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.).

Lack of fit with the neighbourhood social environment as a risk factor for psychosis - a national cohort study.

BACKGROUND: Many studies report an ethnic density effect whereby psychosis incidence among ethnic minority groups is higher in low co-ethnic density areas. It is unclear whether an equivalent density effect applies with other types of socioeconomic disadvantages. METHODS: We followed a population cohort of 2 million native Danes comprising all those born on 1st January 1965, or later, living in Denmark on their 15th birthday. Socioeconomic disadvantage, based on parents' circumstances at age 15 (low income, manual occupation, single parent and unemployed), was measured alongside neighbourhood prevalence of these indices. RESULTS: Each indicator was associated with a higher incidence of non-affective psychosis which remained the same, or was slightly reduced, if neighbourhood levels of disadvantage were lower. For example, for individuals from a low-income background there was no difference in incidence for those living in areas where a low-income was least common [incidence rate ratio (IRR) 1.01; 95% confidence interval (CI) 0.93-1.10 v. those in the quintile where a low income was most common. Typically, differences associated with area-level disadvantage were the same whether or not cohort members had a disadvantaged background; for instance, for those from a manual occupation background, incidence was lower in the quintile where this was least v. most common (IRR 0.83; 95% CI 0.71-0.97), as it was for those from a non-manual background (IRR 0.77; 95% CI 0.67-0.87). CONCLUSION: We found little evidence for group density effects in contrast to previous ethnic density studies. Further research is needed with equivalent investigations in other countries to see if similar patterns are observed.

Polygenic liability, stressful life events and risk for secondary-treated depression in early life: a nationwide register-based case-cohort study.

BACKGROUND: In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark. METHODS: Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions. RESULTS: Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (ß = -0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15. CONCLUSIONS: These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.

Schizophrenia spectrum disorders in Denmark between 2000 and 2018: Incidence and early diagnostic transition.

BACKGROUND: Schizophrenia spectrum disorders (SSD) comprise a group of related mental disorders, which share clinical features and common genetic disposition, but it is unknown if there is a diagnostic transition between these disorders over time. We aimed to study the incidence at the first SSD diagnosis between 2000 and 2018, defined as schizophrenia, schizotypal or schizoaffective disorder, and the early diagnostic transition between these disorders. METHODS: Using Danish nationwide healthcare registers, we identified all individuals aged 15-64 years during the period from 2000 to 2018 in Denmark and calculated the yearly incidence rates for the specific SSDs. We studied the diagnostic pathways from the first ever diagnosis of an SSD across the subsequent two treatment courses with an SSD diagnosis to evaluate early diagnostic stability, and explore potential changes over time. RESULTS: Among 21,538 patients, yearly incidence rates per 10,000 individuals were similar during the observation period for schizophrenia (2000: 1.8; 2018: 1.6), lower for schizoaffective disorder (2000: 0.3; 2018: 0.1) and increasing for schizotypal disorder (2000: 0.7; 2018: 1.3). Among the subgroup of 13,417 individuals with three separate treatment courses, early diagnostic stability was present among 89.9% which differed between the disorders (schizophrenia: 95.4%; schizotypal disorder: 78.0%; schizoaffective disorder: 80.5%). Among 1352 (10.1%) experiencing an early diagnostic transition, 398 (3.0%) were diagnosed with schizotypal disorder after a schizophrenia or schizoaffective disorder diagnosis. CONCLUSION: This study provides comprehensive incidence rates for SSDs. The majority of patients experienced early diagnostic stability, but sizable proportions of people with initial schizophrenia or schizoaffective disorder are subsequently diagnosed with schizotypal disorder.

Perspectives on environment and health research in Denmark.

AIMS: We provide an overview of nationwide environmental data available for Denmark and its linkage potentials to individual-level records with the aim of promoting research on the potential impact of the local surrounding environment on human health. BACKGROUND: Researchers in Denmark have unique opportunities for conducting large population-based studies treating the entire Danish population as one big, open and dynamic cohort based on nationally complete population and health registries. So far, most research in this area has utilised individual- and family-level information to study the clustering of disease in families, comorbidities, risk of, and prognosis after, disease onset, and social gradients in disease risk. Linking environmental data in time and space to individuals enables novel possibilities for studying the health effects of the social, built and physical environment. METHODS: We describe the possible linkage between individuals and their local surrounding environment to establish the exposome - that is, the total environmental exposure of an individual over their life course. CONCLUSIONS: The currently available nationwide longitudinal environmental data in Denmark constitutes a valuable and globally rare asset that can help explore the impact of the exposome on human health.

