Incidence Rates and Cumulative Incidences of the Full Spectrum of Diagnosed Mental Disorders in Childhood and Adolescence | Adolescent Medicine | JAMA Psychiatry | JAMA Network
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Figure 1.  Sex- and Age-Specific Incidence Rates and Cumulative Incidences for Any Mental Disorder, Schizophrenia Spectrum Disorder, Mood Disorders, and Anxiety Disorder
Sex- and Age-Specific Incidence Rates and Cumulative Incidences for Any Mental Disorder, Schizophrenia Spectrum Disorder, Mood Disorders, and Anxiety Disorder

Any mental disorder was identified as ICD-10 Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research (ICD-10-DCR), codes F00 to F99; schizophrenia spectrum disorder, as ICD-10-DCR codes F20 to F29; mood disorders, as ICD-10-DCR codes F30 to F39; and anxiety disorder, as ICD-10-DCR codes F40 to F48 and F93. Error bars show the 95% CIs in designated age ranges. Owing to the large sample size, the 95% CIs for the cumulative incidences are very close to the estimates and are therefore not shown. Because the cumulative incidences are estimated continuously with respect to age and the incidence rates are estimated in 1-year age intervals, the abscissa for the cumulative incidence measures the exact age, whereas the abscissa for the incidence rates measures the lowest cutoff point for the age interval. The y-axis scales differ by disorder to correspond to the range of observed outcomes.

Figure 2.  Sex- and Age-Specific Incidence Rates and Cumulative Incidences for Obsessive-Compulsive Disorder, Eating Disorders, Intellectual Disability, and Autism Spectrum Disorders
Sex- and Age-Specific Incidence Rates and Cumulative Incidences for Obsessive-Compulsive Disorder, Eating Disorders, Intellectual Disability, and Autism Spectrum Disorders

Obsessive-compulsive disorder was identified as ICD-10 Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research (ICD-10-DCR), code F42; eating disorders, as ICD-10-DCR code F50; intellectual disability, as ICD-10-DCR codes F70 to F79; and autism spectrum disorders, as ICD-10-DCR codes F84.x, excluding F84.2 to F84.4. Error bars show the 95% CIs in designated age ranges. Owing to the large sample size, the 95% CIs for the cumulative incidences are very close to the estimates and are therefore not shown. Because the cumulative incidences are estimated continuously with respect to age and the incidence rates are estimated in 1-year age intervals, the abscissa for the cumulative incidence measures the exact age, whereas the abscissa for the incidence rates measures the lowest cutoff point for the age interval. The y-axis scales differ by disorder to correspond to the range of observed outcomes.

Figure 3.  Sex- and Age-Specific Incidence Rates and Cumulative Incidences for Attention-Deficit/Hyperactivity Disorder (ADHD), ADHD-Inattentive Type, Oppositional Defiant Disorder/Conduct Disorder, and Tic Disorders
Sex- and Age-Specific Incidence Rates and Cumulative Incidences for Attention-Deficit/Hyperactivity Disorder (ADHD), ADHD-Inattentive Type, Oppositional Defiant Disorder/Conduct Disorder, and Tic Disorders

ADHD was identified as ICD-10 Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research (ICD-10-DCR), codes F90 and F98.8; ADHD-inattentive type, as ICD-10-DCR code F98.8; oppositional defiant disorder/conduct disorder, as ICD-10-DCR codes F91 plus F90.1; and tic disorders, as ICD-10-DCR code F95. Error bars show the 95% CIs in designated age ranges. Owing to the large sample size, the 95% CIs for the cumulative incidences are very close to the estimates and are therefore not shown. Because the cumulative incidences are estimated continuously with respect to age and the incidence rates are estimated in 1-year age intervals, the abscissa for the cumulative incidence measures the exact age, whereas the abscissa for the incidence rates measures the lowest cutoff point for the age interval. The y-axis scales differ by disorder to correspond to the range of observed outcomes.

