuropsychiatric disorder, has a complex pathogenesis that has not yet been fully elucidated, posing significant challenges to clinical treatment. In recent years, the role of the purinergic signaling system in the pathophysiological processes of depression has garnered increasing attention. The purinergic signaling primarily involves extracellular purine compounds such as ATP and adenosine, which act as transmitters by binding to their corresponding purine receptors (P1 and P2). Purinergic signaling can participate in depression by affecting the function of astrocytes, neuronal plasticity, and the activity of microglia. This paper systematically reviews the latest research advancements in purinergic signaling related to depression by searching for articles on the pubmed using the keywords "purinergic" OR "ATP" OR "adenosine" and "depression". It focuses on the molecular mechanisms of action and discusses the limitations and controversial issues present in current research, aiming to provide new theoretical foundations and treatment strategies for the precise treatment of depression.
Cui et al. (2026) studied this question.