A longitudinal comparison of emotional, behavioral and attention problems in autistic and typically developing children.

BACKGROUND: Mental health problems are elevated in autistic individuals but there is limited evidence on the developmental course of problems across childhood. We compare the level and growth of anxious-depressed, behavioral and attention problems in an autistic and typically developing (TD) cohort. METHODS: Latent growth curve models were applied to repeated parent-report Child Behavior Checklist data from age 2-10 years in an inception cohort of autistic children (Pathways, N = 397; 84% boys) and a general population TD cohort (Wirral Child Health and Development Study; WCHADS; N = 884, 49% boys). Percentile plots were generated to quantify the differences between autistic and TD children. RESULTS: Autistic children showed elevated levels of mental health problems, but this was substantially reduced by accounting for IQ and sex differences between the autistic and TD samples. There was small differences in growth patterns; anxious-depressed problems were particularly elevated at preschool and attention problems at late childhood. Higher family income predicted lower base-level on all three dimensions, but steeper increase of anxious-depressed problems. Higher IQ predicted lower level of attention problems and faster decline over childhood. Female sex predicted higher level of anxious-depressed and faster decline in behavioral problems. Social-affect autism symptom severity predicted elevated level of attention problems. Autistic girls' problems were particularly elevated relative to their same-sex non-autistic peers. CONCLUSIONS: Autistic children, and especially girls, show elevated mental health problems compared to TD children and there are some differences in predictors. Assessment of mental health should be integrated into clinical practice for autistic children.

The phenotypic manifestations of rare genic CNVs in autism spectrum disorder.

Significant evidence exists for the association between copy number variants (CNVs) and Autism Spectrum Disorder (ASD); however, most of this work has focused solely on the diagnosis of ASD. There is limited understanding of the impact of CNVs on the 'sub-phenotypes' of ASD. The objective of this paper is to evaluate associations between CNVs in differentially brain expressed (DBE) genes or genes previously implicated in ASD/intellectual disability (ASD/ID) and specific sub-phenotypes of ASD. The sample consisted of 1590 cases of European ancestry from the Autism Genome Project (AGP) with a diagnosis of an ASD and at least one rare CNV impacting any gene and a core set of phenotypic measures, including symptom severity, language impairments, seizures, gait disturbances, intelligence quotient (IQ) and adaptive function, as well as paternal and maternal age. Classification analyses using a non-parametric recursive partitioning method (random forests) were employed to define sets of phenotypic characteristics that best classify the CNV-defined groups. There was substantial variation in the classification accuracy of the two sets of genes. The best variables for classification were verbal IQ for the ASD/ID genes, paternal age at birth for the DBE genes and adaptive function for de novo CNVs. CNVs in the ASD/ID list were primarily associated with communication and language domains, whereas CNVs in DBE genes were related to broader manifestations of adaptive function. To our knowledge, this is the first study to examine the associations between sub-phenotypes and CNVs genome-wide in ASD. This work highlights the importance of examining the diverse sub-phenotypic manifestations of CNVs in ASD, including the specific features, comorbid conditions and clinical correlates of ASD that comprise underlying characteristics of the disorder.

Service utilization in a sample of preschool children with autism spectrum disorder: A Canadian snapshot.

OBJECTIVE: To describe services received by preschool children diagnosed with autism spectrum disorder (ASD) during the five-year period following their diagnosis. METHOD: An inception cohort of preschoolers diagnosed with ASD from Halifax (Nova Scotia), Montreal (Quebec), Hamilton (Ontario), Edmonton (Alberta) and Vancouver (British Columbia) were invited to participate. Parents/caregivers (n=414) described the services provided to their children at four time points: baseline (T1; within four months of diagnosis; mean age three years); six months later (T2); 12 months later (T3); and at school entry (T4). Data were first coded into 11 service types and subsequently combined into four broader categories (no services, behavioural, developmental and general) for analysis. RESULTS: More than 80% of children at T1, and almost 95% at T4 received some type of service, with a significant number receiving >1 type of service at each assessment point. At T1, the most common service was developmental (eg, speech-language therapy). Subsequently, the most common services were a combination of behavioural and developmental (eg, intensive therapy based on applied behaviour analysis and speech-language therapy). Service provision varied across provinces and over time. DISCUSSION: Although most preschool children with ASD residing in urban centres were able to access specialized services shortly after diagnosis, marked variation in services across provinces remains a concern.