Table 1.  Diagnostic Classification of Mental Disorders According to the ICD-10-DCR and the Number of New Cases During Follow-up of the Cohorta
Diagnostic Classification of Mental Disorders According to the ICD-10-DCR and the Number of New Cases During Follow-up of the Cohorta
Table 2.  Cumulative Incidences of Diagnosed Mental Disorders in Childhood and Adolescence in a Nationwide Cohorta
Cumulative Incidences of Diagnosed Mental Disorders in Childhood and Adolescence in a Nationwide Cohorta
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    1 Comment for this article
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    Sex Differences in Schizophrenia Across the Lifespan
    Thomas Reilly, MRCPsych | 1. Institute of Psychiatry, Psychology and Neuroscience, King's College London. 2. South London and Maudsley NHS Foundation Trust
    Dalsgaard et al. (1) present the results of a national data linkage study, providing incidence rates for a variety of mental disorders. One interesting finding is an increased cumulative incidence of schizophrenia spectrum disorders in girls before the age of 18, compared with boys. When restricted to the narrower diagnosis of schizophrenia, the difference in cumulative incidence between boys and girls was not statistically significant, with overlapping confidence intervals. This may be due to fewer individuals being diagnosed with this specific disorder. Broadly, these findings are in agreement with studies of early onset schizophrenia but is contrary to the widespread belief that schizophrenia is more common in boys than girls.

    Female puberty is characterised by large increases and then fluctuations in circulating oestrogen and progesterone. During reproductive years, levels of these hormones continuing to fluctuate with the menstrual cycle, which may underlie significantly increased admission rates for psychosis around the time of menstruation (2). Another life event associated with hormonal changes is childbirth, with steep drops in oestrogen and progesterone, following which there is a dramatically increased risk of incident psychosis (3).

    The menopause is the cessation of menstruation, caused by a fall in oestrogen produced by the ovaries and usually occurs between the ages of 45 and 55. The authors claim that a meta-analysis by van der Werf et al. (4) shows schizophrenia incidence to be greater in males than females in all age groups. In fact, van der Werf et al. report that, following the age of 50, the incidence is greater in females. Increased incidence rates in women over the age of 45 has also reported by Kirkbride et al. (5) who conducted a meta-analysis of schizophrenia incidence rates in England and identified a secondary peak of incidence in middle aged women.

    Dalsgaard et al. should be congratulated for their contribution to the field; further evidence of the importance of female life stages in the expression of schizophrenia spectrum illnesses.

    Dr Thomas J Reilly (MRCPsych)1,2,
    Dr Fiona Gaughran (MD, FRCP(I), FRCP, FRCP(Edin), FRCPsych)1,2

    1. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, UK
    2. South London and Maudsley NHS Foundation Trust


    References
    1. Dalsgaard S, Thorsteinsson E, Trabjerg BB, et al. Incidence Rates and Cumulative Incidences of the Full Spectrum of Diagnosed Mental Disorders in Childhood and Adolescence. JAMA Psychiatry. 2019. doi:10.1001/jamapsychiatry.2019.3523
    2. Reilly TJ, Sagnay de la Bastida VC, Joyce DW, Cullen AE, McGuire P. Exacerbation of Psychosis During the Perimenstrual Phase of the Menstrual Cycle: Systematic Review and Meta-analysis. Schizophr Bull. 2019. doi:10.1093/schbul/sbz030
    3. Bergink V, Rasgon N, Wisner KL. Postpartum psychosis: Madness, mania, and melancholia in motherhood. Am J Psychiatry. 2016. doi:10.1176/appi.ajp.2016.16040454
    4. Van Der Werf M, Hanssen M, Köhler S, et al. Systematic review and collaborative recalculation of 133 693 incident cases of schizophrenia. Psychol Med. 2014. doi:10.1017/S0033291712002796
    5. Kirkbride JB, Errazuriz A, Croudace TJ, et al. Incidence of schizophrenia and other psychoses in England, 1950-2009: A systematic review and meta-analyses. PLoS One. 2012. doi:10.1371/journal.pone.0031660
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Original Investigation
    November 20, 2019

