[Show abstract][Hide abstract] ABSTRACT: Bullying is a common childhood experience that involves repeated mistreatment to improve or maintain one's status. Victims display long-term social, psychological, and health consequences, whereas bullies display minimal ill effects. The aim of this study is to test how this adverse social experience is biologically embedded to affect short- or long-term levels of C-reactive protein (CRP), a marker of low-grade systemic inflammation. The prospective population-based Great Smoky Mountains Study (n = 1,420), with up to nine waves of data per subject, was used, covering childhood/adolescence (ages 9-16) and young adulthood (ages 19 and 21). Structured interviews were used to assess bullying involvement and relevant covariates at all childhood/adolescent observations. Blood spots were collected at each observation and assayed for CRP levels. During childhood and adolescence, the number of waves at which the child was bullied predicted increasing levels of CRP. Although CRP levels rose for all participants from childhood into adulthood, being bullied predicted greater increases in CRP levels, whereas bullying others predicted lower increases in CRP compared with those uninvolved in bullying. This pattern was robust, controlling for body mass index, substance use, physical and mental health status, and exposures to other childhood psychosocial adversities. A child's role in bullying may serve as either a risk or a protective factor for adult low-grade inflammation, independent of other factors. Inflammation is a physiological response that mediates the effects of both social adversity and dominance on decreases in health.
Proceedings of the National Academy of Sciences 05/2014; · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We tested whether sleep problems co-occur with, precede, and/or follow common psychiatric disorders during childhood and adolescence. We also clarified the role of comorbidity and tested for specificity of associations among sleep problems and psychiatric disorders.
Data came from the Great Smoky Mountains Study, a representative population sample of 1,420 children, assessed 4 to 7 times per person between ages 9 and 16 years for major Diagnostic and Statistical Manual-Fourth Edition (DSM-IV) disorders and sleep problems. Sleep-related symptoms were removed from diagnostic criteria when applicable.
Sleep problems during childhood and adolescence were common, with restless sleep and difficulty falling asleep being the most common symptoms. Cross-sectional analyses showed that sleep problems co-occurred with many psychiatric disorders. Longitudinal analyses revealed that sleep problems predicted increases in the prevalence of later generalized anxiety disorder (GAD) and high GAD/depression symptoms, and oppositional defiant disorder (ODD). In turn, GAD and/or depression and ODD predicted increases in sleep problems over time.
Sleep problems both predict and are predicted by a diagnostic cluster that includes ODD, GAD, and depression. Screening children for sleep problems could offer promising opportunities for reducing the burden of mental illness during the early life course.
Journal of the American Academy of Child and Adolescent Psychiatry 05/2014; 53(5):550-8. · 6.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE Disruptive mood dysregulation disorder (DMDD) is a new disorder for DSM-5 that is uncommon and frequently co-occurs with other psychiatric disorders. Here, the authors test whether meeting diagnostic criteria for this disorder in childhood predicts adult diagnostic and functional outcomes. METHOD In a prospective, population-based study, individuals were assessed with structured interviews up to six times in childhood and adolescence (ages 10 to 16 years; 5,336 observations of 1,420 youths) for symptoms of DMDD and three times in young adulthood (ages 19, 21, and 24-26 years; 3,215 observations of 1,273 young adults) for psychiatric and functional outcomes (health, risky/illegal behavior, financial/educational functioning, and social functioning). RESULTS Young adults with a history of childhood DMDD had elevated rates of anxiety and depression and were more likely to meet criteria for more than one adult disorder relative to comparison subjects with no history of childhood psychiatric disorders (noncases) or individuals meeting criteria for psychiatric disorders other than DMDD in childhood or adolescence (psychiatric comparison subjects). Participants with a history of DMDD were more likely to have adverse health outcomes, be impoverished, have reported police contact, and have low educational attainment as adults compared with either psychiatric or noncase comparison subjects. CONCLUSIONS The long-term prognosis of children with DMDD is one of pervasive impaired functioning that in many cases is worse than that of other childhood psychiatric disorders.
American Journal of Psychiatry 04/2014; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aims of this study were 2-fold: to provide a brief introduction to the prospective longitudinal Great Smoky Mountains Study and review recent findings; and to use this sample to conduct an epidemiologic analysis of common childhood anxiety disorders.
