Heterotypic Comorbidity Research Articles

Anxiety disorders as comorbid conditions in neuropsychiatric diseases in children

The variants of heterotypic comorbidity of anxiety disorders (AD) with attention deficit hyperactivity disorder, autism spectrum disorders, speech and language development disorders, specific learning disabilities (dyslexia, dysgraphia, dyscalculia), migraine, tension type headache in children and adolescents are discussed. In cases of heterotypic comorbidity the patients with AD referrals to specialists may be primarily associated with their emotional problems. Meanwhile, the comorbidity of AD with these diseases leads to a deterioration of their clinical manifestations and a worsening of the prognosis, and anxiety symptoms often not only persist, but also increase with age. It should be borne in mind that AD in children with neurodevelopmental disorders contribute to a decrease in the quality of life, academic failure, have a negative impact on peer relationships and the family environment, and in young adulthood, patients have an increased risk of depression and substance abuse. Therefore, early intervention and a comprehensive therapeutic approach with a dynamic assessment of the patient's condition are becoming important. When choosing pharmacotherapy, it is advisable to choose medictions that have a complex effect on the pathogenetic mechanisms of the underlying disease and concomitant AD, which include Tenoten for children.

A Register Study Suggesting Homotypic and Heterotypic Comorbidity Among Individuals With Learning Disabilities

The present study examined whether learning disabilities (LD) in reading and/or math (i.e., reading disability [RD], math disability [MD], and RD+MD) co-occur with other diagnoses. The data comprised a clinical sample (n = 430) with LD identified in childhood and a sample of matched controls (n = 2,140). Their medical diagnoses (according to the International Classification of Diseases nosology) until adulthood (20–39 years) were analyzed. The co-occurrence of LD with neurodevelopmental disorders was considered a homotypic comorbidity, and co-occurrence with disorders or diseases from the other diagnostic categories (i.e., mental and behavioral disorders, diseases of the nervous system, injuries, other medical or physical diagnoses) was considered a heterotypic comorbidity. Both homotypic and heterotypic comorbidity were more common in the LD group. Co-occurring neurodevelopmental disorders were the most prominent comorbid disorders, but mental and behavioral disorders, diseases of the nervous system, and injuries were also pronounced in the LD group. Accumulation of diagnoses across the diagnostic categories was more common in the LD group. No differences were found among the RD, MD, and RD+MD subgroups. The findings are relevant from the theoretical perspective, as well as for clinical and educational practice, as they provide understanding regarding individual distress and guiding for the planning of support.

Internalizing-externalizing comorbidity and regional brain volumes in the ABCD study.

Despite nonoverlapping diagnostic criteria, internalizing and externalizing disorders show substantial comorbidity. This comorbidity is attributable, at least in part, to transdiagnostic neuroaffective mechanisms. Both unipolar depression and externalizing disorders are characterized by structural and functional compromises in the striatum and its projections to the anterior cingulate cortex (ACC) and other frontal regions. Smaller volumes and dampened reward responding in these regions are associated with anhedonia and irritability - mood states that cut across the internalizing and externalizing spectra. In contrast, smaller amygdala volumes and dampened amygdala function differentiate externalizing disorders from internalizing disorders. Little is known, however, about associations between internalizing-externalizing comorbidity and brain volumes in these regions, or whether such patterns differ by sex. Using a transdiagnostic, research domain criteria (RDoC)-informed approach, we evaluate associations between heterotypic (Internalizing × Externalizing) symptom interactions and striatal, amygdalar, and ACC volumes among participants in the Adolescent Brain Cognitive Development study (N = 6,971, mean age 9.9 years, 51.6% female). Heterotypic symptoms were associated with ACC volumes for both sexes, over and above the main effects of internalizing and externalizing alone. However, heterotypic comorbidity was associated with larger ACC volumes for girls, but with smaller ACC volumes for boys. These findings suggest a need for further studies and transdiagnostic assessment by sex.

