Early life adversity and psychopathology in preschoolers: mechanisms and moderators.

Developmental theories suggest that exposure to early life adversity (ELA) alters developing emotional response systems, predicting risk for psychopathology across the life span. The present study examines whether negative emotionality (NE), a trait-like measure of emotionality that develops during early childhood, mediates the association between ELA and psychopathology in a representative sample of 917 preschoolers (Mage = 3.84). Additionally, we explored whether cognitive control, which supports attentional focusing and inhibition and has been identified as a transdiagnostic protective factor, moderates the impact of heightened emotionality following adversity on psychopathology risk. We utilized parent report of adversity, psychopathology, and NE and parent report and task-based measures of cognitive control. Structural equation modeling of cross-sectional data revealed that NE partially mediated the link between ELA and psychopathology symptoms. Moreover, parent-reported cognitive control buffered this link such that the effect of ELA on psychopathology through NE was stronger in children with low versus high cognitive control. These results identify elevated NE as one mechanism linking ELA and psychopathology, specifically among children with poorer top-down control, informing our understanding of key risk and protective factors among adversity-exposed children.

Association of adversity with psychopathology in early childhood: Dimensional and cumulative approaches.

BACKGROUND: The association between adversity and psychopathology in adolescents and adults is characterized by equifinality. These associations, however, have not been assessed during early childhood when psychopathology first emerges. Defining adversity using both dimensional and cumulative risk approaches, we examined whether specific types of adversity are differentially associated with psychopathology in preschool-aged children. METHODS: Measures of threat, deprivation, and total adversities (i.e., cumulative risk) were calculated based on parent-reported information for 755 2- to 5-year old children recruited from pediatric primary care clinics. Logistic regression was used to estimate cross-sectional associations between type of adversity and anxiety, depression, ADHD, and behavioral disorder diagnoses. RESULTS: Threat and cumulative risk exhibited independent associations with psychopathology. Threat was strongly related to behavioral disorders. Cumulative risk was consistently related to all psychopathologies. CONCLUSIONS: Using mutually adjusted models, we identified differential associations between threat and psychopathology outcomes in preschool-aged children. This selectivity may reflect different pathways through which adversity increases the risk for psychopathology during this developmentally important period. As has been observed at other ages, a cumulative risk approach also effectively identified the cumulative impact of all forms of adversity on most forms of psychopathology during early childhood.

Parental perception of mental health needs in young children.

BACKGROUND: There is evidence of unmet psychiatric needs in children under 6. These young children are dependent on their parents to identify their mental health needs. This study tested child and parent associations with parent perception of young child mental health need. METHOD: Parents of 917 children (aged 2-6 years) completed a diagnostic interview about their child assessing depression, anxiety, ODD/CD, ADHD, and impairment. Parents were surveyed about their own depression, anxiety, and asked about their psychiatric impairment. Parents were also asked whether they perceived their child as having a mental health need. RESULTS: Only 38.8% of children who met criteria for a diagnosis were perceived by their parents as having a need, similar to previously studied rates in school-aged children. Perception of need was associated with higher levels of symptoms and impairment. Thresholds for at least half of parents perceiving their child as having a need were relatively high: 19 or more symptoms, or 4 or more impairments. There was evidence of specificity: children with depressive disorders were more likely to be perceived as in need compared with other disorders. In terms of parent factors, more parental depressive symptoms were associated with higher perception of child need when the child had a diagnosis. Parental psychological impairment was associated with higher perception of need when the child had no diagnosis. CONCLUSIONS: Most preschool children that meet criteria for a psychiatric disorder are not perceived as needing help by their parents, which is dependent on both child and parent factors.

Use of a Digital Modified Checklist for Autism in Toddlers - Revised with Follow-up to Improve Quality of Screening for Autism.