Analysis of mortality metrics associated with a comprehensive range of disorders in Denmark, 2000 to 2018: A population-based cohort study.

BACKGROUND: The provision of different types of mortality metrics (e.g., mortality rate ratios [MRRs] and life expectancy) allows the research community to access a more informative set of health metrics. The aim of this study was to provide a panel of mortality metrics associated with a comprehensive range of disorders and to design a web page to visualize all results. METHODS AND FINDINGS: In a population-based cohort of all 7,378,598 persons living in Denmark at some point between 2000 and 2018, we identified individuals diagnosed at hospitals with 1,803 specific categories of disorders through the International Classification of Diseases-10th Revision (ICD-10) in the National Patient Register. Information on date and cause of death was obtained from the Registry of Causes of Death. For each of the disorders, a panel of epidemiological and mortality metrics was estimated, including incidence rates, age-of-onset distributions, MRRs, and differences in life expectancy (estimated as life years lost [LYLs]). Additionally, we examined models that adjusted for measures of air pollution to explore potential associations with MRRs. We focus on 39 general medical conditions to simplify the presentation of results, which cover 10 broad categories: circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, mental, and neurologic conditions and cancer. A total of 3,676,694 males and 3,701,904 females were followed up for 101.7 million person-years. During the 19-year follow-up period, 1,034,273 persons (14.0%) died. For 37 of the 39 selected medical conditions, mortality rates were larger and life expectancy shorter compared to the Danish general population. For these 37 disorders, MRRs ranged from 1.09 (95% confidence interval [CI]: 1.09 to 1.10) for vision problems to 7.85 (7.77 to 7.93) for chronic liver disease, while LYLs ranged from 0.31 (0.14 to 0.47) years (approximately 16 weeks) for allergy to 17.05 (16.95 to 17.15) years for chronic liver disease. Adjustment for air pollution had very little impact on the estimates; however, a limitation of the study is the possibility that the association between the different disorders and mortality could be explained by other underlying factors associated with both the disorder and mortality. CONCLUSIONS: In this study, we show estimates of incidence, age of onset, age of death, and mortality metrics (both MRRs and LYLs) for a comprehensive range of disorders. The interactive data visualization site (https://nbepi.com/atlas) allows more fine-grained analysis of the link between a range of disorders and key mortality estimates.

Temporal changes in sex- and age-specific incidence profiles of mental disorders-A nationwide study from 1970 to 2016.

OBJECTIVE: Information on mental disorders over time is critical for documenting changes in population burden, and aiding understanding of potential causal and non-causal factors. The aim of this study was to provide temporal changes in the sex- and age-specific incidence rates (IR) of mental disorders diagnosed in Danish hospitals during five decades and investigate whether such changes may be attributable to changes in administrative reporting practice. METHODS: This population-based cohort study included all people living in Denmark between 1970 and 2016. Mental disorders diagnoses were obtained from the Danish Psychiatric Central Research Register. We estimated the IR of each mental disorder (all persons, and sex- and age-specific IRs) and examined the impact of two administrative changes. RESULTS: Our study included 9 107 157 people, followed for 233.0 million person-years. During follow-up, 9.5% were diagnosed with at least one mental disorder. The IR for any mental disorder was 39.0 per 10,000 person-years. Despite fluctuations, this increased between 1970-84 and 2005-2016, from 28.9 to 63.0 per 10,000 person-years. Increases were most pronounced for younger age groups. Administrative changes did appear to influence incidence rates. CONCLUSION: Mental disorder IRs have increased in Denmark since 1970, with age of diagnosis shifting downwards. Both trends were likely impacted by administrative changes, while the latter is likely to be (partly) attributable to earlier detection and increased reporting of child-onset conditions. Our findings may provide valuable context of the epidemiology of mental disorders across age groups for comparison with other studies and populations.

Exposure to ambient air pollution during childhood and subsequent risk of self-harm: A national cohort study.