Concomitant Trajectories of Internalising, Externalising, and Peer Problems Across Childhood: a Person-centered Approach

This study investigated trajectories of concomitant internalising, externalising, and peer problems, and associated risk factors for group-membership, using a person-centered approach to better understand heterogeneity in subgroups identified. A cohort of 7,507 children in Ireland was followed from infancy to late childhood (50.3%, males; 84.9% Irish). The parent-version of the Strengths and Difficulties Questionnaire was used when children were 3, 5, 7 and 9 years of age. Information on antecedent risk factors was collected when children were 9 months. Group-based multi-trajectory modelling and multinomial logistic regression were used. Six subgroups of children with distinct profiles were identified, evidencing both homotypic and heterotypic comorbidity. No support of a ‘pure’ internalising, externalising or peer problems group was found in any identified trajectory group. Difficulties in one problem domain indicated the presence of difficulty in another problem domain for all children in elevated groups. Risk factors associated with group-membership were complex, with only three common factors across elevated groups: prenatal exposure to smoking, maternal education, and maternal stress. Specific risk factors for group-membership included low birth weight, sex, maternal age, maternal depression, family composition, social class, medical card status and quality of attachment. Despite some overlap in predictors, the combination of predictors specific to each group would suggest tailored programming. For children with the most acute problems, programming targets should include families with boys, born with low birth weight, exposed to smoking prenatally, with mothers who have lower levels of education, postnatal depression, increased stress and fewer financial resources.

Editorial: The Co-Occurrence of Diseases

Editorial: The Co-Occurrence of Diseases

Emotion Regulation as a Transdiagnostic Feature in Children with Neurodevelopmental Disorders

Emotion regulation is recognized as a core underlying dimension common across psychiatric disorders and could be conceptualized as a transdiagnostic feature (i.e., mechanism underlying comorbidity). This review highlights recent research examining emotion regulation in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Difficulties with emotion regulation are increasingly recognized as common deficits in children with ADHD and ASD. Research indicates that emotion regulation transmits risk for co-occurring disorders within a diagnostic grouping (i.e., neurodevelopment disorders; homotypic comorbidity) and across different diagnostic groupings (i.e., neurodevelopmental disorder–mood disorder; heterotypic comorbidity) in children with ADHD and ASD. While this review provides support for the conceptualization of emotion regulation as a transdiagnostic feature in ADHD and ASD, further research examining emotion regulation in children with other neurodevelopmental disorders is needed. The field of neurodevelopmental disorders should examine emotion regulation from a developmental perspective and needs to develop valid assessments of emotion regulation.

RDoC and Psychopathology among Youth: Misplaced Assumptions and an Agenda for Future Research

ABSTRACT Now over 10 years old, the Research Domain Criteria (RDoC) has gained impressive traction in the adult psychopathology literature, but enthusiasm among child and adolescent psychopathologists lags somewhat behind. We consider possible reasons why RDoC has not been embraced fully in the child and adolescent literatures. We emphasize common, interrelated, and sometimes outdated assumptions that impede scientific progress that RDoC could facilitate. Traditionally, child and adolescent psychopathologists have used behavioral syndromes as gold standards against which biological markers are validated, even though behavioral syndromes are often measured with less precision; sought to identify large main effects of single biological functions on single behavioral syndromes, thereby ignoring (even if implicitly) the overwhelming etiological complexity of psychopathology; expected 1:1 correspondencies between biological functions and behaviors, despite evidence that core biological systems subserving behavior are functionally interdependent (i.e., modulate one another); and failed to consider neurobiological mechanisms of homotypic and heterotypic comorbidity and continuity. Using examples from our work, we show how a developmental, RDoC-informed approach to externalizing behavior enriches our understanding of psychopathology. We also provide an agenda for future research, which includes calls to (1) adopt neural-systems-first approaches over disorder-first approaches when studying psychopathology, (2) eschew biological reductionism by integrating environmental risk mediators into our etiopathophysiological models, (3) integrate neural vulnerabilities into the empirical latent structure of psychopathology, and (4) replace null hypothesis significance testing with computational approaches that accommodate etiological complexity by evaluating functional dependencies among RDoC constructs, including positive valence systems (approach), negative valence systems (avoidance), and arousal/regulatory systems (self-regulation).

Prevalence of DSM-5 anxiety disorders, comorbidity, and persistence of symptoms in Spanish early adolescents.