OBJECTIF: Décrire les services qu'ont reçus des enfants d'âge préscolaire ayant un trouble du spectre autistique (TSA) pendant la période de cinq ans suivant leur diagnostic. MÉTHODOLOGIE: Une cohorte initiale d'enfants d'âge préscolaire ayant un TSA diagnostiqué et qui provenaient de Halifax (Nouvelle-Écosse), de Montréal (Québec), de Hamilton (Ontario), d'Edmonton (Alberta) ou de Vancouver (Colombie-Britannique) a été invitée à participer à l'étude. Les parents et les tuteurs (n=414) ont décrit les services fournis à leur enfant à quatre moments : au début (T1; dans les quatre mois suivant le diagnostic, âge moyen de trois ans); six mois plus tard (T2); 12 mois plus tard (T3) et à l'entrée à l'école (T4). Les chercheurs ont d'abord codé les données en 11 types de services, pour ensuite les regrouper en quatre catégories plus vastes (absence de services, comportementaux, développementaux et généraux) en vue de leur analyse. RÉSULTATS: Plus de 80 % des enfants ont reçu certains services à T1, et près de 95 % à T4, et un nombre significatif a reçu plus d'un type de services à chaque évaluation. À T1, le service le plus courant était de type développemental (p. ex., orthophonie). Par la suite, les services les plus courants étaient un mélange de services comportementaux et développementaux (p. ex., thérapie intensive selon l'analyse de comportement appliquée et orthophonie). La prestation des services variait selon les provinces et au fil du temps. EXPOSÉ: Même si la plupart des enfants d'âge préscolaire ayant un TSA qui habitaient dans un centre urbain avaient accès à des services spécialisés peu après le diagnostic, les variations marquées des services entre les provinces demeurent préoccupantes.

Non-verbal IQ and change in restricted and repetitive behavior throughout childhood in autism: a longitudinal study using the Autism Diagnostic Interview-Revised.

BACKGROUND: Restricted and repetitive behavior (RRB) is one of the characteristic features of Autism Spectrum Disorder. This domain of symptoms includes a broad range of behaviors. There is a need to study each behavior individually to better understand the role of each in the development of autistic children. Moreover, there are currently no longitudinal studies investigating change in these behaviors over development. METHODS: The goal of the present study was to explore the association between age and non-verbal IQ (NVIQ) on 15 RRB symptoms included in the Autism Diagnostic Interview-Revised (ADI-R) over time. A total of 205 children with ASD were assessed using the ADI-R at time of diagnosis, at age 6 years, and at age 11 years, and with the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) at age 8 years. RESULTS: The proportion of children showing each RRB tended to diminish with increasing age, except for sensitivity to noise and circumscribed interests, where the proportion increased over time. Although there was no significant main effect of NVIQ, there was a significant interaction between age and NVIQ. This was mainly driven by Difficulties with change in routine, for which higher NVIQ was associated with the behavior remaining relatively stable with age, while lower NVIQ was associated with the behavior becoming more prevalent with age. LIMITATIONS: The study focused on the presence/absence of each RRB but did not account for potential changes in frequency or severity of the behaviors over development. Furthermore, some limitations are inherent to the measures used. The ADI-R relies on parent report and hence has some level of subjectivity, while the Wechsler intelligence scales can underestimate the intellectual abilities of some autistic children. CONCLUSIONS: These results confirm that specific RRB are differentially linked to age and NVIQ. Studying RRB individually is a promising approach to better understanding how RRB change over the development of autistic children and are linked to other developmental domains.

Genome-wide association study of emotional empathy in children.

The genetic contribution to different aspects of empathy is now established, although the exact loci are unknown. We undertook a genome-wide association study of emotional empathy (EE) as measured by emotion recognition skills in 4,780 8-year old children from the ALSPAC cohort who were genotyped and imputed to Phase 1 version 3 of the 1000 Genomes Project. We failed to find any genome-wide significant signal in either our unstratified analysis or analysis stratified according to sex. A gene-based association analysis similarly failed to find any significant loci. In contrast, our transcriptome-wide association study (TWAS) with a whole blood reference panel identified two significant loci in the unstratified analysis, residualised for the effects of age, sex and IQ. One signal was for CD93 on chromosome 20; this gene is not strongly expressed in the brain, however. The other signal was for AL118508, a non-protein coding pseudogene, which completely lies within CD93's genomic coordinates, thereby explaining its signal. Neither are obvious candidates for involvement in the brain processes that underlie emotion recognition and its developmental pathways.

Examining Trajectories of Daily Living Skills over the Preschool Years for Children with Autism Spectrum Disorder.

