Effects of antipsychotic drugs: cross talk between the nervous and innate immune system

TY - JOUR

T1 - Effects of antipsychotic drugs: cross talk between the nervous and innate immune system

AU - Dinesh, Ayushi

AU - Islam, Juned

AU - Khan, Javad

AU - Turkheimer, Federico

AU - Vernon, Anthony

PY - 2020/8/27

Y1 - 2020/8/27

N2 - Converging lines of evidence suggest that activation of microglia (innate immune cells in the CNS) is present in a subset of schizophrenia cases. To what extent 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 schizophrenia patients 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 found evidence that clozapine, but not other antipsychotics, increases brain TSPO radioligand binding, suggestive of central gliosis. Consistent with this view, we found evidence that chronic antipsychotic exposure may influence central microglia density and morphology. These effects were however 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 can 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. We lack however 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.

AB - Converging lines of evidence suggest that activation of microglia (innate immune cells in the CNS) is present in a subset of schizophrenia cases. To what extent 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 schizophrenia patients 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 found evidence that clozapine, but not other antipsychotics, increases brain TSPO radioligand binding, suggestive of central gliosis. Consistent with this view, we found evidence that chronic antipsychotic exposure may influence central microglia density and morphology. These effects were however 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 can 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. We lack however 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.

M3 - Review article

SN - 1172-7047

JO - CNS Drugs

JF - CNS Drugs

ER -