Anxiety Disorders (AD) are the most prevalent mental disorders in children and adolescents and a relevant public health problem. The study aimed to determine the prevalence of ADs, the comorbidity, the sociodemographic correlates, and the functional impairment in Spanish school children. The initial sample included 1514 subjects (720 boys; mean age = 10.2), who filled out the Screen for Children's Anxiety-Related Emotional Disorders (SCARED). In a second phase, 562 subjects at risk and not-at-risk of anxiety were assessed with the Mini-International Neuropsychiatric Interview for Children and Adolescents to obtain DSM-5 diagnoses. Two years later (third phase; mean age 13.5), the SCARED was re-administered. The weighted prevalence of any AD was 11.8%. The most prevalent subtypes were specific phobia (16.2%) and generalized anxiety disorder (GAD) (6.9%). Girls showed higher rates of social anxiety (5.5%) than boys. Apart from being female, low socioeconomic status was also a risk factor for AD. The heterotypic comorbidity of any AD was 40.7%, and the homotypic comorbidity was 35.6%. After controlling for age and other ADs, we found that subjects with GAD had the highest risk of having other depressive disorders and ADs. Only 33.3% of the subjects with any AD had sought professional help. 52.9% of the subjects diagnosed with any of the ADs still had anxiety symptoms after a 2-year follow-up. These findings highlight that in Spain, ADs in early adolescence are an important public health problem and that detection and access to treatment need to be improved.

Comorbidity and continuity of depression and conduct problems from elementary school to adolescence.

Despite nonoverlapping criterion sets, conduct disorder and depression co-occur at much higher rates than expected by chance. Contemporary model-based approaches to explaining heterotypic comorbidity use factor analysis and its variants to evaluate interrelations among symptoms in large population-based and twin samples. These analyses invariably yield broadband internalizing and externalizing factors, which load on a higher-order general liability factor-findings that are robust across age and informant. Although model-based approaches elucidate structural aspects of comorbidity, they are variable-centered, and usually cross-sectional. Most therefore do not assess developmental continuity of comorbidity, or whether noncomorbid individuals are prospectively vulnerable to heterotypic comorbidity. We use an accelerated longitudinal design to evaluate growth in parent-reported conduct problems (CPs) and depression among children, ages 8-15 years, who were recruited at study entry into depressed only (n = 27), CPs only (n = 28), comorbid (n = 81), and control (n = 70) groups based on levels of symptoms. Consistent with normative developmental trends across this age range, steep growth in depression was exhibited by all groups, including those who reported only CPs at study entry. In contrast, growth in CPs was restricted to those who reported high symptoms at intake (with or without comorbid depression), compared with low and stable among depressed only and control participants. To our knowledge, this is the first study to demonstrate, using carefully ascertained "pure" versus comorbid groups who were followed naturalistically, that comorbid depression is likely to develop among those with pure CPs, but comorbid CPs are not likely to develop among those with pure depression. (PsycINFO Database Record

Neurodevelopmental disorders: prevalence and comorbidity in children referred to mental health services

Background: Accurate prevalence rates of the neurodevelopmental disorders (ND) and comorbid conditions in child and adolescent mental health services (CAMHS) are essential for treatment planning and organization of health care. However, valid and reliable prevalence estimates from Nordic CAMHS populations are scarce, and the published findings vary.Aims: To report prevalence rates of ND (attention-deficit hyperactivity disorder: ADHD, tic disorder: TD or autism spectrum disorder: ASD) and comorbid disorders by a validated diagnostic instrument in children referred to CAMHS outpatient clinics.Methods: Parents of 407 consecutively referred children aged 7–13 years were interviewed with the semistructured interview schedule for affective disorders and schizophrenia, present and lifetime version (Kiddie-SADS-PL) at time of admittance.Results: One or more ND was diagnosed in 226 children (55.5%; 69.9% boys): ADHD (44.5%; 68.5% boys); TD (17.7%; 77.8% boys) and ASD (6.1%; 76% boys). Among children with ND 70 (31.0%) had only one ND with no comorbid disorder, 49 (21.7%) had more than one ND (homotypic comorbidity) and 131 (58%) had a non-ND psychiatric disorder (heterotypic comorbidity). Anxiety disorders were the most frequently occurring heterotypic comorbidity in all three ND. Comorbid depressive disorder was associated with older age, and comorbid anxiety disorder with female gender.Conclusion: In children referred to CAMHS, ND constitute the most frequently occurring group of disorders, with high rates of both homotypic and heterotypic comorbidity. This needs to be taken into consideration in health service planning and treatment delivery.

Neural substrates of trait impulsivity, anhedonia, and irritability: Mechanisms of heterotypic comorbidity between externalizing disorders and unipolar depression.