Preschool children with autism spectrum disorder (ASD) experience slower development of daily living skills (DLS) that are essential for independent functioning compared to typically developing children. Few studies have examined the trajectories of DLS in preschoolers with ASD and the existing literature has reported conflicting results. This study examined DLS trajectories and potential covariates for preschoolers with ASD from a multi-site longitudinal study following children from diagnosis to the end of grade 1. Multi-level modeling was conducted with DLS domain scores from the Vineland Adaptive Behavior Scales-2. The results demonstrated a positive trajectory of increasing scores over time, associations of age of diagnosis, developmental level, stereotypy, and language skills with the mean score at T4 or age 6 years, whereas rate of change was only associated with ASD symptom severity, such that an improvement in DLS trajectory was associated with lower and improving ASD symptom severity.

Functional DNA methylation signatures for autism spectrum disorder genomic risk loci: 16p11.2 deletions and CHD8 variants.

BACKGROUND: Autism spectrum disorder (ASD) is a common and etiologically heterogeneous neurodevelopmental disorder. Although many genetic causes have been identified (> 200 ASD-risk genes), no single gene variant accounts for > 1% of all ASD cases. A role for epigenetic mechanisms in ASD etiology is supported by the fact that many ASD-risk genes function as epigenetic regulators and evidence that epigenetic dysregulation can interrupt normal brain development. Gene-specific DNAm profiles have been shown to assist in the interpretation of variants of unknown significance. Therefore, we investigated the epigenome in patients with ASD or two of the most common genomic variants conferring increased risk for ASD. Genome-wide DNA methylation (DNAm) was assessed using the Illumina Infinium HumanMethylation450 and MethylationEPIC arrays in blood from individuals with ASD of heterogeneous, undefined etiology (n = 52), and individuals with 16p11.2 deletions (16p11.2del, n = 9) or pathogenic variants in the chromatin modifier CHD8 (CHD8+/-, n = 7). RESULTS: DNAm patterns did not clearly distinguish heterogeneous ASD cases from controls. However, the homogeneous genetically-defined 16p11.2del and CHD8+/- subgroups each exhibited unique DNAm signatures that distinguished 16p11.2del or CHD8+/- individuals from each other and from heterogeneous ASD and control groups with high sensitivity and specificity. These signatures also classified additional 16p11.2del (n = 9) and CHD8 (n = 13) variants as pathogenic or benign. Our findings that DNAm alterations in each signature target unique genes in relevant biological pathways including neural development support their functional relevance. Furthermore, genes identified in our CHD8+/- DNAm signature in blood overlapped differentially expressed genes in CHD8+/- human-induced pluripotent cell-derived neurons and cerebral organoids from independent studies. CONCLUSIONS: DNAm signatures can provide clinical utility complementary to next-generation sequencing in the interpretation of variants of unknown significance. Our study constitutes a novel approach for ASD risk-associated molecular classification that elucidates the vital cross-talk between genetics and epigenetics in the etiology of ASD.

Clinical assessment of autism in high-risk 18-month-olds.

Earlier intervention improves outcomes for children with autism spectrum disorders (ASDs), but existing identification tools are at the limits of standardization with 18-month-olds. We assessed potential behavioural markers of ASD at 18 months in a high-risk cohort of infant siblings of children with ASD. Prospective data were collected using the Autism Diagnostic Observation Schedule (ADOS) and Autism Observation Scale for Infants (AOSI) on 155 infant siblings and 73 low-risk controls at 18 months. Infants were classified into three groups (ASD sibs, non-ASD sibs, controls) based on blind best-estimate diagnosis at age 3. Fisher's exact tests, followed by discriminant function analyses, revealed that the majority of informative ADOS items came from the social and behavioural domains, and AOSI items measuring behavioural reactivity and motor control contributed additional information. Findings highlight the importance of considering not only social-communication deficits, but also basic dimensions of temperament including state regulation and motor control when assessing toddlers with suspected ASD.

Widespread abiotic methane in chromitites.

Recurring discoveries of abiotic methane in gas seeps and springs in ophiolites and peridotite massifs worldwide raised the question of where, in which rocks, methane was generated. Answers will impact the theories on life origin related to serpentinization of ultramafic rocks, and the origin of methane on rocky planets. Here we document, through molecular and isotopic analyses of gas liberated by rock crushing, that among the several mafic and ultramafic rocks composing classic ophiolites in Greece, i.e., serpentinite, peridotite, chromitite, gabbro, rodingite and basalt, only chromitites, characterized by high concentrations of chromium and ruthenium, host considerable amounts of 13C-enriched methane, hydrogen and heavier hydrocarbons with inverse isotopic trend, which is typical of abiotic gas origin. Raman analyses are consistent with methane being occluded in widespread microfractures and porous serpentine- or chlorite-filled veins. Chromium and ruthenium may be key metal catalysts for methane production via Sabatier reaction. Chromitites may represent source rocks of abiotic methane on Earth and, potentially, on Mars.

