Evidence map›Paper›PMID 28038920›Full record

SynthesisSchizophrenia research2017

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

Brian J Lee, Luigi Marchionni, Carrie E Andrews, Alexis L Norris, Leslie G Nucifora, Yeewen Candace Wu, Robert A Wright, Jonathan Pevsner, Christopher A Ross, Russell L Margolis and 2 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Schizophrenia research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.1field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Upregulation of vitamin D-related genes in schizophrenic patients.Neuropsychiatric disease and treatment · 2018
    Article
  9. Review
  10. Clozapine as a Model for Antipsychotic Development.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Brian J LeeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA; Cellular and Molecular Medicine Program, Johns Hopkins University School of Medicine, 1830 E. Monument St., Baltimore, MD 21205, USA.
Luigi MarchionniSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401 N. Broadway, Baltimore, MD 21287, USA.
Carrie E AndrewsDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA.
Alexis L NorrisDepartment of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, USA; Department of Neurology, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, 707 N. Broadway, Baltimore, MD 21205, USA.
Leslie G NuciforaDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA.
Yeewen Candace WuDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA.
Robert A WrightWilliam H. Welch Medical Library, Johns Hopkins University, 1900 E. Monument St., Baltimore, MD 21205, USA.
Jonathan PevsnerDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, USA; Department of Neurology, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, 707 N. Broadway, Baltimore, MD 21205, USA.
Christopher A RossDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA; Cellular and Molecular Medicine Program, Johns Hopkins University School of Medicine, 1830 E. Monument St., Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, USA.
Russell L MargolisDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA; Cellular and Molecular Medicine Program, Johns Hopkins University School of Medicine, 1830 E. Monument St., Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, USA.
Akira SawaDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA; Cellular and Molecular Medicine Program, Johns Hopkins University School of Medicine, 1830 E. Monument St., Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, USA.
Frederick C NuciforaDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA. Electronic address: nucifora@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Project 3P50MH094268 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SAWA, AKIRA · 2011 to 2020
$19.9M
DISC1-dependent defects in neural fate, corticogenesis and cognition in psychosisR01MH105660 · NIMH · JOHNS HOPKINS UNIVERSITY · PI ISHIZUKA, KOKO, SAWA, AKIRA · 2014 to 2018
$2.8M
Oxidative stress and schizophrenia: combination of cell biology and brain imagingR01MH092443 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SAWA, AKIRA · 2011 to 2015
$1.8M
Preclinical model for co-morbid conditions that are relevant to addiction and depressionR21DA040127 · NIDA · JOHNS HOPKINS UNIVERSITY · PI NIWA, MINAE, SAWA, AKIRA · 2015 to 2016
$443k
NCATS NIH HHS UL1 TR001079NIDA NIH HHS R21 DA040127NIMH NIH HHS P50 MH094268NIMH NIH HHS R01 MH092443NIMH NIH HHS R01 MH105660
6 · The paper itself

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.

Indexed as

SchizophreniaAntipsychotic AgentsAutopsyBrainClozapineDatabases, BibliographicFemaleGene ExpressionHumansMaleSignal TransductionAntipsychotic AgentsClozapineAntipsychoticBipolar affective disorderMicroarraySchizophrenia

Identifiers

PMID28038920
PMCPMC6541388
OpenAlexW2563122328

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.