Medication and procedural abortions before 13 weeks gestation and risk of psychiatric disorders.

BACKGROUND: The proportion of abortions provided by medication in the United States and worldwide has increased greatly since the U.S. Food and Drug Administration approved mifepristone in 2000. While existing research has shown that abortion does not increase risk of mental health problems, no population-based study has examined specifically whether a procedural or medication abortion increases risk of mental health disorders. OBJECTIVE: This study examined whether mental health disorders increased in the shorter and longer-term after a medication or procedural abortion. STUDY DESIGN: Using Danish population registers' data, we conducted a prospective cohort study in which we included 72,424 females born in Denmark between 1980 and 2006, who were ages 12 to 38 during the study period and had a first first-trimester abortion before 13 weeks gestation in 2000 to 2018. Females with no previous psychiatric diagnoses were followed from 1 year before their abortion until their first psychiatric diagnosis, December 31, 2018, emigration from Demark, or death, whichever came first. Risk of any first psychiatric disorder was defined as a recorded psychiatric diagnosis at an in- or out-patient facility from the 1 year after to more than 5 years after a medication or procedural abortion relative to the year beforehand. Results were adjusted for calendar year, age, gestational age, partner status, prior mental and physical health, childbirth history, childhood environment, and parental mental health history. RESULTS: Females having medication (n=37,155) and procedural abortions (n=35,269) had the same risk of any first psychiatric diagnosis in the year after their abortion relative to the year before their abortion (medication abortion adjusted incidence rate ratio [MaIRR]=1.02, 95% confidence interval [CI]: 0.93-1.12; procedural abortion adjusted incidence rate ratio [PaIRR]=0.94, 95% CI: 0.86-1.02). Moreover, as more time from the abortion passed, the risk of a psychiatric diagnoses decreased relative to the year before their abortion for each abortion method (MaIRR 1-2 years after=0.89, 95% CI: 0.80-0.98; PaIRR 1-2 years after=0.81, 95% CI: 0.88-1.05; MaIRR 2-5 years after=0.77, 95% CI: 0.71-0.84; PaIRR 2-5 years after=0.72, 95% CI: 0.67-0.78; MaIRR 5+ years after=0.58, 95% CI: 0.53-0.63; PaIRR 5+ years after=0.54, 95% CI: 0.50-0.58). CONCLUSION: Because the risk of psychiatric diagnoses was the same in the year after relative to the year before a medication and procedural abortion and the risk did not increase as more time after the abortion increased, neither abortion method increased risk of mental health disorders in the shorter or longer-term.

Mapping morbidity 10 years prior to a diagnosis of young onset Alzheimer's disease.

INTRODUCTION: Early symptoms in young onset Alzheimer's disease (YOAD) may be misinterpreted, causing delayed diagnosis. This population-based study aimed to map morbidity prior to YOAD diagnosis. METHODS: In a register-based incidence density matched nested case-control study, we examined hospital-diagnosed morbidity for people diagnosed with YOAD in Danish memory clinics during 2016-2020 compared to controls in a 10-year period. Conditional logistic regression produced incidence rate ratios (IRRs). RESULTS: The study included 1745 cases and 5235 controls. YOAD patients had a higher morbidity burden in the year immediately before dementia diagnosis, for certain disorders up to 10 years before. This was especially evident for psychiatric morbidity with the highest increased IRRs throughout the entire period and IRR 1.43 (95% confidence interval 1.14-1.79) in the 5-10-years before dementia diagnosis. DISCUSSION: YOAD patients display a different pattern of morbidity up to 10 years prior to diagnosis. Awareness of specific alterations in morbidity may improve efforts toward a timely diagnosis. HIGHLIGHTS: Retrospective, nested case-control study of young onset Alzheimer's disease (YOAD). YOAD cases had a higher morbidity burden than controls. YOAD cases had a higher psychiatric morbidity burden up to 10 years before diagnosis. Altered morbidity patterns could serve as an early warning sign of YOAD.

Association between Mental Disorders and Subsequent Medical Conditions.

