Epilepsy in childhood and school performance: a nation-wide cohort study.

Childhood epilepsy has been linked to poor academic performance, but large-scale studies are lacking. In this nation-wide study of school-aged children, we examined the association between childhood epilepsy and school performance in standardized tests according to phenotypic and treatment-related characteristics. We performed a matched register-based cohort study of children born in Denmark (1997-2009) who participated in the Danish National School Test Programme between 2010 and 2019. We used population and health registers to identify children with epilepsy and a randomly sampled sex- and age-matched reference cohort without epilepsy (ratio 1:10). Norm-based test scores from language and mathematics reflecting performance as a percentile of the nation-wide distribution of scores (scale 1-100) were used to assess academic performance. Adjusted differences in mean standardized scores between children with and without epilepsy were estimated using linear regression models. Among 582 840 children participating in the School Test Programme, we identified 4659 (0.8%) children with epilepsy (52.8% males) and 46 590 matched reference children. Median age at epilepsy onset was 7.5 years (interquartile range: 4.0-10.6). Childhood epilepsy was associated with poorer school performance overall (mean score = 48.2 versus references = 56.7; adjusted difference = -6.7, 95% CI: -7.4 to -6.0), and worse performance was found in all epilepsy subgroups, including in 3534 children with uncomplicated epilepsy (i.e. no other pre-existing neurologic or intellectual disabilities and no identified possible cause for epilepsy; adjusted difference = -6.0, 95% CI: -6.8 to -5.2). No major variation by sex, age or subject was observed, but larger score differences were seen in children using antiseizure medication at time of testing (e.g. valproate monotherapy, adjusted difference = -9.3, 95% CI: -11.5 to -7.0 and lamotrigine monotherapy, adjusted difference = -13.1, 95% CI: -15.0 to -11.3) and in children with psychiatric comorbidity, especially epilepsy with comorbid intellectual disability (adjusted difference = -27.0, 95% CI: -30.0 to -23.9) and epilepsy with comorbid attention deficit/hyperactivity disorder (adjusted difference = -15.7, 95% CI: -19.0 to -12.4). Children with epilepsy scored significantly lower than their unaffected siblings (adjusted difference = -6.2, 95% CI: -7.1 to -5.4). In conclusion, childhood epilepsy was associated with impaired academic performance throughout schooling, which suggest that there is a widespread need for educational support of children with epilepsy, even when the child has no other comorbidities and when the epilepsy appears well-managed.

Interaction between mental disorders and social disconnectedness on mortality: a population-based cohort study.

BACKGROUND: Despite the recognised importance of mental disorders and social disconnectedness for mortality, few studies have examined their co-occurrence. AIMS: To examine the interaction between mental disorders and three distinct aspects of social disconnectedness on mortality, while taking into account sex, age and characteristics of the mental disorder. METHOD: This cohort study included participants from the Danish National Health Survey in 2013 and 2017 who were followed until 2021. Survey data on social disconnectedness (loneliness, social isolation and low social support) were linked with register data on hospital-diagnosed mental disorders and mortality. Poisson regression was applied to estimate independent and joint associations with mortality, interaction contrasts and attributable proportions. RESULTS: A total of 162 497 individuals were followed for 886 614 person-years, and 9047 individuals (5.6%) died during follow-up. Among men, interaction between mental disorders and loneliness, social isolation and low social support, respectively, accounted for 47% (95% CI: 21-74%), 24% (95% CI: -15 to 63%) and 61% (95% CI: 35-86%) of the excess mortality after adjustment for demographics, country of birth, somatic morbidity, educational level, income and wealth. In contrast, among women, no excess mortality could be attributed to interaction. No clear trends were identified according to age or characteristics of the mental disorder. CONCLUSIONS: Mortality among men, but not women, with a co-occurring mental disorder and social disconnectedness was substantially elevated compared with what was expected. Awareness of elevated mortality rates among socially disconnected men with mental disorders could be of importance to qualify and guide prevention efforts in psychiatric services.

Contribution of severe mental disorders to fatally harmful effects of physical disorders: national cohort study.