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

    Author Affiliations
    • 1The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
    • 2National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark
    • 3Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark
    • 4Geological Survey of Denmark and Greenland, Aarhus, Denmark
    • 5Department of Public Health, Aarhus University, Aarhus, Denmark
    • 6Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, Australia
    • 7Queensland Brain Institute, University of Queensland, Brisbane, Australia
    JAMA Psychiatry. 2020;77(2):155-164. doi:10.1001/jamapsychiatry.2019.3523
    Key Points

    Question  What are the age- and sex-specific incidence rates and cumulative incidences of the full spectrum of diagnosed mental disorders during childhood and adolescence?

    Findings  In this nationwide cohort study of 1.3 million individuals in Denmark, the risk (cumulative incidence) of being diagnosed with a mental disorder before 18 years of age was 14.63% in girls and 15.51% in boys. Distinct age- and sex-specific patterns of occurrence were found across mental disorders in children and adolescents.

    Meaning  These findings suggest that precise estimates of rates and risks of all mental disorders during childhood and adolescence are essential for future planning of services and care and for etiological research.

    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 the ICD-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.

    Introduction

    Since 1990, studies on the global burden of disease have continuously ranked mental disorders as some of the most impairing conditions worldwide.1,2 The Global Burden of Disease studies recently reported that in children and adolescents, mental disorders account for the most years lived with disability.3 The World Health Organization emphasized in their Mental Health Action Plan 2013-2020 the strong need for age- and sex-specific data on child mental health.4 The United States and Australia have good survey data, but only 7% of all countries worldwide have such data,5 and in 2013, none of 29 member states in the European Union could provide data on incidence of mental disorders in children or adolescents.6

    Knowledge of the age-specific risks of mental disorders forms the backbone for public health decisions, prioritization of resources, evidence-based medicine, and research on risk factors and outcomes. Occurrence of a condition in a population is measured as prevalence (cases at a specific point) or incidence (new cases per unit of time). The cumulative incidence estimates the risk of developing the condition before a specified age, taking into consideration individual follow-up time.7 Estimates of the prevalence of mental health disorders in childhood are often based on information from adolescents or parents and are thus prone to recall, information, and survival biases.

    In adults, health registry data have made important contributions to our understanding of the incidence of the full spectrum of mental disorders8 and their risk factors and outcomes.9-13 In children and adolescents, similar methods have been informative about the frequency of a few certain mental disorders14-16 and their comorbidities,17 risk factors,18-20 and outcomes.21-24 These findings have been supplemented by prevalence estimates from surveys, most often at a single point25-27 and sometimes with repeated assessments.28,29 Hence, surveys estimating prevalence rates and registry studies estimating incidence rates of diagnoses complement each other and each have their own limitations.

    Nevertheless, evidence on the incidence of the full spectrum of mental disorders in children and adolescents is lacking. The objective of this study was to estimate the incidence rates and cumulative incidences of any diagnosed mental disorder and 27 specific categories of diagnosed mental disorders during childhood and adolescence, with age- and sex-specific estimates, in a nationwide cohort in Denmark.

    Methods
    Study Population

    The Danish Civil Registration System,30 established in 1968, holds data on the personal identification number, sex, date of birth, and continuously updated information on vital status of all persons in Denmark. This enables accurate linkage of individual-level data across all registers and prevents duplication of prior events. Our study population included all live-born singletons born in Denmark from January 1, 1995, through December 31, 2016. This study was approved by the Danish Data Protection Agency. By Danish law, informed consent is not required for register-based studies. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

    Assessment of Mental Illness

    The Danish Psychiatric Central Research Register and the Danish National Patient Register provided data on diagnosed mental disorders for all individuals within the study population.31 These registers include nationwide data on all hospital contacts (inpatient, outpatient, and emergency ward visits) from 1995 onward. In Denmark, hospital treatment is free of charge, all visits are registered, and diagnoses of mental disorders are made according the ICD-10 Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research (ICD-10-DCR), since 1994.32 The ICD-10-DCR codes of the categories of disorders are shown in Table 1, and observation time, stratified by sex, is presented in eTable 1 in the Supplement. Individuals with more than 1 disorder were included in the numerator for each specific disorder. Age at diagnosis was defined as the first day of the first contact, given the diagnosis of interest.

