Pattern of expression of Toll like receptor (TLR)-3 and -4 genes in drug-naïve and antipsychotic treated patients diagnosed with schizophrenia

Renu Balaji; Manjula Subbanna; Venkataram Shivakumar; Fazal Abdul; Ganesan Venkatasubramanian; Monojit Debnath

doi:10.1016/j.psychres.2019.112727

Pattern of expression of Toll like receptor (TLR)-3 and -4 genes in drug-naïve and antipsychotic treated patients diagnosed with schizophrenia

Psychiatry Res. 2020 Mar:285:112727. doi: 10.1016/j.psychres.2019.112727. Epub 2019 Dec 4.

Authors

Renu Balaji¹, Manjula Subbanna², Venkataram Shivakumar³, Fazal Abdul¹, Ganesan Venkatasubramanian³, Monojit Debnath⁴

Affiliations

¹ Department of Human Genetics, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore 560029, Karnataka, India.
² Department of Human Genetics, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore 560029, Karnataka, India; Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
³ Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
⁴ Department of Human Genetics, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore 560029, Karnataka, India. Electronic address: monojit-d@nimhans.ac.in.

PMID: 31837816
DOI: 10.1016/j.psychres.2019.112727

Abstract

Toll like receptors (TLRs), a class of conserved immune molecules are crucially involved in initiating innate immune response to infection. TLR activation and subsequent inflammation are linked to pathogenesis of many brain disorders. Preliminary studies indicate a possible role of TLR-driven immuno-inflammatory responses in schizophrenia. However, gene expression data of TLRs in drug-naïve as well as antipsychotic treated patients diagnosed with schizophrenia are albeit limited. In this study, expression profile of TLR3 and TLR4 genes in peripheral blood mononuclear cells (PBMCs) was compared between drug-naïve patients diagnosed with schizophrenia (N = 31) and healthy controls (N = 30). In addition, the pattern of expression of TLR3 and TLR4 genes were also examined after three months of antipsychotic medication in patients. Compared to healthy controls, gene expression levels of only TLR4 (F = 3.87, p = 0.05, η_p² = 0.06), not TLR3 (F = 0.17, p = 0.71, η_p² = 0.003) was significantly up-regulated in drug-naïve patients. The changes in the levels of gene expression of TLR3 (t = 0.09, p = 0.93, d = 0.02) and TLR4 (t = 0.29, p = 0.77, d = 0.06) before and after antipsychotic medication were not found to be statistically significant. This finding suggests possible contribution of TLR4 in immunopathogenetic pathway of schizophrenia.

Keywords: Antipsychotic drugs; Schizophrenia; Toll like receptor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antipsychotic Agents / pharmacology
Antipsychotic Agents / therapeutic use*
Female
Gene Expression
Humans
Immunity, Innate / drug effects
Immunity, Innate / physiology
Leukocytes, Mononuclear / drug effects
Leukocytes, Mononuclear / physiology
Male
Middle Aged
Schizophrenia / drug therapy*
Schizophrenia / genetics*
Schizophrenia / immunology
Toll-Like Receptor 3 / biosynthesis
Toll-Like Receptor 3 / genetics*
Toll-Like Receptor 4 / biosynthesis
Toll-Like Receptor 4 / genetics*

Substances

Antipsychotic Agents
TLR3 protein, human
TLR4 protein, human
Toll-Like Receptor 3
Toll-Like Receptor 4