Excess early mortality in schizophrenia Laursen, Thomas Munk; Nordentoft, Merete; Mortensen, Preben Bo
Annual review of clinical psychology,
01/2014, Letnik:
10
Journal Article
Recenzirano
Odprti dostop
Schizophrenia is often referred to as one of the most severe mental disorders, primarily because of the very high mortality rates of those with the disorder. This article reviews the literature on ...excess early mortality in persons with schizophrenia and suggests reasons for the high mortality as well as possible ways to reduce it. Persons with schizophrenia have an exceptionally short life expectancy. High mortality is found in all age groups, resulting in a life expectancy of approximately 20 years below that of the general population. Evidence suggests that persons with schizophrenia may not have seen the same improvement in life expectancy as the general population during the past decades. Thus, the mortality gap not only persists but may actually have increased. The most urgent research agenda concerns primary candidates for modifiable risk factors contributing to this excess mortality, i.e., side effects of treatment and lifestyle factors, as well as sufficient prevention and treatment of physical comorbidity.
The exome sequences of approximately 8,000 children with autism spectrum disorder (ASD) and/or attention deficit hyperactivity disorder (ADHD) and 5,000 controls were analyzed, finding that ...individuals with ASD and individuals with ADHD had a similar burden of rare protein-truncating variants in evolutionarily constrained genes, both significantly higher than controls. This motivated a combined analysis across ASD and ADHD, identifying microtubule-associated protein 1A (MAP1A) as a new exome-wide significant gene conferring risk for childhood psychiatric disorders.
Summary Background Attention deficit hyperactivity disorder (ADHD) is a common mental disorder associated with factors that are likely to increase mortality, such as oppositional defiant disorder or ...conduct disorder, criminality, accidents, and substance misuse. However, whether ADHD itself is associated with increased mortality remains unknown. We aimed to assess ADHD-related mortality in a large cohort of Danish individuals. Methods By use of the Danish national registers, we followed up 1·92 million individuals, including 32 061 with ADHD, from their first birthday through to 2013. We estimated mortality rate ratios (MRRs), adjusted for calendar year, age, sex, family history of psychiatric disorders, maternal and paternal age, and parental educational and employment status, by Poisson regression, to compare individuals with and without ADHD. Findings During follow-up (24·9 million person-years), 5580 cohort members died. The mortality rate per 10 000 person-years was 5·85 among individuals with ADHD compared with 2·21 in those without (corresponding to a fully adjusted MRR of 2·07, 95% CI 1·70–2·50; p<0·0001). Accidents were the most common cause of death. Compared with individuals without ADHD, the fully adjusted MRR for individuals diagnosed with ADHD at ages younger than 6 years was 1·86 (95% CI 0·93–3·27), and it was 1·58 (1·21–2·03) for those aged 6–17 years, and 4·25 (3·05–5·78) for those aged 18 years or older. After exclusion of individuals with oppositional defiant disorder, conduct disorder, and substance use disorder, ADHD remained associated with increased mortality (fully adjusted MRR 1·50, 1·11–1·98), and was higher in girls and women (2·85, 1·56–4·71) than in boys and men (1·27, 0·89–1·76). Interpretation ADHD was associated with significantly increased mortality rates. People diagnosed with ADHD in adulthood had a higher MRR than did those diagnosed in childhood and adolescence. Comorbid oppositional defiant disorder, conduct disorder, and substance use disorder increased the MRR even further. However, when adjusted for these comorbidities, ADHD remained associated with excess mortality, with higher MRRs in girls and women with ADHD than in boys and men with ADHD. The excess mortality in ADHD was mainly driven by deaths from unnatural causes, especially accidents. Funding This study was supported by a grant from the Lundbeck Foundation.
Understanding the epidemiologic profile of the life course of mental disorders is fundamental for research and planning for health care. Although previous studies have used population surveys, ...informative and complementary estimates can be derived from population-based registers.
To derive comprehensive and precise estimates of the incidence rate of and lifetime risk for any mental disorder and a range of specific mental disorders.
