title: Antipsychotics influence Toll-like receptor (TLR) expression and its relationship with cognitive functions in schizophrenia.
abstract: Increasing evidence suggests that altered immune functions are related to the pathophysiology of schizophrenia. Relatively little information is available on Toll-like receptors (TLRs), which are implicated in the recognition of molecular patterns associated with pathogens and internal cellular damage signals. By using immunophenotyping and flow cytometry, we investigated TLRs in CD14+ monocytes, CD4+CD25+Foxp3+ regulatory T cells (Treg), and CD3+CD4+CD25+ activated T cells (Tact) in 35 drug-naïve patients with schizophrenia before and after an 8-week period of antipsychotic treatment with risperidone or olanzapine. As compared with 30 healthy control individuals, drug-naïve patients with schizophrenia exhibited an increased percentage of TLR4+ and TLR5+ monocytes and TLR5+ Treg/Tactcells. At the end of the treatment period, we observed normalized TLR4+ monocytes and an up-regulation of TLR2+ monocytes and Treg/Tactcells. Mean fluorescent intensity values, indicating receptor density, were consistent with these findings. In the drug-naïve state, but not after treatment, higher percentages of TLR4+ and TLR5+ monocytes were correlated with more severe cognitive deficits. Positive, negative, and general clinical symptoms were not associated with TLRs. There were no significant differences between patients receiving olanzapine and risperidone. These results indicate that abnormal expression of TLRs can be detected in the earliest stage of schizophrenia, which is modulated by antipsychotics. Immunological alterations in unmedicated schizophrenia patients may be linked to cognitive deficits.
authors.affiliation: Department of Cognitive Science, Budapest University of Technology and Economics, Budapest, Hungary; Nyírő Gyula Hospital - National Institute of Psychiatry and Addictions, Budapest, Hungary; Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary. Electronic address: szkeri@cogsci.bme.hu.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Kéri
authors.affiliation: Nyírő Gyula Hospital - National Institute of Psychiatry and Addictions, Budapest, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Szabó
authors.affiliation: Department of Behavioral Science, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Oguz
authors.initials: O
authors.lastname: Kelemen
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009483:Neuropsychological Tests; D000077152:Olanzapine; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D012565:Schizophrenic Psychology; D051193:Toll-Like Receptors / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D051193:Toll-Like Receptors; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine
keywords: Cognitive functions; Monocytes; Regulatory T cells; Schizophrenia; Toll-like receptors