Long Non-Coding RNAs Associated with Heterochromatin Function in Immune Cells in Psychosis

Abstract

Psychosis is associated with chronic immune dysregulation. Many long non-coding RNAs (lncRNAs) display abnormal expression during activation of immune responses, and play a role in heterochromatic regulation of gene promoters. We have measured lncRNAs MEG3, PINT and GAS5, selected for their previously described association with heterochromatin. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples collected from 86 participants with a diagnosis of psychosis and 44 control participants. Expression was assessed in relation to diagnosis, illness acuity status, and treatment with antipsychotic medication. We observed diagnostic differences with MEG3, PINT and GAS5, and symptom acuity effect with MEG3 and GAS5. Medication effects were evident in those currently on treatment with antipsychotics when compared to drug-naïve participants. We observed that clinical diagnosis and symptom acuity predict selected lncRNA expression. Particular noteworthy is the differential expression of MEG3 in drug naïve participants compared to those treated with risperidone. Additionally, an in vitro cell model using M2tol macrophages was used to test the effects of the antipsychotic drug risperidone on the expression of these lncRNAs using quantitative real-time PCR (qRT-PCR). Significant but differential effects of risperidone were observed in M2tol macrophages indicating a clear ability of antipsychotic medications to modify lncRNA expression.

Keywords

• lncRNAs
• heterochromatin
• antipsychotic response
• chronic inflammation
• schizophrenia
• psychosis