BACKGROUND: It remains unknown whether severe mental disorders contribute to fatally harmful effects of physical illness. AIMS: To investigate the risk of all-cause death and loss of life-years following the onset of a wide range of physical health conditions in people with severe mental disorders compared with matched counterparts who had only these physical health conditions, and to assess whether these associations can be fully explained by this patient group having more clinically recorded physical illness. METHOD: Using Czech national in-patient register data, we identified individuals with 28 physical health conditions recorded between 1999 and 2017, separately for each condition. In these people, we identified individuals who had severe mental disorders recorded before the physical health condition and exactly matched them with up to five counterparts who had no recorded prior severe mental disorders. We estimated the risk of all-cause death and lost life-years following each of the physical health conditions in people with pre-existing severe mental disorders compared with matched counterparts without severe mental disorders. RESULTS: People with severe mental disorders had an elevated risk of all-cause death following the onset of 7 out of 9 broadly defined and 14 out of 19 specific physical health conditions. People with severe mental disorders lost additional life-years following the onset of 8 out 9 broadly defined and 13 out of 19 specific physical health conditions. The vast majority of results remained robust after considering the potentially confounding role of somatic multimorbidity and other clinical and sociodemographic factors. CONCLUSIONS: A wide range of physical illnesses are more likely to result in all-cause death in people with pre-existing severe mental disorders. This premature mortality cannot be fully explained by having more clinically recorded physical illness, suggesting that physical disorders are more likely to be fatally harmful in this patient group.

A comprehensive analysis of age of onset and cumulative incidence of mental disorders: A Danish register study.

BACKGROUND: The age of onset (AOO), incidence and cumulative incidence of mental disorders are critical epidemiological measures, providing essential insights into the development and course of these disorders across the lifespan. This study aims to provide up-to-date estimates of the AOO, age-specific incidence, and cumulative incidence for a comprehensive range of mental disorders using data from Danish registers. METHODS: We conducted a follow-up study encompassing all Danish residents from January 1, 2004, to December 31, 2021, totaling 91,613,465 person-years. Data were sourced from the Danish Psychiatric Central Research Register, identifying individuals treated for various mental disorders in psychiatric hospitals, outpatient departments, and accident/emergency departments, that is, treated in secondary care settings. We investigated specific categories of mental disorders, including substance abuse disorders, schizophrenia, mood disorders, anxiety, eating disorders, borderline personality disorders, intellectual disabilities, pervasive developmental disorders, and behavioral and emotional disorders. Age-sex-specific incidence rates were estimated using Poisson generalized linear models, and cumulative incidence was calculated using Aalen-Johansen's competing risks model. The study provides estimates of AOO, incidence, and cumulative incidence for various mental disorders, including their age and sex distributions. RESULTS: The cumulative incidence by age 80 years for any mental disorder was 30.72% (95% confidence interval: 30.62%-30.83%) for males and 34.46% (34.35%-34.57%) for females. The most common types of mental disorders were anxiety-related disorders 16.27% (16.19%-16.36%) for males and 23.39% (23.29%-23.50%) for females, and followed by mood disorder 10.34% (10.27%-10.41%) for males and 16.67% (16.58%-16.77%) for females. For those who develop mental disorder, half will have developed their disorder by approximately age 22 years (median and interquartile range: males 21.37 (11.85-36.00); females 22.55 (16.31-36.08)). CONCLUSIONS: Approximately one in three individuals will seek treatment for at least one mental disorder in a secondary care setting by age 80. Given that half of these individuals develop mental disorders before age 22, it is crucial to tailor service planning to meet the specific needs of young individuals. Web-based interactive data-visualization tools are provided for clinical utility.

The Intergenerational Transfer of Mental Disorders: A Population-Based Multigenerational Linkage Study: Le transfert intergénérationnel des troubles mentaux : une étude sur les liens multigénérationnels basée sur la population.

OBJECTIVES: The aetiology of mental disorders involves genetic and environmental factors, both reflected in family health history. We examined the intergenerational transmission of multiple mental disorders from parents and grandparents using population-based, objectively measured family histories. METHODS: This population-based retrospective cohort study used administrative healthcare databases in Manitoba, Canada and included adults living in Manitoba from 1977 to 2020 with linkages to at least one parent and one grandparent. Index date was when individuals turned 18 or 1 April 1977, whichever occurred later. Mental disorder diagnoses (mood and anxiety, substance use and psychotic disorders) were identified in individuals, parents and grandparents from hospitalization and outpatient records. Cox proportional hazards regression models included sociodemographic characteristics, individual's comorbidity and mental disorder history in a grandparent, mother and father. RESULTS: Of 109,359 individuals with no mental disorder prior to index date, 47.1% were female, 36.3% had a mental disorder during follow-up, and 90.9% had a parent or grandparent with a history of a mental disorder prior to the index date. Both paternal and maternal history of a mental disorder increased the risk of the disorder in individuals. Psychotic disorders had the strongest association with parental history and were mostly influenced by paternal (hazards ratio [HR] 3.73, 95% confidence interval [CI] 2.99 to 4.64) compared to maternal history (HR 2.23, 95% CI, 1.89 to 2.64). Grandparent history was independently associated with the risk of all mental disorders but had the strongest influence on substance use disorders (HR 1.42, 95% CI, 1.34 to 1.50). CONCLUSIONS: Parental history of mental disorders was associated with an increased risk of all mental disorders. Grandparent history of mental disorders was associated with a small risk increase of the disorders above and beyond parental history influence. This three-generation study further highlights the need for family-based interventional programs in families affected by mental disorders. PLAIN LANGUAGE SUMMARY TITLE: The Intergenerational Transfer of Mental Illnesses.

