O5.4. NATURAL CAUSE MORTALITY IN PERSONS WITH SCHIZOPHRENIA AND BIPOLAR DISORDER

Abstract Background It is now well established that persons with schizophrenia and with bipolar disorder have a reduced life expectancy but the reasons for this premature mortality are not known with certainty. The aim of the current investigation was to identify the determinants of natural-cause mortality in a cohort of individuals with schizophrenia or bipolar disorder. To our knowledge, our investigation is unique in studying patients who were assessed at baseline with an in-person clinical assessment and blood sample and then subsequently evaluated regarding their mortality status and cause of death. Methods Persons with schizophrenia (n=789) and bipolar disorder (n=498), mean age of 38 (s.d. 12.6) years, underwent an in-person clinical assessment. They also had a blood sample drawn which was tested by enzyme immunoassay tests for IgG class antibodies to Herpes Simplex Virus type 1 (HSV-1), Cytomegalovirus (CMV), Epstein Barr Virus Nuclear Antigen (EBV), Human Herpesvirus Type 6 and Toxoplasma gondii. Participants were followed for a median observation period of 7.87 years (range 1 day – 16.9 years); the total number of person-years of observation was 10,859.3 person-years. Mortality was subsequently determined utilizing data from the US National Death Index. Results A total of 6.8% (87/1287) of persons died of natural causes. There were 70 deaths in the schizophrenia and 17 in the bipolar disorder participants. The mean age at death of those who died from natural causes was 56.7 years (range 19.4 – 79.1 years). The standardized mortality ratio (SMR), the age-adjusted ratio of the number of observed deaths in this study sample to that expected in the general population, was 2.57 (95% CI 1.24 – 4.75). Natural cause mortality was predicted in a multivariate model by baseline cigarette smoking (RR=6.29, 95% CI 1.41, 3.72, p=0.00076); divorced or widowed status (RR=1.90, CI 1.21, 2.99); reduced cognitive score (RR=0.73, CI 0.61, 0.87); receipt of antidepressant medication (RR=1.74, CI 1.12, 2.71); elevated levels of antibodies to Epstein Barr Virus (EBV) (RR=1.29, CI 1.01, 1.66); and a genitourinary (RR 1.82, CI 1.16, 2.86), respiratory (RR 1.82, CI 1.16, 2.86), or cardiac (RR 2.09, CI 1.33, 3.29) condition. Interaction models showed evidence of additive effects of smoking and both cardiac and respiratory condition. Compared to non-smokers without a cardiac condition, non-smokers with a cardiac condition had a more than threefold elevation of mortality risk (RR=3.76, 95% CI 1.47 – 9.63, p=0.0057) as did smokers without a cardiac condition (RR=3.63, 95% CI 1.49 – 8.85, p=0.0046), while the presence of both smoking and a cardiac condition increased mortality risk by more than six-fold (RR=6.75, 95% CI 2.84 – 16.0, p<0.0001). Compared to non-smokers without a respiratory condition, mortality risk more than doubled for non-smokers with a respiratory condition (RR=2.30, 95% CI 0.97 – 5.46, p=0.058), as well as for smokers without a respiratory condition (RR=2.37, 95% CI 1.31 – 4.28, p=0.0044), while the mortality risk more than quadrupled for smokers with a respiratory condition (RR=4.72, 95% CI 2.45 – 9.09, p<0.0001). There was not a significant interaction between smoking and elevated EBV antibody levels. There was a synergistic effect of antidepressant use and cardiac disease on mortality risk: participants with both risk factors had a more than threefold elevation of mortality risk compared to persons with neither risk factor (RR=3.10, 95% CI 1.71 – 5.63, p=0.0002). Discussion Multiple factors contribute to the excess mortality of persons with schizophrenia and bipolar disorder, but cigarette smoking is a major preventative cause. The delivery of smoking cessation treatments should be a high priority.


O5.3. A COMPREHENSIVE NATIONWIDE STUDY OF COMORBIDITY WITHIN TREATED MENTAL DISORDERS -A DANISH REGISTER-BASED STUDY
Oleguer Plana Ripoll* ,1 , Carsten Pedersen 1 , Esben Agerbo 1 , Thomas Munk Laursen 2 , Preben Bo Mortensen 1 , John McGrath 3 1 Aarhus University, National Center for Register-based Research; 2 Aarhus University; 3 University of Queensland, Queensland Brain Institute Background: Comorbidity has been the focus of a substantial body of research and it is acknowledged that different mental disorders tend to co-occur more frequently than expected. Many studies of mental disorder comorbidity have been published in recent decades, but these studies tend to be restricted to subsets of disorders, and are difficult to combine based on different methodologies. There is a need to examine comorbidity within mental disorders in a manner that covers a comprehensive range of mental disorders. The aim of this study was to use high-quality registers to (a) provide bidirectional pairwise estimates between the major groups of mental disorders, (b) investigate if associations changed depending on time since first diagnosis, (c) explore sex-specific patterns of comorbidity, and (d) estimate absolute risks rather than only incidence rate ratios of developing certain disorders after being diagnosed with one specific disorder. This abstract focus on results based on schizophrenia.

