Excess Early Mortality in Schizophrenia Laursen, Thomas Munk; Nordentoft, Merete; Mortensen, Preben Bo
Annual review of clinical psychology,
01/2014, Letnik:
10, Številka:
1
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.
Several studies and meta-analyses have shown that mortality in people with schizophrenia is higher than that in the general population but have used relative measures, such as standardised mortality ...ratios. We did a systematic review and meta-analysis to estimate years of potential life lost and life expectancy in schizophrenia, which are more direct, absolute measures of increased mortality.
We searched MEDLINE, PsycINFO, Embase, Cinahl, and Web of Science for published studies on years of potential life lost and life expectancy in schizophrenia. Data from individual studies were combined in meta-analyses as weighted averages. We did subgroup analyses for sex, geographical region, timing of publication, and risk of bias (estimated with the Newcastle-Ottawa Scale).
We identified 11 studies in 13 publications covering all inhabited continents except South America (Africa n=1, Asia n=1, Australia n=1, Europe n=7, and North America n=3) that involved up to 247 603 patients. Schizophrenia was associated with a weighted average of 14·5 years of potential life lost (95% CI 11·2-17·8), and was higher for men than women (15·9, 13·8-18·0 vs 13·6, 11·4-15·8). Loss was least in the Asian study and greatest in Africa. The overall weighted average life expectancy was 64·7 years (95% CI 61·1-71·3), and was lower for men than women (59·9 years, 95% CI 55·5-64·3 vs 67·6 years, 63·1-72·1). Life expectancy was lowest in Asia and Africa. Timing of publication and risk of bias had little effect on results.
The effects of schizophrenia on years potential life lost and life expectancy seem to be substantial and not to have lessened over time. Development and implementation of interventions and initiatives to reduce this mortality gap are urgently needed.
None.
Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This ...study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology.
Combining two nationwide registers, the Danish Twin Register and the Danish Psychiatric Research Register, we identified a sample of twins born between 1951 and 2000 (N = 31,524 twin pairs). Twins were followed until June 1, 2011. Liability threshold models adjusting for censoring with inverse probability weighting were used to estimate probandwise concordance rates and heritability of the diagnoses of SZ and SZ spectrum disorders.
The probandwise concordance rate of SZ is 33% in monozygotic twins and 7% in dizygotic twins. We estimated the heritability of SZ to be 79%. When expanding illness outcome to include SZ spectrum disorders, the heritability estimate was almost similar (73%).
The key strength of this study is the application of a novel statistical method accounting for censoring in the follow-up period to a nationwide twin sample. The estimated 79% heritability of SZ is congruent with previous reports and indicates a substantial genetic risk. The high genetic risk also applies to a broader phenotype of SZ spectrum disorders. The low concordance rate of 33% in monozygotic twins demonstrates that illness vulnerability is not solely indicated by genetic factors.
