Effects of Antipsychotic Drugs: Cross Talk Between the Nervous and Innate Immune System

Converging lines of evidence suggest that activation of microglia (innate immune cells in the central nervous system [CNS]) is present in a subset of patients with schizophrenia. The extent to which antipsychotic drug treatment contributes to or combats this effect remains unclear. To address this question, we reviewed the literature for evidence that antipsychotic exposure influences brain microglia as indexed by in vivo neuroimaging and post-mortem studies in patients with schizophrenia and experimental animal models. We found no clear evidence from clinical studies for an effect of antipsychotics on either translocator protein (TSPO) radioligand binding (an in vivo neuroimaging measure of putative gliosis) or markers of brain microglia in post-mortem studies. In experimental animals, where drug and illness effects may be differentiated, we also found no clear evidence for consistent effects of antipsychotic drugs on TSPO radioligand binding. By contrast, we found evidence that chronic antipsychotic exposure may influence central microglia density and morphology. However, these effects were dependent on the dose and duration of drug exposure and whether an immune stimulus was present or not. In the latter case, antipsychotics were generally reported to suppress expression of inflammatory cytokines and inducible inflammatory enzymes such as cyclooxygenase and microglia activation. No clear conclusions could be drawn with regard to any effect of antipsychotics on brain microglia from current clinical data. There is evidence to suggest that antipsychotic drugs influence brain microglia in experimental animals, including possible anti-inflammatory actions. However, we lack detailed information on how these drugs influence brain microglia function at the molecular level. The clinical relevance of the animal data with regard to beneficial treatment effects and detrimental side effects of antipsychotic drugs also remains unknown, and further studies are warranted.