OBJECTIVES: To assess changes in quality of care for children at risk for autism spectrum disorders (ASD) due to process improvement and implementation of a digital screening form. STUDY DESIGN: The process of screening for ASD was studied in an academic primary care pediatrics clinic before and after implementation of a digital version of the Modified Checklist for Autism in Toddlers - Revised with Follow-up with automated risk assessment. Quality metrics included accuracy of documentation of screening results and appropriate action for positive screens (secondary screening or referral). Participating physicians completed pre- and postintervention surveys to measure changes in attitudes toward feasibility and value of screening for ASD. Evidence of change was evaluated with statistical process control charts and χ2 tests. RESULTS: Accurate documentation in the electronic health record of screening results increased from 54% to 92% (38% increase, 95% CI 14%-64%) and appropriate action for children screening positive increased from 25% to 85% (60% increase, 95% CI 35%-85%). A total of 90% of participating physicians agreed that the transition to a digital screening form improved their clinical assessment of autism risk. CONCLUSIONS: Implementation of a tablet-based digital version of the Modified Checklist for Autism in Toddlers - Revised with Follow-up led to improved quality of care for children at risk for ASD and increased acceptability of screening for ASD. Continued efforts towards improving the process of screening for ASD could facilitate rapid, early diagnosis of ASD and advance the accuracy of studies of the impact of screening.

Magnetic susceptibility of brain iron is associated with childhood spatial IQ.

Iron is an essential micronutrient for healthy brain function and development. Because of the importance of iron in the brain, iron deficiency results in widespread and lasting effects on behavior and cognition. We measured iron in the basal ganglia of young children using a novel MRI method, quantitative susceptibility mapping, and examined the association of brain iron with age and cognitive performance. Participants were a community sample of 39 young children recruited from pediatric primary care who were participating in a 5-year longitudinal study of child brain development and anxiety disorders. The children were ages 7 to 11years old (mean age: 9.5years old) at the time of the quantitative susceptibility mapping scan. The differential abilities scale was administered when the children were 6years old to provide a measure of general intelligence and verbal (receptive and expressive), non-verbal, and spatial performance. Magnetic susceptibility values, which are linearly related to iron concentration in iron-rich areas, were extracted from regions of interest within iron-rich deep gray matter nuclei from the basal ganglia, including the caudate, putamen, substantia nigra, globus pallidus, and thalamus. Controlling for scan age, there was a significant positive association between iron in the basal ganglia and spatial IQ, with this effect being driven by iron in the right caudate We also replicated previous findings of a significant positive association between iron in the bilateral basal ganglia and age. Our finding of a positive association between spatial IQ and mean iron in the basal ganglia, and in the caudate specifically, suggests that iron content in specific regions of the iron-rich deep nuclei of the basal ganglia influences spatial intelligence. This provides a potential neurobiological mechanism linking deficits in spatial abilities reported in children who were severely iron deficient as infants to decreased iron within the caudate.

DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5: SELECTIVE REVIEWS FROM A NEW NOSOLOGY FOR EARLY CHILDHOOD PSYCHOPATHOLOGY.

The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-5; ZERO TO THREE) is scheduled to be published in 2016. The articles in this section are selective reviews that have been undertaken as part of the process of refining and updating the nosology. They provide the rationales for new disorders, for disorders that had not been included previously in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-3R; ZERO TO THREE, 2005), and for changes in how certain types of disorders are conceptualized.

Behavior and emotion modulation deficits in preschoolers at risk for bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is highly familial, but studies have yet to examine preschoolers at risk for BD using standardized, developmentally appropriate clinical assessment tools. We used such methods to test whether preschoolers at familial risk for BD have more observed difficulty modulating emotions and behaviors than do low-risk preschoolers. Identification of emotional and behavioral difficulties in at-risk preschoolers is crucial for developing new approaches for early intervention and prevention of BD. METHODS: Using the standardized disruptive behavior diagnostic observation schedule (DB-DOS) protocol for preschoolers, we compared 23 preschoolers (M(age): 4.53 ± 0.73 years; 18 males) with a first-degree relative with BD to 21 preschoolers (M(age): 4.65 ± 0.84 years; 11 males) without a family history of BD. We characterized psychopathology in this sample using the Preschool Aged Psychiatric Assessment and behavioral and emotional problems using the Child Behavior Checklist. RESULTS: High-risk preschoolers demonstrated significantly more intense, pervasive, and clinically concerning problems in anger modulation and behavior dysregulation on the DB-DOS than the low-risk group. High-risk relative to low-risk preschoolers, were also more likely to have maternal-reported anxiety and oppositional defiant disorders and internalizing and externalizing problems. CONCLUSIONS: Clinically concerning problems in anger modulation and behavior regulation, measured during standardized laboratory observation, differentiate preschoolers at high familial risk for BD from those at low risk. Investigation in a large longitudinal sample is critical for replication and for determining whether these observed behavioral differences can be reliably used as prodromal indicators of mood disorders.

