Showing papers by "Carsten Bøcker Pedersen published in 2020"

Association between Mental Disorders and Subsequent Medical Conditions

Abstract: 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 c...

Incidence Rates and Cumulative Incidences of the Full Spectrum of Diagnosed Mental Disorders in Childhood and Adolescence.

Abstract: Importance Knowledge about the epidemiology of mental disorders in children and adolescents is essential for research and planning of health services. Surveys can provide prevalence rates, whereas population-based registers are instrumental to obtain precise estimates of incidence rates and risks. Objective To estimate age- and sex-specific incidence rates and risks of being diagnosed with any mental disorder during childhood and adolescence. Design This cohort study included all individuals born in Denmark from January 1, 1995, through December 31, 2016 (1.3 million), and followed up from birth until December 31, 2016, or the date of death, emigration, disappearance, or diagnosis of 1 of the mental disorders examined (14.4 million person-years of follow-up). Data were analyzed from September 14, 2018, through June 11, 2019. Exposures Age and sex. Main Outcomes and Measures Incidence rates and cumulative incidences of all mental disorders according to theICD-10 Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research,diagnosed before 18 years of age during the study period. Results A total of 99 926 individuals (15.01%; 95% CI, 14.98%-15.17%), including 41 350 girls (14.63%; 95% CI, 14.48%-14.77%) and 58 576 boys (15.51%; 95% CI, 15.18%-15.84%), were diagnosed with a mental disorder before 18 years of age. Anxiety disorder was the most common diagnosis in girls (7.85%; 95% CI, 7.74%-7.97%); attention-deficit/hyperactivity disorder (ADHD) was the most common in boys (5.90%; 95% CI, 5.76%-6.03%). Girls had a higher risk than boys of schizophrenia (0.76% [95% CI, 0.72%-0.80%] vs 0.48% [95% CI, 0.39%-0.59%]), obsessive-compulsive disorder (0.96% [95% CI, 0.92%-1.00%] vs 0.63% [95% CI, 0.56%-0.72%]), and mood disorders (2.54% [95% CI, 2.47%-2.61%] vs 1.10% [95% CI, 0.84%-1.21%]). Incidence peaked earlier in boys than girls in ADHD (8 vs 17 years of age), intellectual disability (5 vs 14 years of age), and other developmental disorders (5 vs 16 years of age). The overall risk of being diagnosed with a mental disorder before 6 years of age was 2.13% (95% CI, 2.11%-2.16%) and was higher in boys (2.78% [95% CI, 2.44%-3.15%]) than in girls (1.45% [95% CI, 1.42%-1.49%]). Conclusions and Relevance This nationwide population-based cohort study provides a first comprehensive assessment of the incidence and risks of mental disorders in childhood and adolescence. By 18 years of age, 15.01% of children and adolescents in this study were diagnosed with a mental disorder. The incidence of several neurodevelopmental disorders peaked in late adolescence in girls, suggesting possible delayed detection. The distinct signatures of the different mental disorders with respect to sex and age may have important implications for service planning and etiological research.

Association of Mental Disorder in Childhood and Adolescence With Subsequent Educational Achievement.

Abstract: Importance Onset of mental disorders during childhood or adolescence has been associated with underperformance in school and impairment in social and occupational life in adulthood, which has important implications for the affected individuals and society. Objective To compare the educational achievements at the final examination of compulsory schooling in Denmark between individuals with and those without a mental disorder. Design, Setting, and Participants This population-based cohort study was conducted in Denmark and obtained data from the Danish Civil Registration System and other nationwide registers. The 2 cohorts studied were (1) all children who were born in Denmark between January 1, 1988, and July 1, 1999, and were alive at age 17 years (n = 629 622) and (2) all children who took the final examination at the end of ninth grade in both Danish and mathematics subjects between January 1, 2002, and December 31, 2016 (n = 542 500). Data analysis was conducted from March 1, 2018, to March 1, 2019. Exposures Clinical diagnosis by a psychiatrist of any mental disorder or 1 of 29 specific mental disorders before age 16 years. Main Outcomes and Measures Taking the final examination at the end of ninth grade and mean examination grades standardized aszscores with differences measured in SDs (standardized mean grade difference). Results Of the total study population (n = 629 622; 306 209 female and 323 413 male), 523 312 individuals (83%) took the final examination before 17 years of age and 38 001 (6%) had a mental disorder before that age. Among the 542 500 individuals (274 332 female and 268 168 male), the mean (SD) age was 16.1 (0.33) years for the females and 16.2 (0.34) years for the males. Among the 15 843 female and 22 158 male students with a mental disorder, a lower proportion took the final examination (0.52; 95% CI, 0.52-0.53) compared with individuals without a mental disorder (0.88; 95% CI, 0.88-0.88). Mental disorders affected the grades of male individuals (standardized mean grade difference, –0.30; 95% CI, –0.32 to –0.28) more than the grades of their female peers (standardized mean grade difference, –0.24; 95% CI, –0.25 to –0.22) when compared with same-sex individuals without mental disorders. Most specific mental disorders were associated with statistically significantly lower mean grades, with intellectual disability associated with the lowest grade in female and male students (standardized mean grade difference, –1.07 [95% CI, –1.23 to –0.91] and –1.03 [95% CI, –1.17 to –0.89];P = .76 for sex differences in the mean grades). Female and male students with anorexia nervosa achieved statistically significantly higher grades on the final examination (standardized mean grade difference, 0.38 [95% CI, 0.32-0.44] and 0.31 [95% CI, 0.11-0.52];P = .54 for sex differences in the mean grades) compared with their peers without this disorder. For those with anxiety, attachment, attention-deficit/hyperactivity, and other developmental disorders, female individuals attained relatively lower standardized mean grades compared with their male counterparts. Conclusions and Relevance Results of this study suggest that, in Denmark, almost all mental disorders in childhood or adolescence may be associated with a lower likelihood of taking the final examination at the end of ninth grade; those with specific disorders tended to achieve lower mean grades on the examination; and female, compared with male, individuals with certain mental disorders appeared to have relatively more impairment. These findings appear to emphasize the need to provide educational support to young people with mental disorders.

