An Integrated Deep-Mutational-Scanning Approach Provides Clinical Insights on PTEN Genotype-Phenotype Relationships.

Germline variation in PTEN results in variable clinical presentations, including benign and malignant neoplasia and neurodevelopmental disorders. Despite decades of research, it remains unclear how the PTEN genotype is related to clinical outcomes. In this study, we combined two recent deep mutational scanning (DMS) datasets probing the effects of single amino acid variation on enzyme activity and steady-state cellular abundance with a large, well-curated clinical cohort of PTEN-variant carriers. We sought to connect variant-specific molecular phenotypes to the clinical outcomes of individuals with PTEN variants. We found that DMS data partially explain quantitative clinical traits, including head circumference and Cleveland Clinic (CC) score, which is a semiquantitative surrogate of disease burden. We built logistic regression models that use DMS and CADD scores to separate clinical PTEN variation from gnomAD control-only variation with high accuracy. By using a survival-like analysis, we identified molecular phenotype groups with differential risk of early cancer onset as well as lifetime risk of cancer. Finally, we identified classes of DMS-defined variants with significantly different risk levels for classical hamartoma-related features (odds ratio [OR] range of 4.1-102.9). In stark contrast, the risk for developing autism or developmental delay does not significantly change across variant classes (OR range of 5.4-12.4). Together, these findings highlight the potential impact of combining DMS datasets with rich clinical data and provide new insights that might guide personalized clinical decisions for PTEN-variant carriers.

Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries.

Autism spectrum disorder (ASD) substantially contributes to the burden of mental disorders. Improved awareness and changes in diagnostic criteria of ASD may have influenced the diagnostic rates of ASD. However, while data on trends in diagnostic rates in some individual countries have been published, updated estimates of diagnostic rate trends and ASD-related disability at the global level are lacking. Here, we used the Global Burden of Diseases, Injuries, and Risk Factors Study data to address this gap, focusing on changes in prevalence, incidence, and disability-adjusted life years (DALYs) of ASD across the world. From 1990 to 2019, overall age-standardized estimates remained stable globally. Both prevalence and DALYs increased in countries with high socio-demographic index (SDI). However, the age-standardized incidence decreased in some low SDI countries, indicating a need to improve awareness. The male/female ratio decreased between 1990 and 2019, possibly accounted for by increasing clinical attention to ASD in females. Our results suggest that ASD detection in low SDI countries is suboptimal, and that ASD prevention/treatment in countries with high SDI should be improved, considering the increasing prevalence of the disorder. Additionally, growing attention is being paid to ASD diagnosis in females, who might have been left behind by ASD epidemiologic and clinical research previously. ASD burden estimates are underestimated as GBD does not account for mortality in ASD.

Editorial: Is autism overdiagnosed?

After attention was drawn in the late 1960s to the poor reproducibility of psychiatric diagnosis between clinicians, methods and procedures used to diagnose psychiatric disorders were greatly improved. Sources of variance contributing to the poor reliability of psychiatric diagnosis were identified that included: information variance (how clinicians go about enquiring about symptoms), interpretation variance (how clinicians weigh the observed symptomatology towards diagnostic formulations), and criterion variance (how clinicians arrange symptom constellations to generate specific diagnoses). To improve the reliability of diagnosis, progresses were made in two major directions. First, diagnostic instruments were developed to standardize the way symptoms are elicited, evaluated, and scored. These diagnostic interviews were either highly structured for use in large-scale studies (e.g. the DIS), by lay interviewers without a clinical background, and with a style of questioning that emphasized adherence to the exact wording of probes, reliance on closed questions with simple response formats (Yes/No) and recording respondents' answers without interviewer's judgment contribution. By contrast, semi-structured interviews (e.g. the SADS) were designed to be used by clinically trained interviewers and adopted a more flexible, conversational style, using open-ended questions, utilizing all behavioral descriptions generated in the interview, and developing scoring conventions that called upon the clinical judgment of the interviewer. Second, diagnostic criteria and algorithms were introduced in nosographies in 1980 for the DSM and soon after in ICD. Algorithm-derived diagnoses could subsequently be tested for their validity using follow-up, family history, treatment response studies, or other external criteria.

A framework for measuring the cost to families of caring for children's health: the design, methodology, and study population of the r-Kids study.