The population-based Great Smoky Mountains Study assessed 1,420 participants from 11 counties in the southeastern United States up to 11 times between ages 9 and 26 years with the structured Child and Adolescent Psychiatric Assessment and its upward extension, the Young Adult Psychiatric Assessment.
The U-shaped age prevalence curve for any anxiety disorder was the product of high levels of childhood separation anxiety and adult panic, agoraphobia, and generalized anxiety. More than 1 in 5 subjects met criteria for an anxiety disorder by early adulthood. In terms of cumulative comorbidity, there was evidence of overlap between anxiety disorders, but the level of overlap was generally consistent with what is seen among other common childhood disorders. All childhood anxiety disorders were associated with adverse functioning in at least 1 young adult functional domain, with the poorest outcomes for childhood generalized anxiety and DSM-III-R overanxious disorder.
Clinically significant anxiety is a common mental health problem to have had by adulthood. There was little evidence to support the consolidation of anxiety disorders, and some evidence to justify reintroduction of DSM-III-R overanxious disorder. The transition to young adulthood appears to be a key period for understanding the development of common adult anxiety disorders such as panic and agoraphobia.
Journal of the American Academy of Child and Adolescent Psychiatry 01/2014; 53(1):21-33. · 6.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The effect of conduct disorder (CD) as a major risk factor of substance use disorder (SUD), controlling for other psychiatric problems, has been well established in the literature. However, other psychiatric problems are associated as confounders with an increased risk of SUD. When confounding exists, the use of the standard survival analysis approach would lead to a biased estimate of the effect of a time-varying exposure on the time to event. Methods: The authors used a G-estimation approach to estimate the causal effect of CD while controlling for time-varying confounders. Results: The present study (N = 1420) found a substantial difference in the estimated hazard ratio of CD (4.49 vs. 1.93) when the results from G-estimation and Cox regression were compared. Conclusions: G-estimation fixed the problem of underestimating the hazard ratio of conduct disorder (CD) while controlling for all measured covariates.
[Show abstract][Hide abstract] ABSTRACT: We sought to establish prevalence rates and detail patterns of comorbidity for generalized anxiety disorder, separation anxiety disorder, and social phobia in preschool-aged children.
The Duke Preschool Anxiety Study, a screen-stratified, cross-sectional study, drew from pediatric primary care and oversampled for children at risk for anxiety. A total of 917 parents of preschool children (aged 2-5 years) completed the Preschool Age Psychiatric Assessment.
Generalized anxiety disorder, separation anxiety disorder, and social phobia are common in preschool-aged children attending pediatric primary care. Three-fourths of preschoolers with an anxiety disorder only had a single anxiety disorder. Generalized anxiety disorder displayed the greatest degree of comorbidity: with separation anxiety disorder (odds ratio [OR] = 4.1, 95% CI = 2.0-8.5), social phobia (OR = 6.4, 95% CI = 3.1-13.4), disruptive behavior disorders (OR = 5.1, 95% CI = 1.6-15.8), and depression (OR = 3.7, 95% CI = 1.1-12.4).
The weakness of association between generalized anxiety disorder and depression stands in contrast to substantial associations between these 2 disorders reported in older individuals. Attenuated associations in preschool-aged children could translate into clinical opportunities for targeted early interventions, aimed at modifying the developmental trajectory of anxiety disorders.
Journal of the American Academy of Child and Adolescent Psychiatry 12/2013; 52(12):1294-1303.e1. · 6.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE This study examined 12-month rates of service use for mental, emotional, and behavioral disorders among adolescents. METHODS Data were from the National Comorbidity Survey Adolescent Supplement (NCS-A), a survey of DSM-IV mental, emotional, and behavioral disorders and service use. RESULTS In the past 12 months, 45.0% of adolescents with psychiatric disorders received some form of service. The most likely were those with ADHD (73.8%), conduct disorder (73.4%), or oppositional defiant disorder (71.0%). Least likely were those with specific phobias (40.7%) and any anxiety disorder (41.4%). Among those with any disorder, services were more likely to be received in a school setting (23.6%) or in a specialty mental health setting (22.8%) than in a general medical setting (10.1%). Youths with any disorder also received services in juvenile justice settings (4.5%), complementary and alternative medicine (5.3%), and human services settings (7.9%). Although general medical providers treated a larger proportion of youths with mood disorders than with behavior disorders, they were more likely to treat youths with behavior disorders because of the larger number of the latter (11.5% of 1,465 versus 13.9% of 820). Black youths were significantly less likely than white youths to receive specialty mental health or general medical services for mental disorders. CONCLUSIONS Findings from this analysis of NCS-A data confirm those of earlier, smaller studies, that only a minority of youths with psychiatric disorders receive treatment of any sort. Much of this treatment was provided in service settings in which few providers were likely to have specialist mental health training.
