title: Anti-Inflammatory properties of antipsychotics via microglia modulations: are antipsychotics a 'fire extinguisher' in the brain of schizophrenia?
abstract: Schizophrenia is one of the most severe psychiatric diseases noted for its chronic and often debilitating processes; affecting approximately 1% of the world's population, while its etiology and therapeutic strategies still remain elusive. In the 1950s, the discovery of antipsychotic effects of haloperidol and chlorpromazine shifted the paradigm of schizophrenia. These drugs proved to be antagonists of dopamine D2 receptor (D2R), thus dopamine system dysfunction came to be hypothesized in the pathophysiology of schizophrenia, and D2R antagonism against dopamine neurons has been considered as the primary therapeutic target for schizophrenia. In addition, abnormalities of glutamatergic neurons have been indicated in the pathophysiology of schizophrenia. On the other hand, recent neuroimaging studies have shown that not only dementia but also schizophrenic patients have a significant volume reduction of some specific regions in the brain, which indicates that schizophrenia may involve some neurodegenerative process. Microglia, major sources of various inflammatory cytokines and free radicals such as superoxide and nitric oxide (NO) in the CNS, play a crucial role in a variety of neurodegenerative diseases such as dementia. Recent postmortem and positron emission computed tomography (PET) studies have indicated that activated microglia may be present in schizophrenic patients. Recent in vitro studies have suggested the anti-inflammatory effects of antipsychotics on microglial activation. In this article, we review the anti-inflammatory effects of antipsychotics on microglia, and propose a novel therapeutic hypothesis of schizophrenia from the perspective of microglial modulation.
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences, and Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
authors.forename: T A
authors.initials: TA
authors.lastname: Kato
authors.forename: A
authors.initials: A
authors.lastname: Monji
authors.forename: Y
authors.initials: Y
authors.lastname: Mizoguchi
authors.forename: S
authors.initials: S
authors.lastname: Hashioka
authors.forename: H
authors.initials: H
authors.lastname: Horikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Seki
authors.forename: M
authors.initials: M
authors.lastname: Kasai
authors.forename: H
authors.initials: H
authors.lastname: Utsumi
authors.forename: S
authors.initials: S
authors.lastname: Kanba
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D014150:Antipsychotic Agents; D016207:Cytokines; D017448:Receptors, Dopamine D2