BACKGROUND: All families experience financial and time costs related to caring for their children's health. Understanding the economic burden faced by families of children with chronic health conditions (CHC) is crucial for designing effective policies to support families. METHODS: In this prospective study we used electronic health records to identify children between 3 and 17 years old with autism spectrum disorder (ASD), asthma, or neither (control) from three Kaiser Permanente regions and several community health centers in the OCHIN network. We oversampled children from racial and ethnic minority groups. Parent/guardian respondents completed surveys three times, approximately four months apart. The surveys included the Family Economic Impact Inventory (measuring financial, time, and employment costs of caring for a child's health), and standardized measures of children's quality of life, behavioral problems, and symptom severity for children with ASD or asthma. We also assessed parenting stress and parent physical and mental health. All materials were provided in English and Spanish. RESULTS: Of the 1,461 families that enrolled (564 ASD, 468 asthma, 429 control), children were predominantly male (79%), with a mean age of 9.0 years, and racially and ethnically diverse (43% non-Hispanic white; 22% Hispanic; 35% Asian, Black, Native Hawaiian, or another race/ethnicity). The majority of survey respondents were female (86%), had a college degree (62%), and were married/partnered (79%). ASD group respondents were less likely to be employed (73%) than those in the asthma or control groups (both 80%; p = .023). Only 32% of the control group reported a household income ≤ $4,000/month compared with 41% of asthma and 38% of ASD families (p = .006). CONCLUSIONS: Utilizing a novel measure assessing family economic burden, we successfully collected survey responses from a large and diverse sample of families. Drawing upon the conceptual framework, survey measures, and self-report data described herein we will conduct future analyses to examine the economic burdens related to CHC and the incremental differences in these burdens between health groups. This information will help policy makers to design more equitable health and social policies that could reduce the burden on families.

Autism and attention-deficit/hyperactivity disorders and symptoms in children with neurofibromatosis type 1.

AIM: To evaluate if autism symptoms and diagnoses are more common in children with neurofibromatosis type 1 (NF1) than in typically developing children, to which levels, and to determine if co-occurring attention-deficit/hyperactivity disorder (ADHD) symptomatology accounts for this increase. METHOD: We searched hospital electronic medical records (EMR) for International Classification of Diseases, 10th Revision NF1 and co-occurring diagnoses codes. We recruited a subsample of 45 children (mean age 9y 2mo; SD 2y 7mo; range 5-12y; 22 males, 23 females) and collected parental reports of autism symptomatology, adaptive behavior, and behavioral problems that were compared to those of 360 age- and sex-matched controls from the Simons Simplex Collection (SSC) with autism spectrum disorder (ASD; SSC-ASD) or typically developing (SSC-TD). RESULTS: The EMR search identified 968 children with NF1; 8.8% had ADHD and 2.1% had ASD co-occurring diagnoses. In the subsample, the mean autism scale score for participants with NF1 was below cut-off for significant autism symptoms. Participants with NF1 had significantly more autism and behavioral symptoms than SSC-TD participants, and significantly less than SSC-ASD participants, with one exception: ADHD symptom levels were similar to those of SSC-ASD participants. In analyses that controlled for internalizing, ADHD, and communication scores, the difference in autism symptom levels between participants with NF1 and typically developing controls disappeared almost entirely. INTERPRETATION: Our results do not support an association between NF1 and autism, both at the symptom and disorder levels. WHAT THIS PAPER ADDS: Diagnoses of attention-deficit/hyperactivity disorder (ADHD) were more common in children with neurofibromatosis type 1 (NF1) than in the general child population. Diagnoses of autism spectrum disorder were no more common in children with NF1 than in the general child population. Increases in autism symptoms did not reach clinically significant thresholds. Co-occurring ADHD symptoms accounted for increased autism questionnaire scores. Adaptive behavior in participants with NF1 showed normal socialization but lower communication proficiency.

Maternal Interleukin-6 Is Associated With Macaque Offspring Amygdala Development and Behavior.

Human and animal cross-sectional studies have shown that maternal levels of the inflammatory cytokine interleukin-6 (IL-6) may compromise brain phenotypes assessed at single time points. However, how maternal IL-6 associates with the trajectory of brain development remains unclear. We investigated whether maternal IL-6 levels during pregnancy relate to offspring amygdala volume development and anxiety-like behavior in Japanese macaques. Magnetic resonance imaging (MRI) was administered to 39 Japanese macaque offspring (Female: 18), providing at least one or more time points at 4, 11, 21, and 36 months of age with a behavioral assessment at 11 months of age. Increased maternal third trimester plasma IL-6 levels were associated with offspring's smaller left amygdala volume at 4 months, but with more rapid amygdala growth from 4 to 36 months. Maternal IL-6 predicted offspring anxiety-like behavior at 11 months, which was mediated by reduced amygdala volumes in the model's intercept (i.e., 4 months). The results increase our understanding of the role of maternal inflammation in the development of neurobehavioral disorders by detailing the associations of a commonly examined inflammatory indicator, IL-6, on amygdala volume growth over time, and anxiety-like behavior.

Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.