[Show abstract][Hide abstract] ABSTRACT: Dysregulated immune function and elevated inflammation markers are seen in adults with chronic diseases, including some psychiatric disorders, but evidence on inflammation in the case of drug abuse is conflicting.
To test the concurrent and predictive relations between C-reactive protein (CRP) and use and abuse of alcohol, nicotine and cannabis in a longitudinal, population sample of adolescents and young adults, at the period of highest increase in drug use.
Data from the prospective population-based Great Smoky Mountains Study (N=1420) were used, covering children in the community assessed at ages 9-16, 19, and 21. Structured interviews were used to assess substance abuse symptoms and DSM-IV substance use disorders. Bloodspots were collected at each assessment and assayed for CRP.
CRP levels were higher in the presence of nicotine, alcohol, and cannabis use and nicotine dependence. In prospective analyses, higher CRP levels predicted cannabis use and nicotine dependence, and nicotine use predicted higher CRP levels, once covariates were included in the models. Significant covariates were age, race (American Indian), and obesity.
The inter-relationship of CRP and substance abuse has implications for the later health risks associated with early drug and alcohol use and abuse.
Drug and alcohol dependence 09/2013; · 3.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bullying is a serious problem for schools, parents, and public-policymakers alike. Bullying creates risks of health and social problems in childhood, but it is unclear if such risks extend into adulthood. A large cohort of children was assessed for bullying involvement in childhood and then followed up in young adulthood in an assessment of health, risky or illegal behavior, wealth, and social relationships. Victims of childhood bullying, including those that bullied others (bully-victims), were at increased risk of poor health, wealth, and social-relationship outcomes in adulthood even after we controlled for family hardship and childhood psychiatric disorders. In contrast, pure bullies were not at increased risk of poor outcomes in adulthood once other family and childhood risk factors were taken into account. Being bullied is not a harmless rite of passage but throws a long shadow over affected people's lives. Interventions in childhood are likely to reduce long-term health and social costs.
[Show abstract][Hide abstract] ABSTRACT: To test whether children and adolescents with co-occurring asthma and depression are at risk for elevated inflammation-concurrently and at the next assessment.
Up to 6 yearly assessments per person from the prospective, population-based Great Smoky Mountains Study (N = 1420) were used, covering children in the community aged 10-16 years old. High-sensitivity C-reactive protein (CRP) was assayed from annual bloodspot collections and provided indicators of elevated inflammation at CRP > 1, CRP > 2, and CRP > 3 mg/L. Depression was assessed with the Child and Adolescent Psychiatric Assessment. Asthma was assessed using a form adapted from the Centers for Disease Control and Prevention National Health Interview Survey.
Controlling common covariates of CRP, the co-occurrence of asthma and depression predicted heightened CRP-concurrently and at the next assessment. In turn, elevated CRP was relatively stable from one assessment to the next.
The co-occurrence of asthma and depression in childhood poses a risk for substantially elevated inflammation concurrently and over time, which could contribute to pathophysiological processes involved in the development of additional chronic diseases and also to asthma-related morbidity and mortality.
The Journal of pediatrics 08/2013; · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: DSM-IV grants episodic irritability an equal status to low mood as a cardinal criterion for the diagnosis of depression in youth, yet not in adults; however, evidence for irritability as a major criterion of depression in youth is lacking. This article examines the prevalence, developmental characteristics, associations with psychopathology, and longitudinal stability of irritable mood in childhood and adolescent depression.