Air pollution and family related determinants of asthma onset and persistent wheezing in children: nationwide case-control study.

Abstract: Objective To identify risk factors (air pollution and family related) for the onset of asthma and persistent wheezing in children Design Nationwide case-control study Setting Denmark Participants All Danish children born from 1997 to 2014 and followed for asthma onset and persistent wheezing from age 1 year to 15 years Main outcome measure Onset of asthma and persistent wheezing Results A higher incidence of asthma was found in children of parents with asthma (adjusted hazard ratio 229 (95% confidence interval 222 to 235) and mothers who smoked during pregnancy (120, 118 to 122), whereas a lower incidence was found in children of parents with high educational attainment (072, 069 to 075) and high incomes (085, 081 to 089) Exposure to particulate matter ≤25 µm (PM25) and ≤10 µm (PM10) and nitrate was associated with an increased risk of asthma and persistent wheezing, with hazard ratios per 5 µg/m3 increase in pollutant concentrations 105 (103 to 107) for PM25, 104 (102 to 106) for PM10, and 104 (103 to 104) for nitrogen dioxide Only the positive association of PM25 with asthma and persistent wheezing remained robust across the different models and in sensitivity analyses Conclusions The findings of this study suggest that children exposed to higher levels of PM25 are more likely to develop asthma and persistent wheezing than children who are not exposed Other risk factors associated with these outcomes were parental asthma, parental education, and maternal smoking during pregnancy

Comorbidity within mental disorders : A comprehensive analysis based on 145 990 survey respondents from 27 countries

Abstract: AIMS: Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys. METHODS: The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women. RESULTS: Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2-110.8, interquartile range = 6.0-19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1-2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs. CONCLUSIONS: Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.

Exposure to Manganese in Drinking Water during Childhood and Association with Attention-Deficit Hyperactivity Disorder: A Nationwide Cohort Study

Abstract: Background: Manganese (Mn) in drinking water may increase the risk of several neurodevelopmental outcomes, including attention-deficit hyperactivity disorder (ADHD). Earlier epidemiological studies...

The Association between Residential Green Space in Childhood and Development of Attention Deficit Hyperactivity Disorder: A Population-Based Cohort Study.

Abstract: Background: Access to green space has been hypothesized to have a beneficial impact on children’s mental well-being and cognitive development. The underlying mechanisms of the mental health benefit...

Association between parental income during childhood and risk of schizophrenia later in life

