Genetic and other aspects of sudden cardiac death in schizophrenia.

Abstract

Background: The incidence of sudden cardiac death (SCD) in patients with schizophrenia is 3 to 4 times higher than in the general population. While the majority of SCD in patients with schizophrenia are due to ischaemic or structural heart disease, many deaths remain unexplained. In recent reviews of premature deaths in patients with schizophrenia, these deaths were postulated to be secondary to malignant cardiac arrhythmias. Method(s): A retrospective study conducted jointly by the Victorian Institute of Forensic Medicine (VIFM) and the Department of Genomic Medicine, Royal Melbourne Hospital (RMH), 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 needed a source of DNA to be available. Result(s): 37 individuals met the study inclusion criteria, age range 18-65 years; 25 male and 12 female. 13 next of kin (NOK) consented to involvement in the study. 12 individuals underwent whole exome sequencing (WES) via a research platform. Two clinically actionable results were detected - a likely pathogenic DES variant and a DPYD pharmacogenomic variant. Both families chose to receive results. Conclusion(s): Genes that are currently associated with inherited arrhythmia syndromes were not found in the study group. The pathogenic DES would likely have been found had the family accepted referral that was offered to a Cardiac Genetics service, at the time of death.Copyright © 2024