We conducted a follow-up study of all Danish residents (5.6 million persons), to whom all treatment is provided by the government health care system without charge to the patient, from January 1, 2000, through December 31, 2012 (total follow-up, 59.5 million person-years). During the study period, 320,543 persons received first lifetime treatment in a psychiatric setting for any mental disorder; 489,006 persons were censored owing to death; and 69,987 persons were censored owing to emigration. Specific categories of mental disorders investigated included organic mental disorders, substance abuse disorders, schizophrenia, mood disorders, anxiety, eating disorders, personality disorders, mental retardation, pervasive developmental disorders, and behavioral and emotional disorders.
Age and sex.
Sex- and age-specific incidence rates and cumulative incidences and sex-specific lifetime risks.
During the course of life, 37.66% of females (95% CI, 37.52%-37.80%) and 32.05% of males (31.91%-32.19%) received their first treatment in a psychiatric setting for any mental disorder. The occurrence of mental disorders varied markedly between diagnostic categories and by sex and age. The sex- and age-specific incidence rates for many mental disorders had a single peak incidence rate during the second and third decades of life. Some disorders had a second peak in the sex- and age-specific incidence rate later in life.
This nationwide study provides a first comprehensive assessment of the lifetime risks for treated mental disorders. Approximately one-third of the Danish population received treatment for mental disorders. The distinct signatures of the different mental disorders with respect to sex and age have important implications for service planning and etiologic research.
Recent studies suggest that familial autoimmunity plays a part in the pathogenesis of ASDs. In this study we investigated the association between family history of autoimmune diseases (ADs) and ...ASDs/infantile autism. We perform confirmatory analyses based on results from previous studies, as well as various explorative analyses.
The study cohort consisted of all of the children born in Denmark from 1993 through 2004 (689 196 children). Outcome data consisted of both inpatient and outpatient diagnoses reported to the Danish National Psychiatric Registry. Information on ADs in parents and siblings of the cohort members was obtained from the Danish National Hospital Register. The incidence rate ratio of autism was estimated by using log-linear Poisson regression.
A total of 3325 children were diagnosed with ASDs, of which 1089 had an infantile autism diagnosis. Increased risk of ASDs was observed for children with a maternal history of rheumatoid arthritis and celiac disease. Also, increased risk of infantile autism was observed for children with a family history of type 1 diabetes.
Associations regarding family history of type 1 diabetes and infantile autism and maternal history of rheumatoid arthritis and ASDs were confirmed from previous studies. A significant association between maternal history of celiac disease and ASDs was observed for the first time. The observed associations between familial autoimmunity and ASDs/infantile autism are probably attributable to a combination of a common genetic background and a possible prenatal antibody exposure or alteration in fetal environment during pregnancy.
Suicide risk was addressed in relation to the joint effect of factors regarding family structure, socioeconomics, demographics, mental illness, and family history of suicide and mental illness, as ...well as gender differences in risk factors.
Data were drawn from four national Danish longitudinal registers. Subjects were all 21,169 persons who committed suicide in 1981-1997 and 423,128 live comparison subjects matched for age, gender, and calendar time of suicide by using a nested case-control design. The effect of risk factors was estimated through conditional logistic regression. The interaction of gender with the risk factors was examined by using the log likelihood ratio test. The population attributable risk was calculated.
Of the risk factors examined in the study, a history of hospitalization for psychiatric disorder was associated with the highest odds ratio and the highest attributable risk for suicide. Cohabiting or single marital status, unemployment, low income, retirement, disability, sickness-related absence from work, and a family history of suicide and/or psychiatric disorders were also significant risk factors for suicide. Moreover, these factors had different effects in male and female subjects. A psychiatric disorder was more likely to increase suicide risk in female than in male subjects. Being single was associated with higher suicide risk in male subjects, and having a young child with lower suicide risk in female subjects. Unemployment and low income had stronger effects on suicide in male subjects. Living in an urban area was associated with higher suicide risk in female subjects and a lower risk in male subjects. A family history of suicide raised suicide risk slightly more in female than in male subjects.
Suicide risk is strongly associated with mental illness, unemployment, low income, marital status, and family history of suicide. The effect of most risk factors differs significantly by gender.
Studies investigating the relationship between head injury and subsequent psychiatric disorders often suffer from methodological weaknesses and show conflicting results. The authors investigated the ...incidence of severe psychiatric disorders following hospital contact for head injury.