BACKGROUND: Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions. METHODS: We used a population-based cohort from Danish national registries that included data on more than 5.9 million persons born in Denmark from 1900 through 2015 and followed them from 2000 through 2016, for a total of 83.9 million person-years. We assessed 10 broad types of mental disorders and 9 broad categories of medical conditions (which encompassed 31 specific conditions). We used Cox regression models to calculate overall hazard ratios and time-dependent hazard ratios for pairs of mental disorders and medical conditions, after adjustment for age, sex, calendar time, and previous mental disorders. Absolute risks were estimated with the use of competing-risks survival analyses. RESULTS: A total of 698,874 of 5,940,299 persons (11.8%) were identified as having a mental disorder. The median age of the total population was 32.1 years at entry into the cohort and 48.7 years at the time of the last follow-up. Persons with a mental disorder had a higher risk than those without such disorders with respect to 76 of 90 pairs of mental disorders and medical conditions. The median hazard ratio for an association between a mental disorder and a medical condition was 1.37. The lowest hazard ratio was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval [CI], 0.80 to 0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11 to 4.22). Several specific pairs showed a reduced risk (e.g., schizophrenia and musculoskeletal conditions). Risks varied according to the time since the diagnosis of a mental disorder. The absolute risk of a medical condition within 15 years after a mental disorder was diagnosed varied from 0.6% for a urogenital condition among persons with a developmental disorder to 54.1% for a circulatory disorder among those with an organic mental disorder. CONCLUSIONS: Most mental disorders were associated with an increased risk of a subsequent medical condition; hazard ratios ranged from 0.82 to 3.62 and varied according to the time since the diagnosis of the mental disorder. (Funded by the Danish National Research Foundation and others; COMO-GMC ClinicalTrials.gov number, NCT03847753.).

Association of homelessness and skin conditions: a Danish population-based cohort study.

BACKGROUND: Research has linked homelessness with an increased risk of skin conditions. However, representative studies of diagnosis-specific information on skin conditions in people experiencing homelessness are lacking. OBJECTIVES: To examine the association between homelessness and diagnosed skin conditions, prescribed medication and type of -consultation. METHODS: This cohort study included data from the Danish nationwide health, social and administrative registers from 1 January 1999 to 31 December 2018. All people of Danish origin living in Denmark and aged at least 15 years at some point during the study period were included. Homelessness, measured by homeless shelter contacts, was the exposure. The outcome was any diagnosis of a skin disorder and specific skin disorders recorded in the Danish National Patient Register. Information on diagnostic consultation type (i.e. dermatological, nondermatological and emergency room) and dermatological prescriptions was studied. We estimated adjusted incidence rate ratio (aIRR) (adjusted for sex, age and calendar year) and cumulative incidence. RESULTS: In total, 5 054 238 individuals (50.6% female) were included in the study population, accounting for 73 477 258 person-years at risk, with a start mean (SD) age of 39.4 (21.1) years. Of the total number of individuals, 759 991 (15.0%) received a skin diagnosis and 38 071 (0.7%) experienced homelessness. A 2.31-times [95% confidence interval (CI) 2.25-2.36] higher IRR of any diagnosed skin condition was associated with homelessness, higher for nondermatological and emergency room consultations. Homelessness was associated with a reduced IRR of a skin neoplasm diagnosis (aIRR 0.76, 95% CI 0.71-8.82) compared with no homelessness. By the end of follow-up, 2.8% (95% CI 2.5-3.0) of individuals experiencing homelessness had a skin neoplasm diagnosis vs. 5.1% (95% CI 4.9-5.3) of individuals not experiencing homelessness. Five or more shelter contacts during the first year from first contact was associated with the highest aIRR of any diagnosed skin condition (7.33, 95% CI 5.57-9.65) compared with no contacts. CONCLUSIONS: Individuals experiencing homelessness have high rates of most diagnosed skin conditions, but a lower occurrence of skin cancer diagnosis. Diagnostic and medical patterns for skin disorders differed clearly between people experiencing homelessness and individuals without these experiences. The time after first homeless shelter contact is an important window of opportunity for mitigating and preventing skin disorders.

Identification of women at high risk of postpartum psychiatric episodes: A population-based study quantifying relative and absolute risks following exposure to selected risk factors and genetic liability.

BACKGROUND: We quantified relative and absolute risks of postpartum psychiatric episodes (PPE) following risk factors: Young age, past personal or family history of psychiatric disorders, and genetic liability. METHODS: We conducted a register-based study using the iPSYCH2012 case-cohort sample. Exposures were personal history of psychiatric episodes prior to childbirth, being a young mother (giving birth before the age of 21.5 years), having a family history of psychiatric disorders, and a high (highest quartile) polygenic score (PGS) for major depression. PPE was defined within 12 months postpartum by prescription of psychotropic medication or in- and outpatient contact to a psychiatric facility. We included primiparous women born 1981-1999, giving birth before January 1st, 2016. We conducted Cox regression to calculate hazard ratios (HRs) of PPE, absolute risks were calculated using cumulative incidence functions. RESULTS: We included 8174 primiparous women, and the estimated baseline PPE risk was 6.9% (95% CI 6.0%-7.8%, number of PPE cases: 2169). For young mothers with a personal and family history of psychiatric disorders, the absolute risk of PPE was 21.6% (95% CI 15.9%-27.8%). Adding information on high genetic liability to depression, the risk increased to 29.2% (95% CI 21.3%-38.4%) for PPE. CONCLUSIONS: Information on prior personal and family psychiatric episodes as well as age may assist in estimating a personalized risk of PPE. Furthermore, additional information on genetic liability could add even further to this risk assessment.