An inversion inv(4)(p12-p15.3) in autistic siblings implicates the 4p GABA receptor gene cluster.

INTRODUCTION: We describe the case of two brothers diagnosed with autism who both carry a paracentic inversion of the short arm of chromosome 4 (46,XY, inv(4)(p12-p15.3)). We have determined that this inversion is inherited from an apparently unaffected mother and unaffected maternal grandfather. Methods/ RESULTS: Using fluorescence in situ hybridisation analysis and Southern blot hybridisation we identified the breakpoints. The proximal breakpoint (4p12) maps to a region containing a cluster of gamma-aminobutyric acid A (GABA(A)) receptor genes, and directly interrupts the GABRG1 gene, the distal-most gene of the cluster. We also identified an insertion/deletion polymorphism for a approximately 2 kb LINE1 (L1) element that occurs within intron 7 of GABRG1. Our genotype analysis amongst autism families indicated that the L1 deletion allele did not show increased transmission to affected individuals. No linkage disequilibrium was evident between the L1 and single nucleotide polymorphisms in adjacent GABA(A) receptor genes on 4p, where a recent study has identified significant association with autism. DISCUSSION: Despite this, the identification of an inversion breakpoint disrupting GABRG1 provides solid support for the genetic involvement of the short arm of chromosome 4 in the genetic aetiology of autism, and for the hypothesis of disrupted GABA neurotransmission in autism.

Prolongation of brainstem auditory-evoked responses in autistic probands and their unaffected relatives.

BACKGROUND: Brain function, as indexed by brain electrical activity, is heritable in humans, and it may be impaired in autism. Autism also has strong genetic determinants, and like all major psychiatric disorders, its complex clinical phenotype renders genetic studies difficult. Innovative strategies focused on alternative biological phenotypes are needed. METHODS: The early brain auditory-evoked response was assessed in 73 autistic probands and 251 relatives who were compared with 521 normal controls. RESULTS: We first confirmed in the autistic probands the presence of a slowing in nerve conduction in the auditory system as expressed by the prolongation of early brain auditory-evoked response under the form of I-III interpeak latencies (IPLs). Furthermore, we observed the same I-III IPL prolongation in the unaffected first degree relatives of the autistic probands compared with controls. Despite clear evidence of a coaggregation of autism and I-III IPL prolongation in families, the IPLs did not seem to be the sole liability factor for autism as suggested by the observation of 52% of families in which the autistic proband and relatives showed normal IPLs. CONCLUSION: A prolongation of the early brain auditory-evoked response IPLs may be a marker for one of several deficits underlying autism and deserves further analysis as a potential alternative phenotype for the disorder.

Adequacy of interviews vs checklists for classifying childhood psychiatric disorder based on parent reports.

BACKGROUND: The advantages and disadvantages of lay-administered structured interviews and self-administered problem checklists for estimating prevalence and associated features of childhood psychiatric disorder have attracted little comment. This article compares the scientific adequacy of these 2 instruments for classifying DSM-III-R categories of childhood psychiatric disorder in general population samples. METHODS: Study data are from parental assessments of 251 children aged 6 to 16 years participating in a 2-stage measurement evaluation study. Reliability and validity were compared between the Diagnostic Interview for Children and Adolescents (the structured interview in the study) and the revised Ontario Child Health Study scales (the self-administered problem checklist used in the study). RESULTS: Reliability estimates based on the kappa statistic were comparable for the 2 instruments and ranged from 0.21 (conduct disorder) to 0.70 (depression) on the lay interview and from 0.17 (depression) to 0.61 (oppositional defiant disorder) on the self-administered checklist. Validity coefficients tended to favor the checklist categories, but only marginally. CONCLUSIONS: On balance, differences in reliability and validity were small between the 2 instruments. These differences would appear to have no discernible impact on the knowledge about prevalence and associated features of disorder generated by use of such instruments in general population surveys.

Ontario Child Health Study. I. Methodology.