Abstract: Importance Evidence linking parental socioeconomic position and offspring’s schizophrenia risk has been inconsistent, and how risk is associated with parental socioeconomic mobility has not been investigated. Objective To elucidate the association between parental income level and income mobility during childhood and subsequent schizophrenia risk. Design, Setting, and Participants National cohort study of all persons born in Denmark from January 1, 1980, to December 31, 2000, who were followed up from their 15th birthday until schizophrenia diagnosis, emigration, death, or December 31, 2016, whichever came first. Data analyses were from March 2018 to June 2019. Exposure Parental income, measured at birth year and at child ages 5, 10, and 15 years. Main Outcomes and Measures Hazard ratios (HRs) for schizophrenia were estimated using Cox proportional hazard regression. Cumulative incidence values (absolute risks) were also calculated. Results The cohort included 1 051 033 participants, of whom 51.3% were male. Of the cohort members, 7544 (4124 [54.7%] male) were diagnosed with schizophrenia during 11.6 million person-years of follow-up. There was an inverse association between parental income level and subsequent schizophrenia risk, with children from lower income families having especially elevated risk. Estimates were attenuated, but risk gradients remained after adjustment for urbanization, parental mental disorders, parental educational levels, and number of changes in child-parent separation status. A dose-response association was observed with increasing amount of time spent in low-income conditions being linked with higher schizophrenia risk. Regardless of parental income level at birth, upward income mobility was associated with lower schizophrenia risk compared with downward mobility. For example, children who were born and remained in the lowest income quintile at age 15 years had a 4.12 (95% CI, 3.71-4.58) elevated risk compared with the reference group, those who were born in and remained in the most affluent quintile, but even a rise from the lowest income quintile at birth to second lowest at age 15 years appeared to lessen the risk elevation (HR, 2.80; 95% CI, 2.46-3.17). On the contrary, for those born in the most affluent quintile, downward income mobility between birth and age 15 years was associated with increased risks of developing schizophrenia. Conclusions and Relevance This study’s findings suggest that parental income level and income mobility during childhood may be linked with schizophrenia risk. Although both causation and selection mechanisms could be involved, enabling upward income mobility could influence schizophrenia incidence at the population level.

The iPSYCH2015 Case-Cohort sample: updated directions for unravelling genetic and environmental architectures of severe mental disorders

Abstract: The Lundbeck Foundation Integrative Psychiatric Research (iPSYCH) consortium has almost doubled its Danish population-based Case–Cohort sample (iPSYCH2012). The newly updated cohort, named iPSYCH2015, expands the study base with 56,233 samples, to a combined total of 141,265 samples. The cohort is nested within the Danish population born between 1981 and 2008 and is a Case-Cohort design including 50,615 population controls. We added more cases to the existing phenotypes identified with, schizophrenia (Nnew=4,131/Ntotal=8,113), autism (Nnew=8,056 / Ntotal=24,975), attention-deficit/hyperactivity disorder (Nnew=10,026/Ntotal=29,668) and affective disorder (Nnew=13,999/Ntotal=40,482) of which a subset has bipolar affective disorder (N-new=1,656/Ntotal=3,819). We also added two additional focus phenotypes, schizophrenia spectrum disorder (N=16,008) and post-partum disorder (N=3,421). In total, the expanded iPSYCH2015 sample consists of 93,608 unique individuals in the case groups and 50,615 population controls. For the sample expansion, DNA was extracted and amplified from dried blood spots samples stored within the Danish Neonatal Screening Biobank and genotyped using the Illumina Global Screening Array. The Biobank sample retrieval rate was 95%, and the genotyping success rate was 92% (97% of retrieved). We expanded the follow-up period by three years, including data such as longitudinal information on health, prescribed medicine, social and socioeconomic information.

Association Between Childhood Green Space, Genetic Liability, and the Incidence of Schizophrenia

Abstract: Childhood exposure to green space has previously been associated with lower risk of developing schizophrenia later in life. It is unclear whether this association is mediated by genetic liability or whether the 2 risk factors work additively. Here, we investigate possible gene-environment associations with the hazard ratio (HR) of schizophrenia by combining (1) an estimate of childhood exposure to residential-level green space based on the normalized difference vegetation index (NDVI) from Landsat satellite images, with (2) genetic liability estimates based on polygenic risk scores for 19 746 genotyped individuals from the Danish iPSYCH sample. We used information from the Danish registers of health, residential address, and socioeconomic status to adjust HR estimates for established confounders, ie, parents' socioeconomic status, and family history of mental illness. The adjusted HRs show that growing up surrounded by the highest compared to the lowest decile of NDVI was associated with a 0.52-fold (95% confidence interval [CI]: 0.40 to 0.66) lower schizophrenia risk, and children with the highest polygenic risk score had a 1.24-fold (95% CI: 1.18 to 1.30) higher schizophrenia risk. We found that NDVI explained 1.45% (95% CI: 1.07 to 1.90) of the variance on the liability scale, while polygenic risk score for schizophrenia explained 1.01% (95% CI: 0.77 to 1.46). Together they explained 2.40% (95% CI: 1.99 to 3.07) with no indication of a gene-environment interaction (P = .29). Our results suggest that risk of schizophrenia is associated additively with green space exposure and genetic liability, and provide no support for an environment-gene interaction between NDVI and schizophrenia.

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

Abstract: 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. 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. 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. 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.

Self-harm and violent criminality linked with parental death during childhood.