Infections and inflammatory processes have been associated with the development of schizophrenia and affective disorders; however, no study has yet systematically reviewed all available studies on ...cerebrospinal fluid (CSF) immune alterations. We aimed to systematically review the CSF immunological findings in schizophrenia spectrum and affective disorders. We identified all studies investigating CSF inflammatory markers in persons with schizophrenia or affective disorders published prior to March 23, 2017 searching PubMed, CENTRAL, EMBASE, Psychinfo, and LILACS. Literature search, data extraction and bias assessment were performed by two independent reviewers. Meta-analyses with standardized mean difference (SMD) including 95% confidence intervals (CI) were performed on case-healthy control studies. We identified 112 CSF studies published between 1942-2016, and 32 case-healthy control studies could be included in meta-analyses. Studies varied regarding gender distribution, age, disease duration, treatment, investigated biomarkers, and whether recruitment happened consecutively or based on clinical indication. The CSF/serum albumin ratio was increased in schizophrenia (1 study 54 patients; SMD = 0.71; 95% CI 0.33-1.09) and affective disorders (4 studies 298 patients; SMD = 0.41; 95% CI 0.23-0.60, I
= 0%), compared to healthy controls. Total CSF protein was elevated in both schizophrenia (3 studies 97 patients; SMD = 0.41; 95% CI 0.15-0.67, I
= 0%) and affective disorders (2 studies 53 patients; SMD = 0.80; 95% CI 0.39-1.21, I
= 0%). The IgG ratio was increased in schizophrenia (1 study 54 patients; SMD = 0.68; 95% CI 0.30-1.06), whereas the IgG Albumin ratio was decreased (1 study 32 patients; SMD = -0.62; 95% CI -1.13 to -0.12). Interleukin-6 (IL-6) levels (7 studies 230 patients; SMD = 0.55; 95% CI 0.35-0.76; I
= 1%) and IL-8 levels (3 studies 95 patients; SMD = 0.46; 95% CI 0.17-0.75, I
= 0%) were increased in schizophrenia but not significantly increased in affective disorders. Most of the remaining inflammatory markers were not significantly different compared to healthy controls in the meta-analyses. However, in the studies which did not include healthy controls, CSF abnormalities were more common, and two studies found CSF dependent re-diagnosis in 3.2-6%. Current findings suggest that schizophrenia and affective disorders may have CSF abnormalities including signs of blood-brain barrier impairment and inflammation. However, the available evidence does not allow any firm conclusion since all studies showed at least some degree of bias and vastly lacked inclusion of confounding factors. Moreover, only few studies investigated the same parameters with healthy controls and high-quality longitudinal CSF studies are lacking, including impact of psychotropic medications, lifestyle factors and potential benefits of anti-inflammatory treatment in subgroups with CSF inflammation.
Cancer and schizophrenia Nordentoft, Merete; Plana-Ripoll, Oleguer; Laursen, Thomas Munk
Current opinion in psychiatry,
2021-May-01, 2021-05-00, 20210501, Letnik:
34, Številka:
3
Journal Article
Recenzirano
On the basis of articles published in 2018, 2019 and 2020, the first aim of this review is to present estimates of incidence rates and excess mortality of overall cancer and organ-specific cancers ...for patients with schizophrenia compared with the general population.The second aim is to explore if underdiagnosis and undertreatment can explain - at least partly - the increased mortality of cancer in patients with schizophrenia compared with the general population.
Patients diagnosed with schizophrenia have an approximately 50% increased risk of death by cancer compared to age and sex-matched people in the general population. Studies have confirmed an increased mortality from breast, lung and colon cancer in patients with schizophrenia.Analyses of incidence of cancer revealed contradicting results, with some studies showing no increase in incidence and others a modestly increased incidence in overall cancer. Studies of incidence of specific types of cancers showed modestly increased risk of pancreas, oesophagus, breast cancer and contradicting results regarding lung cancer.In studies identified that compared to the general population, patients with schizophrenia were at an increased risk of not being diagnosed or treated for cancer before death of cancer. In addition, patients with schizophrenia had lower chances of getting optimal treatment for colon cancer after diagnosis.
This review indicates that patients with schizophrenia are at increased risk of dying of cancer and of several specific types of cancer. This increased mortality can be reduced if the price of tobacco is increased, if smoking cessation programmes are offered systematically, screening programs better implemented in this highly vulnerable group, and if procedures to facilitate access to early diagnosis and effective treatment are implemented.
ABSTRACTSuicide is a serious public health problem, with more than 800,000 deaths taking place worldwide each year. Mental disorders are associated with increased risk of suicide. In schizophrenia ...and other psychotic disorders, the lifetime risk of suicide death is estimated to be 5.6%. The risk is particularly high during the first year of the initial contact with mental health services, being almost twice as high as in the later course of the illness. The most consistently reported risk factor for suicide among people with psychotic disorders is a history of attempted suicide and depression. Suicide risk in psychosis in Denmark decreased over time, most likely because of improved quality of inpatient and outpatient services. There is a high proportion of young people with first-episode psychosis who attempted suicide before their first contact with mental health services. This finding suggests that the mortality rates associated with psychotic disorders may be underreported because of suicide deaths taking place before first treatment contact. However, currently, no data exist to confirm or refute this hypothesis. Attempted suicide can be an early warning sign of later psychotic disorder. Data from different studies indicate that the risk of suicide attempt during the first year of treatment is as high as 10%. The most important risk factors for attempted suicide after the first contact are young age, female sex, suicidal plans, and a history of suicide attempt. Early intervention services are helpful in first-episode psychosis, and staff members should, in collaboration with the patients, monitor the risk of suicide and develop and revise crisis plans.