A growing body of evidence indicates that exposure to air pollution not only impacts on physical health but is also linked with a deterioration in mental health. We conducted the first study to investigate exposure to ambient particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) and nitrogen dioxide (NO2) during childhood and subsequent self-harm risk. The study cohort included persons born in Denmark between January 1, 1979 and December 31, 2006 (N = 1,424,670), with information on daily exposures to PM2.5 and NO2 at residence from birth to 10th birthday. Follow-up began from 10th birthday until first hospital-presenting self-harm episode, death, or December 31, 2016, whichever came first. Incidence rate ratios estimated by Poisson regression models revealed a dose relationship between increasing PM2.5 exposure and rising self-harm risk. Exposure to 17-19 µg/m3 of PM2.5 on average per day from birth to 10th birthday was associated with a 1.45 fold (95% CI 1.37-1.53) subsequently elevated self-harm risk compared with a mean daily exposure of <13 µg/m3, whilst those exposed to 19 µg/m3 or above on average per day had a 1.59 times (1.45-1.75) elevated risk. Higher mean daily exposure to NO2 during childhood was also linked with increased self-harm risk, but the dose-response relationship observed was less evident than for PM2.5. Covariate adjustment attenuated the associations, but risk remained independently elevated. Although causality cannot be assumed, these novel findings indicate a potential etiological involvement of ambient air pollution in the development of mental ill health.

Parental income as a marker for socioeconomic position during childhood and later risk of developing a secondary care-diagnosed mental disorder examined across the full diagnostic spectrum: a national cohort study.

BACKGROUND: Links between parental socioeconomic position during childhood and subsequent risks of developing mental disorders have rarely been examined across the diagnostic spectrum. We conducted a comprehensive analysis of parental income level, including income mobility, during childhood and risks for developing mental disorders diagnosed in secondary care in young adulthood. METHODS: National cohort study of persons born in Denmark 1980-2000 (N = 1,051,265). Parental income was measured during birth year and at ages 5, 10 and 15. Follow-up began from 15th birthday until mental disorder diagnosis or 31 December 2016, whichever occurred first. Hazard ratios and cumulative incidence were estimated. RESULTS: A quarter (25.2%; 95% CI 24.8-25.6%) of children born in the lowest income quintile families will have a secondary care-diagnosed mental disorder by age 37, versus 13.5% (13.2-13.9%) of those born in the highest income quintile. Longer time spent living in low-income families was associated with higher risks of developing mental disorders. Associations were strongest for substance misuse and personality disorders and weaker for mood disorders and anxiety/somatoform disorders. An exception was eating disorders, with low parental income being associated with attenuated risk. For all diagnostic categories examined except for eating disorders, downward socioeconomic mobility was linked with higher subsequent risk and upward socioeconomic mobility with lower subsequent risk of developing mental disorders. CONCLUSIONS: Except for eating disorders, low parental income during childhood is associated with subsequent increased risk of mental disorders diagnosed in secondary care across the diagnostic spectrum. Early interventions to mitigate the disadvantages linked with low income, and better opportunities for upward socioeconomic mobility could reduce social and mental health inequalities.

Antiepileptic Drugs and Suicide: Role of Prior Suicidal Behavior and Parental Psychiatric Disorder.

OBJECTIVE: To examine whether prior suicidal behavior and familial predisposition to psychiatric disorders modify the association between antiepileptic drug use and completed suicide. METHODS: Using the Danish National Prescription Register, we identified all incident users of antiepileptic drugs aged 15 years or older in Denmark between July 1997 and December 2015. We carried out a nested case-control study and defined exposure to antiepileptic drugs at the index date (ie, time of suicide). Conditional logistic regressions were used to estimate mortality rate ratios (MRRs) of suicide in current versus previous users of antiepileptic drugs. We also analyzed suicide risk associated with the 9 most commonly used antiepileptic drugs. RESULTS: We identified 1,759 individuals completing suicide. Current versus previous use of any antiepileptic drug was associated with an increased risk of suicide (MRR = 1.26, 95% confidence interval [CI] = 1.13-1.40). This excess risk was observed in individuals with a history of suicidal behavior (MRR = 1.28, 95% CI = 1.07-1.54) and in those without (MRR = 1.26, 95% CI = 1.11-1.43), and in individuals with a familial predisposition to psychiatric disorders (MRR = 1.48, 95% CI = 1.18-1.87) and in those without (MRR = 1.21, 95% CI = 1.07-1.35). INTERPRETATION: Use of antiepileptic drugs was associated with an increased risk of suicide. The findings do not support that the risk of suicide following treatment with antiepileptic drugs identified in randomized trials is explained by prior suicidality or familial predisposition to psychiatric disorders. The additional risk of suicide associated with use of antiepileptic drugs was generally low and should be balanced against benefits of treatment. ANN NEUROL 2019;86:951-961.

