Evidence map›Paper›PMID 19369910›Full record

Trial reportPharmacogenetics and genomics2009

The efficacies of clozapine and haloperidol in refractory schizophrenia are related to DTNBP1 variation.

Lingjun Zuo, Xingguang Luo, John H Krystal, Joyce Cramer, Dennis S Charney, Joel Gelernter

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Pharmacogenetics and genomics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% 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, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Genomics and pharmacogenomics of schizophrenia.CNS neuroscience & therapeutics · 2011
    Review
  9. Article
  10. The promise and reality of pharmacogenetics in psychiatry.The Psychiatric clinics of North America · 2010
    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

6 authors at 3 institutions in 1 country.

Lingjun ZuoDepartments of Psychiatry, West Haven Campus, Connecticut, USA.
Xingguang Luo
John H Krystal
Joyce Cramer
Dennis S Charney
Joel Gelernter
VA Connecticut Healthcare System · USIcahn School of Medicine at Mount Sinai · USYale University · US

Funding

Translational Technologies CoreP50AA012870 · NIAAA · YALE UNIVERSITY · PI John H. Krystal · 2001 to 2026
$43.7M
Sex-specific analysis of opioid dependence GWAS and beyondR01DA012690 · NIDA · YALE UNIVERSITY · PI GELERNTER, JOEL · 2000 to 2017
$14.0M
GENETICS OF COCAINE DEPENDENCER01DA012849 · NIDA · YALE UNIVERSITY · PI GELERNTER, JOEL · 1999 to 2010
$11.5M
Presynaptic Mechanisms of D1 Receptor Effects on Cortical FunctionP50MH068789 · NIMH · YALE UNIVERSITY · PI MCCORMICK, DAVID · 2004 to 2008
$10.3M
Linkage Disequilibrium Studies of Alcohol DependenceR01AA011330 · NIAAA · YALE UNIVERSITY · PI GELERNTER, JOEL · 1997 to 2013
$6.4M
AMINO ACID NEUROTRANSMITTER DYSREGULATION IN ALCOHOLISMK05AA014906 · NIAAA · YALE UNIVERSITY · PI KRYSTAL, JOHN H. · 2004 to 2008
$918k
The risk loci for alcoholism in ADH gene cluster/ALDH2R01AA016015 · NIAAA · YALE UNIVERSITY · PI LUO, XINGGUANG · 2006 to 2010
$714k
Approaches to the Genetics of Substance DependenceK24DA015105 · NIDA · YALE UNIVERSITY · PI GELERNTER, JOEL · 2003 to 2007
$603k
NIAAA NIH HHS K05 AA014906NIAAA NIH HHS K05 AA 14906-04NIAAA NIH HHS P50 AA012870NIAAA NIH HHS P50-AA12870NIAAA NIH HHS R01 AA011330NIAAA NIH HHS R01 AA016015NIAAA NIH HHS R01-AA016015NIAAA NIH HHS R01-AA11330NIDA NIH HHS K24 DA015105NIDA NIH HHS K24-DA15105NIDA NIH HHS R01 DA012690NIDA NIH HHS R01 DA012849NIDA NIH HHS R01-DA12690NIDA NIH HHS R01-DA12849NIMH NIH HHS P50 MH068789NIMH NIH HHS P50 MH068789-03
6 · The paper itself

Abstract

objectiveThe prototypical atypical antipsychotic agent, clozapine, is more efficacious for refractory schizophrenia than the 'typical' antipsychotics, but the mechanism underlying this enhanced efficacy is still under investigation. Since 2002, at least 22 association studies have shown that the DTNBP1 can be associated with the risk for schizophrenia. We hypothesized that DTNBP1 might also influence the response to antipsychotic treatments. This study aimed to investigate the relationship between the DTNBP1 and the effects of clozapine and haloperidol on refractory schizophrenia.

methodsPatients with refractory schizophrenia were assigned to clozapine (n=85) or haloperidol (n=96) and followed for 3 months. Symptom improvement was evaluated by Positive and Negative Syndrome Scale score. Six markers at DTNBP1 and 38 ancestry-informative markers were genotyped in all participants. The relationships between the effects of antipsychotics and the diplotypes, haplotypes, genotypes, and alleles of DTNBP1 were tested by analysis of covariance, analysis of variance, and t-test.

resultsPatients with diplotype ACCCTC/GTTGCC, genotypes T/T+T/C, or allele T of marker rs742105 (P1333) have better response to clozapine (0.005< or =P< or =0.049), and patients with diplotype ACCCTC/GCCGCC, genotype A/G, or allele A of marker rs909706 (P1583) have better response to haloperidol (0.007< or =P< or =0.080) in European-Americans, African-Americans, and/or the combined sample; European-American patients with diplotype ACCCTC/GCCGCC have worse response to clozapine on positive symptoms (P=0.011).

conclusionThis study shows that the DTNBP1 gene modulates the effects of both the atypical antipsychotic clozapine and the typical antipsychotic haloperidol. Participants with different DTNBP1 diplotypes, haplotypes, genotypes, or alleles might have different responses to these antipsychotics.

Indexed as

Genetic VariationAntipsychotic AgentsBlack or African AmericanCarrier ProteinsClozapineDouble Bind InteractionDysbindinDystrophin-Associated ProteinsGenotypeHaloperidolHaplotypesHumansSchizophreniaTreatment OutcomeWhite PeopleAntipsychotic AgentsCarrier ProteinsClozapineDTNBP1 protein, humanDysbindinDystrophin-Associated ProteinsHaloperidol

Identifiers

PMID19369910
PMCPMC2857717
OpenAlexW2001795619

What OpenQuestion holds

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Registered trials

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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.