We developed the methodology for a community survey to determine the prevalence of emotional and behavioral disorders among children 4 to 16 years of age in Ontario, Canada. Our discussion includes the objectives of the survey, the measurement of disorder, sampling methods and survey design, and a description of the data collected and instrumentation. Among 2052 households with eligible children, 1869 (91%) participated in the survey. The results can be used to help plan the future allocation of mental health resources in Ontario.

Ontario Child Health Study. II. Six-month prevalence of disorder and rates of service utilization.

We studied the six-month prevalence of four child psychiatric disorders (conduct disorder, hyperactivity, emotional disorder, and somatization) and patterns of service utilization for mental health and social services, ambulatory medical care and special education by different regions of Ontario, urban-rural residence, and age and sex groupings. Among children 4 to 16 years of age, the overall six-month prevalence rate of one or more of these disorders was 18.1%. The prevalences of hyperactivity and one or more disorders were significantly higher in urban areas than rural areas. The utilization data indicated that children with these psychiatric disorders, compared with children without these disorders, were almost four times more likely to have received mental health or social services in the six months preceding this study. However, five of six of these children had not received these specialized services in the previous six-month period. Over 50% of the children in the province had received ambulatory medical care in the last six months. Over 15% of the children in the province had received special education services at some time thus far in their school careers. Implications of these findings, especially for the provision of child mental health services, are discussed.

Familial aggregation of emotional and behavioral problems of childhood in the general population.

OBJECTIVE: This study sought to evaluate the existence and implications of familial aggregation of emotional and behavioral problems of childhood in a general population sample. METHOD: The children included in the study were chosen with the use of a sampling technique that identified households in which there were two or more children aged 4-16 years living at home at the time of the survey. Ratings on checklists of emotional and behavioral problems were obtained from parents, teachers of children in elementary school, and the children themselves if they were adolescents aged 12-16. Children were classified as having problems if their scores on scales of conduct, attention deficit, or emotional problems were in the top 10% of the distribution of scores from any informant. RESULTS: There was evidence for familial aggregation of these problems, particularly conduct and emotional problems. However, this was largely derived from the parents' reports of symptoms, not the teachers' or adolescents' reports. The degree of familial aggregation varied according to certain sibship characteristics and patterns of comorbidity. CONCLUSIONS: Familial aggregation of emotional and behavioral problems does exist in a community population and is not simply an artifact of clinic attendance.

Two-year outcome of preschool children with autism or Asperger's syndrome.

OBJECTIVE: DSM-IV specifies that Asperger's disorder is a type of pervasive developmental disorder without clinically significant cognitive or language delay. There are no data, however, on the outcome of children with Asperger's disorder or on whether their outcome differs from that of children with autism. The objectives of this study were to compare the outcome of groups of children with these disorders over a period of 2 years on variables independent of the defining criteria and to identify variables that might account for these differences. METHOD: All children 4-6 years of age who came for assessment or were currently in treatment at a pervasive developmental disorder service of one of several centers in a large geographic region were identified. Children who received a diagnosis of autism (N=46) or Asperger's syndrome (N=20) on the basis of a diagnostic interview and had an IQ in the nonretarded range were given a battery of cognitive, language, and behavioral tests. Families were contacted roughly 2 years after the date of their enrollment in the study, and many of the tests were readministered. RESULTS: Children with Asperger's syndrome had better social skills and fewer autistic symptoms 2 years after study enrollment than the children with autism. The differences in outcome could not be explained by initial differences in IQ and language abilities. Children with autism who had developed verbal fluency at follow-up were very similar to the children with Asperger's syndrome at study enrollment. CONCLUSIONS: Although the exact mechanism for the differences in outcome remain to be determined, it appears that Asperger's disorder and autism represent parallel but potentially overlapping developmental trajectories.

Field trial for autistic disorder in DSM-IV.

OBJECTIVE: This project focused on the development of the definition of autism for DSM-IV. METHOD: Multiple sites were involved in obtaining information regarding 977 patients with the following clinician-assigned diagnoses: autism (N = 454), other pervasive developmental disorders (N = 240), and other disorders (N = 283). A standard coding system was used, and the raters (N = 125) had a range of experience in the diagnosis of autism. Patterns of agreement among existing diagnostic systems were examined, as was the rationale for inclusion of other disorders within the class of pervasive developmental disorders. RESULTS: The DSM-III-R definition of autism was found to be overly broad. The proposed ICD-10 definition most closely approximated the clinicians' diagnoses. Inclusion of other disorders within pervasive developmental disorders appeared justified. Partly on the basis of these data, modifications in the ICD-10 definition were made; this and the DSM-IV definition are conceptually identical. CONCLUSIONS: The resulting convergence of the DSM-IV and ICD-10 systems should facilitate both research and clinical service.