The authors used linkable Danish nationwide population-based registers to investigate the incidence of schizophrenia spectrum disorders, unipolar depression, bipolar disorder, and organic mental disorders in 113,906 persons who had suffered head injuries. Data were analyzed by survival analysis and adjusted for gender, age, calendar year, presence of a psychiatric family history, epilepsy, infections, autoimmune diseases, and fractures not involving the skull or spine.
Head injury was associated with a higher risk of schizophrenia (incidence rate ratio IRR=1.65, 95% CI=1.55-1.75), depression (IRR=1.59 95% CI=1.53-1.65), bipolar disorder (IRR=1.28, 95% CI=1.10-1.48), and organic mental disorders (IRR=4.39, 95% CI=3.86-4.99). This effect was larger than that of fractures not involving the skull or spine for schizophrenia, depression, and organic mental disorders, which suggests that the results were not merely due to accident proneness. Head injury between ages 11 and 15 years was the strongest predictor for subsequent development of schizophrenia, depression, and bipolar disorder. The added risk of mental illness following head injury did not differ between individuals with and without a psychiatric family history.
This is the largest study to date investigating head injury and subsequent mental illness. The authors demonstrated an increase in risk for all psychiatric outcomes after head injury. The effect did not seem to be solely due to accident proneness, and the added risk was not more pronounced in persons with a psychiatric family history.
Individuals with schizophrenia and their relatives tend to have either higher or lower than expected prevalences of autoimmune disorders, especially rheumatoid arthritis, celiac disease, autoimmune ...thyroid diseases, and type 1 diabetes. The purpose of the study was to estimate the association of schizophrenia with these disorders as well as a range of other autoimmune diseases in a single large epidemiologic study.
The Danish Psychiatric Register, the National Patient Register, and a register with socioeconomic information were linked to form a data file that included all 7,704 persons in Denmark diagnosed with schizophrenia from 1981 to 1998 and their parents along with a sample of matched comparison subjects and their parents. The data linkage required that the autoimmune disease occur before the diagnosis of schizophrenia.
A history of any autoimmune disease was associated with a 45% increase in risk for schizophrenia. Nine autoimmune disorders had higher prevalence rates among patients with schizophrenia than among comparison subjects (crude incidence rate ratios ranging from 1.9 to 12.5), and 12 autoimmune diseases had higher prevalence rates among parents of schizophrenia patients than among parents of comparison subjects (adjusted incidence rate ratios ranging from 1.3 to 3.8). Thyrotoxicosis, celiac disease, acquired hemolytic anemia, interstitial cystitis, and Sjögren's syndrome had higher prevalence rates among patients with schizophrenia than among comparison subjects and also among family members of schizophrenia patients than among family members of comparison subjects.
Schizophrenia is associated with a larger range of autoimmune diseases than heretofore suspected. Future research on comorbidity has the potential to advance understanding of pathogenesis of both psychiatric and autoimmune disorders.
Summary Background Studies have linked epilepsy with an increased suicide risk, but the association might be modified by psychiatric, demographic, and socioeconomic factors. Methods Suicide cases ...were identified in the Cause of Death Register in Denmark from 1981 to 1997. Up to 20 controls, matched by sex, birth year, and calendar date, were assigned to each suicide case. Findings We identified 21 169 cases of suicide and 423 128 controls. 492 (2·32%) individuals who committed suicide had epilepsy compared with 3140 (0·74%) controls, corresponding to a three times higher risk (rate ratio RR 3·17 95% CI 2·88–3·50; p<0·0001). The RR remained high after excluding those with a history of psychiatric disease and adjusting for socioeconomic factors (1·99, 1·71–2·32; p<0·0001). The highest risk of suicide was identified in patients with epilepsy and comorbid psychiatric disease, even after adjusting for socioeconomic factors (13·7, 11·8–16·0; p<0·0001). In individuals with epilepsy, the highest risk of suicide was found during the first half year after diagnosis was made (5·35, 3·43–8·33; p<0·0001), and was especially high in those with a history of comorbid psychiatric disease (29·2, 16·4–51·9; p<0·0001). Interpretation Individuals with epilepsy have a higher risk of suicide, even if coexisting psychiatric disease, demographic differences, and socioeconomic factors are taken into account. Our study identifies people with newly diagnosed epilepsy as a vulnerable group that require special attention.
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