From population to neuron: exploring common mediators for metabolic problems and mental illnesses.

Major mental illnesses such as schizophrenia (SZ) and bipolar disorder (BP) frequently accompany metabolic conditions, but their relationship is still unclear, in particular at the mechanistic level. We implemented an approach of "from population to neuron", combining population-based epidemiological analysis with neurobiological experiments using cell and animal models based on a hypothesis built from the epidemiological study. We characterized high-quality population data, olfactory neuronal cells biopsied from patients with SZ or BP, and healthy subjects, as well as mice genetically modified for insulin signaling. We accessed the Danish Registry and observed (1) a higher incidence of diabetes in people with SZ or BP and (2) higher incidence of major mental illnesses in people with diabetes in the same large cohort. These epidemiological data suggest the existence of common pathophysiological mediators in both diabetes and major mental illnesses. We hypothesized that molecules associated with insulin resistance might be such common mediators, and then validated the hypothesis by using two independent sets of olfactory neuronal cells biopsied from patients and healthy controls. In the first set, we confirmed an enrichment of insulin signaling-associated molecules among the genes that were significantly different between SZ patients and controls in unbiased expression profiling data. In the second set, olfactory neuronal cells from SZ and BP patients who were not pre-diabetic or diabetic showed reduced IRS2 tyrosine phosphorylation upon insulin stimulation, indicative of insulin resistance. These cells also displayed an upregulation of IRS1 protein phosphorylation at serine-312 at baseline (without insulin stimulation), further supporting the concept of insulin resistance in olfactory neuronal cells from SZ patients. Finally, Irs2 knockout mice showed an aberrant response to amphetamine, which is also observed in some patients with major mental illnesses. The bi-directional relationships between major mental illnesses and diabetes suggest that there may be common pathophysiological mediators associated with insulin resistance underlying these mental and physical conditions.

Temporally ordered associations between type 2 diabetes and brain disorders - a Danish register-based cohort study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is linked with several neurodegenerative and psychiatric disorders, either as a comorbid condition or as a risk factor. We aimed to expand the evidence by examining associations with a broad range of brain disorders (psychiatric and neurological disorders, excluding late-onset neurodegenerative disorders), while also accounting for the temporal order of T2DM and these brain disorders. METHODS: In a population-based cohort-study of 1,883,198 Danish citizens, born 1955-1984 and followed until end of 2016, we estimated associations between T2DM and 16 brain disorders first diagnosed between childhood and mid-adulthood. We calculated odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) in temporally ordered analyses (brain disorder diagnosis after T2DM and vice versa), adjusted for sex, age, follow-up, birth year, and parental factors. RESULTS: A total of 67,660 (3.6%) of the study population were identified as T2DM cases after age 30 and by a mean age of 45 years (SD of 8 years). T2DM was associated with most psychiatric disorders. Strongest associations were seen with other (i.e. non-anorectic) eating disorders (OR [95% CI]: 2.64 [2.36-2.94]) and schizophrenia spectrum disorder (2.73 [2.63-2.84]). Among neurological disorders especially inflammatory brain diseases (1.73 [1.57-1.91]) and epilepsy (1.67 [1.60-1.75]) were associated with T2DM. Most associations remained in both directions in the temporally ordered analyses. For most psychiatric disorders, associations were strongest in females. CONCLUSIONS: T2DM was associated with several psychiatric and neurological disorders, and most associations were consistently found for both temporal order of disorders. This suggests a shared etiology of T2DM and those brain disorders. This study can form the starting point for studies directed at further elucidating potential causal links between disorders and shared biological mechanisms.

Systemic lupus erythematosus during pregnancy is not associated with school performance in offspring - A Danish population-based study.