Trait impulsivity, which is often defined as a strong preference for immediate over delayed rewards and results in behaviors that are socially inappropriate, maladaptive, and short-sighted, is a predisposing vulnerability to all externalizing spectrum disorders. In contrast, anhedonia is characterized by chronically low motivation and reduced capacity to experience pleasure, and is common to depressive disorders. Although externalizing and depressive disorders have virtually nonoverlapping diagnostic criteria in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, heterotypic comorbidity between them is common. Here, we review common neural substrates of trait impulsivity, anhedonia, and irritability, which include both low tonic mesolimbic dopamine activity and low phasic mesolimbic dopamine responding to incentives during reward anticipation and associative learning. We also consider how other neural networks, including bottom-up emotion generation systems and top-down emotion regulation systems, interact with mesolimbic dysfunction to result in alternative manifestations of psychiatric illness. Finally, we present a model that emphasizes a translational, transdiagnostic approach to understanding externalizing/depression comorbidity. This model should refine ways in which internalizing and externalizing disorders are studied, classified, and treated.

Anxiety Disorders among Adolescents referred to General Psychiatry for Multiple Causes: Clinical Presentation, Prevalence, and Comorbidity

Abstract Background Reports of anxiety disorder characteristics among youth in clinical settings typically include descriptions of patients who have been specifically referred for anxiety treatment. At odds with a large body of evidence which demonstrates these disorders to be most common among young people, prevalence studies in samples referred to general psychiatry for multiple causes are scarce and report highly discrepant estimates. Methods For this study and regardless of their presenting symptoms, 125 adolescents (57.6% girls) between the ages of 12 and 18 years who were consecutively referred to two child and adolescent general psychiatry clinics in Sweden were assessed for anxiety disorders and comorbidity using the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Self-ratings of anxiety symptoms and difficulties with family, school, friends, sleep, and body aches were also obtained. Results At least one anxiety disorder was found in 46% of participants. Among anxious adolescents, homotypic comorbidity (concurrent anxiety) was observed in 43%, and heterotypic comorbidity (concurrent non-anxiety psychiatric disorders) was observed in 91%. No comorbidity was observed in 5%. Trauma, ache, and difficulties making friends were more common among anxious adolescents as compared with psychiatrically referred adolescents without anxiety. Conclusions The finding that only 21% of adolescents diagnosed with anxiety disorders were referred for anxiety further supports the routine use of standardized and structured instruments—irrespective of referral cause—to improve both precision and detection rates in the clinical setting. Comprehensive assessments are of utmost importance to fully address the complexity of the symptoms in this patient group.

Non-obsessive–compulsive anxiety disorders in child and adolescent mental health services – Are they underdiagnosed, and how accurate is referral information?

Background: Previous studies have reported low prevalence of non-obsessive–compulsive (OCD) anxiety disorders in child and adolescent mental health services (CAMHSs), suggesting that these disorders may go unrecognized. Possible reasons may be lack of routinely used standardized diagnostic instruments, and/or an under-reporting of anxiety symptoms in the referral information. Aims: To examine the frequency of non-OCD anxiety disorders in referred children based on a standardized diagnostic interview, to compare the results with data from the Norwegian Patient Register (NPR), and to explore the correspondence between anxiety as a referral symptom and anxiety as a diagnosis, and the influence of heterotypic co-morbidity on this correspondence. Methods: Parents of 407 consecutive referrals to CAMHS aged 7–13 years were interviewed with the semi-structured diagnostic interview Kiddie-SADS-PL at the time of admittance. Referral symptoms were collected from national referral forms. Results: A total of 133 referred children (32.7%) met the criteria for a non-OCD anxiety disorder compared with about 5% in the NPR. Half of those who met diagnostic criteria for an anxiety disorder did not have anxiety as a referral symptom. Co-morbid ADHD or disruptive disorder was significantly associated with a lower probability of having anxiety as a referral symptom. Conclusions: The use of a standardized diagnostic interview in consecutively referred children yielded significantly higher rates of anxiety disorders than the NPR prevalence rates. Co-morbid ADHD or disruptive disorder may contribute to the underdiagnosing of anxiety disorders. Diagnostic instruments covering the whole range of child psychiatric symptoms should be implemented routinely in CAMHS.

Neural responses to monetary incentives among self-injuring adolescent girls.