Adolescent residential mobility, genetic liability and risk of schizophrenia, bipolar disorder and major depression.

BACKGROUND: Residential mobility during upbringing, and especially adolescence, is associated with multiple negative mental health outcomes. However, whether associations are confounded by unmeasured familial factors, including genetic liability, is unclear. AIMS: We used a population-based case-cohort study to assess whether polygenic risk scores (PRSs) for schizophrenia, bipolar disorder and major depression were associated with mobility from ages 10-14 years, and whether PRS and parental history of mental disorder together explained associations between mobility and each disorder. METHOD: Information on cases (n = 4207 schizophrenia, n = 1402 bipolar disorder, n = 18 215 major depression) and a random population sample (n = 17 582), born 1981-1997, was linked between Danish civil and psychiatric registries. Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of separate, large meta-analyses. RESULTS: PRSs for schizophrenia and major depression were weakly associated with moving once (odds ratio 1.07, 95% CI 1.00-1.16; and odds ratio 1.10, 95% CI 1.04-1.17, respectively), but not twice or three or more times. Mobility was positively associated with each disorder, with more moves associated with greater risk. Adjustment for PRS produced slight reductions in the magnitude of associations. Adjustment for PRS and parental history of mental disorder together reduced estimates by 5-11%. In fully adjusted models mobility was associated with all three disorders; hazard ratios ranged from 1.33 (95% CI 1.08-1.62; one move and bipolar disorder) to 3.05 (95% CI 1.92-4.86; three or more moves and bipolar disorder). CONCLUSIONS: Associations of mobility with schizophrenia, bipolar disorder and depression do not appear to be attributable to genetic liability as measured here. Potential familial confounding of mobility associations may be predominantly environmental in nature.

Temporal trends in incidence of hospital-treated self-harm among adolescents in Denmark: national register-based study.

BACKGROUND: Studies conducted in the UK and in Ireland have reported increased rates of self-harm in adolescent females from around the time of the 2008 economic recession and through periods of subsequent national austerity programme implementation. It is not known if incidence rates have increased similarly in other Western European countries during this period. METHODS: Data from interlinked national administrative registers were extracted for individuals born in Denmark during 1981-2006. We estimated gender- and age-specific incidence rates (IRs) per 10,000 person-years at risk for hospital-treated non-fatal self-harm during 2000-2016 at ages 10-19 years. RESULTS: Incidence of self-harm peaked in 2007 (IR 25.1) and then decreased consistently year on year to 13.8 in 2016. This pattern was found in all age groups, in both males and females and in each parental income tertile. During the last 6 years of the observation period, 2011-2016, girls aged 13-16 had the highest incidence rates whereas, among boys, incidence was highest among 17-19 year olds throughout. CONCLUSIONS: The temporal increases in incidence rates of self-harm among adolescents observed in some Western European countries experiencing major economic recession were not observed in Denmark. Restrictions to sales of analgesics, access to dedicated suicide prevention clinics, higher levels of social spending and a stronger welfare system may have protected potentially vulnerable adolescents from the increases seen in other countries. A better understanding of the specific mechanisms behind the temporal patterns in self-harm incidence in Denmark is needed to help inform suicide prevention in other nations.

Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders.

