Abstract
Treatment-resistant schizophrenia (TRS) affects around one-third of individuals with schizophrenia. Although a number of sociodemographic and clinical predictors of TRS have been identified, data on the genetic risk of TRS are sparse. We aimed to investigate the association between a polygenic risk score for schizophrenia and treatment resistance in patients with schizophrenia. We conducted a nationwide, population-based follow-up study among all Danish individuals born after 1981 and with an incident diagnosis of schizophrenia between 1999 and 2007. Based on genome-wide data polygenic risk scores for schizophrenia were calculated in 862 individuals with schizophrenia. TRS was defined as either clozapine initiation or at least 2 periods of different antipsychotic monotherapies and still being hospitalized. We estimated hazard rate ratios (HRs) for TRS in relation to the polygenic risk score while adjusting for population stratification, age, sex, geographical area at birth, clinical treatment setting, psychiatric comorbidity, and calendar year. Among the 862 individuals with schizophrenia, 181 (21.0%) met criteria for TRS during 4674 person-years of follow-up. We found no significant association between the polygenic risk score and TRS, adjusted HR = 1.13 (95% CI: 0.95-1.35). Based on these results, the use of the polygenic risk score for schizophrenia to identify individuals with TRS is at present inadequate to be of clinical utility at the individual patient level. Future research should include larger genetic samples in combination with non-genetic markers. Moreover, a TRS-specific developed polygenic risk score would be of great interest towards early prediction of TRS.
Original language | English |
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Pages (from-to) | 1064-1069 |
Number of pages | 6 |
Journal | Schizophrenia Bulletin |
Volume | 43 |
Issue number | 5 |
DOIs | |
Publication status | Published - Sept 1 2017 |
Externally published | Yes |
Bibliographical note
Funding Information:This study was approved by the Danish Data Protection Agency and the Danish Health and Medicines authority. J.H.M. was funded by the NIHR Biomedical Research Centre for Mental Health at King’s College London and the South London and Maudsley NHS Foundation Trust. S.M.M. received further funding from the Mental Health Services, Capital Region, Copenhagen, Denmark. All other authors have declared that there are no conflicts of interest in relation to the subject of this study.
Publisher Copyright:
© The Author 2017.
ASJC Scopus Subject Areas
- Psychiatry and Mental health
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't