Substance Abuse and Excessive Mortality Among Forensic Psychiatric Patients : A Finnish Nationwide Cohort Study

Background: Forensic psychiatric patients are known to have reduced life expectancy. The aim of this study was to explore to what extent substance abuse disorders account for this increased mortality. Methods: Data up to December 31, 2016 for mortality (causes of death register) and substance abuse (forensic psychiatric examinations) were collected for all of the 950 patients committed to involuntary forensic psychiatric hospital care in Finland during 1980-2009 and discharged no later than December 31, 2016. Patients were then classified as suffering or not suffering from substance abuse disorders and their causes of death were examined. The standardized mortality ratio was then calculated for these groups on the basis of sex-, age-, and calendar-period-specific mortality rates for the general Finnish population. Results: During the follow-up time (mean 13.4 years), 354 (320 men, 34 women) patients died, resulting in a standardized mortality ratio of 3.5. The standardized mortality ratio for the patients with a history of substance abuse disorders was 4.1 compared to 2.8 for those with no such history. Among men, but not women, the age-adjusted proportion of death was significantly higher for those with a history of substance abuse disorders. In addition, in patients with a history of substance abuse disorders, the male age-adjusted competing risk of mortality was higher for unnatural causes, but not natural causes. Furthermore, a prominent proportion (16%) of all deaths and a majority of the accidental deaths (64%) occurred under the influence of some substance. Conclusions: Substance abuse is a major factor causing excessive mortality among forensic psychiatric patients. The management of substance abuse problems should be one cornerstone of the treatment of patients with both severe mental disorders and substance abuse disorders during their time in hospital and this should be extended to outpatient care.Peer reviewe

Sex-specific transcriptional and proteomic signatures in schizophrenia

It has remained unclear why schizophrenia typically manifests after adolescence and which neurobiological mechanisms are underlying the cascade leading to the actual onset of the illness. Here we show that the use of induced pluripotent stem cell-derived neurons of monozygotic twins from pairs discordant for schizophrenia enhances disease-specific signal by minimizing genetic heterogeneity. In proteomic and pathway analyses, clinical illness is associated especially with altered glycosaminoglycan, GABAergic synapse, sialylation, and purine metabolism pathways. Although only 12% of all 19,462 genes are expressed differentially between healthy males and females, up to 61% of the illness-related genes are sex specific. These results on sex-specific genes are replicated in another dataset. This implies that the pathophysiology differs between males and females, and may explain why symptoms appear after adolescence when the expression of many sex-specific genes change, and suggests the need for sex-specific treatments.Peer reviewe