ObjectivesBoth genetics and environmental factors, such as poverty, maltreatment and parental education, have a role in the development of mental illnesses. Some genetic and environmental risk factors for mental illnesses are shared within families. We conducted a large study to test the extent to which mental illnesses are passed down through generations.MethodsThis study used healthcare data from Manitoba, Canada captured during the delivery of healthcare services for administrative purposes. These data included all adults from 1977 to 2020 who had at least one parent and one grandparent with linked data. Mental illnesses were diagnosed in individuals, parents and grandparents by doctors during hospitalizations or physician visits. The illnesses included mood and anxiety, substance use, and psychotic illnesses. We estimated the likelihood of developing a mental illness when parents and/or grandparents had a mental illness as well.ResultsThe study included 109,359 individuals; a third developed a mental illness during the study period. The majority had a history of a mental illness in a parent or grandparent. We found that a history of mental illness in a mother and father increased the chance of developing the illness. Psychotic illnesses had the strongest relation with parental history. In particular, having a father with a psychotic illness increased the chance of developing the illness by four times. The likelihood of developing a mental illness was higher if a grandparent had a mental illness, above and beyond parental history influence, particularly for substance use disorders.ConclusionsHaving a parent or grandparent with a mental illness increases an individual's chance of developing a mental illness. Family-based intervention programs are needed to support families affected by mental illnesses in coping with their heavy burden.

Average lifespan variation among people with mental disorders in Denmark: a nationwide, register-based cohort study.

AIMS: Mortality associated with mental disorders has been estimated using metrics such as mortality rate ratios and life expectancy. However, the variation around the average life expectancy has never been quantified. The main aim of this study was to measure life disparity for people with mental disorders as a measure of inequality at the time of death. METHODS: Using data from Danish registries, average life disparity was introduced and calculated to measure the lifespan variation associated with major types of mental disorders. Average life expectancy is also reported for completeness. RESULTS: Compared with the general population, people with mental disorders not only had shorter average life expectancy, but experienced larger average life disparity. For those diagnosed with a mental disorder, average life expectancy increased between 1995 and 2021; however, average life disparity declined in women only, and did not change for men. In addition, the differences in both metrics between those with mental disorders and the general population were largest for substance use disorders and schizophrenia spectrum disorders. For these disorders, the differences even increased during the study period. CONCLUSIONS: Mortality rates for individuals with mental disorders have been declining in recent decades in Denmark; however, the increase in the average life disparity emphasizes the increasing heterogeneity and inequality in lifespans within this group, which requires measures to promote a longer and more equal life for those with mental disorders.

Mental Health Conditions in Partners and Adult Children of Stroke Survivors.