    Study Design

    In this nationwide cohort study, all included children were followed up from birth. Follow-up was terminated at the date of the first diagnosis of the disorder (for each disorder separately), death, emigration from Denmark, or December 31, 2016, whichever came first. Ignoring censoring from emigration and/or death would have biased the incidence rates toward underestimation and the cumulative incidences toward overestimation.33 Competing risk is present when the failure event may be one of several distinct failure types, in this case date of onset, death, disappearance, or emigration.

    Statistical Analysis

    Data were analyzed from September 14, 2018, through June 11, 2019. We estimated sex- and age-specific incidence rates (incident cases per 10 000 person-years) and cumulative incidences (probability per 100 persons in the population diagnosed before a given age) of any psychiatric disorder (ICD-10-DCR codes F00-F99) and each of the separate mental disorders before 6, 13, and 18 years of age. We refer to cumulative incidence as the risk of a disorder. In Figures 1, 2, and 3, incidence rates are shown in 1-year age intervals (or expanded intervals including >10 cases). In a sensitivity analysis, we estimated the cumulative incidences at 13 years of age, including only individuals born from 1995 through 2003 for whom complete follow-up data were available to examine possible cohort effects.34

    We used the GENMOD procedure in SAS software, release 9.4 (SAS Institute, Inc),35 to perform a Poisson regression analysis with the logarithm of person-years as an offset and to produce likelihood ratio–based incidence rates, 95% CIs, and 2-sided P values at a significance level of .05. This level is equivalent to a Cox proportional hazards regression under the assumption of piecewise constant incidence rates. The cumulative incidence was estimated in the presence of competing risk using the SAS-macro comprisk.36

    Results

    The study population consisted of 1.3 million children born in Denmark from 1995 through 2016 and was followed up until December 31, 2016, resulting in 14 million person-years of observation. In total, 99 926 individuals (41 350 girls and 58 576 boys) had a diagnosis of a mental disorder before 18 years of age. Among the overall study population, 2.7% were censored before the end of follow-up owing to death (n = 4962), disappearance (n = 515), and emigration from Denmark (n = 31 019).

    Risks of Mental Disorders by 18 Years of Age

    The risk of being diagnosed with any mental disorder before 18 years of age was 15.01% (95% CI, 14.98%-15.17%) in all individuals, 14.63% (95% CI, 14.48%-14.77%) in girls, and 15.51% (95% CI, 15.18%-15.84%) in boys (Table 2). The disorder with the highest cumulative incidence by 18 years of age in girls was anxiety disorder (7.85%; 95% CI, 7.74%-7.97%); in boys, attention-deficit/hyperactivity disorder (ADHD) (5.90%; 95% CI, 5.76%-6.03%). Figures 1 through 3 and eFigures 1 through 4 in the Supplement show the age-specific incidence rates and cumulative incidences for any mental disorder and each of the specific mental disorders investigated for boys and girls separately.