INTRODUCTION: Systemic lupus erythematosus (SLE) in pregnancy is considered a risk factor for a range of adverse outcomes in the offspring. Studies have indicated increased risk of neurodevelopmental disorders such as autism spectrum disorders, dyslexia and ADHD. However, the overall long-term cognitive development of children born to women with SLE has scarcely been examined. In this study, we compare test scores from the Danish National School Tests of children born to women SLE with children of the background population. METHODS: We included all singleton children born in Denmark between 1995 and 2008, who were listed in the Danish National School Test Register (n=738,862). Children born to women with SLE were identified through linkage of national healthcare registers. We assessed the children's performance in the national school tests between 2nd and 8th grade, in reading and mathematics. Information on the mothers' redeemed prescriptions in pregnancy was included in stratified analyses. Differences of mean test scores were derived from linear regressions and compared according to maternal SLE status, and predefined categories of medication exposures. RESULTS: In total, 312 (0.04%) children were born to mothers with SLE. There were no differences in performance in neither reading nor mathematics tests between those born to mothers with SLE and children born to mothers without SLE. When stratifying on medication exposures among children whose mothers had SLE, there was a non-significant tendency towards poorer results among those exposed to hydroxychloroquine and/or immunosuppressants (n=31), compared to those not exposed to these medications. A similar tendency was not observed among children whose mothers received hydroxychloroquine for non-SLE reasons (n=1,235). CONCLUSION: This study indicates no major harmful effect on the child's neurocognitive development from exposure in utero to SLE, hydroxychloroquine and/or immunosuppressants, as measured by school performance.

Antiherpetic medication and incident dementia: Observational cohort studies in four countries.

BACKGROUND AND PURPOSE: Several epidemiological studies from Taiwan, all using the same data resource, found significant associations between herpes virus infection, antiherpetic medication, and subsequent dementia. We conducted a multicenter observational cohort study using health registry data from Wales, Germany, Scotland, and Denmark to investigate potential associations between antiherpetic medication and incident dementia, and also to comprehensively investigate such associations broken down according to medication type and dose, type of herpes virus, and dementia subtype. METHODS: A total of 2.5 million individuals aged 65 years or more were followed up using linked electronic health records in four national observational cohort studies. Exposure and outcome were classified using coded data from primary and secondary care. Data were analyzed using survival analysis with time-dependent covariates. RESULTS: Results were heterogeneous, with a tendency toward decreased dementia risk in individuals exposed to antiherpetic medication. Associations were not affected by treatment number, herpes subtype, dementia subtype, or specific medication. In one cohort, individuals diagnosed with herpes but not exposed to antiherpetic medication were at higher dementia risk. CONCLUSIONS: Short-term antiherpetic medication is not markedly associated with incident dementia. Because neither dementia subtype nor herpes subtype modified the association, the small but significant decrease in dementia incidence with antiherpetic administration may reflect confounding and misclassification.

A comprehensive analysis of mortality-related health metrics associated with mental disorders: a nationwide, register-based cohort study.

BACKGROUND: Systematic reviews have consistently shown that individuals with mental disorders have an increased risk of premature mortality. Traditionally, this evidence has been based on relative risks or crude estimates of reduced life expectancy. The aim of this study was to compile a comprehensive analysis of mortality-related health metrics associated with mental disorders, including sex-specific and age-specific mortality rate ratios (MRRs) and life-years lost (LYLs), a measure that takes into account age of onset of the disorder. METHODS: In this population-based cohort study, we included all people younger than 95 years of age who lived in Denmark at some point between Jan 1, 1995, and Dec 31, 2015. Information on mental disorders was obtained from the Danish Psychiatric Central Research Register and the date and cause of death was obtained from the Danish Register of Causes of Death. We classified mental disorders into ten groups and causes of death into 11 groups, which were further categorised into natural causes (deaths from diseases and medical conditions) and external causes (suicide, homicide, and accidents). For each specific mental disorder, we estimated MRRs using Poisson regression models, adjusting for sex, age, and calendar time, and excess LYLs (ie, difference in LYLs between people with a mental disorder and the general population) for all-cause mortality and for each specific cause of death. FINDINGS: 7 369 926 people were included in our analysis. We found that mortality rates were higher for people with a diagnosis of a mental disorder than for the general Danish population (28·70 deaths [95% CI 28·57-28·82] vs 12·95 deaths [12·93-12·98] per 1000 person-years). Additionally, all types of disorders were associated with higher mortality rates, with MRRs ranging from 1·92 (95% CI 1·91-1·94) for mood disorders to 3·91 (3·87-3·94) for substance use disorders. All types of mental disorders were associated with shorter life expectancies, with excess LYLs ranging from 5·42 years (95% CI 5·36-5·48) for organic disorders in females to 14·84 years (14·70-14·99) for substance use disorders in males. When we examined specific causes of death, we found that males with any type of mental disorder lost fewer years due to neoplasm-related deaths compared with the general population, although their cancer mortality rates were higher. INTERPRETATION: Mental disorders are associated with premature mortality. We provide a comprehensive analysis of mortality by different types of disorders, presenting both MRRs and premature mortality based on LYLs, displayed by age, sex, and cause of death. By providing accurate estimates of premature mortality, we reveal previously underappreciated features related to competing risks and specific causes of death. FUNDING: Danish National Research Foundation.