Importance: Family caregiving after critical illness has been associated with several adverse health outcomes, including various aspects of mental health, but research focusing specifically on family members of stroke survivors is limited. Objectives: To examine the associations of stroke in a partner or parent with the risk of depression, substance use disorders, anxiety disorders, and self-harm or suicide. Design, Setting, and Participants: This nationwide, population-based cohort study used data from Danish nationwide administrative and clinical registries (2004-2021). Participants included partners and adult children of survivors of stroke. Data analysis was performed from March to December 2023. Exposure: Having a partner or parent who survived stroke. Main Outcomes and Measures: The Aalen-Johansen estimator was used to compute propensity score-weighted 3-year absolute risks, risk differences, and risk ratios for depression, substance use disorders, anxiety disorders, and self-harm or suicide among partners or children of survivors of stroke compared with partners or children of survivors of myocardial infarction (MI) and matched individuals from the general population. Results: The study included a total of 1 923 732 individuals: 70 917 partners of stroke survivors (median [IQR] age, 68 [59-76] years; 46 369 women [65%]), 70 664 partners of MI survivors (median [IQR] age, 65 [55-73] years; 51 849 women [73%]), 354 570 partners of individuals from the general population (median [IQR] age, 68 [59-76] years; 231 833 women [65%]), 207 386 adult children of stroke survivors (median [IQR] age, 45 [36-52] years; 99 382 women [48%]), 183 309 adult children of MI survivors (median [IQR] age, 42 [33-49] years; 88 078 women [48%]), and 1 036 886 adult children of individuals from the general population (median [IQR] age, 45 [36-52] years; 496 875 women [48%]). Baseline characteristics were well balanced across cohorts after propensity score weighting. Among partners of stroke survivors, the 3-year absolute risk was 1.0% for depression, 0.7% for substance use disorders, 0.3% for anxiety disorders, and 0.04% for self-harm or suicide. Risk ratio point estimates for the assessed outcomes ranged from 1.14 to 1.42 compared with the general population and from 1.04 to 1.09 compared with partners of MI survivors. The elevated risk of depression in partners of stroke survivors was more pronounced after severe or moderate stroke than after mild stroke. Among adult children of stroke survivors, the 3-year absolute risk was 0.6% for depression, 0.6% for substance use disorders, 0.2% for anxiety disorders, and 0.05% for self-harm or suicide. Both absolute risks and risk ratios for adult children of stroke survivors were smaller than those reported in the partner analyses. Conclusions and Relevance: In this cohort study of partners and adult children of stroke survivors, risks of several mental health conditions and self-harm or suicide were moderately higher compared with the general population and, to a lesser extent, partners and adult children of MI survivors. These findings highlight the potential consequences of stroke among family members, particularly partners, and its findings may possibly serve as a quantitative foundation for the development of future stroke rehabilitation services.

Exploring the association between metabolic syndrome, its components and subsequent cancer incidence: A cohort study in Catalonia.

BACKGROUND: Metabolic syndrome (MS) has emerged as a significant global health concern. The relationship between MS and the risk of cancer doesn't seem clear, whether examining by components or in combination. The objective of this study is to examine the relationship between MS, its components, and the overall risk of cancer, including the risk of 13 specific cancer types. METHODS: We included 3,918,781 individuals aged 40 years or older sourced from the SIDIAP database between 2008 and 2017. Cox models were employed with MS components and their combinations. A subsample was created using a matched cohort (by age and sex). Incidence curves were computed to determine the time elapsed between the date of having 1-5 MS components and cancer incidence, compared to matched participants with no MS components, which showed that individuals who had one MS component experienced a greater incidence of cancer over 5 and 10 years than individuals with no MS, and the incidence rose with an increase in the number of MS components. RESULTS: Individuals exposed to MS components were diagnosed with cancer earlier than those who were not exposed to them. In the Cox model, HDL (HR 1.46, 95% CI: 1.41-1.52) and Glycemia (HR 1.40, 95% CI: 1.37-1.44) were the individual combinations with the highest risk of overall cancer. In combinations with two components, the highest HR was HDL+Glycemia (HR 1.52, 95% CI: 1.45-1.59) and Glycemia+HBP (HR 1.48, 95% CI: 1.45-1.50). In combinations with three components, the highest HR was HDL+Glycemia+HBP (HR 1.58, 95% CI: 1.55-1.62). CONCLUSION: In summary, having one or more MS components raises the risk of developing at least 11 cancer types and these risk differ according to type of component included. Some sex differences are also observed. Our findings suggest that implementing prevention measures aimed at specific MS components may lower the risk of various cancer types.

Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians.

Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

Quantifying the Relative Importance of Genetics and Environment on the Comorbidity between Mental- and Cardiometabolic Disorders: A Comprehensive Analysis of National Register Data from 17 million Scandinavians.

Mental disorders (MDs) are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders (CMDs). Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and complete genealogies of Denmark and Sweden (n=17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six MDs and 14 CMDs. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with CMDs, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with CMDs was mainly or fully driven by environmental factors. These findings provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

The cost of mental disorders in Denmark: a register-based study.

The aim of the study was to undertake a detailed analysis of healthcare cost, public transfer payments, and income loss associated with a broad range of mental disorders in Denmark. Based on all persons living in Denmark, we identified those with a hospital diagnosis of one of 18 types of mental disorders and 10 age- and sex-matched controls per case. For each mental disorder, the outcomes were nationwide totals, cost per case, and cost per capita, investigated by sex, age strata, and the number of years after diagnosis. We found a substantial annual income loss of 5 billion Euros and excess healthcare cost of 1 billion Euros for persons with any mental disorder. Each mental disorder was associated with an income loss, excess healthcare cost, and excess public transfer payments compared to matched controls. An interactive data visualisation site with summary data is available at https://nbepi.com/cost .