    Sex Differences

    The incidence rate of schizophrenia spectrum disorders (Figure 1B) was low before 13 years of age, after which it increased in girls and boys. By 18 years of age, the cumulative incidence was higher in girls (0.76%; 95% CI, 0.72%-0.80%) than in boys (0.48%; 95% CI, 0.39%-0.59%). Similar patterns showing higher risks in girls were found for mood disorders (2.54% [95% CI, 2.47%-2.61%] vs 1.10% [95% CI, 0.84%-1.21%) (Figure 1C), depression (2.41% [95% CI, 2.34%-2.48%] vs 0.92% [95% CI, 0.76%-1.12%]) (Table 2), anxiety disorders (7.85% [95% CI, 7.74%-7.97%] vs 4.58% [95% CI, 4.33%-4.84%]) (Figure 1D), obsessive-compulsive disorder (OCD) (0.96% [95% CI, 0.92%-1.00%] vs 0.63% [95% CI, 0.56%-0.72%]) (Figure 2A), eating disorders (1.80% [95% CI, 1.74%-1.86%] vs 0.28% [95% CI, 0.19%-0.41%]) (Figure 2B), and personality disorders (1.05% [95% CI, 1.00%-1.10%] vs 0.30% [95% CI, 0.18%-0.49%]) (eFigure 3C in the Supplement). In most of these individuals, incidence peaked in late adolescence (approximately at 17-18 years of age).

    Compared with girls, boys had higher risks of intellectual disability (1.52% [95% CI, 1.46%-1.59%] vs 0.88% [95% CI, 0.85%-0.92%]), autism spectrum disorders (ASD) (4.26% [95% CI, 4.16%-4.36%] vs 1.77% [95% CI, 1.72%-1.82%]), other developmental disorders (2.74% [95% CI, 2.67%-2.81%] vs 1.41% [95% CI, 1.37%-1.46%]), ADHD (5.90% [95% CI, 5.76%-6.03%] vs 3.04% [95% CI, 2.97%-3.11%]), oppositional defiant disorder/conduct disorder (ODD/CD) (1.28% [95% CI, 1.23%-1.33%] vs 0.46% [95% CI, 0.44%-0.49%]), attachment disorders (0.71% [95% CI, 0.66%-0.75%] vs 0.52% [95% CI, 0.49%-0.54%]), and tic disorders (1.36% [95% CI, 1.32%-1.41%] vs 0.42% [95% CI, 0.40%-0.45%]) (Table 2). For boys, the ASD incidence sharply increased from birth to peak at 4 years of age, after which it was almost constant until 15 years of age, when it declined (Figure 2D). For girls, the ASD incidence was low until 10 years of age, then increased and peaked in early adolescence. In ADHD (Figure 3A), the incidence in boys increased steadily until it peaked at 8 years of age, then steadily declined, whereas the incidence in girls was almost constant from 7 to 12 years of age, after which it increased to peak at 17 years of age, where the incidence of ADHD in girls was higher than in boys. Similar patterns with a late adolescent peak in girls (but not in boys) were seen in ODD/CD (Figure 3C), other developmental disorders (eFigure 3D in the Supplement), and attachment disorders (eFigure 4D in the Supplement).

    Risks of Mental Disorders by 6 and 13 Years of Age

    The cumulative incidence of any mental disorder before 6 and 13 years of age was higher in boys (2.78% [95% CI, 2.44%-3.15%] and 10.23% [95% CI, 9.90%-10.57%], respectively) than in girls (1.45% [95% CI, 1.42%-1.49%] and 5.17% [95% CI, 5.10%-5.24%], respectively) (eTables 2 and 3 in the Supplement). Risk in total of being diagnosed before 6 years of age was 2.13% (95% CI, 2.11%-2.16%) (eTable 3 in the Supplement). The risk of anxiety disorders by 6 and 13 years of age was higher in boys (0.31% [95% CI, 0.13%-0.67%] and 2.17% [95% CI, 1.93%-2.44%], respectively) than in girls (0.27% [95% CI, 0.26%-0.29%] and 1.88% [95% CI, 1.83%-1.92%], respectively). However, by 18 years of age, the pattern was reversed, with a higher risk of anxiety disorders in girls (7.85%; 95% CI, 7.74%-7.97%) than in boys (4.58%; 95% CI, 4.33%-4.84%).