Methods:
We designed a population-based cohort study including all Danish residents between 2000 and 2016 (N = 5,940,778). Information on incident cases of mental diseases was obtained from the Danish Psychiatric Research Register, and we classified different disorders into 10 main groups: organic mental disorders (ICD10 F00-F09), substance abuse disorders (F10-F19), schizophrenia spectrum disorders (F20-F29), mood disorders (F30-F39), neurotic disorders (F40-F48), eating disorders (F50), personality disorders (F60), mental retardation (F70-F79), pervasive developmental disorders (F84) and behavioural and emotional disorders (F90-F98). We examined associations between all pairs of mental disorders. Hazard ratios (HR) were estimated using Cox Proportional Hazards models with age as time scale, and adjusting for sex, calendar time and other psychiatric comorbidity. Finally, we estimated the absolute risk of being diagnosed with other mental disorders after being diagnosed with a specific disorder. Results: All mental disorders were associated between them, with HR ranging from 1.1 to 19.5. There were 21,909 men and 20,106 women who were diagnosed with schizophrenia spectrum disorder (SSD) for the first time between 2000 and 2016. After onset of SSD, the rate of being diagnosed with substance abuse disorders was more than 4 times higher, compared to those without SSD (HR=4.4 [95%CI: 4.3-4.5]); the difference was larger within the first 6 months after being diagnosed with SSD (HR=31.8 [95%CI: 30.5-33.1]), although the rates remained higher even 15 years after the diagnosis (HR=3.2 [95%CI: 3.0-3.4]). Within the first 10 years after diagnosis of SSD, 23.8% [95%CI: 23.1-24.5] of men and 10.6% [95%CI: 10.2-11.1] of women were diagnosed for the first time with substance abuse disorders. Regarding mood disorders, the incidence rate was almost 3 times higher on individuals previously diagnosed with SSD than undiagnosed (HR=2.7 [95%CI: 2.6-2.7]). Analogous time-trends were observed, with larger differences within the first 6 months after diagnosis (HR=18.  : 20.2-21.5] of women with a diagnosis of SSD were diagnosed with mood disorders within 10 years. Discussion: In this population-based comprehensive study, we observed that comorbidity is pervasive and usually bidirectional. We observed that after being diagnosed with a specific disorder, the risk of being diagnosed with an additional disorder is particularly higher in the first 6 months, but even after 15 years the risk is higher compared to undiagnosed individuals.

O5.4. NATURAL CAUSE MORTALITY IN PERSONS WITH SCHIZOPHRENIA AND BIPOLAR DISORDER
Faith Dickerson* ,1 1 Sheppard Pratt Background: It is now well established that persons with schizophrenia and with bipolar disorder have a reduced life expectancy but the reasons for this premature mortality are not known with certainty. The aim of the current investigation was to identify the determinants of natural-cause mortality in a cohort of individuals with schizophrenia or bipolar disorder. To our knowledge, our investigation is unique in studying patients who were assessed at baseline with an in-person clinical assessment and blood sample and then subsequently evaluated regarding their mortality status and cause of death. Methods: Persons with schizophrenia (n=789) and bipolar disorder (n=498), mean age of 38 (s.d. 12.6) years, underwent an in-person clinical assessment. They also had a blood sample drawn which was tested by enzyme immunoassay tests for IgG class antibodies to Herpes Simplex Virus type 1 (HSV-1), Cytomegalovirus (CMV), Epstein Barr Virus Nuclear Antigen (EBV), Human Herpesvirus Type 6 and Toxoplasma gondii. Participants were followed for a median observation period of 7.87 years (range 1 day -16.9 years); the total number of person-years of observation was 10,859.3 person-years. Mortality was subsequently determined utilizing data from the US National Death Index.