People with mental disorders evince excess mortality due to natural and unnatural deaths. The relative life expectancy of people with mental disorders is a proxy measure of effectiveness of social ...policy and health service provision.
To evaluate trends in health outcomes of people with serious mental disorders.
We examined nationwide 5-year consecutive cohorts of people admitted to hospital for mental disorders in Denmark, Finland and Sweden in 1987-2006. In each country the risk population was identified from hospital discharge registers and mortality data were retrieved from cause-of-death registers. The main outcome measure was life expectancy at age 15 years.
People admitted to hospital for a mental disorder had a two- to threefold higher mortality than the general population in all three countries studied. This gap in life expectancy was more pronounced for men than for women. The gap decreased between 1987 and 2006 in these countries, especially for women. The notable exception was Swedish men with mental disorders. In spite of the positive general trend, men with mental disorders still live 20 years less, and women 15 years less, than the general population.
During the era of deinstitutionalisation the life expectancy gap for people with mental disorders has somewhat diminished in the three Nordic countries. Our results support further development of the Nordic welfare state model, i.e. tax-funded community-based public services and social protection. Health promotion actions, improved access to healthcare and prevention of suicides and violence are needed to further reduce the life expectancy gap.
Patients who recover from an acute episode of psychosis are frequently prescribed prophylactic antipsychotics for many years, especially if they are diagnosed as having schizophrenia. However, there ...is a dearth of evidence concerning the long-term effectiveness of this practice, and growing concern over the cumulative effects of antipsychotics on physical health and brain structure. Although controversy remains concerning some of the data, the wise psychiatrist should regularly review the benefit to each patient of continuing prophylactic antipsychotics against the risk of side-effects and loss of effectiveness through the development of supersensitivity of the dopamine D2 receptor. Psychiatrists should work with their patients to slowly reduce the antipsychotic to the lowest dose that prevents the return of distressing symptoms. Up to 40% of those whose psychosis remits after a first episode should be able to achieve a good outcome in the long term either with no antipsychotic medication or with a very low dose.
IMPORTANCE: Neurological disorders have been linked to suicide, but the risk across a broad spectrum of neurological disorders remains to be assessed. OBJECTIVES: To examine whether people with ...neurological disorders die by suicide more often than other people and to assess for temporal associations. DESIGN, SETTING, AND PARTICIPANTS: Nationwide, retrospective cohort study on all persons 15 years or older living in Denmark, from 1980 through 2016 (N = 7 300 395). EXPOSURES: Medical contact for head injury, stroke, epilepsy, polyneuropathy, diseases of myoneural junction, Parkinson disease, multiple sclerosis, central nervous system infections, meningitis, encephalitis, amyotrophic lateral sclerosis, Huntington disease, dementia, intellectual disability, and other brain diseases from 1977 through 2016 (n = 1 248 252). MAIN OUTCOMES AND MEASURES: Death by suicide during 1980-2016. Adjusted incidence rate ratio (IRRs) were estimated using Poisson regressions, adjusted for sociodemographics, comorbidity, psychiatric diagnoses, and self-harm. RESULTS: Of the more than 7.3 million individuals observed over 161 935 233 person-years (49.1% males), 35 483 died by suicide (median duration of follow-up, 23.6 years; interquartile range, 10.0-37.0 years; mean age, 51.9 years; SD, 17.9 years). Of those, 77.4% were males, and 14.7% (n = 5141) were diagnosed with a neurological disorder, equivalent to a suicide rate of 44.0 per 100 000 person-years