    Sensitivity Analyses

    When including only individuals with complete follow-up data available, the estimated cumulative incidence of mental disorders tended to be lower than in our main analyses (eTable 4 in the Supplement). In girls, risks were lower for 8 of the 27 mental disorders investigated; in boys, risks were lower for 5 of the disorders. For girls and boys, the largest difference from our main analyses was seen in the cumulative incidence of childhood autism (sensitivity analysis, 0.20% [95% CI, 0.19%-0.22%] in girls and 0.85% [95% CI, 0.80%-0.89%] in boys; main analysis, 0.44% [95% CI, 0.42-0.46] in girls and 1.48% [95% CI, 1.43%-1.53%] in boys).

    Discussion

    Worldwide, this nationwide study is the first, to our knowledge, of the incidence of the full spectrum of diagnosed mental disorders in childhood and adolescence. Herein, we will discuss 4 key findings.

    Risk of Mental Disorders

    We found that 15.01% of all children and adolescents were diagnosed with a mental disorder before reaching 18 years of age, which is consistent with the overall prevalence of 13% to 20% in US surveys26,37-40 and the estimated worldwide prevalence of mental disorders in young people of 13.4%.41 The prevalence of anxiety disorders in US surveys was 4.4% in girls and 5.0% in boys (7.85% and 4.58%, respectively, in our study).40 Depression was more prevalent in the United States (3.7% in girls and 4.1% in boys)40 compared with our sample (2.41% and 0.92%, respectively), especially in boys. Our study is likely biased toward capture of the more severe cases with depression, whereas surveys in the US studies are often based on retrospective information from the participating parents (potentially leading to misclassification and recall and selection bias), and the methodological aspects may explain some of these differences.

    Sex Differences in Peaks in Incidence Rates

    Although we obtained statistically significantly different estimates of the risk of any mental disorder in girls and boys, these rates were conceptually identical. Our study is the first, to our knowledge, to report girls having later peaks in the incidence of ASD, ADHD, ODD/CD, other developmental disorders, and attachment disorders compared with boys. Indeed, most girls with neurodevelopmental disorders were diagnosed during late adolescence despite these disorders having an early age of onset. Cumulative incidence of any mental disorders by 13 years of age was also higher in boys than in girls but equal between sexes by 18 years of age. These findings suggest a delayed detection of mental disorders in girls. In support of this possibility, studies of time trends42,43 have found larger increases in the number of girls being diagnosed with ASD and ADHD compared with the increase in the number of boys being diagnosed. Further, compared with boys, girls have been found to be more likely to have undiagnosed ADHD.44

    Previous studies on the incidence rates of OCD in children and adolescents have found no differences or mixed sex differences in occurrence45 or higher rates in boys.46,47 We found equal incidence rates before 10 years of age, after which the incidence rate increased more in girls than in boys; by 18 years of age, the risk of OCD was higher in girls than boys. The incidence of OCD peaked in both sexes in early adolescence rather than in late adolescence, contrary to previous reports.45 For eating disorders48-50 and mood disorders,51 our findings on age at peak of incidences were consistent with previous studies.

    Sex Differences in the Risk of Selected Mental Disorders

    We found that girls were more likely to be diagnosed with schizophrenia spectrum disorder (ie, early-onset), mood disorders, anxiety disorders, OCD, eating disorders, and personality disorders, and boys were more likely to be diagnosed with intellectual disability, ASD, other developmental disorders, ADHD, ODD/CD, attachment disorders, and tic disorders. Despite girls having a higher risk of anxiety disorder by 18 years of age, boys had a higher risk of anxiety disorders by 13 years of age compared with girls, which has also, to our knowledge, not previously been reported.

    Our finding of the female preponderance of early-onset schizophrenia spectrum disorder is novel. A meta-analysis of incident cases of schizophrenia52 found male preponderance in all age groups, including those with the first diagnosis before 20 years of age. Three other studies examining changes in the incidence of schizophrenia53,54 and early-onset schizophrenia55 over time have pointed toward sex differences similar to those found in our study, with higher incidence rates in girls than in boys in the youngest group. Another study56 has also found the mean age of onset of schizophrenia to be lower in girls compared with boys. Still, the sex difference in risk of early-onset schizophrenia spectrum disorder to date has not previously been estimated as accurately as in our sample.