Data from the prospective population-based Great Smoky Mountains Study (N = 1,420) were used. We divided observations on 9- to 16-year-olds who met criteria for a diagnosis of depression into 3 groups: those with depressed mood and no irritability, those with irritability and no depressed mood, and those with both depressed and irritable mood. We compared these groups using robust regression models on adolescent characteristics and early adult (ages 19-21 years) depression outcomes.
Depressed mood was the most common cardinal mood in youth meeting criteria for depression (58.7%), followed by the co-occurrence of depressed and irritable mood (35.6%); irritable mood alone was rare (5.7%). Youth with depressed and irritable mood were similar in age and developmental stage to those with depression, but had significantly higher rates of disruptive disorders. The co-occurrence of depressed and irritable mood was associated with higher risk for comorbid conduct disorder in girls (gender-by-group interaction, F1,132 = 4.66, p = .03).
Our study findings do not support the use of irritability as a cardinal mood criterion for depression. However, the occurrence of irritability in youth depression is associated with increased risk of disruptive behaviors, especially in girls.
Journal of the American Academy of Child and Adolescent Psychiatry 08/2013; 52(8):831-40. · 6.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Sex differences in levels of C-reactive protein (CRP) are well established in adulthood, but little is known about when and why they emerge. Here, we tested longitudinal models of CRP levels from ages 9 to 21, when marked physical and behavioral changes could contribute to growing sex disparities in CRP. METHODS: Data from the community-based prospective-longitudinal Great Smoky Mountains Study (N=1420) were used. Participants were 9-13 years old at intake and were followed through age 21. High-sensitivity C-reactive protein (CRP) was assayed from up to nine bloodspot collections per person. BMI, physical/sexual maturation, substance use, and control variables were assessed during yearly interviews to age 16, and at ages 19 and 21. RESULTS: Multilevel models revealed that the development of CRP in females was best described by a quadratic trend: after slow increases in CRP until age 15, the rate of increase accelerated thereafter. Changes in CRP in males were best described by a smaller, linear increase. After sex-differentiated associations with BMI, physical/sexual maturation, and substance use variables had been accounted for, increases in CRP after age 15 no longer differed by sex. CONCLUSION: Physical/sexual maturation and behavioral changes during adolescence could initiate life-long sex disparities in CRP.
[Show abstract][Hide abstract] ABSTRACT: Although schools are identified as critical for detecting youth mental disorders, little is known about whether the number of mental health providers and types of resources that they offer influence student mental health service use. Such information could inform the development and allocation of appropriate school-based resources to increase service use. This article examines associations of school resources with past-year mental health service use among students with 12-month DSM-IV mental disorders.
Data come from the U.S. National Comorbidity Survey Adolescent Supplement (NCS-A), a national survey of adolescent mental health that included 4,445 adolescent-parent pairs in 227 schools in which principals and mental health coordinators completed surveys about school resources and policies for addressing student emotional problems. Adolescents and parents completed the Composite International Diagnostic Interview and reported mental health service use across multiple sectors. Multilevel multivariate regression was used to examine associations of school mental health resources and individual-level service use.
Nearly half (45.3%) of adolescents with a 12-month DSM-IV disorder received past-year mental health services. Substantial variation existed in school resources. Increased school engagement in early identification was significantly associated with mental health service use for adolescents with mild/moderate mental and behavior disorders. The ratio of students to mental health providers was not associated with overall service use, but was associated with sector of service use.
School mental health resources, particularly those related to early identification, may facilitate mental health service use and may influence sector of service use for youths with DSM disorders.