compared with 20.1 per 100 000 person-years among individuals not diagnosed with a neurological disorder. People diagnosed with a neurological disorder had an adjusted IRR of 1.8 (95% CI, 1.7-1.8) compared with those not diagnosed. The excess adjusted IRRs were 4.9 (95% CI, 3.5-6.9) for amyotrophic lateral sclerosis, 4.9 (95% CI, 3.1-7.7) for Huntington disease, 2.2 (95% CI, 1.9-2.6) for multiple sclerosis, 1.7 (95% CI, 1.6-1.7) for head injury, 1.3 (95% CI, 1.2-1.3) for stroke, and 1.7 (95% CI, 1.6-1.8) for epilepsy. The association varied according to time since diagnosis with an adjusted IRR for 1 to 3 months of 3.1 (95% CI, 2.7-3.6) and for 10 or more years, 1.5 (95% CI, 1.4 to 1.6, P < .001). Compared with those who were not diagnosed with a neurological disorder, those with dementia had a lower overall adjusted IRR of 0.8 (95% CI, 0.7-0.9), which was elevated during the first month after diagnosis to 3.0 (95% CI, 1.9-4.6; P < .001). The absolute risk of suicide for people with Huntington disease was 1.6% (95% CI, 1.0%-2.5%). CONCLUSIONS AND RELEVANCE: In Denmark from 1980 through 2016, there was a significantly higher rate of suicide among those with a diagnosed neurological disorder than persons not diagnosed with a neurological disorder. However, the absolute risk difference was small.
IMPORTANCE: Individuals with mental disorders often develop comorbidity over time. Past studies of comorbidity have often restricted analyses to a subset of disorders and few studies have provided ...absolute risks of later comorbidity. OBJECTIVES: To undertake a comprehensive study of comorbidity within mental disorders, by providing temporally ordered age- and sex-specific pairwise estimates between the major groups of mental disorders, and to develop an interactive website to visualize all results and guide future research and clinical practice. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included all individuals born in Denmark between January 1, 1900, and December 31, 2015, and living in the country between January 1, 2000, and December 31, 2016. The analyses were conducted between June 2017 and May 2018. MAIN OUTCOMES AND MEASURES: Danish health registers were used to identify mental disorders, which were examined within the broad 10-level International Statistical Classification of Diseases and Related Health Problems, 10th Revision, subchapter groups (eg, codes F00-F09 and F10-F19). For each temporally ordered pair of disorders, overall and lagged hazard ratios and 95% CIs were calculated using Cox proportional hazards regression models. Absolute risks were estimated using competing risks survival analyses. Estimates for each sex were generated. RESULTS: A total of 5 940 778 persons were included in this study (2 958 293 men and 2 982 485 women; mean SD age at beginning of follow-up, 32.1 25.4 years). They were followed up for 83.9 million person-years. All mental disorders were associated with an increased risk of all other mental disorders when adjusting for sex, age, and calendar time (hazard ratios ranging from 2.0 95% CI, 1.7-2.4 for prior intellectual disabilities and later eating disorders to 48.6 95% CI, 46.6-50.7 for prior developmental disorders and later intellectual disabilities). The hazard ratios were temporally patterned, with higher estimates during the first year after the onset of the first disorder, but with persistently elevated rates during the entire observation period. Some disorders were associated with substantial absolute risks of developing specific later disorders (eg, 30.6% 95% CI, 29.3%-32.0% of men and 38.4% 95% CI, 37.5%-39.4% of women with a diagnosis of mood disorders before age 20 years developed neurotic disorders within the following 5 years). CONCLUSIONS AND RELEVANCE: Comorbidity within mental disorders is pervasive, and the risk persists over time. This study provides disorder-, sex-, and age-specific relative and absolute risks of the comorbidity of mental disorders. Web-based interactive data visualization tools are provided for clinical utility.
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