    To our knowledge, the incidences and risks of attachment disorders and personality disorders in children and adolescents have not been previously reported. As in adults,57 we found female preponderance in personality disorders. Very few individuals were diagnosed with personality disorder before 13 years of age, which is in accordance with diagnostic classifications and international clinical guidelines.32,58,59 Finally, we found no sex difference in the risk of substance use disorders before 18 years of age, which contrasts with findings from studies of adults.8

    Risk of Mental Disorders in Preschool Children

    In preschool children, the overall risk of being diagnosed with a mental disorder was 2.78% in boys and 1.45% in girls (2.13% in total). Apart from a handful of studies related to tic disorders14 and ASD,14,42 our study, to our knowledge, provides the most detailed estimates for the risk of being diagnosed with a broader range of mental disorder in children younger than 6 years of age.

    Relevance

    We believe the novelty of this report is the comprehensive estimates of risks of diagnosed mental disorders throughout childhood and adolescence in a total nationwide population, and this adds new knowledge to the field of mental health. The existing literature mainly reports prevalence rates in a population alive at a certain point, only obtaining data on surviving individuals, thereby potentially missing data on those with the most severe psychopathologic diagnoses who did not survive until start of the study. Surveys estimating lifetime prevalence rates retrospectively are also prone to recall bias and selection bias, and the occurrence of episodic or remitting disorders may be underestimated in prevalence studies. However, to fully understand the epidemiology of mental disorders in children and adolescents, surveys on prevalence rates and register-based studies on incidence rates are both required.

    As such, with unprecedented comprehensiveness (covering an entire nation) examining the broad diagnostic spectrum and reporting detailed sex- and age-specific patterns, our study offers additional new knowledge on the occurrence of mental disorders in children and adolescents. Our estimates of incidence and risks would likely be broadly representative of many high-income nations. Many of the presented findings, including our main finding of 15.01% being diagnosed with a mental disorder at younger than 18 years, concurs with estimates of prevalence rates obtained in the previous surveys using the most rigorous methods. Our findings may also be thought of as important comparisons for studies evaluating prevalence rates of mental disorders in children in low-income countries or living in situations of extreme circumstances, such as war, natural disasters, or other humanitarian emergencies, all of which may influence the occurrence of mental disorders in children.60-62

    According to the World Health Organization’s most recent Mental Health Atlas from 2017, only 18% of the member states had a plan or strategy for child and adolescent mental health.63 We believe the evidence presented in this study of the patterns of distribution and probabilities of all diagnosed mental disorders across ages and sexes during childhood and adolescence may strengthen advocacy and governance for child and adolescent mental health and form an important platform to guide future policies on access to mental health care, planning of services, prioritizing of resources in public health care, the promotion of human rights of young people with mental disorders, and future research on preventive measures, risk factors, course, and outcome of mental disorders in this age group.

    Strengths and Limitations

    This study has some strengths. The applied design has previously been used in a study of adults,8 and its main strength lies in the complete and nationwide data coverage during several decades and in the high quality of the diagnostic data, which is based on comprehensive clinical assessments of all mental disorders by cross-disciplinary clinical teams, including child and adolescent psychiatrists. Public health care in Denmark is free of charge, and monetary factors are thus less likely to affect the likelihood of receiving treatment in our study compared with studies performed in other countries.