Depressive comorbidity in preschool anxiety disorder.

BACKGROUND: The threshold for clinical relevance of preschool anxiety has recently come under increasing scrutiny in view of large variations in prevalence estimates. We studied the impact of presence/absence of additional depressive comorbidity (symptoms and/or diagnosis) on preschoolers with anxiety disorders in relation to clinical phenomenology, family, and peer problems compared to healthy controls. METHOD: A population of 1738 preschoolers were screened and oversampled for internalizing symptoms from community sites, yielding a sample of 236 children. RESULTS: Using a multi-informant approach (mother, father, teacher, child), we found evidence that children with anxiety disorders and depressive comorbidity display a greater internalizing symptom-load, more peer problems and live in families with more psychosocial impairment (poor family functioning, family adversity, maternal mental health problems). The pure anxiety group was merely dissociable from controls with regard to internalizing symptoms and family adversity. CONCLUSION: The presence of depressive comorbidity in anxiety disorders may mark the transition to a more detrimental and impairing disorder at preschool age.

Associations of preschool reactive bed-sharing with sociodemographic factors, sleep disturbance, and psychopathology.

OBJECTIVE: To advance understanding of early childhood bed-sharing and its clinical significance, we examined reactive bed-sharing rates, sociodemographic correlates, persistence, and concurrent and longitudinal associations with sleep disturbances and psychopathology. METHODS: Data from a representative cohort of 917 children (mean age 3.8 years) recruited from primary pediatric clinics in a Southeastern city for a preschool anxiety study were used. Sociodemographics and diagnostic classifications for sleep disturbances and psychopathology were obtained using the Preschool Age Psychiatric Assessment (PAPA), a structured diagnostic interview administered to caregivers. A subsample of 187 children was re-assessed approximately 24.7 months after the initial PAPA interview. RESULTS: Reactive bed-sharing was reported by 38.4% of parents, 22.9% nightly and 15.5% weekly, and declined with age. At follow-up, 48.9% of nightly bed-sharers and 88.7% of weekly bed-sharers were no longer bed-sharing. Sociodemographics associated with nightly bed-sharing were Black and (combined) American Indian, Alaska Native and Asian race and ethnicity, low income and parent education less than high school. Concurrently, bed-sharing nightly was associated with separation anxiety and sleep terrors; bed-sharing weekly was associated with sleep terrors and difficulty staying asleep. No longitudinal associations were found between reactive bed-sharing and sleep disturbances or psychopathology after controlling for sociodemographics, baseline status of the outcome and time between interviews. CONCLUSIONS: Reactive bed-sharing is relatively common among preschoolers, varies significantly by sociodemographic factors, declines during the preschool years and is more persistent among nightly than weekly bed-sharers. Reactive bed-sharing may be an indicator of sleep disturbances and/or anxiety but there is no evidence that bed-sharing is an antecedent or consequence of sleep disturbances or psychopathology.

Psychometric Properties of the Preschool Age Psychiatric Assessment (PAPA) in Farsi: Based on DSM-5.

Objectives: The first onset of many psychiatric disorders usually occurs in childhood or adolescence. The structured interview of Preschool Age Psychiatric Assessment (PAPA) was developed in response to the need for a standardized and reliable method to assess psychiatric disorders in preschool-age children. This study aimed to translate DSM-5-based PAPA into Farsi and evaluate its face and content validity and reliability. Materials & methods: The procedure was a forward translation of PAPA to Farsi, evaluation for face and content validity, finalization of items within the expert panel, backward translation to English, matching the original PAPA with randomly selected items from the backward translation version, and revision as needed, and finally evaluation for the validity of the changes for localization and cultural considerations. The interviews based on the final Farsi version were performed on thirty parents of children from two to five years old (chosen from Tabriz health centers) to determine the reliability and were repeated at an interval of two weeks. Results:  The mean of CVI=0.91 and Modified Kappa=0.90 were obtained, and reliability with Cronbach's alpha was 0.89. Conclusion:  The Farsi version of the DSM-5-based PAPA diagnostic interview has good face and content validity and reliability.

Distinct Associations of Deprivation and Threat With Alterations in Brain Structure in Early Childhood.