Accidental deaths in young people with epilepsy and psychiatric comorbidity-A Danish nationwide cohort study.

OBJECTIVE: The objective of this study was to investigate the accident-related mortality among people younger than 55 years of age with epilepsy compared with the general population and to study how psychiatric comorbidity influences this risk. METHODS: This is a population-based cohort study of individuals born in Denmark between 1960 and 2015 (n = 3, 665 616). Persons diagnosed with epilepsy and psychiatric disorders were identified in the Danish National Patient Register and the Danish Central Psychiatric Central Register. We estimated the hazard ratio (HR) with 95% confidence intervals (CIs) of accidental death in people with epilepsy compared with persons without epilepsy. RESULTS: We identified 61 330 persons (1.7%) diagnosed with epilepsy. Median age at end of follow-up was 27.8 years. In people with epilepsy, 5253 died during follow-up, 480 (9%) of whom died from accidents. Among people without epilepsy, 52 588 died during follow-up, of whom 1280 (2.4%) died from accidents. People with epilepsy had a 3.7-fold (95% CI 3.4-4.1) increased risk of accidental death compared with persons without epilepsy. When we adjusted for psychiatric disorders, the risk remained significantly elevated in people with epilepsy compared to people without epilepsy (adjusted HR [aHR] 2.44, 95% CI 2.22-2.69). When stratifying the analyses on epilepsy and psychiatric disorders, people with epilepsy and psychiatric disorders had an aHR of 4.95 (95% CI 3.82-6.41) when compared with persons without epilepsy and psychiatric disorders. SIGNIFICANCE: The risk of accidental death was increased in people with epilepsy and was particularly high among people with epilepsy with psychiatric comorbidity. The findings highlight the need for awareness and prevention strategies in people with epilepsy, especially in people with comorbid psychiatric disorders.

Vascular Pathology and Trajectories of Late-Life Major Depressive Disorder in Secondary Psychiatric Care.

OBJECTIVE: To examine 5-year trajectories of psychiatrist-treated late-life major depressive disorder (MDD), and evaluate whether previous vascular pathology is associated with more severe trajectories of late-life MDD. METHODS: Data were obtained from nationally representative civil, psychiatric, hospital, and prescription registers in Denmark. The sample included 11,092 older adults (≥60 years) who received their first diagnosis of MDD in a psychiatric facility in Denmark between 2000 and 2007. Trajectories of inpatient or outpatient contact at psychiatric hospitals for MDD over the 5-year period following index MDD diagnosis were modeled using latent class growth analysis. Measures of vascular disease (stroke, heart disease, vascular dementia) and vascular risk factors (hypertension, diabetes) were defined based on medication prescriptions and hospital-based diagnoses. Other predictors included demographic characteristics and characteristics of the index MDD diagnosis. RESULTS: The final model included 4 trajectories with consistently low (66% of the sample), high decreasing (19%), consistently high (9%), and moderate fluctuating (6%) probabilities of contact at a psychiatric hospital for MDD during the 5-year period following the index MDD diagnosis. We found no significant associations between any form of vascular pathology and trajectory class membership. Relative to the consistently low class, older age, greater severity and >12 months of prior antidepressant medication use predicted membership in the other three classes. CONCLUSIONS: A notable proportion (34%) of individuals diagnosed with MDD in late-life require secondary psychiatric treatment for extended time periods. We did not find evidence that vascular pathology predicts hospital contact trajectories in secondary-treated late-life MDD.

Increased mortality among people with anxiety disorders: total population study.

