Predictors of Mortality Following a Schizophrenia Spectrum Diagnosis: Evidence From the 20-Year Follow-up of the OPUS Randomized Controlled Trial.

BACKGROUND AND HYPOTHESIS: The life expectancy of patients diagnosed with schizophrenia is 10-12 years lower than in the general population and the mortality gap seems to be worsening. Many of these deaths might be avoidable. We aimed to determine mortality rates and causes of death after a first-episode psychosis, and to examine if clinical characteristics at baseline or during illness could predict mortality. STUDY DESIGN: The OPUS study was a randomized controlled trial of 578 patients first diagnosed with schizophrenia spectrum disorders. Patients were clinically assessed after 2, 5, 10, and 20 years. Information about time and cause of death was obtained from the Danish Cause of Death Register. Hazard ratios were used to assess predictors of death. STUDY RESULTS: In total, 82 (14.4%) participants died during 20 years of follow-up. The most common cause of death was suicide (27%). At baseline employment (HR 0.47 P = .049), psychotic disorder other than schizophrenia (HR 0.36, P = .017), and longer duration of untreated psychosis (HR 0.57 P = .042) predicted lower mortality while substance use predicted higher mortality (HR 2.56, P < .001). During follow-up, symptom remission without antipsychotic medication and recovery predicted lower mortality (HR 0.08 P = .013 and HR 0.21, P = .028) while substance use (HR 3.64 P < .001), and all chronic illnesses predicted increased risk. CONCLUSIONS: There is an increased risk of early mortality in schizophrenia compared to the background population, and there is an urgent need for new efforts to improve the disparities in health that lead to this increased mortality.

Annual incidence of cannabis-induced psychosis, other substance-induced psychoses and dually diagnosed schizophrenia and cannabis use disorder in Denmark from 1994 to 2016.

BACKGROUND: Worldwide, cannabis is the most used illegal substance, and the use of cannabis has increased over the years. An increase in the level of tetrahydrocannabinol (THC) in cannabis has also been seen. It is currently unclear whether this has led to an increase in the incidence of cannabis-induced psychosis. We aimed to investigate (1) the development of incidence of cannabis-induced psychosis over time compared with other substance-induced psychoses and (2) the development of incident cases of cannabis-induced psychosis over time compared with dual diagnosis defined as schizophrenia and a cannabis use disorder. METHOD: Data on psychiatric diagnoses were extracted from the Danish Psychiatric Central Research Register and summarized per year as both absolute incidence (number of cases) and incidence rates per 100 000 person years. RESULTS: The incidence rate of cannabis-induced psychosis increased steadily from 2.8 per 100 000 person years in 2006 to 6.1 per 100 000 person years in 2016. There was a corresponding increase in dual diagnosis with schizophrenia and cannabis use disorder, but a decrease in alcohol-induced psychosis. The data showed no trend in the other substance-induced psychosis investigated in this thesis. CONCLUSION: The increase in cannabis-induced psychosis follows both the increase in the level of THC in cannabis, and the increase in cannabis use. The change in diagnostic practice does not appear to explain the increase in incidence of cannabis-induced psychosis.

Infections as a Risk Factor for and Prognostic Factor After Substance-Induced Psychoses.

OBJECTIVE: Previous studies have suggested that infections increase the risk of schizophrenia. In this study, the authors aimed to investigate 1) whether infections increase the risk of substance-induced psychosis, and 2) whether infections increase the risk of converting from substance-induced psychosis to schizophrenia. METHODS: The study data were drawn from the combined nationwide Danish registers and included all people born in Denmark since 1981. The authors used Cox proportional hazards regression with infections as time-varying covariates, estimating hazard ratios and 95% confidence intervals. Infections were operationalized both as any infection and by the site of infection. RESULTS: The study included 2,256,779 individuals, for whom 3,618 cases of incident substance-induced psychosis were recorded. Any infection increased the risk of substance-induced psychosis (hazard ratio=1.30, 95% CI=1.22-1.39). For the first 2 years, the risk was doubled. Hepatitis was the infection most strongly associated with substance-induced psychosis (hazard ratio=3.42, 95% CI=2.47-4.74). Different types of infections were linked with different types of substance-induced psychosis. Most associations remained significant after controlling for potential confounders, such as substance use disorders. Only hepatitis predicted conversion to schizophrenia after substance-induced psychosis (hazard ratio=1.87, 95% CI=1.07- 3.26). CONCLUSIONS: The study results support the hypothesis of an immunological component to psychosis.

Rates and Predictors of Conversion to Schizophrenia or Bipolar Disorder Following Substance-Induced Psychosis.

OBJECTIVE: The authors investigated the rates of conversion to schizophrenia and bipolar disorder after a substance-induced psychosis, as well as risk factors for conversion. METHOD: All patient information was extracted from the Danish Civil Registration System and the Psychiatric Central Research Register. The study population included all persons who received a diagnosis of substance-induced psychosis between 1994 and 2014 (N=6,788); patients were followed until first occurrence of schizophrenia or bipolar disorder or until death, emigration, or August 2014. The Kaplan-Meier method was used to obtain cumulative probabilities for the conversion from a substance-induced psychosis to schizophrenia or bipolar disorder. Cox proportional hazards regression models were used to calculate hazard ratios for all covariates. RESULTS: Overall, 32.2% (95% CI=29.7-34.9) of patients with a substance-induced psychosis converted to either bipolar or schizophrenia-spectrum disorders. The highest conversion rate was found for cannabis-induced psychosis, with 47.4% (95% CI=42.7-52.3) converting to either schizophrenia or bipolar disorder. Young age was associated with a higher risk of converting to schizophrenia. Self-harm after a substance-induced psychosis was significantly linked to a higher risk of converting to both schizophrenia and bipolar disorder. Half the cases of conversion to schizophrenia occurred within 3.1 years after a substance-induced psychosis, and half the cases of conversion to bipolar disorder occurred within 4.4 years. CONCLUSIONS: Substance-induced psychosis is strongly associated with the development of severe mental illness, and a long follow-up period is needed to identify the majority of cases.