Predicting substance use in late adolescence: results from the Ontario Child Health Study follow-up.

OBJECTIVE: The purpose of this study was to evaluate the relationship between use of tobacco, alcohol, marijuana, and hard drugs (substance use) and psychiatric disorder in early adolescence and substance use in late adolescence. METHOD: Adolescents included in the study were identified by means of a household sampling frame and participated in the Ontario Child Health Study in 1983 and the follow-up in 1987. There were 726 12-16-year-olds (369 boys and 357 girls) in 1983 who had complete information in 1987. Data on substance use were collected from adolescents by using a structured, self-administered questionnaire. Data on psychiatric disorder were collected in 1983 from both adolescents and their parents by using problem checklists to assess conduct disorder, attention deficit disorder, and emotional disorder. RESULTS: Prior substance use in 1983 was associated strongly with subsequent use in 1987. Among the psychiatric disorders assessed in 1983, only conduct disorder made an independent contribution to predicting use of marijuana (relative odds = 3.46) and other hard drugs (relative odds = 6.82) in 1987, after prior use of these substances and coexisting attention deficit and emotional disorders were controlled. Corresponding estimates of attributable risk (the expected contribution of exposure to conduct disorder to the development of substance use) were 5.7% and 11.1%, respectively. CONCLUSIONS: Although a statistically significant relationship existed between conduct disorder in early adolescence and use of marijuana and hard drugs in late adolescence, the potential is limited for preventing substance use in the general population by treating conduct disorder early on.

Clinical and methodological factors related to reliability of the best-estimate diagnostic procedure.

OBJECTIVE: The reliability and accuracy of the best-estimate diagnostic procedure were examined, and factors associated with reliability were determined. METHOD: The subjects were 134 members of large multigenerational pedigrees densely affected by bipolar disorders or schizophrenia. Three best-estimate diagnoses were derived: first, by a research psychiatrist and research assistant unblind to the relatives' diagnoses; second, by two blind independent psychiatrists; third, by a panel of four blind psychiatrists. The subjects were characterized on several clinical and methodological variables, which were used to compare the agreements of two types of best-estimate diagnoses with the disagreements. RESULTS: There was satisfactory agreement between the unblind and blind consensus best-estimate diagnoses and between the two blind independent psychiatrists. Latent class analyses revealed that limited sensitivity was the main source of imperfect reliability. Confusability analyses revealed that the most problematic diagnostic distinctions involved schizoaffective disorder, which was confused with schizophrenia, bipolar I disorder, and schizophreniform disorder. Blindness significantly affected diagnostic outcome in latent class analyses. Moreover, for diagnostic disagreements, unblind diagnoses had greater continuity with the most predominant diagnosis in the pedigree than did blind diagnoses. Diagnostic disagreements were associated with the presence of mixed affective and psychotic symptoms, less diagnostic certainty, and shorter duration of illness. CONCLUSIONS: These results suggest that it is possible to identify cases that are more likely to lead to diagnostic disagreements in family and epidemiological studies and that blind diagnoses may help to prevent false positive diagnoses, which may be particularly detrimental to genetic linkage analyses.

Chronic illness, disability, and mental and social well-being: findings of the Ontario Child Health Study.

Chronic childhood illness, disability, and psychosocial problems are receiving major attention in current pediatric care. Much of the evidence associating chronic physical problems and mental health and adjustment problems has come from clinic-based studies and is often inconsistent in its conclusions. This paper reports the findings of the Ontario Child Health Study, an epidemiologic survey of 3,294 children 4 to 16 years of age in the general community, concerning the relationship of psychiatric disorders and social adjustment problems among children with chronic illness, medical conditions, and long-term disability in contrast to children free of chronic physical health problems. Age- and sex-adjusted risks for psychiatric disorders and social problems, compared with those for healthy peers, were calculated: children with both chronic illness and associated disability were at greater than threefold risk for psychiatric disorders and considerable risk for social adjustment problems. Children with chronic medical conditions, but no disability, were at considerably less risk: about a twofold increase in psychiatric disorders but little increased risk for social adjustment problems was observed. A relative underuse of specialized mental health services by children who might benefit supports the opinion that all physicians in the community who care for children with chronic health problems should become skilled in the recognition of existing or incipient mental health and social problems and familiar with preventive and treatment approaches that may lessen the excessive burden of psychosocial problems among those with chronic ill-health.