A Study of Sudden Cardiac Death in Schizophrenia
Open accessAbstract
Background The incidence of sudden cardiac death (SCD) in patients with schizophrenia is three to four times higher than in the general population. While the majority of SCD in patients with schizophrenia are due to ischaemic or structural heart disease, about 10% of deaths remain unexplained. In recent reviews of premature deaths in patients with schizophrenia, these deaths were postulated to be secondary to malignant cardiac arrhythmias.Methods A retrospective study conducted jointly by the Victorian Institute of Forensic Medicine and the Department of Genomic Medicine, The Royal Melbourne Hospital, Australia, was designed to identify novel genomic loci that link schizophrenia and sudden unexplained death. Cases included deceased patients over a 5-year period (2016-2021) with an in-life diagnosis of schizophrenia and an unascertained cause of death after comprehensive post-mortem histopathological and toxicological assessment. Individuals also required a source of DNA to be available.Results Thirty-six individuals, 26 males and 10 females, age range 18-65 years, met the study inclusion criteria. Autopsy revealed 10 individuals had cardiomegaly, six had cardiac hypertrophy, six had a body mass index (BMI) >40, and four had mild myocardial fibrosis. Thirteen next of kin (NOK) (36%) consented to involvement in the study and 12 individuals (92%) underwent whole exome sequencing (WES) via a research platform. Two clinically actionable results were detected-a pathogenic Desmoplakin (DES) variant and a dihydropyrimidine dehydrogenase (DPYD) pharmacogenomic variant.Conclusion Our study, with comprehensive autopsy examination adds to the literature on SCD in schizophrenia. Genes that are currently associated with inherited arrhythmias or schizophrenia such as Neuregulin 1 were not found in this study group. The pathogenic DES variant would likely have been found had the family accepted referral to a Cardiac Genetics service, at the time of death.
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Most sudden deaths in schizophrenia are linked to structural heart disease or antipsychotic exposure, while only a minority remain unexplained.
“A recent forensic-genomic study confirmed that most sudden deaths in schizophrenia are linked to structural heart disease or antipsychotic exposure, while only a minority remain unexplained, suggesting that rare inherited arrhythmia syndromes may account for some cases [18].”
From Trends in Sudden Death Among Schizophrenia Inpatients (2025) · cites this paper as [18]
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Trends in Sudden Death Among Schizophrenia Inpatients
Popa, A.-V., Ifteni, P. I., Petric, P. S., Țâbian, D., & Teodorescu, A. (2025) · Medicina · doi:10.3390/medicina61122081
“A recent forensic-genomic study confirmed that most sudden deaths in schizophrenia are linked to structural heart disease or antipsychotic exposure, while only a minority remain unexplained, suggesting that rare inherited arrhythmia syndromes may account for some cases [18].”
The end of fragmented consciousness: deaths in schizophrenia—an autopsy-based study
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Chen, Y., & Yan, F. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1578123
- Authors
- Vohra, J., Thompson, T., Morgan, N., Parsons, S., Zentner, D., Thompson, B., Verma, K., & Winship, I.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Victorian Institute of Forensic Medicine (AU)
- Monash Medical Centre (AU)
- Corresponding author
- Vohra, Jitendra
- ORCID
- Venue
- Heart Lung and Circulation
- Publisher
- Elsevier BV
- Published
- 2025-06
- Volume
- 34
- Issue
- 6
- Pages
- 613-618
- ISSN
- 1443-9506 (ISSN-L)
- OpenAlex
- W4409693362
- Cited by
- 3
- References
- 22
- Citations by year
- 2026: 2 · 2025: 1
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- green
- dx.doi.org
- Locations
- Heart Lung and Circulation (publishedVersion)
- SSRN Electronic Journal (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- The Royal Melbourne Hospital
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Keywords
- sudden cardiac death, schizophrenia, sudden unexplained death, desmoplakin, dihydropyrimidine dehydrogenase, inherited arrhythmia, cardiomegaly, cardiac hypertrophy, myocardial fibrosis, exome sequencing, cardiac genetics
- MeSH terms
- Adolescent, Adult, Aged, Australia, Autopsy, Cause of Death, Female, Humans, Male, Middle Aged, Retrospective Studies, Schizophrenia, Incidence, Death, Sudden, Cardiac, Young Adult
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