OBJECTIVE: The dimensional model of adversity and psychopathology hypothesizes deprivation and threat impact distinct neurobiological pathways, such as brain structure. This hypothesis has not been examined longitudinally or in young children. This study tested longitudinal associations between threat and deprivation measured in preschool and brain structure in childhood. It was hypothesized that threat would be associated with amygdala and hippocampal subcortical volume and deprivation would be associated with cortical thickness in association cortex. METHOD: The study included T1-weighted scans from 72 children (5-10 years old, 54.2% female participants). Threat was measured by the presence of domestic violence, sexual abuse, physical abuse, or neighborhood violence. Deprivation was measured by the presence of neglect. Associations of deprivation or threat with brain structure were examined controlling for other dimension (deprivation or threat) and nuisance covariates using whole-brain vertex-wise analyses. Subcortical volume was extracted, and the same associations were examined using multiple regression. RESULTS: Threat was associated with widespread decreases in cortical surface area across the prefrontal cortex and other regions. Threat was not associated with amygdala or hippocampal volume. Deprivation was associated with increased thickness in occipital cortex, insula, and cingulate. CONCLUSION: Results suggest distinct associations of deprivation and threat on brain structure in early childhood. Threat is associated with widespread differences in surface area, and deprivation is associated with differences in cortical thickness. These observations are consistent with work in adolescence and adulthood and reflect how dimensions of adversity differentially impact neural structure.

Prevalence of psychiatric disorders in preschoolers.

BACKGROUND: Many disorders in childhood and adolescence were already present in the preschool years. However, there is little empirical research on the prevalence of psychiatric disorders in young children. A true community study using structured diagnostic tools has yet to be published. METHODS: All children born in 2003 or 2004 in the city of Trondheim, Norway, who attended the regular community health check-up for 4-year-olds (97.2% of eligible children) whose parents consented to take part in the study (N = 2,475, 82.0%) were screened for behavioral and emotional problems with the Strengths and Difficulties Questionnaire (SDQ). A screen-stratified subsample of 1,250 children took part in a furthermore comprehensive study including a structured diagnostic interview (the Preschool Age Psychiatric Assessment, PAPA), which 995 parents (79.6%) completed. RESULTS: The estimated population rate for any psychiatric disorder (excluding encopresis - 6.4%) was 7.1%. The most common disorders were attention deficit hyperactivity disorder (1.9%), oppositional defiant disorder (1.8%), conduct disorder (0.7%), anxiety disorders (1.5%), and depressive disorders (2.0%). Comorbidity among disorders was common. More emotional and behavioral disorders were seen in children whose parents did not live together and in those of low socioeconomic status. Boys more often had attention-deficit/hyperactivity disorder (ADHD) and depressive disorders than girls. CONCLUSIONS: The prevalence of disorders among preschoolers was lower than in previous studies from the USA. Comorbidity was frequent and there was a male preponderance in ADHD and depression at this early age. These results underscore the fact that the most common disorders of childhood can already be diagnosed in preschoolers. However, rates of disorder in Norway may be lower than in the USA.

Adaptive Behavior in Young Autistic Children: Associations with Irritability and ADHD Symptoms.

Attention-deficit/hyperactivity disorder (ADHD) symptoms affect 40-60% of autistic children and have been linked to differences in adaptive behavior. It is unclear whether adaptive behavior in autistic youth is directly impacted by co-occurring ADHD symptoms or by another associated feature of both autism and ADHD, such as increased irritability. The current study examined relationships between irritability, ADHD symptoms, and adaptive behavior in 3- to 7-year-old autistic children. Results suggest that, after adjusting for co-occurring ADHD symptoms, higher levels of irritability are associated with differences in social adaptive behavior specifically. Understanding relationships between irritability, ADHD, and adaptive behavior in autistic children is critical because measures of adaptive behavior, such as the Vineland Scales of Adaptive Functioning, are often used as a proxy for global functioning, as well as for developing intervention plans and measuring outcomes as primary endpoints in clinical trials.

Structural connectivity of the frontal lobe in children with drug-resistant partial epilepsy.