Rates of self-inflicted injury among adolescents have risen in recent years, yet much remains to be learned about the pathophysiology of such conduct. Self-injuring adolescents report high levels of both impulsivity and depression behaviorally. Aberrant neural responding to incentives, particularly in striatal and prefrontal regions, is observed among both impulsive and depressed adolescents, and may mark common vulnerability to symptoms of anhedonia, irritability, and low positive affectivity. To date, however, no studies have examined associations between central nervous system reward responding and self-injury. In the current study, self-injuring (n = 19) and control (n = 19) adolescent females, ages 13-19 years, participated in a monetary incentive delay task in which rewards were obtained on some trials and losses were incurred on others. Consistent with previous findings from impulsive and depressed samples, self-injuring adolescents exhibited less activation in both striatal and orbitofrontal cortex regions during anticipation of reward than did controls. Self-injuring adolescents also exhibited reduced bilateral amygdala activation during reward anticipation. Although few studies to date have examined amygdala activity during reward tasks, such findings are common among adults with mood disorders and borderline personality disorder. Implications for neural models of impulsivity, depression, heterotypic comorbidity, and development of both self-injury and borderline personality traits are discussed.

ADad 7: Relationship Between Depression and Anxiety Disorders Among Adolescents in a Rural Community Population in India

Anxiety Disorders (AD) often co-exist with the heterotypic co-morbidity of Major Depressive Disorder (MDD) and Dysthymia (DysD). This study documents the prevalence of concurrent Depressive Disorder and its subtypes among AD, relationship between specific AD and Depressive Disorders, influence of severity of Depressive Disorders (DD) on AD and vice-versa, as well as the effect of age and gender on this co-morbidity. In a prospective community survey of 500 adolescents, independent raters administered the Screen for Child Anxiety Related Emotional Disorders, Beck Depression Inventory and Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Version to collect the required data. Descriptive statistics, Independent t tests and Chi-square tests were done to evaluate the prevalence of concurrent Depressive Disorders among AD, relationship between specific AD and Depressive Disorders, severity of DD, and effect of age and gender on this co-morbidity. Depressive Disorders were concurrently present in 23.7% of adolescents with AD, while 13.9% had concurrently only MDD, 8.3% had only DysD and 1.5% had both. More adolescents with AD had multiple mood disorders than otherwise. Twenty percent of adolescents with Panic Disorder, 12.1% with Generalised anxiety Disorder, 5.3% with Separation Anxiety Disorder and 12% with Social Anxiety Disorder had Depressive Disorders. Dysthymic disorder was statistically significantly more among those with PD (P = 0.009). Depressive Disorders were more severe among those with AD (P = 0.001) and the AD was more severe in those with DD (P = 0.01). As the severity of AD increased the severity of the DD also increased (P = 0.001). While DD were more prevalent among the late adolescence (P = 0.001), gender did not have any influence. The two-way overlap between AD and DD is prevalent. Adolescents with Anxiety Disorders should be screened for Depressive Disorders, and when present should be treated.

Aggregation of lifetime Axis I psychiatric disorders through age 30: incidence, predictors, and associated psychosocial outcomes.

Longitudinal data from representative birth cohorts on the aggregation of psychiatric disorders, or the cumulative number of unique diagnosed disorders experienced by persons within a circumscribed period, are limited. As a consequence, risk factors for and psychosocial implications of lifetime disorder aggregation in the general population remain largely unknown. This research evaluates the incidence, predictors, and psychosocial sequela of lifetime disorder aggregation from childhood through age 30. Over a 14-year period, participants in the Oregon Adolescent Depression Project (probands; N = 816) were repeatedly evaluated for psychiatric disorders and assessed with multiple measures of psychosocial functioning. First-degree relatives of probands (N = 2,414) were also interviewed to establish their lifetime psychiatric history. The cumulative prevalence of common lifetime psychiatric disorders for the proband sample was 71%. Three-quarters of all proband psychiatric disorders occurred among 37% of the sample, and 82% of all disorder diagnoses were made among persons who met criteria for at least one other lifetime disorder. Lifetime disorder aggregation in probands was predicted by lifetime psychiatric disorder densities among first-degree relatives and was related to heterotypic comorbidity patterns that included disorders from both internalizing and externalizing domains, most notably major depressive and alcohol use disorders. By age 30, disorder aggregation was significantly associated with mental health care service utilization and predictive of personality disorder pathology and numerous indicators of poor psychosocial functioning. Possible implications of disorder aggregation on the conceptualization of lifetime psychiatric disorder comorbidity are discussed.

