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 Resjournal_title
Schizophrenia researchauthors
Lee BJ,Marchionni L,Andrews CE,Norris AL,Nucifora LG,Wu YC,Wright RA,Pevsner J,Ross CA,Margolis RL,Sawa A,Nucifora FC Jrdoi
10.1016/j.schres.2016.12.017subject
Has Abstractpub_date
2017-07-01 00:00:00pages
58-66eissn
0920-9964issn
1573-2509pii
S0920-9964(16)30591-6journal_volume
185pub_type
杂志文章,meta分析abstract::Impaired fiber bundle connectivity between brain regions is a key neuropathological finding in schizophrenia. Symptom dimensions in schizophrenia can be clustered into factor models. Single syndromes have been related to grey and white matter brain structure alterations. We associated all core syndromes of schizophren...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2016.11.045
更新日期:2017-06-01 00:00:00
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更新日期:2010-07-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2016-07-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2016.01.029
更新日期:2016-03-01 00:00:00
abstract:BACKGROUND:To develop a pharmacokinetic-pharmacodynamic (PK-PD) model using individual-level data of Positive and Negative Syndrome Scale (PANSS) total score to characterize the antipsychotic drug effect taking into account the placebo effect and dropout rate. In addition, a clinical utility (CU) criterion that describ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2013.02.011
更新日期:2013-05-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.schres.2018.06.012
更新日期:2018-11-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2007.07.006
更新日期:2007-12-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.schres.2007.03.030
更新日期:2007-08-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2018.03.030
更新日期:2018-09-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2010.09.003
更新日期:2011-03-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2014.03.003
更新日期:2014-05-01 00:00:00
abstract::Glutamate cycling is critically important for neurotransmission, and may be altered in schizophrenia. The excitatory amino acid transporters (EAATs) facilitate the reuptake of glutamate from the synaptic cleft and have a key role in glutamate cycling. We hypothesized that expression of the EAATs and the EAAT regulatin...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2008.06.012
更新日期:2008-09-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2019.12.021
更新日期:2020-02-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2012.10.003
更新日期:2012-12-01 00:00:00
abstract::Language disturbance is one of the main diagnostic features in schizophrenia and abnormalities of brain language areas have been consistently found in schizophrenic patients. The main aim of this study was to describe the impairment of micro and macrolinguistic abilities in a group of twenty-nine schizophrenic patient...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2008.07.011
更新日期:2008-10-01 00:00:00
abstract::Non-compliance problems may rise to 50% among patients undergoing neuroleptic treatment. There are no direct measures available to predict compliance, if previous non-compliance is not taken into account. Attitudes towards neuroleptic treatment and insight into psychotic symptoms may vary during the course of the trea...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(99)00204-2
更新日期:2000-10-27 00:00:00
abstract::In view of prior reports suggesting associations between polymorphisms of the tumor necrosis factor gene (TNF) and schizophrenia, we sequenced all exons, introns and 7 kb flanking sequence at TNF in DNA pooled from 125 Caucasian schizophrenia cases and 200 controls. We identified 18 SNPs of which we selected and genot...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2005.12.853
更新日期:2006-03-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(00)00115-8
更新日期:2001-03-01 00:00:00
abstract::Glutamate transporters facilitate the buffering, clearance and cycling of glutamate and play an important role in maintaining synaptic and extrasynaptic glutamate levels. Alterations in glutamate transporter expression may lead to abnormal glutamate neurotransmission contributing to the pathophysiology of schizophreni...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2012.12.019
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:Recovery is the ultimate goal of psychosis treatment. Basic self-disturbances (BSDs) are non-psychotic phenomena associated with clinical outcome, present in prodromal, psychotic and residual phases of psychotic disorders. AIM:To investigate the relationship between BSDs and recovery seven years after first...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2019.08.009
更新日期:2019-10-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(01)00378-4
更新日期:2002-11-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2003.08.007
更新日期:2004-04-01 00:00:00
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journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2005.01.001
更新日期:2005-07-15 00:00:00
abstract::Three-channel actometry was used to study neuroleptic-induced akathisia (NIA), a common and often serious disorder in association of traditional neuroleptic therapy. The aim was to explore the diagnostic possibilities of actometry in NIA and to examine in detail the motor phenomenology of the disorder in detail. The a...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(99)00045-6
更新日期:1999-11-30 00:00:00
abstract:BACKGROUND:Biochemical, physiological and genetic evidence suggests dysregulation of central nicotinic acetylcholine receptor (nAChR) systems in schizophrenia, which may contribute to neuropsychological dysfunction and the high rates of smoking in this disorder. To evaluate the effects of nAChR blockade on neuropsychol...
journal_title:Schizophrenia research
pub_type: 临床试验,杂志文章
doi:10.1016/j.schres.2006.03.025
更新日期:2006-07-01 00:00:00
abstract::A prior study in a US state hospital suggested that schizophrenia is more closely associated with tobacco smoking when compared with other severe mental illnesses. This second study, in a neighborhood hospital, tries to (1) replicate that schizophrenia is associated with smoking and heavy smoking, and (2) rule out tha...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(01)00192-x
更新日期:2002-07-01 00:00:00
abstract::Omega-3 treatment studies for multi-episode schizophrenia or clinical high risk for conversion to psychosis states have had variable, and often negative, results. To examine adjunctive omega-3 treatment for recent onset psychosis, participants aged 15-40 years with recent onset schizophrenia-spectrum (n = 46) or bipol...
journal_title:Schizophrenia research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.schres.2018.09.006
更新日期:2019-02-01 00:00:00
abstract::Studying Klinefelter syndrome (47,XXY), a genetically defined disorder characterized by the presence of an additional X chromosome, can reveal insights into genotype-phenotype associations. Increased vulnerability to psychiatric disorders characterized by difficulties in social interactions, such as schizophrenia and ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2006.02.020
更新日期:2006-06-01 00:00:00
abstract::Various theories have been proposed to account for poor insight in schizophrenia. This study examined the relationships between insight, mood, schizophrenic symptoms and cognitive functioning. The relationship between longitudinal changes in insight and changes in symptoms and mood was also investigated. One-hundred p...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(98)00142-x
更新日期:1999-02-15 00:00:00