The superior longitudinal fasciculus (SLF) II and cingulum are two white matter tracts important for attention and other frontal lobe functions. These functions are often disturbed in children with drug-resistant (DR) partial epilepsy, even when no abnormalities are seen on conventional MRI. We set out to determine whether abnormalities in these structures might be depicted on diffusion tensor imaging (DTI) studies in the absence of abnormalities on conventional MRI. We compared the DTI findings of 12 children with DR partial epilepsy with those of 12 age- and gender-matched controls. We found that the SLF II fractional anisotropy (FA) values of the patients were significantly lower than those of the controls (means: 0.398±0.057 and 0.443±0.059, respectively, P=0.002). Similarly, apparent diffusion coefficient (ADC) and parallel diffusivity values for SLF II were also significantly lower in the patients. There were no differences in the FA and ADC values of the cingulum. Our findings are consistent with abnormal structural connectivity of the frontal lobe in children with DR partial epilepsy and provide a possible explanation for the previously reported functional abnormalities related to the SLF II in these patients.

Epidemiology of psychiatric disorders in very young children in a Romanian pediatric setting.

A growing literature demonstrates that early clinical intervention can reduce risks of adverse psychosocial outcomes. A first step necessary for developing early intervention services is to know the prevalence of clinical disorders, especially in systems that are rebuilding, such as Romania, where the mental health system was dismantled under Ceausescu. No epidemiologic studies have examined prevalence of psychiatric disorders in young children in Romania. The objective of this study was to determine the prevalence of psychiatric disorders in Romanian children 18-60 months in pediatric settings. Parents of 1,003 children 18-60 months in pediatric waiting rooms of two pediatric hospitals completed background information, the Child Behavior Checklist (CBCL). A subgroup over-sampled for high mental health problems were invited to participate in the Preschool Age Psychiatric Assessment. Rates of mental health problems were similar to the US norms on the CBCL. The weighted prevalence of psychiatric disorders in these children was 8.8%, with 5.4% with emotional disorders and 1.4% with behavioral disorders. Comorbidity occurred in nearly one-fourth of the children with a psychiatric disorder and children who met diagnostic criteria had more functional impairment than those without. Of children who met criteria for a psychiatric disorder, 10% of parents were concerned about their child's emotional or behavioral health. This study provides prevalence rates of psychiatric disorders in young Romanian children, clinical characteristic of the children and families that can guide developing system of care. Cultural differences in parental report of emotional and behavioral problems warrant further examination.

Psychometric properties of the Persian version of preschool age psychiatric assessment (PAPA) for attention-deficit/hyperactivity disorder: Based on DSM-5.

Childhood and adolescence psychiatric disorders affect subsequent stages; early diagnosis of these disorders, such as attention-deficit/hyperactivity disorder (ADHD), is necessary. There is no reliable and valid diagnostic interview for ADHD in Asian Persian or Farsi speaking countries. The DSM 5-based version of the interview was sent to the 14 child and adolescent and general psychiatrists to ensure the validity of the ADHD section of the PAPA interview through an online website. Out of 59 health centers, 15 centers were selected via systematic random sampling. Three hundred children participated in the study. ADHD questions of the PAPA had the power to differentiate, with a sensitivity of 0.92, a specificity of 0.01. It had positive diagnostic value = 95.83 %, negative diagnostic value = 98.91 %, negative correlation ratio = 0.12, overall diagnostic accuracy = 98.67 % and diagnostic chance ratio = 2085.35. ADHD questions of the PAPA diagnostic interview can diagnose ADHD in preschool as a reliable tool based on DSM-5.

Digital Behavioral Phenotyping Detects Atypical Pattern of Facial Expression in Toddlers with Autism.

Commonly used screening tools for autism spectrum disorder (ASD) generally rely on subjective caregiver questionnaires. While behavioral observation is more objective, it is also expensive, time-consuming, and requires significant expertise to perform. As such, there remains a critical need to develop feasible, scalable, and reliable tools that can characterize ASD risk behaviors. This study assessed the utility of a tablet-based behavioral assessment for eliciting and detecting one type of risk behavior, namely, patterns of facial expression, in 104 toddlers (ASD N = 22) and evaluated whether such patterns differentiated toddlers with and without ASD. The assessment consisted of the child sitting on his/her caregiver's lap and watching brief movies shown on a smart tablet while the embedded camera recorded the child's facial expressions. Computer vision analysis (CVA) automatically detected and tracked facial landmarks, which were used to estimate head position and facial expressions (Positive, Neutral, All Other). Using CVA, specific points throughout the movies were identified that reliably differentiate between children with and without ASD based on their patterns of facial movement and expressions (area under the curves for individual movies ranging from 0.62 to 0.73). During these instances, children with ASD more frequently displayed Neutral expressions compared to children without ASD, who had more All Other expressions. The frequency of All Other expressions was driven by non-ASD children more often displaying raised eyebrows and an open mouth, characteristic of engagement/interest. Preliminary results suggest computational coding of facial movements and expressions via a tablet-based assessment can detect differences in affective expression, one of the early, core features of ASD. LAY SUMMARY: This study tested the use of a tablet in the behavioral assessment of young children with autism. Children watched a series of developmentally appropriate movies and their facial expressions were recorded using the camera embedded in the tablet. Results suggest that computational assessments of facial expressions may be useful in early detection of symptoms of autism.