Abstract: Background Adverse health and social outcomes are known to occur more frequently following parental death during childhood, but evidence is lacking for comparing long-term risks of internalised v. externalised harm. Methods This national register-based cohort study consisted of Danish persons born 1970–2000. The Civil Registration System and National Causes of Death Register were linked to ascertain parental deaths by cause before cohort members' 15th birthdays. From age 15 years, hospital-treated self-harm episodes were ascertained through linkage to the National Patient Register and the Psychiatric Central Research Register, and violent crimes were identified via linkage to the National Crime Register. Hazard ratio and cumulative incidence values were estimated. Results Self-harm and violent criminality risks were elevated following parental death during childhood. Covariate adjustment for gender, birth year and first-degree relatives' mental illnesses attenuated these associations, although significantly heightened risks persisted. The estimated hazard ratios did not differ greatly according to which parent died, but losing both parents conferred particularly large risk increases. Risks for both adverse outcomes were higher in relation to unnatural v. natural parental death; violent criminality risk was especially raised among individuals exposed to parental death by unnatural causes other than suicide. The association was strongest when pre-school age children experienced parental death. Conclusions Effective early intervention is needed to help youngsters who have experienced the death of one or both parents to develop immediate and sustained coping strategies. Enhanced cooperation between health and social services and criminal justice agencies may mitigate risks for these two destructive behaviours.

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.

Abstract: 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. 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. 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. 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.

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

Abstract: 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.

Adverse Childhood Experiences and Risk of Subsequently Engaging in Self-Harm and Violence towards Other People-"Dual Harm".

Abstract: The etiology of “dual harm” (the co-occurrence of self-harm and externalized violence in the same individual) is under-researched. Risk factors have mostly been investigated for each behavior separately. We aimed to examine adversities experienced between birth and age 15 years among adolescents and young adults with histories of self-harm and violent criminality, with a specific focus on dual harm. Three nested case-control studies were delineated using national interlinked Danish registers; 58,409 cases in total aged 15–35 were identified: 28,956 with a history of violent criminality (but not self-harm), 25,826 with a history of self-harm (but not violent criminality), and 3987 with dual-harm history. Each case was matched by date of birth and gender to 20 controls who had not engaged in either behavior. We estimated exposure prevalence for cases versus controls for each of the three behavior groups, and incidence rate ratios (IRRs). Experiencing five or more childhood adversities was more prevalent among individuals with dual-harm history (19.3%; 95% CI 18.0, 20.8%) versus self-harm (10.9%; 10.5, 11.3%) and violence (11.4%; 11.0%, 11.8%) histories. The highest IRRs for dual harm were linked with parental unemployment (5.15; 95% CI 4.71, 5.64), parental hospitalization following self-harm (4.91; 4.40, 5.48) or assault (5.90; 5.07, 6.86), and parental violent criminality (6.11; 5.57, 6.70). Growing up in environments that are characterized by poverty, violence, and substance misuse, and experiencing multiple adversities in childhood, appear to be especially strongly linked with elevated dual-harm risk. These novel findings indicate potential etiologic pathways to dual harm.

Elevated DNA Methylation Gestational Age is associated with the Risk of Later Bipolar Disorder and Anorexia Nervosa in Twins

Abstract: Background Foetal development indicates the risk of later disease, but has only been associated with few psychiatric disorders. An aggregated molecular marker of development - DNA methylation based estimates of gestational age (DNAmGA) adjusted for GA, can be indicative of foetal health and development. Twins have the same chronological GA and monozygotic (MZ) twins share genetic liability. We leveraged this to examine whether DNAmGA in neonates associate with later psychiatric disorder, independent of chronological GA, maternal characteristics, genetic influences, and shared environmental factors. Method We estimated DNAmGA in 260 MZ and 396 dizygotic (DZ) twin pairs, later diagnosed with schizophrenia, bipolar disorder, affective/depressive mood disorder, autism spectrum disorder, attention deficit hyperactivity disorder or anorexia. DNAmGA was tested for association with psychiatric outcome by mean discordant twin differences and by linear mixed model (LMM), adjusting for relatedness and potential confounders. Results We found elevated DNAmGA to associate with anorexia between discordant DZ and MZ twins (0.74 weeks, 95%CI[0.34:1.14] and 0.28 weeks, 95%CI[0.04:0.53], respectively), and with bipolar disorder between discordant MZ twins (0.85 weeks, 95%CI[0.16:1.53]). Elevated DNAmGA associated significantly with both in the LMM analysis (0.56 weeks, 95%CI[0.32:0.83] and 0.89 weeks, 95%CI[0.32:1.51], respectively). Conclusions Elevated DNAmGA is associated with two later onset psychiatric disorders in twins, and thus supports a developmental origin of disease. This association was not confounded by variation in conventional measures of foetal development nor genetic liability. We therefore propose that a novel molecular marker of development, can differentiate between later psychiatric outcome in newborn twins.