BACKGROUND: Anxiety disorders and depression are the most common mental disorders worldwide and have a striking impact on global disease burden. Although depression has consistently been found to increase mortality; the role of anxiety disorders in predicting mortality risk is unclear. AIMS: To assess mortality risk in people with anxiety disorders. METHOD: We used nationwide Danish register data to conduct a prospective cohort study with over 30 million person-years of follow-up. RESULTS: In total, 1066 (2.1%) people with anxiety disorders died during an average follow-up of 9.7 years. The risk of death by natural and unnatural causes was significantly higher among individuals with anxiety disorders (natural mortality rate ratio (MRR) = 1.39, 95% CI 1.28-1.51; unnatural MRR = 2.46, 95% CI 2.20-2.73) compared with the general population. Of those who died from unnatural causes, 16.5% had comorbid diagnoses of depression (MRR = 11.72, 95% CI 10.11-13.51). CONCLUSIONS: Anxiety disorders significantly increased mortality risk. Comorbidity of anxiety disorders and depression played an important part in the increased mortality.

Divorce or Separation Following Postpartum Psychiatric Episodes: A Population-Based Cohort Study.

Objective: Psychiatric disorders are an established risk factor for divorce or separation. Despite the fact that 10%-15% of new mothers experience postpartum psychiatric episodes (PPEs), no previous studies have investigated the effects of PPEs on the probability of divorce in these new families. Therefore, this study aimed to investigate and quantify the probability of subsequent divorce/separation among women with either mild/moderate or severe PPE compared to mothers without PPE.Methods: This cohort study based on the national Danish registers included all cohabitating, primiparous women without previous psychiatric history who gave birth from 1996 through 2014. At 6 months postpartum, each woman's PPE status was evaluated and categorized as follows: (1) mild/moderate PPE (prescription of psychotropic medication-Anatomical Therapeutic Chemical Classification codes N03-N07), (2) severe PPE (psychiatric inpatient or outpatient treatment-International Classification of Disease, 10th Edition codes F00-F99, excluding codes for organic mental disorders, substance abuse, and mental retardation), and (3) no PPE (reference group). Subsequently, the status of cohabitation was assessed a maximum of 5 times (every January 1).Results: A total of 266,771 new mothers were included; 4,442 had a first mild/moderate PPE and 1,141 had a first severe PPE within 6 months postpartum. Compared to mothers without PPE, women with mild/moderate PPE had a significantly higher probability of later divorce (adjusted hazard ratio [HR] = 1.23; 95% CI, 1.15-1.31); for women with severe PPE, the probability was even greater (adjusted HR = 1.64; 95% CI, 1.45-1.85).Conclusions: Women experiencing their first-ever PPE following childbirth have a higher probability of divorce in the years following their diagnosis than mothers without PPE. Further, this study showed a dose-response relationship between the severity of PPE and the probability of divorce.

Association of Rheumatoid Arthritis in Pregnancy With School Performance of Offspring: A Danish Nationwide Register-Based Study.

OBJECTIVE: To examine the overall cognitive development of children exposed to maternal rheumatoid arthritis (RA) in utero by comparing their school test scores to those of their peers. METHODS: Children born in Denmark during 1995-2008 and listed in the National School Test Register were included (n = 738,862). Children exposed to maternal RA were identified through linkage of national registers. In separate analyses, exposure was subdivided according to maternal serostatus. Preclinical maternal RA was included as a separate exposure. The Danish national school tests are mandatory standardized tests. Results from all reading tests (grades 2, 4, 6, and 8) and mathematics tests (grades 3 and 6) from 2010-2017 were included. Test scores were compared according to maternal RA exposure for each test separately using linear regressions. RESULTS: We identified 934 children exposed to maternal RA in utero. There were no differences in reading test scores between maternal RA exposed and unexposed children. RA exposed children scored poorer in both mathematics tests (adjusted differences of mean score -0.14 SD (95% confidence interval [95% CI] -0.23, -0.06) and -0.16 SD (95% CI -0.26, -0.07). There was no appreciable difference between children by maternal RA serostatus. Children exposed to preclinical RA (n = 589) showed the same pattern of performance as children exposed to RA. CONCLUSION: RA-exposed children scored slightly poorer in mathematics tests but performed as well as their unexposed peers in the reading tests. The results do not suggest that RA in pregnancy has a major impact on offspring school performance.

lillies: An R package for the estimation of excess Life Years Lost among patients with a given disease or condition.

