Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in Schizophrenia

Abstract

Recent evidence suggests a possible relationship between the immune system and schizophrenia spectrum disorders (SSDs), as neuroinflammation appears to play a role in major psychiatric conditions. Neuroinflammation is as a broad concept representing a physiological protective response to infection or injury, but in some cases, especially if chronic, it may represent an expression of mala-daptive processes, potentially driving to clinical dysfunction and neurodegeneration. Several studies are concurrently highlighting the importance of microglia, the resident immune cells of the central nervous system, in a huge number of neurodegenerative diseases, including multiple sclerosis, Alzheimer’s and Parkinson’s diseases, as well as SSDs. A more fundamental phenomenon of maladaptive coupling of microglia may contribute to the genesis of dysfunctional brain inflammation involved in SSDs, from the onset of their neurophenomenological evolution. Clozapine and other antipsychotic drugs seem to express a provable immunomodulant effect and a more specific action on microglia, while neuroactive steroids and nonsteroidal anti-inflammatory drugs may reduce some SSDs symptoms in add-on therapy. Given these theoretical premises, this article aims to summarize and interpret the available scientific evidence about psychotropic and anti-inflammatory drugs that could express an immunomodulant activity on microglia.

Haloperidol, Olanzapine, and Risperidone Induce Morphological Changes in an In Vitro Model of Human Hippocampal Neurogenesis

“…A widely accepted hypothesis formulates that inappropriate pruning contributes to the pathomechanism of schizophrenia, and it might relate to the elevated level of cytokines and inflammatory factors. Since dopamine receptors D1 and D2 are expressed by microglia as well, the dopamine-antagonist psychotropic agents can modulate microglial activity and may exert a favorable effect for patients by this mechanism as well [ 32 , 33 , 34 , 35 ].…”