BACKGROUND: Common infectious pathogens have been associated with psychiatric disorders, self-violence and risk-taking behavior. METHODS: This case-control study reviews register data on 81,912 individuals from the Danish Blood Donor Study to identify individuals who have a psychiatric diagnosis (N = 2591), have attempted or committed suicide (N = 655), or have had traffic accidents (N = 2724). For all cases, controls were frequency matched by age and sex, resulting in 11,546 participants. Plasma samples were analyzed for immunoglobulin G (IgG) antibodies against Toxoplasma gondii and cytomegalovirus (CMV). RESULTS: T. gondii was detected in 25·9% of the population and was associated with schizophrenia (odds ratio [OR], 1·47; 95% confidence interval [CI], 1·03-2·09). Accounting for temporality, with pathogen exposure preceding outcome, the association was even stronger (IRR, 2·78; 95% CI, 1·27-6·09). A very weak association between traffic accident and toxoplasmosis (OR, 1·11; 95% CI, 1·00-1·23, p = 0.054) was found. CMV was detected in 60·8% of the studied population and was associated with any psychiatric disorder (OR, 1·17; 95% CI, 1·06-1·29), but also with a smaller group of neurotic, stress-related, and somatoform disorders (OR, 1·27; 95% CI, 1·12-1·44), and with attempting or committing suicide (OR, 1·31; 95% CI, 1·10-1·56). Accounting for temporality, any psychiatric disorder (IRR, 1·37; 95% CI, 1·08-1·74) and mood disorders (IRR, 1·43; 95% CI, 1·01-2·04) were associated with exposure to CMV. No association between traffic accident and CMV (OR, 1·06; 95% CI, 0·97-1·17) was found. CONCLUSIONS: This large-scale serological study is the first study to examine temporality of pathogen exposure and to provide evidence of a causal relationship between T. gondii and schizophrenia, and between CMV and any psychiatric disorder.

Premature mortality in persons with epilepsy and schizophrenia: A population-based nationwide cohort study.

OBJECTIVE: To determine the mortality for persons with epilepsy and schizophrenia by absolute and relative measures. METHODS: This is a population-based nationwide cohort study of persons born in Denmark from 1960 to 1987 who were alive and residing in Denmark on their 25th birthday. We identified persons diagnosed with epilepsy and schizophrenia prior to their 25th birthday and followed them to death, emigration, or December 31, 2012, whichever came first. The primary outcome was overall mortality. Data were analyzed using Cox regressions. RESULTS: Persons were followed for 24 167 573 person years; the median was 15 years. The mortality rate ratio was 4.4 (95% confidence interval [CI] = 4.1-4.7) for persons with epilepsy, 6.6 (95% CI = 6.1-7.1) for persons with schizophrenia, and 12.8 (95% CI = 9.1-18.1) for persons with both disorders, compared with persons without these disorders. The estimated cumulative mortality at the age of 50 years was 3.1% (95% CI = 3.0-3.1) for persons without epilepsy and schizophrenia, 10.7% (95% CI = 9.7-11.8) for persons with epilepsy, 17.4% (95% CI = 16.0-18.8) for persons with schizophrenia, and 27.2% (95% CI = 15.7-40.1) for persons with both disorders. SIGNIFICANCE: Persons with epilepsy and schizophrenia have very high mortality; more than one in four persons with both disorders died between the age of 25 and 50 years, indicating that these patients need special clinical attention.

Nitrate in drinking water and colorectal cancer risk: A nationwide population-based cohort study.

Nitrate in drinking water may increase risk of colorectal cancer due to endogenous transformation into carcinogenic N-nitroso compounds. Epidemiological studies are few and often challenged by their limited ability of estimating long-term exposure on a detailed individual level. We exploited population-based health register data, linked in time and space with longitudinal drinking water quality data, on an individual level to study the association between long-term drinking water nitrate exposure and colorectal cancer (CRC) risk. Individual nitrate exposure was calculated for 2.7 million adults based on drinking water quality analyses at public waterworks and private wells between 1978 and 2011. For the main analyses, 1.7 million individuals with highest exposure assessment quality were included. Follow-up started at age 35. We identified 5,944 incident CRC cases during 23 million person-years at risk. We used Cox proportional hazards models to estimate hazard ratios (HRs) of nitrate exposure on the risk of CRC, colon and rectal cancer. Persons exposed to the highest level of drinking water nitrate had an HR of 1.16 (95% CI: 1.08-1.25) for CRC compared with persons exposed to the lowest level. We found statistically significant increased risks at drinking water levels above 3.87 mg/L, well below the current drinking water standard of 50 mg/L. Our results add to the existing evidence suggesting increased CRC risk at drinking water nitrate concentrations below the current drinking water standard. A discussion on the adequacy of the drinking water standard in regards to chronic effects is warranted.