Children's Beliefs about Pain: An Exploratory Analysis.

Functional abdominal pain (FAP) is one of the most common childhood medical complaints, associated with significant distress and impairment. Little is known about how children understand their pain. Do they attribute it to personal weakness? Do they perceive pain as having global impact, affecting a variety of activities? How do they cope with pain? We explored the pain beliefs of 5- to 9-year-old children with FAP using a novel Teddy Bear Interview task in which children answered questions about a Teddy bear's pain. Responses were analyzed quantitatively and qualitatively. Results indicate that the majority of young children with FAP are optimistic about pain outcomes. Children generated many types of coping strategies for Teddy's pain and adjusted their calibration of Teddy's pain tolerance dependent on the activity being performed. Early warning signs also emerged: a subset of children were pessimistic about Teddy's pain, and several children identified coping strategies that, while developmentally appropriate, could lead to excessive help seeking if not intervened upon (e.g., physician consultation and shot). The Teddy Bear Interview allows children to externalize their pain, making it a useful tool to access cognitive pain constructs in younger children. Thus, these findings highlight the importance of early intervention for childhood FAP.

Computer Vision Analysis for Quantification of Autism Risk Behaviors.

Observational behavior analysis plays a key role for the discovery and evaluation of risk markers for many neurodevelopmental disorders. Research on autism spectrum disorder (ASD) suggests that behavioral risk markers can be observed at 12 months of age or earlier, with diagnosis possible at 18 months. To date, these studies and evaluations involving observational analysis tend to rely heavily on clinical practitioners and specialists who have undergone intensive training to be able to reliably administer carefully designed behavioural-eliciting tasks, code the resulting behaviors, and interpret such behaviors. These methods are therefore extremely expensive, time-intensive, and are not easily scalable for large population or longitudinal observational analysis. We developed a self-contained, closed-loop, mobile application with movie stimuli designed to engage the child's attention and elicit specific behavioral and social responses, which are recorded with a mobile device camera and then analyzed via computer vision algorithms. Here, in addition to presenting this paradigm, we validate the system to measure engagement, name-call responses, and emotional responses of toddlers with and without ASD who were presented with the application. Additionally, we show examples of how the proposed framework can further risk marker research with fine-grained quantification of behaviors. The results suggest these objective and automatic methods can be considered to aid behavioral analysis, and can be suited for objective automatic analysis for future studies.

Longitudinal dimensionality of adolescent psychopathology: testing the differentiation hypothesis.

BACKGROUND: The differentiation hypothesis posits that the underlying liability distribution for psychopathology is of low dimensionality in young children, inflating diagnostic comorbidity rates, but increases in dimensionality with age as latent syndromes become less correlated. This hypothesis has not been adequately tested with longitudinal psychiatric symptom data. METHODS: Confirmatory factor analyses of DSM-IV symptoms from seven common Axis I syndromes--major depression, generalized anxiety, separation anxiety, social anxiety, attention deficient hyperactivity, conduct, and oppositional defiant disorders--were conducted longitudinally, from ages 9 to 16, using the general-population Great Smoky Mountains Study sample. RESULTS: An eight-syndrome model fit well at all ages, and in both genders. It included social anxiety, separation anxiety, oppositional defiant, and conduct syndromes, along with a multidimensional attention deficit-hyperactivity syndrome (i.e., inattention, hyperactivity, and impulsivity) and a unidimensional major depression/generalized anxiety syndrome. A high degree of measurement invariance across age was found for all syndromes, except for major depression/generalized anxiety. Major depression and generalized anxiety syndromes slightly diverged at age 14-16, when they also began to explain more symptom variance. Additionally, correlations between some emotional and disruptive syndromes showed slight differentiation. CONCLUSIONS: Marked developmental differentiation of psychopathology, as implied by the orthogenetic principle, is not a prominent cause of preadolescent and adolescent psychiatric comorbidity.