Title:Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in
Schizophrenia
Volume: 22
Issue: 7
Author(s): Andrea Amerio*, Luca Magnani, Gabriele Arduino, Fabio Fesce, Renato de Filippis, Alberto Parise, Alessandra Costanza, Khoa D. Nguyen, Daniele Saverino, Domenico De Berardis, Andrea Aguglia, Andrea Escelsior, Gianluca Serafini, Pasquale De Fazio and Mario Amore
Affiliation:
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
Keywords:
Clozapine, immunomodulation, microglia, neuroinflammation, schizophrenia, SSDs.
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 maladaptive
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.