Longitudinal patterns of autonomic nervous system responding to emotion evocation among children with conduct problems and/or depression

Conduct disorder (CD) and depression co-occur at far greater levels than chance, despite largely separate diagnostic criteria. One potential shared mechanism of this comorbidity is emotion dysregulation, which characterizes both internalizing and externalizing disorders. Previous research demonstrates that respiratory sinus arrhythmia (RSA)-a peripheral biomarker of emotion regulation-is attenuated among children with CD, and among children with depression. However, few studies have examined biomarkers of emotion regulation as a function of heterotypic comorbidity. We evaluated longitudinal patterns of RSA and RSA reactivity to emotion evocation across three annual assessments among 207 children diagnosed at ages 8-12 years with CD (n = 30), depression (n = 28), comorbid CD and depression (n = 80), or no psychiatric condition (n = 69). Using continuous symptom counts as predictors, Depression × CD interactions were observed for both Time 1 resting RSA and Time 1 RSA reactivity. CD, depression, and their interaction were all associated with low resting RSA at Time 1. In addition, concurrently elevated CD and depression scores predicted the greatest RSA reactivity to emotion evocation. Psychopathology scores were unrelated to developmental changes in RSA and RSA reactivity over time.

Neuroanatomical Correlates of Heterotypic Comorbidity in Externalizing Male Adolescents

Children and adolescents with externalizing behavior disorders including attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) often present with symptoms of comorbid internalizing psychopathology. However, few studies have examined central nervous system correlates of such comorbidity. We evaluated interactions between externalizing and internalizing symptoms in predicting mesolimbic, septo-hippocampal, and anterior cingulate volumes among 12- to 16-year-old boys with either ADHD, ADHD and CD, or no psychiatric condition (n = 35). These regions were chosen given established links to trait impulsivity, trait anxiety, and behavior regulation, respectively. Collapsed across groups, Externalizing × Internalizing symptom interactions accounted for individual differences in gray matter densities in each region. Externalizing youth with comorbid internalizing symptoms showed smaller reductions in gray matter than individuals with externalizing psychopathology alone. These results suggest that internalizing symptoms are associated with less severe structural compromises in brain regions subserving motivation and behavior regulation among externalizing boys.

Effectiveness of psychosocial intervention for children and adolescents with comorbid problems: a systematic review.

Comorbidity is common among child clinical samples. Reviews on effective intervention for comorbid problems are lacking. Based on a literature search of three databases (PsycINFO, MEDLINE and ERIC), initial data analysis was carried out on 865 studies; of these,10 randomised trials fully met study inclusion criteria and were subject to final analysis, with quality assessments and effect sizes calculated. Overall, effect sizes for externalising (M = 1.12) and internalising (M = 1.09) outcomes were large. Effect sizes were large for family-based (M = 1.80) compared to individual (M = 0.78) and group-based (M = 0.54) interventions. Studies with homotypic comorbidity (M= 1.18) displayed larger treatment effect sizes than ones with heterotypic comorbidity (M = 0.54). While the overall quality ratings of the reviewed studies varied from mediocre to good, with a variety of measures used across studies to assess the same outcomes, findings suggest that current interventions are effective for reducing internalising and externalising problems in children with comorbidity. More substantive evidence for the beneficial effects of psychosocial interventions for children with comorbid problems may arise as more robust studies, which more explicitly address and describe comorbidity, become available.

Prevalence and co-morbidity among anxiety disorders in a national cohort of psychiatrically referred children and adolescents

The paper provides prevalence estimates of anxiety disorders as well as homotypic (e.g., other anxiety disorders) and heterotypic (e.g., mood, externalizing) co-morbidity in a national sample of children and adolescents referred to the psychiatric system in Denmark. Data were gathered from a database containing 83% of all youth referred from 2004 to 2007 ( N = 13,241). A prevalence of 5.7% of anxiety disorder was found in the sample. Homotypic co-morbidity was found in only 2.8%, whereas heterotypic co-morbidity was found in 42.9% of the cohort. A total of 73.6% had a principal anxiety disorder as opposed to 26.4% who had other principal diagnoses and a secondary anxiety disorder. The national database not only provides a valuable prevalence estimate of anxiety disorders in every-day non-research psychiatric settings, but also highlights the importance of applying standardized screening instruments as routine to increase the precision in recognizing and reporting on childhood anxiety disorders.