Parental age and risk of epilepsy: A nationwide register-based study.

OBJECTIVE: This study aims to examine the association between maternal age, paternal age, and parental age difference at the time of birth and the risk of epilepsy in the offspring. METHODS: We carried out a prospective population-based register study of all singletons born in Denmark between 1981 and 2012. Cox regression was used to estimate hazard ratios (HRs) of epilepsy and their corresponding 95% confidence intervals (CIs), adjusted for relevant confounders. RESULTS: We followed 1 587 897 individuals for a total of ~25 million person-years and identified 21 797 persons with epilepsy during the study period. An excess risk of epilepsy was found in individuals born to mothers younger than 20 years (HR = 1.17, 95% CI = 1.07-1.29) and born to parental couples where paternal age exceeded maternal age by at least 5 years. The risk of epilepsy increased with increasing parental age gap and was highest when the father was ≥15 years older than the mother (adjusted HR = 1.28, 95% CI = 1.16-1.41). In contrast to maternal age, we found that paternal age did not independently contribute to offspring epilepsy risk, once we accounted for the parental age difference (P = .1418). The observed associations with maternal age and parental age gap were invariant to epilepsy subtypes, but were modified by age of epilepsy onset, with the effect being most pronounced in the first 10 years of the child's life. SIGNIFICANCE: Maternal age and parental age gap, but not paternal age, were associated with the offspring's risk of epilepsy. Our results do not support the hypothesis that de novo mutations associated with advanced paternal age increase the risk of epilepsy in the offspring.

Induced first-trimester abortion and risk of mental disorder.

BACKGROUND: Concern has been expressed about potential harm to women's mental health in association with having an induced abortion, but it remains unclear whether induced abortion is associated with an increased risk of subsequent psychiatric problems. METHODS: We conducted a population-based cohort study that involved linking information from the Danish Civil Registration system to the Danish Psychiatric Central Register and the Danish National Register of Patients. The information consisted of data for girls and women with no record of mental disorders during the 1995-2007 period who had a first-trimester induced abortion or a first childbirth during that period. We estimated the rates of first-time psychiatric contact (an inpatient admission or outpatient visit) for any type of mental disorder within the 12 months after the abortion or childbirth as compared with the 9-month period preceding the event. RESULTS: The incidence rates of first psychiatric contact per 1000 person-years among girls and women who had a first abortion were 14.6 (95% confidence interval [CI], 13.7 to 15.6) before abortion and 15.2 (95% CI, 14.4 to 16.1) after abortion. The corresponding rates among girls and women who had a first childbirth were 3.9 (95% CI, 3.7 to 4.2) before delivery and 6.7 (95% CI, 6.4 to 7.0) post partum. The relative risk of a psychiatric contact did not differ significantly after abortion as compared with before abortion (P = 0.19) but did increase after childbirth as compared with before childbirth (P < 0.001). CONCLUSIONS: The finding that the incidence rate of psychiatric contact was similar before and after a first-trimester abortion does not support the hypothesis that there is an increased risk of mental disorders after a first-trimester induced abortion.

Absolute and relative risk of violent victimisation and perpetration following onset of mental illness: a Danish register-based study.

