Evidence map›Paper›PMID 36454006›Full record

ArticleSchizophrenia bulletin2023

Increased Prevalence of Rare Copy Number Variants in Treatment-Resistant Psychosis.

Martilias Farrell, Tyler E Dietterich, Matthew K Harner, Lisa M Bruno, Dawn M Filmyer, Rita A Shaughnessy, Maya L Lichtenstein, Allison M Britt, Tamara F Biondi, James J Crowley and 10 more

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

Article in Schizophrenia bulletin, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

13 citing papers in PubMed, 27 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 3 countries.

Martilias FarrellDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Tyler E DietterichTranslational Neuroscience, LLC, Conshohocken, PA, USA.
Matthew K HarnerTranslational Neuroscience, LLC, Conshohocken, PA, USA.
Lisa M BrunoTranslational Neuroscience, LLC, Conshohocken, PA, USA.
Dawn M FilmyerTranslational Neuroscience, LLC, Conshohocken, PA, USA.
Rita A ShaughnessyTranslational Neuroscience, LLC, Conshohocken, PA, USA.
Maya L LichtensteinDepartment of Neurology, Geisinger Health System, Wilkes Barre, PA, USA.
Allison M BrittSchool of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Tamara F BiondiOffice of the Vice Chancellor for Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
James J CrowleyDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Gabriel Lázaro-MuñozCenter for Bioethics, Harvard Medical School, Boston, MA, USA.
Annika E ForsingdalDepartment of Bioinformatics, H. Lundbeck A/S, Valby, Denmark.
Jacob NielsenDivision of Neuroscience, H. Lundbeck A/S, Valby, Denmark.
Michael DidriksenDivision of Neuroscience, H. Lundbeck A/S, Valby, Denmark.
Jonathan S BergDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jia WenDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jin SzatkiewiczDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Rose Mary XavierSchool of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Patrick F SullivanDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Richard C JosiassenTranslational Neuroscience, LLC, Conshohocken, PA, USA.ORCID 0000-0002-2572-975X
University of North Carolina at Chapel Hill · USLundbeck (Denmark) · DKGeisinger Health System · USHarvard University · US

Funding

Biostatstics for Research in Environmental HealthT32ES007018 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel, Rebecca Fry · 1985 to 2026
$31.3M
Finding causal variants within schizophrenia risk lociR01MH106611 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SZATKIEWICZ, JIN PENG · 2015 to 2019
$3.3M
OCD: Novel Comparative Genomic Approaches to Identify Disease and Treatment MechanismsR01MH110427 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CROWLEY, JAMES JOSEPH · 2016 to 2021
$3.0M
The Genomics of Highly Treatment Resistant SchizophreniaK01MH108894 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FARRELL, MARTILIAS STEPHEN · 2016 to 2019
$567k
Ethical Legal and Social Implications of Translational Psychiatric Genomics ResearchK99HG008689 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LAZARO-MUNOZ, GABRIEL · 2015 to 2016
$176k
NHGRI NIH HHS K99 HG008689NIEHS NIH HHS T32 ES007018NIMH NIH HHS K01 MH108894NIMH NIH HHS R01 MH106611NIMH NIH HHS R01 MH110427
6 · The paper itself

Abstract

backgroundIt remains unknown why ~30% of patients with psychotic disorders fail to respond to treatment. Previous genomic investigations of treatment-resistant psychosis have been inconclusive, but some evidence suggests a possible link between rare disease-associated copy number variants (CNVs) and worse clinical outcomes in schizophrenia. Here, we identified schizophrenia-associated CNVs in patients with treatment-resistant psychotic symptoms and then compared the prevalence of these CNVs to previously published schizophrenia cases not selected for treatment resistance.

methodsCNVs were identified using chromosomal microarray (CMA) and whole exome sequencing (WES) in 509 patients with treatment-resistant psychosis (a lack of clinical response to ≥3 adequate antipsychotic medication trials over at least 5 years of psychiatric hospitalization). Prevalence of schizophrenia-associated CNVs in this sample was compared to that in a previously published large schizophrenia cohort study.

resultsIntegrating CMA and WES data, we identified 47 cases (9.2%) with at least one CNV of known or possible neuropsychiatric risk. 4.7% (n = 24) carried a known neurodevelopmental risk CNV. The prevalence of well-replicated schizophrenia-associated CNVs was 4.1%, with duplications of the 16p11.2 and 15q11.2-q13.1 regions, and deletions of the 22q11.2 chromosomal region as the most frequent CNVs. Pairwise loci-based analysis identified duplications of 15q11.2-q13.1 to be independently associated with treatment resistance.

conclusionsThese findings suggest that CNVs may uniquely impact clinical phenotypes beyond increasing risk for schizophrenia and may potentially serve as biological entry points for studying treatment resistance. Further investigation will be necessary to elucidate the spectrum of phenotypic characteristics observed in adult psychiatric patients with disease-associated CNVs.

Indexed as

Psychotic DisordersSchizophreniaCohort StudiesDNA Copy Number VariationsGenetic Predisposition to DiseaseHumansPrevalence15q11.2-q13.1 duplication16p11.2 duplicationcopy number variantsneurodevelopmental disordersrare variantsschizophreniatreatment-resistant psychosisultra-TRS

Identifiers

PMID36454006
PMCPMC10318882
OpenAlexW4310490795

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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.