Analysis of differential gene expression mediated by clozapine in human postmortem brains.

Abstract:

:Clozapine is the only medication indicated for treating refractory schizophrenia, due to its superior efficacy among all antipsychotic agents, but its mechanism of action is poorly understood. To date, no studies of human postmortem brain have characterized the gene expression response to clozapine. Therefore, we addressed this question by analyzing expression data extracted from published microarray studies involving brains of patients on antipsychotic therapy. We first performed a systematic review and identified four microarray studies of postmortem brains from antipsychotic-treated patients, then extracted the expression data. We then performed generalized linear model analysis on each study separately, and identified the genes differentially expressed in response to clozapine compared to other atypical antipsychotic medications, as well as their associated canonical pathways. We also found a number of genes common to all four studies that we analyzed: GCLM, ZNF652, and GYPC. In addition, pathway analysis highlighted the following processes in all four studies: clathrin-mediated endocytosis, SAPK/JNK signaling, 3-phosphoinositide synthesis, and paxillin signaling. Our analysis yielded the first comprehensive compendium of genes and pathways differentially expressed upon clozapine treatment in the human brain, which may provide insight into the mechanism and unique efficacy of clozapine, as well as the pathophysiology of schizophrenia.

journal_name

Schizophr Res

journal_title

Schizophrenia research

authors

Lee BJ,Marchionni L,Andrews CE,Norris AL,Nucifora LG,Wu YC,Wright RA,Pevsner J,Ross CA,Margolis RL,Sawa A,Nucifora FC Jr

doi

10.1016/j.schres.2016.12.017

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

58-66

eissn

0920-9964

issn

1573-2509

pii

S0920-9964(16)30591-6

journal_volume

185

pub_type

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