Journal of the American Academy of Child and Adolescent Psychiatry 05/2013; 52(5):501-10. · 6.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The potential importance of DNA methylation in the etiology of complex diseases has led to interest in the development of methylome-wide association studies (MWAS) aimed at interrogating all methylation sites in the human genome. When using blood as biomaterial for a MWAS the DNA is typically extracted directly from fresh or frozen whole blood that was collected via venous puncture. However, DNA extracted from dry blood spots may also be an alternative starting material. In the present study, we apply a methyl-CpG binding domain (MBD) protein enrichment-based technique in combination with next generation sequencing (MBD-seq) to assess the methylation status of the ~27 million CpGs in the human autosomal reference genome. We investigate eight methylomes using DNA from blood spots. This data are compared with 1,500 methylomes previously assayed with the same MBD-seq approach using DNA from whole blood. When investigating the sequence quality and the enrichment profile across biological features, we find that DNA extracted from blood spots gives comparable results with DNA extracted from whole blood. Only if the amount of starting material is ≤ 0.5µg DNA we observe a slight decrease in the assay performance. In conclusion, we show that high quality methylome-wide investigations using MBD-seq can be conducted in DNA extracted from archived dry blood spots without sacrificing quality and without bias in enrichment profile as long as the amount of starting material is sufficient. In general, the amount of DNA extracted from a single blood spot is sufficient for methylome-wide investigations with the MBD-seq approach.
Epigenetics: official journal of the DNA Methylation Society 04/2013; 8(5). · 4.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigate the effect of household cash transfers during childhood on young adult body mass indexes (BMI). The effects of extra income differ depending on the household's initial socioeconomic status (SES). Children from the initially poorest households have a larger increase in BMI relative to children from initially wealthier households. Several alternative mechanisms are examined. Initial SES holds up as the most likely channel behind the heterogeneous effects of extra income on young adult BMI. (JEL D14, H23, H75, I12, J13, J15).
[Show abstract][Hide abstract] ABSTRACT: The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene-environment-development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the National Institute on Drug Abuse-funded Gene-Environment-Development Initiative, our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used of which common characteristics include (1) general population samples, including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol, and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene-environment analyses, of alcohol misuse and stressful life events, some significant gene-environment and gene-development effects were identified. We conclude that in some circumstances, already collected data sets can be combined for gene-environment and gene-development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables.
Twin Research and Human Genetics 03/2013; · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Quantifying diagnostic transitions across development is needed to estimate the long-term burden of mental illness. This study estimated patterns of diagnostic transitions from childhood to adolescence and from adolescence to early adulthood. METHODS: Patterns of diagnostic transitions were estimated using data from three prospective, longitudinal studies involving close to 20,000 observations of 3,722 participants followed across multiple developmental periods covering ages 9-30. Common DSM psychiatric disorders were assessed in childhood (ages 9-12; two samples), adolescence (ages 13-18; three samples), and early adulthood (ages 19 to age 32; three samples) with structured psychiatric interviews and questionnaires. RESULTS: Having a disorder at an early period was associated with at least a threefold increase in odds for having a disorder at a later period. Homotypic and heterotypic transitions were observed for every disorder category. The strongest evidence of continuity was seen for behavioral disorders (particularly ADHD) with less evidence for emotional disorders such as depression and anxiety. Limited evidence was found in adjusted models for behavioral disorders predicting later emotional disorders. Adult substance disorders were preceded by behavioral disorders, but not anxiety or depression. CONCLUSIONS: Having a disorder in childhood or adolescence is a potent risk factor for a range of psychiatric problems later in development. These findings provide further support for prevention and early life intervention efforts and suggest that treatment at younger ages, while justified in its own right, may also have potential to reduce the risk for disorders later in development.