Life expectancy at a given age is a summary measure of mortality rates present in a population (estimated as the area under the survival curve), and represents the average number of years an individual at that age is expected to live if current age-specific mortality rates apply now and in the future. A complementary metric is the number of Life Years Lost, which is used to measure the reduction in life expectancy for a specific group of persons, for example those diagnosed with a specific disease or condition (e.g. smoking). However, calculation of life expectancy among those with a specific disease is not straightforward for diseases that are not present at birth, and previous studies have considered a fixed age at onset of the disease, e.g. at age 15 or 20 years. In this paper, we present the R package lillies (freely available through the Comprehensive R Archive Network; CRAN) to guide the reader on how to implement a recently-introduced method to estimate excess Life Years Lost associated with a disease or condition that overcomes these limitations. In addition, we show how to decompose the total number of Life Years Lost into specific causes of death through a competing risks model, and how to calculate confidence intervals for the estimates using non-parametric bootstrap. We provide a description on how to use the method when the researcher has access to individual-level data (e.g. electronic healthcare and mortality records) and when only aggregated-level data are available.

Association of Specific Mental Disorders With Premature Mortality in the Danish Population Using Alternative Measurement Methods.

Importance: The association of mental disorders with premature mortality published in the Global Burden of Disease (GBD) studies has been underestimated because these analyses have recommended using only a small number of mental disorders as causes of death to estimate years of life lost (YLL). Alternative methods have been introduced, such as estimating life-years lost (LYL), to compare individuals with mental disorders with the general population. Objectives: To generate register-based YLL and LYL estimates and to use these measurement methods to assess the association of specific mental disorders with premature mortality. Design, Setting, and Participants: This population-based cohort study included all persons with and without mental disorders aged 0 to 94 years who were living in Denmark between January 1, 2000, and December 31, 2015. Data were analyzed from January to December 2019. Main Outcomes and Measures: Danish health registers were used to identify mental disorder diagnoses, dates of death, and causes of death. The YLLs were estimated for the set of mental health-associated causes of death, and all-cause and cause-specific LYLs were estimated for 18 specific mental disorders and 3 broad categories of mental disorders that were recommended for use in the GBD studies. The association between the number of comorbid mental disorders (divided into categories of persons with ≥1 type of disorder, ≥2 types of disorders, ≥3 types of disorders, and ≥4 types of disorders) and LYL estimates was also examined. Results: A total of 6 989 627 individuals (3 481 219 male persons [49.8%] and 3 508 408 female persons [50.2%]; mean [SD] age at study enrollment, 32.2 [24.4] years) were followed up for a total of 85 911 461 person-years. The YLL rates per 100 000 person-years were highest for alcohol use disorder (for male individuals, 568.7 [95% CI, 564.4-572.7]; for female individuals, 155.5 [95% CI, 153.5-157.9]) and suicide (for male individuals, 590.1 [95% CI, 583.8-596.5]; for female individuals, 202.3 [95% CI, 198.5-206.4]). Although only 3 of 18 mental and substance use disorders could be associated with YLL, all mental disorders were associated with shorter life expectancies when LYL was used for measurement. Male and female individuals diagnosed with any mental disorder had life expectancies that were shorter by 11.2 years (95% CI, 11.1-11.3 years) and 7.9 years (95% CI, 7.8-8.0 years), respectively, and remaining life expectancy decreased further among those with comorbid mental disorders. Drug use disorders were associated with the highest excess LYL estimates; however, common mental disorders, such as depressive and anxiety disorders, were also associated with substantial premature mortality. Conclusions and Relevance: Mental disorders were observed to be associated with reductions in life expectancy. This finding provides a foundation for future intervention programs designed to reduce the differential mortality gap associated with mental disorders. Register-based studies allow the calculation of precise individual-level YLLs and LYLs, and both measurement methods are informative for health care planning. Compared with YLL, the novel LYL measurement approach may more precisely capture the association of mental disorders with premature mortality and facilitates the exploration of comorbidity and specific causes of death in individuals with mental disorders.

Psychiatric disorder as a first manifestation of cancer: a 10-year population-based study.

To investigate the possibility that psychiatric symptoms could be caused by a yet undetected cancer or be part of a paraneoplastic syndrome, nationwide population-based registers were linked including the Danish Psychiatric Central Register and the Danish Cancer Registry. Data were analysed as a cohort study using survival analysis techniques and incidence rate ratios (IRRs) were used as measures of relative risk. A total of 4,320,623 persons were followed in the 10-year period 1994-2003, resulting in 37,581,600 person-years at risk, 202,144 persons with a first-time psychiatric contact, and 208,995 persons diagnosed with cancer. During the first month after a first-time psychiatric contact, the incidence of all forms of cancer was elevated; IRR: 2.61 (95% CI, 2.31-2.95). Particularly the incidence of brain tumours was elevated; IRR: 18.85 (95% CI, 14.52-24.48), but also the incidence of lung cancer; IRR: 2.98 (95% CI, 2.16-4.12), and especially small-cell lung cancer; IRR: 6.13 (95% CI, 3.39-11.07) was elevated. The elevated IRR for most cancers decreased towards unity within the first 3 months, except for brain tumours, for which the IRR remained significantly elevated during the first 9 months. One of every 63 patients above 50 years of age was diagnosed with malignant cancer within 1 year of first-time psychiatric contact. These results indicate an increased incidence of cancer, especially for brain tumours and small-cell lung cancer, in the first months after a first-time contact to a psychiatric hospital. Clinicians should be aware that first-onset psychiatric symptoms could be a sign of a yet undetected cancer.

