Is PSD-95 entangled in the side effects of antidepressants?

Neurochem Int. 2022 Jul 9;159:105391. doi: 10.1016/j.neuint.2022.105391. Online ahead of print.


PSD-95 is a component and a building block of an excitatory synapse. PSD-95 is a specialized protein that is part of a "combination lock" system responsible for plastic events at the synapse, such as receptor expression, which consequently induces changes in the PSD structure and thus affects synaptic plasticity. The possible involvement of PSD-95 in antidepressant side effects related to cognitive function and psychosis will be considered. An attempt will be made to trace the sequence of events in the proposed mechanism leading to these disorders, focusing mainly on NMDA receptors. Understanding the mechanisms of action of compounds with antidepressant potential may facilitate the design of safer drugs.

Keywords: Antidepressants; Cognition; Excitatory synapse; PSD-95; Psychosis; Side effects.

Publication types

  • Review