Effects of typical and atypical antipsychotic drugs on gene expression profiles in the liver of schizophrenia subjects
Open Access
- 16 September 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Psychiatry
- Vol. 9 (1), 57
- https://doi.org/10.1186/1471-244x-9-57
Abstract
Although much progress has been made on antipsychotic drug development, precise mechanisms behind the action of typical and atypical antipsychotics are poorly understood. We performed genome-wide expression profiling to study effects of typical antipsychotics and atypical antipsychotics in the postmortem liver of schizophrenia patients using microarrays (Affymetrix U133 plus2.0). We classified the subjects into typical antipsychotics (n = 24) or atypical antipsychotics (n = 26) based on their medication history, and compared gene expression profiles with unaffected controls (n = 34). We further analyzed individual antipsychotic effects on gene expression by sub-classifying the subjects into four major antipsychotic groups including haloperidol, phenothiazines, olanzapine and risperidone. Typical antipsychotics affected genes associated with nuclear protein, stress responses and phosphorylation, whereas atypical antipsychotics affected genes associated with golgi/endoplasmic reticulum and cytoplasm transport. Comparison between typical antipsychotics and atypical antipsychotics further identified genes associated with lipid metabolism and mitochondrial function. Analyses on individual antipsychotics revealed a set of genes (151 transcripts, FDR adjusted p < 0.05) that are differentially regulated by four antipsychotics, particularly by phenothiazines, in the liver of schizophrenia patients. Typical antipsychotics and atypical antipsychotics affect different genes and biological function in the liver. Typical antipsychotic phenothiazines exert robust effects on gene expression in the liver that may lead to liver toxicity. The genes found in the current study may benefit antipsychotic drug development with better therapeutic and side effect profiles.Keywords
This publication has 69 references indexed in Scilit:
- Putative psychosis genes in the prefrontal cortex: combined analysis of gene expression microarraysBMC Psychiatry, 2008
- Coagulation and inflammation markers during atypical or typical antipsychotic treatment in schizophrenia patients and drug-free first-degree relativesSchizophrenia Research, 2008
- Shared Gene Expression Alterations in Schizophrenia and Bipolar DisorderBiological Psychiatry, 2008
- Molecular Evidence for Increased Expression of Genes Related to Immune and Chaperone Function in the Prefrontal Cortex in SchizophreniaBiological Psychiatry, 2007
- Inflammation-related genes up-regulated in schizophrenia brainsBMC Psychiatry, 2007
- Altered T-Cell Function in Schizophrenia: A Cellular Model to Investigate Molecular Disease MechanismsPLOS ONE, 2007
- Chlorpromazine exacerbates hepatic insulin sensitivity via attenuating insulin and leptin signaling pathway, while exercise partially reverses the adverse effectsLife Sciences, 2007
- Second-Generation (Atypical) Antipsychotics and Metabolic EffectsCNS Drugs, 2005
- Microarray reality checks in the context of a complex diseaseNature Biotechnology, 2004
- Gene expression profiling in the post-mortem human brain — no cause for dismayJournal of Chemical Neuroanatomy, 2001