Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Feb;46(3):469-76.
doi: 10.1017/S0033291715001701. Epub 2015 Sep 9.

Increased rare duplication burden genomewide in patients with treatment-resistant schizophrenia

A K Martin  1 , B Mowry  1
Affiliations

Increased rare duplication burden genomewide in patients with treatment-resistant schizophrenia

A K Martin et al. Psychol Med. 2016 Feb.

Abstract

Background: A significant number of patients with schizophrenia fail to respond to antipsychotic medication. Although several studies have investigated associated patient characteristics, the emerging findings from genetic studies offer further scope for study.

Method: In 612 schizophrenia patients with detailed clinical information, common genetic variants indexed by polygenic risk scores, and rare variants indexed by deletion and duplication burden genomewide, we explored potential genetic predictors alongside other established risk factors for treatment resistance. Clinical outcomes of treatment resistance were also calculated using lifetime measures of positive, negative/disorganized and mood symptoms as well as number of hospitalizations and suicide attempts.

Results: Logistic regression models identified a significant relationship between treatment resistance and total duplication burden genomewide, years of formal schooling and age at onset. Clinically, treatment-resistant patients were characterized by greater negative/disorganized and positive symptoms and greater number of hospitalizations.

Conclusions: Taken together, these findings suggest genetic information, specifically the genomewide burden of rare copy number variants, may increase our understanding and clinical management of patients with treatment-resistant schizophrenia.

Keywords: Age at onset; clozapine; copy number variants; mutations; predictive models.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

  • Genomic findings in schizophrenia and their implications.
    Owen MJ, Legge SE, Rees E, Walters JTR, O'Donovan MC. Owen MJ, et al. Mol Psychiatry. 2023 Sep;28(9):3638-3647. doi: 10.1038/s41380-023-02293-8. Epub 2023 Oct 18. Mol Psychiatry. 2023. PMID: 37853064 Free PMC article. Review.
  • Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates.
    Diniz E, Fonseca L, Rocha D, Trevizol A, Cerqueira R, Ortiz B, Brunoni AR, Bressan R, Correll CU, Gadelha A. Diniz E, et al. Braz J Psychiatry. 2023 Sep-Oct;45(5):448-458. doi: 10.47626/1516-4446-2023-3126. Epub 2023 Sep 17. Braz J Psychiatry. 2023. PMID: 37718484 Free PMC article.
  • Increased Prevalence of Rare Copy Number Variants in Treatment-Resistant Psychosis.
    Farrell M, Dietterich TE, Harner MK, Bruno LM, Filmyer DM, Shaughnessy RA, Lichtenstein ML, Britt AM, Biondi TF, Crowley JJ, Lázaro-Muñoz G, Forsingdal AE, Nielsen J, Didriksen M, Berg JS, Wen J, Szatkiewicz J, Mary Xavier R, Sullivan PF, Josiassen RC. Farrell M, et al. Schizophr Bull. 2023 Jul 4;49(4):881-892. doi: 10.1093/schbul/sbac175. Schizophr Bull. 2023. PMID: 36454006 Free PMC article.
  • Peripheral biomarkers of treatment-resistant schizophrenia: Genetic, inflammation and stress perspectives.
    Jiao S, Cao T, Cai H. Jiao S, et al. Front Pharmacol. 2022 Oct 12;13:1005702. doi: 10.3389/fphar.2022.1005702. eCollection 2022. Front Pharmacol. 2022. PMID: 36313375 Free PMC article. Review.
  • Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia.
    Pardiñas AF, Smart SE, Willcocks IR, Holmans PA, Dennison CA, Lynham AJ, Legge SE, Baune BT, Bigdeli TB, Cairns MJ, Corvin A, Fanous AH, Frank J, Kelly B, McQuillin A, Melle I, Mortensen PB, Mowry BJ, Pato CN, Periyasamy S, Rietschel M, Rujescu D, Simonsen C, St Clair D, Tooney P, Wu JQ, Andreassen OA, Kowalec K, Sullivan PF, Murray RM, Owen MJ, MacCabe JH, O'Donovan MC, Walters JTR; Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances (STRATA) Consortium and the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC); Ajnakina O, Alameda L, Barnes TRE, Berardi D, Bonora E, Camporesi S, Cleusix M, Conus P, Crespo-Facorro B, D'Andrea G, Demjaha A, Do KQ, Doody GA, Eap CB, Ferchiou A, Di Forti M, Guidi L, Homman L, Jenni R, Joyce EM, Kassoumeri L, Khadimallah I, Lastrina O, Muratori R, Noyan H, O'Neill FA, Pignon B, Restellini R, Richard JR, Schürhoff F, Španiel F, Szöke A, Tarricone I, Tortelli A, Üçok A, Vázquez-Bourgon J. Pardiñas AF, et al. JAMA Psychiatry. 2022 Mar 1;79(3):260-269. doi: 10.1001/jamapsychiatry.2021.3799. JAMA Psychiatry. 2022. PMID: 35019943 Free PMC article.
See all "Cited by" articles

Publication types