    However, the applied methods also have limitations. Our study was not aimed at examining time trends, and, as in other observational studies, our estimates may be biased by cohort effects.34 Our sensitivity analyses suggest slight overestimation of the risk of a few mental disorders in the main analysis. This overestimation may be related to higher incidence rates in younger cohorts and changes over time in thresholds for referral, attitudes toward mental illness, available resources, and/or environmental risk factors. The risks may also be underestimated because register-based studies are unable to detect mental disorders for which the patients or their families do not seek help (eg, “wait and see”). Further, we did not include individuals with mental disorders diagnosed outside hospital departments (by psychiatrists in private practices). However, in Denmark, most children and adolescents assessed and treated for mental disorders receive such care within public hospital departments. For instance, for ADHD, more than 86% of all cases are assessed in a hospital setting;64 for anxiety and depression, this fraction may be lower. In Denmark, only licensed child and adolescent psychiatrists (not general practitioners) are authorized to initiate pharmacological treatment of mental disorders in individuals younger than 18 years, as stipulated by the Danish health authorities.65-67 Finally, although some diagnoses have been validated in Danish registers (eg, schizophrenia, depression, mood disorder, ADHD, and childhood autism),68-75 not all of the diagnostic categories have been validated, especially not in preschool children.

    Conclusions

    This population-based study provides, to our knowledge, a first comprehensive nationwide assessment of the incidence and risks of all mental disorders in childhood and adolescence. For many mental disorders, we believe we have identified age- and sex-specific patterns of occurrence that, to our knowledge, have not been previously reported. The distinct signatures of the different mental disorders with respect to sex and age may have important implications for service planning and etiological research.

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    Article Information

    Accepted for Publication: September 1, 2019.

    Corresponding Author: Søren Dalsgaard, MD, PhD, National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Fuglesangs Allé 26, Bldg R, 8210 Aarhus V, Denmark (sdalsgaard@econ.au.dk).

    Published Online: November 20, 2019. doi:10.1001/jamapsychiatry.2019.3523

    Author Contributions: Ms Thorsteinsson and Dr Pedersen had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Dalsgaard, McGrath, Pedersen.

    Acquisition, analysis, or interpretation of data: Dalsgaard, Thorsteinsson, Trabjerg, Schullehner, Plana-Ripoll, Brikell, Wimberley, Thygesen, Madsen, Timmerman, Schendel, Mortensen, Pedersen.

    Drafting of the manuscript: Dalsgaard.

    Critical revision of the manuscript for important intellectual content: Thorsteinsson, Trabjerg, Schullehner, Plana-Ripoll, Brikell, Wimberley, Thygesen, Madsen, Timmerman, Schendel, McGrath, Mortensen, Pedersen.

    Statistical analysis: Thorsteinsson, Plana-Ripoll, Wimberley, Pedersen.

    Obtained funding: Mortensen.

    Administrative, technical, or material support: Trabjerg, Madsen, Timmerman, Schendel, Mortensen, Pedersen.

    Supervision: Dalsgaard, Trabjerg, Schullehner, Wimberley, Pedersen.

    Conflict of Interest Disclosures: Dr Schullehner reported receiving grants from Aarhus University Research Foundation during the conduct of the study. Dr Mortensen reported receiving grants from the Lundbeck Foundation during the conduct of the study. No other disclosures were reported.

    Funding/Support: This study was supported by grants R102-A9118, R155-2014-1724, and R248-2017-2003 from the Lundbeck Foundation; grant AUFF-E-2015-FLS-8-61 from the Aarhus University Research Foundation (Dr Dalsgaard); grant NNF 22018 from the Novo Nordisk Foundation (Dr Dalsgaard); grant agreement No. 667302 from the European Union’s Horizon 2020 Research and Innovation Programme (Dr Dalsgaard; CoCA Study); grant R01-ES026993 from the National Institutes of Health (Dr Dalsgaard); grant 109399 from the Tryg Foundation (Dr Dalsgaard); grant 19-8-0260 from Helsefonden (Dr Dalsgaard); the Niels Bohr Professorship from the Danish National Research Foundation (Dr McGrath); John Cade Fellowship APP1056929 from National Health and Medical Research Council (Dr McGrath); the Stanley Medical Research Institute (Drs Mortensen and Pedersen); advanced grant 294838 from the European Research Council (Dr Pedersen); and Marie Sklodowska-Curie grant agreement 837180 from the European Union’s Horizon 2020 Research and Innovation Programme (Dr Plana-Ripoll).

    Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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