Journal of Child Psychology and Psychiatry 03/2013; · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE Both bullies and victims of bullying are at risk for psychiatric problems in childhood, but it is unclear if this elevated risk extends into early adulthood. OBJECTIVE To test whether bullying and/or being bullied in childhood predicts psychiatric problems and suicidality in young adulthood after accounting for childhood psychiatric problems and family hardships. DESIGN Prospective, population-based study. SETTING Community sample from 11 counties in Western North Carolina. PARTICIPANTS A total of 1420 participants who had being bullied and bullying assessed 4 to 6 times between the ages of 9 and 16 years. Participants were categorized as bullies only, victims only, bullies and victims (hereafter referred to as bullies/victims), or neither. MAIN OUTCOME MEASURE Psychiatric outcomes, which included depression, anxiety, antisocial personality disorder, substance use disorders, and suicidality (including recurrent thoughts of death, suicidal ideation, or a suicide attempt), were assessed in young adulthood (19, 21, and 24-26 years) by use of structured diagnostic interviews. RESULTS Victims and bullies/victims had elevated rates of young adult psychiatric disorders, but also elevated rates of childhood psychiatric disorders and family hardships. After controlling for childhood psychiatric problems or family hardships, we found that victims continued to have a higher prevalence of agoraphobia (odds ratio [OR], 4.6 [95% CI, 1.7-12.5]; P < .01), generalized anxiety (OR, 2.7 [95% CI, 1.1-6.3]; P < .001), and panic disorder (OR, 3.1 [95% CI, 1.5-6.5]; P < .01) and that bullies/victims were at increased risk of young adult depression (OR, 4.8 [95% CI, 1.2-19.4]; P < .05), panic disorder (OR, 14.5 [95% CI, 5.7-36.6]; P < .001), agoraphobia (females only; OR, 26.7 [95% CI, 4.3-52.5]; P < .001), and suicidality (males only; OR, 18.5 [95% CI, 6.2-55.1]; P < .001). Bullies were at risk for antisocial personality disorder only (OR, 4.1 [95% CI, 1.1-15.8]; P < .04). CONCLUSIONS AND RELEVANCE The effects of being bullied are direct, pleiotropic, and long-lasting, with the worst effects for those who are both victims and bullies.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE No empirical studies on the DSM-5 proposed disruptive mood dysregulation disorder have yet been published. This study estimated prevalence, comorbidity, and correlates of this proposed disorder in the community. METHOD Prevalence rates were estimated using data from three community studies involving 7,881 observations of 3,258 participants from 2 to 17 years old. Disruptive mood dysregulation disorder was diagnosed using structured psychiatric interviews. RESULTS Three-month prevalence rates for meeting criteria for disruptive mood dysregulation disorder ranged from 0.8% to 3.3%, with the highest rate in preschoolers. Rates dropped slightly with the strict application of the exclusion criterion, but they were largely unaffected by the application of onset and duration criteria. Disruptive mood dysregulation co-occurred with all common psychiatric disorders. The highest levels of co-occurrence were with depressive disorders (odds ratios between 9.9 and 23.5) and oppositional defiant disorder (odds ratios between 52.9 and 103.0). Disruptive mood dysregulation occurred with another disorder 62%-92% of the time, and it occurred with both an emotional and a behavioral disorder 32%-68% of the time. Affected children displayed elevated rates of social impairments, school suspension, service use, and poverty. CONCLUSIONS Disruptive mood dysregulation disorder is relatively uncommon after early childhood, frequently co-occurs with other psychiatric disorders, and meets common standards for psychiatric "caseness." This disorder identifies children with severe levels of both emotional and behavioral dysregulation.
American Journal of Psychiatry 02/2013; 170(2):173-9. · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: Comorbidity between psychiatric disorders is common, but pairwise associations between two disorders may be explained by the presence of other diagnoses that are associated with both disorders or "indirect" comorbidity. Materials and Methods: Comorbidities of common childhood psychiatric disorders were tested in three community samples of children ages 6-17 (8931 observations of 2965 subjects). Psychiatric disorder status in all three samples was assessed with the Child and Adolescent Psychiatric Assessment. Indirect comorbidity was defined as A-B associations that decreased from significance to non-significance after adjusting for other disorders. Results: All tested childhood psychiatric disorders were positively associated in bivariate analyses. After adjusting for comorbidities, many associations involving a behavioral disorder and an emotional disorder were attenuated suggesting indirect comorbidity. Generalized anxiety and depressive disorders displayed a very high level of overlap (adjusted OR = 37.9). All analyses were rerun with depressive disorders grouped with generalized anxiety disorder in a single "distress disorders" category. In these revised models, all associations between and emotional disorder and a behavior disorder met our criteria for indirect comorbidity except for the association of oppositional defiant disorder with distress disorders (OR = 11.3). Follow-up analyses suggested that the indirect associations were primarily accounted for by oppositional defiant disorder and the distress disorder category. There was little evidence of either sex differences or differences by developmental period. Conclusion: After accounting for the overlap between depressive disorders with generalized anxiety disorder, direct comorbidity between emotional and behavioral disorders was uncommon. When there was evidence of indirect comorbidity, ODD, and distress disorders were the key intermediary diagnoses accounting for the apparent associations.