Causes of premature mortality in schizophrenia: a review of literature published in 2018.

PURPOSE OF REVIEW: The current review examines the recent literature on the causes of premature mortality in schizophrenia. RECENT FINDINGS: People with schizophrenia have higher premature mortality rates compared with the general population. Suicides and accidents account for a nontrivial part of the excess mortality, but the largest part is attributable to natural causes of death. Five major causes have been identified: first, adverse effects of medication; second, suboptimal lifestyle; third, somatic comorbidity; fourth, suboptimal treatment of somatic disorders; and fifth, accelerated ageing/genetic explanations. The positive aspect is that people with schizophrenia have increasing life expectancy, at least in high-income countries, and this development seems to largely follow the increase in the general population. Especially mortality rates from unnatural causes appear to have a positive impact. Nevertheless, despite more than 100 years of research and progress, the excess mortality in persons with schizophrenia remains unacceptably high, with no prospects of reaching the level in the general population. SUMMARY: The excess mortality in schizophrenia has received much focus. Future studies should explore the reasons for the high rates of natural causes of death, while aiming to disentangle the complex interplay between medication, lifestyle, comorbidity, treatment of somatic disorders, and genetic effects.

The association between first abortion and first-time non-fatal suicide attempt: a longitudinal cohort study of Danish population registries.

BACKGROUND: Suicidal ideation due to abortion has been used to justify restrictive US abortion policies. Much research examining abortion and mental health has relied on self-report, has had low participation rates, and did not consider confounding factors. In the present study, we used data that do not rely on self-report and are not affected by low participation rates to examine the association between abortion and non-fatal suicide attempts, adjusting for confounding factors. METHODS: In this longitudinal cohort study of Danish population registries, we linked data on a cohort of women born in Denmark between Jan 1, 1980, and Dec 30, 1998, who did not die or emigrate from Denmark before their 18th birthday or before study entry. Follow-up started on the woman's 18th birthday or Jan 1, 2000, whichever came last. Follow-up ended at the date of first suicide attempt, date of emigration from Denmark, date of death, or Dec 31, 2016, whichever came first. Women were between the ages of 18 and 36 years during the study period. We used a survival analysis to examine the risk of first suicide attempts or self-harm associated with a first abortion compared with no abortion, in the complete study cohort. To examine incidence rate ratios (IRRs) associated with abortion, we used Poisson regression with the logarithm of woman-years at risk as an offset. We also examined whether the risk of suicide attempts changed before and after the abortion, adjusting for age, calendar year, socioeconomic status, and history of childbirth, mental health, parental mental health, and physical health. FINDINGS: Data on 523 280 women were included in this study. Of these, 48 990 (9·4%) women had a record of at least one first-trimester abortion, and 10 216 (2·0%) had a suicide attempt during the study period. Among 48 990 women who had an abortion, 1402 (2·9%) had a first suicide attempt after the first abortion. In our fully-adjusted model which adjusted for all covariates, the risk of first-time non-fatal suicide attempts was similar in the year before an abortion (IRR 2·46 [95% CI 2·22-2·72]) and the year after an abortion (IRR 2·54 [2·29-2·81], p=0·509) compared with women who had not had an abortion, and decreased with increasing time since the abortion (1-5 years IRR 1·90 [1·75-2·06]; ≥5 years IRR 1·73 [1·53-1·96]). INTERPRETATION: We found that women who had abortions had a higher risk of non-fatal suicide attempts compared with women who did not have an abortion. However, because the increased risk was the same both the year before and after the abortion, it is not attributable to the abortion. Thus, policies based on the notion that abortion increases women's risk of suicide attempts are misinformed. FUNDING: Society of Family Planning, American Foundation for Suicide Prevention, and The Lundbeck Foundation Initiative for Integrative Psychiatric Research.