Evidence map›Paper›PMID 24633560›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014

Identification of candidate single-nucleotide polymorphisms in NRXN1 related to antipsychotic treatment response in patients with schizophrenia.

Aaron Jenkins, José A Apud, Fengyu Zhang, Heather Decot, Daniel R Weinberger, Amanda J Law

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

9 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Childhood-Onset Schizophrenia: Insights from Induced Pluripotent Stem Cells.International journal of molecular sciences · 2018
    Review
  7. Review
  8. Article
  9. Article
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 5 institutions in 1 country.

Aaron Jenkins1] Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institute of Health, National Institutes of Health, Bethesda, MD, USA [2] University of Kentucky College of Medicine, Lexington, KY, USA.
José A ApudClinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institute of Health, National Institutes of Health, Bethesda, MD, USA.
Fengyu ZhangLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Heather DecotClinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institute of Health, National Institutes of Health, Bethesda, MD, USA.
Daniel R Weinberger1] Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA [2] Departments of Psychiatry, Neurology, Neuroscience and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Amanda J LawDepartments of Psychiatry and Cell and Developmental Biology, University of Colorado, School of Medicine, Aurora, CO, USA.
National Institutes of Health · USJohns Hopkins University · USLieber Institute for Brain Development · USNational Institute of Mental Health · USUniversity of Colorado Denver · US

Funding

Genetic Basis Of Cortical Malfunction In SchizophreniaZIAMH002734 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI BERMAN, KAREN FAITH · 2009 to 2014
$17.5M
Biological Characterization of Genetic Mechanisms in Neuropsychiatric DisordersZ01MH002904 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI WEINBERGER, DANIEL · 2007 to 2008
$2.6M
Intramural NIH HHS Z01 MH002904
6 · The paper itself

Abstract

Neurexins are presynaptic neuronal adhesion molecules that interact with postsynaptic neuroligins to form an inter-synaptic complex required for synaptic specification and efficient neurotransmission. Deletions and point mutations in the neurexin 1 (NRXN1) gene are associated with a broad spectrum of neuropsychiatric and neurodevelopmental disorders, including autism, intellectual disability, epilepsy, developmental delay, and schizophrenia. Recently, small nucleotide polymorphisms in NRXN1 have been associated with antipsychotic drug response in patients with schizophrenia. Based on previous suggestive evidence of an impact on clozapine response in patients with schizophrenia, we conducted an association study of NRXN1 polymorphisms (rs12467557 and rs10490162) with antipsychotic treatment response in 54 patients with schizophrenia in a double blind, placebo-controlled NIMH inpatient crossover trial and examined for association with risk for schizophrenia in independent case-control and family-based clinical cohorts. Pharmacogenetic analysis in the placebo controlled trial revealed significant association of rs12467557and rs10490162 with drug response, whereby individuals homozygous for the A allele, at either SNP, showed significant improvement in positive symptoms, general psychopathology, thought disturbance, and negative symptoms, whereas patients carrying the G allele showed no overall response. Although we did not find evidence of the same NRXN1 SNPs being associated with results of the NIMH sponsored CATIE trial, other SNPs showed weakly positive signals. The family and case-control analyses for schizophrenia risk were negative. Our results provide confirmatory evidence of genetically determined differences in drug response in patients with schizophrenia related to NRXN1 variation. Furthermore, these findings potentially implicate NRXN1 in the therapeutic actions of antipsychotic drugs.

Indexed as

Polymorphism, Single NucleotideAdultAntipsychotic AgentsCalcium-Binding ProteinsCase-Control StudiesCell Adhesion Molecules, NeuronalCohort StudiesCross-Over StudiesDouble-Blind MethodFamilyFemaleGenotyping TechniquesHumansMaleNerve Tissue ProteinsNeural Cell Adhesion MoleculesAntipsychotic AgentsCalcium-Binding ProteinsCell Adhesion Molecules, NeuronalNerve Tissue ProteinsNeural Cell Adhesion MoleculesNRXN1 protein, human

Identifiers

PMID24633560
PMCPMC4104334
OpenAlexW1969346503

What OpenQuestion holds

Textmetadata
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.