Results: A total of 6.8% (87/1287) of persons died of natural causes. There were 70 deaths in the schizophrenia and 17 in the bipolar disorder participants. The mean age at death of those who died from natural causes was 56.7 years (range 19.4 -79.1 years). The standardized mortality ratio (SMR), the age-adjusted ratio of the number of observed deaths in this study sample to that expected in the general population, was 2.57 (95% CI 1.24 -4.75). Natural cause mortality was predicted in a multivariate model by baseline cigarette smoking (RR=6.29, 95% CI 1.41, 3.72, p=0.00076); divorced or widowed status (RR=1.90, CI 1.21, 2.99); reduced cognitive score (RR=0.73, CI 0.61, 0.87); receipt of antidepressant medication (RR=1.74, CI 1.12, 2.71); elevated levels of antibodies to Epstein Barr Virus (EBV) (RR=1.29, CI 1.01, 1.66); and a genitourinary (RR 1.82, CI 1.16, 2.86), respiratory (RR 1.82, CI 1.16, 2.86), or cardiac (RR 2.09, CI 1.33, 3.29) condition. Interaction models showed evidence of additive effects of smoking and both cardiac and respiratory condition. Compared to non-smokers without a cardiac condition, non-smokers with a cardiac condition had a more than threefold elevation of mortality risk (RR=3.76, 95% CI 1.47 -9.63, p=0.0057) as did smokers without a cardiac condition (RR=3.63, 95% CI 1.49 -8.85, p=0.0046), while the presence of both smoking and a cardiac condition increased mortality risk by more than six-fold (RR=6.75, 95% CI 2.84 -16.0, p<0.0001). Compared to non-smokers without a respiratory condition, mortality risk more than doubled for non-smokers with a respiratory condition (RR=2.30, 95% CI 0.97 -5.46, p=0.058), as well as for smokers without a respiratory condition (RR=2.37, 95% CI 1.31 -4.28, p=0.0044), while the mortality risk more than quadrupled for smokers with a respiratory condition (RR=4.72, 95% CI 2.45 -9.09, p<0.0001). There was not a significant interaction between smoking and elevated EBV antibody levels. There was a synergistic effect of antidepressant use and cardiac disease on mortality risk: participants with both risk factors had a more than threefold elevation of mortality risk compared to persons with neither risk factor (RR=3.10, 95% CI 1.71 -5.63, p=0.0002). Discussion: Multiple factors contribute to the excess mortality of persons with schizophrenia and bipolar disorder, but cigarette smoking is a major preventative cause. The delivery of smoking cessation treatments should be a high priority.
O5.5. SLEEP IN MAJOR PSYCHIATRIC DISORDERS: RESULTS FROM NATIONWIDE SUPER FINLAND STUDY increased sleep onset latency, increased wake-up time after sleep onset and abnormalities in sleep architecture. The study aimed to characterize the sleep difficulties in a large sample of persons with psychotic disorders and to examine association with age and gender. Methods: Altogether, 5046 persons with a major psychiatric disorder (schizophrenia: 2972, schizoaffective disorder: 640, bipolar disorder: 1097 and psychotic depression: 330) and aged 18-80 participated in a nationwide Super project. The Finnish SUPER (Finnish acronym for "Finnish study on genetic mechanisms of psychotic disorders") study is a part of the international Stanley Global Neuropsychiatric Genomics Initiative. The results were compared with a representative general population sample of 8018 adults (Health 2000). Sleep was assessed in a self-report questionnaire. In the present study we used total sleep time, tiredness (defined as feeling more tired than other people of the same age during day time at least weakly, yes/ no), difficulties in getting sleep without sleep medication often or almost daily (yes/no) and early morning or night awakenings occurring either often or nearly every night (yes/no). Results: Long sleep (> 10h) was most common in persons with schizophrenia or schizoaffective disorder reported by approximately 30% when age was 18-40. The corresponding proportion was approximately 15% in persons with bipolar disorder or psychotic depression and less than 1% in the general population. Tiredness, difficulties in getting sleep and early morning or night awakenings were reported most by persons with bipolar disorder and psychotic depression, but also persons with schizophrenia reported those more than the general population in people with under 60 years of age. Schizoaffective disorder was between schizophrenia and affective psychoses in the sleep variables. In persons over 60, the difference between the groups was smaller than in persons under 60 years of age, because sleeping long and tiredness decreased in all patient groups, and difficulties getting sleep and awakenings increased in the general population sample more than in psychosis patients. Discussion: Sleep disorders seem to be prominent in persons with major psychiatric disorders. Tiredness was common in all diagnosis groups. Long sleep was most common in schizophrenia and difficulties in getting sleep and early morning or night awakenings in affective psychoses. More research is needed on possibilities to prevent and treat sleep disorders in major psychiatric disorders.