Background: Previous research has suggested that people with severe mental illness are at elevated risk of both violence perpetration and violent victimisation, with risk of the latter being perhaps greater than the former. However, few studies have examined risk across both outcomes. Methods: Using a total population approach, the absolute and relative risks of victimisation and perpetration were estimated for young men and women across the full psychiatric diagnostic spectrum. Information on mental disorder status was extracted from national registers and information on violent victimisation and perpetration outcomes from police records. The follow-up was from age 15 to a maximum of 31 years, with most of the person-time at risk pertaining to cohort members aged in their early twenties. Both absolute risk (at 1 and 5 years from onset of illness) and relative risk were estimated. Findings: Both types of violent outcome occurred more frequently amongst those with mental illness than the general population. However, whether risk of one was greater than the other depended on a range of factors, including sex and diagnosis. Men with a mental disorder had higher absolute risks of both outcomes than women [victimisation: Cin (5 year) = 7.15 (6.88-7.42) versus Cin (5 year) = 4.79 (4.61-4.99); perpetration: Cin (5 year) = 8.17 (7.90-8.46) versus Cin (5 year) = 1.86 (1.75-1.98)], as was the case with persons in the general population without a recorded mental illness diagnosis. Women with mental illness had higher absolute risk of victimisation than perpetration, which was also true for men and women without mental illness. However, the opposite was true for men with mental illness. Men and women with diagnoses of personality disorders, substance use disorders, and schizophrenia-spectrum disorders were at highest risk of victimisation and perpetration. Interpretation: Strategies developed to prevent violent victimisation and violence perpetration may need to be tailored for young adults with mental disorders. There may also be a benefit in taking a sex-specific approach to prevention in this group. Funding: This study was supported by an Australian National Health and Medical Research Council Investigator Grant awarded to the first author.

Exposure to air pollution and risk of respiratory tract infections in the adult Danish population-a nationwide study.

OBJECTIVES: The association between air pollution and risk of respiratory tract infection (RTI) in adults needs to be clarified in settings with low to moderate levels of air pollution. We investigated this in the Danish population between 2004 and 2016. METHODS: We included 3 653 490 persons aged 18-64 years in a nested case-control study. Exposure was defined as the average daily concentration at the individual's residential address of CO, NOX, NO2, O3, SO2, NH3, PPM2.5, black carbon, organic carbon, mineral dust, sea salt, secondary inorganic aerosols, SO42-, NO3-, NH4+, secondary organic aerosols, PM2.5, and PM10 during a 3-month exposure window. RTIs were defined by hospitalization for RTIs. Incidence rate ratios (IRRs) and 95% CIs were estimated comparing highest with lowest decile of exposure using conditional logistic regression models. RESULTS: In total, 188 439 incident cases of RTI were identified. Exposure to most air pollutants was positively associated with risk of RTI. For example, NO2 showed an IRR of 1.52 (CI: 1.48-1.55), and PM2.5 showed an IRR of 1.45 (CI: 1.40-1.50). In contrast, exposure to sea salt, PM10, NH3, and O3 was negatively associated with a risk of RTIs. DISCUSSION: In this nationwide study comprising adults, exposure to air pollution was associated with risk of RTIs and subgroups hereof. Sea salt, PM10, NH3, and O3 may be proxies for rural areas, as the levels of these species in Denmark are higher near the western coastlines and/or in rural areas with fewer combustion sources.

PM2.5 air pollution components and mortality in Denmark.

BACKGROUND: Ambient fine particulate matter (PM2.5) causes millions of deaths every year worldwide. Identification of the most harmful types of PM2.5 would facilitate efficient prevention strategies. OBJECTIVES: The aim of this study was to investigate associations between components of PM2.5 and mortality in a nation-wide Danish population. METHODS: Our study base was Danes born 1921-1985 and aged 30-85 years, who were followed up for mortality from 1991 to 2015. We included 678,465 natural cause mortality cases and selected five age, sex and calendar time matched controls to each case from the study base. We retrieved the address history of the study population from Danish registries and assessed five-year average concentrations of eight PM2.5 components using deterministic Chemistry-Transport Models air pollution models. We estimated mortality rate ratios (MRRs) by conditional logistic regression and adjusted for socio-demographical factors at individual and neighborhood level. RESULTS: Single pollutant models showed the strongest associations between natural cause mortality and an interquartile increase in sulfate particles (SO4--) (MRR: 1.123; 95 % CI: 1.100-1.147 per 1.5 µg/m3) and secondary organic aerosol (SOA) (MRR: 1.054; 95 % CI: 1.048-1.061 per 0.050 µg/m3). Two-pollutant models showed robust associations between SO4-- and SOA and natural cause mortality. Elemental carbon and mineral dust showed robust associations with higher respiratory and lung cancer mortality. CONCLUSION: This nation-wide study found robust associations between natural cause mortality and SO4-- particles and SOA, which is in line with the results of previous studies. Elemental carbon and mineral dust showed robust associations with higher respiratory and lung cancer mortality.