Genetic risk factors for autism spectrum disorder (ASD) have yet to be fully elucidated. Postzygotic mosaic mutations (PMMs) have been implicated in several neurodevelopmental disorders and overgrowth syndromes. By leveraging whole-exome sequencing data on a large family-based ASD cohort, the Simons Simplex Collection, we systematically evaluated the potential role of PMMs in autism risk. Initial re-evaluation of published single-nucleotide variant (SNV) de novo mutations showed evidence consistent with putative PMMs for 11% of mutations. We developed a robust and sensitive SNV PMM calling approach integrating complementary callers, logistic regression modeling, and additional heuristics. In our high-confidence call set, we identified 470 PMMs in children, increasing the proportion of mosaic SNVs to 22%. Probands have a significant burden of synonymous PMMs and these mutations are enriched for computationally predicted impacts on splicing. Evidence of increased missense PMM burden was not seen in the full cohort. However, missense burden signal increased in subcohorts of families where probands lacked nonsynonymous germline mutations, especially in genes intolerant to mutations. Parental mosaic mutations that were transmitted account for 6.8% of the presumed de novo mutations in the children. PMMs were identified in previously implicated high-confidence neurodevelopmental disorder risk genes, such as CHD2, CTNNB1, SCN2A, and SYNGAP1, as well as candidate risk genes with predicted functions in chromatin remodeling or neurodevelopment, including ACTL6B, BAZ2B, COL5A3, SSRP1, and UNC79. We estimate that PMMs potentially contribute risk to 3%-4% of simplex ASD case subjects and future studies of PMMs in ASD and related disorders are warranted.

Camouflage and autism.

The theme of camouflage recently gained unexpected momentum in autism research. Symposia and panel discussions are devoted to ' camouflage' in autism conferences. Because of its association with intended deception, the term camouflage has poor fit with the autism world. However, psychopathologists have a long tradition of resorting to camouflage-like terminology, from Freud's reaction formation, to pseudoschizophrenia, to Winnicott's false self, to masked depression, and even to the recent quasi-autism, artfully telling us that what we see is actually not what we see but rather what we cannot see. Is 'Camouflaged Autism' the next in line nosographical pearl?

Childhood social isolation and psychotic experiences in young adulthood: a community based study.

Non-clinical psychotic experiences (PEs) occur at over twice the rate of psychotic disorders along a continuum in the general population and increase risk for progression to diagnoseable disorders. Social isolation is a risk factor for psychotic disorders, although it is unclear if childhood social isolation increases risk for experience of non-clinical PEs later in life. Data come from the Gaz et Electricité (GAZEL) Youth Study (1991-1999) and the Trajectoires Épidémiologiques en Population (TEMPO) Study (2009-2011), a community-based prospective cohort study. Of 1,227 participants whose parents completed questionnaires (1999, participants aged 7-10 years) and who were followed-up (2011, participants aged 25-37 years), 333 had childhood social isolation and young adult PE data. Lifetime prevalence of PEs was 21%. Childhood social isolation was not associated with 0-1 PE in young adulthood (p = 0.74). However, childhood social isolation predicted the experience of ≥ 2 PEs in young adulthood, controlling for gender, age, and general health status (OR = 11.5, 95% CI = 2.5, 52.0, p = 0.002). Childhood social isolation predicts the risk of experiencing two or more lifetime PEs, which may increase the risk for subsequent progression to a diagnoseable psychotic disorder.

Editorial: The passage of time.

In this editorial, the author reflects on changes that occurred in the quality of research on developmental psychopathology over the last 35 years. This is illustrated in the increased quality of nine longitudinal studies that are included in the current issue of JCPP. Using approaches that capitalize on the passage of time, ranging from 28 days to 40 years across investigations, these studies employed multiple levels of analysis, used sophisticated statistical methods to control for confounding factors, included measurement at both the biological, cognitive, and behavioral levels, and collectively provided results that allow improved assessment of causality.

Prevalence and correlates of autism spectrum disorder in Qatar: a national study.

BACKGROUND: Few epidemiological data on autism spectrum disorders (ASD) exist for Arabic countries. We conducted the first survey of ASD in Qatar, a population with high consanguinity level. METHODS: This cross-sectional survey was conducted from 2015 to 2018 in Qatar school-age children (N = 176,960) from national and immigrant families. Children diagnosed with ASD were identified through medical centers and special needs schools. Records were abstracted and supplemented by parental interviews. Additionally, children attending 93 schools were screened; ASD case status was confirmed in random samples of screen-positive and screen-negative children. Prevalence was estimated after taking into account different sampling fractions and participation rates at each survey phase. RESULTS: One thousand three hundred and ninety-three children already diagnosed with ASD were identified. Among 9,074 school survey participants, 760 screen-negative children and 163 screen-positive children were evaluated; 17 were confirmed to have ASD including five children newly diagnosed. Prevalence was 1.14% (95% CI: 0.89-1.46) among 6- to 11-year-olds. ASD was reported in full siblings/extended relatives in 5.9% (95% CI: 0.042-0.080)/11.8% (95% CI: 0.095-0.146) families. First-degree consanguinity in Qatari cases (45%) was comparable to known population levels. Among 844 ASD cases (mean age: 7.2 years; 81% male), most children experienced language delay (words: 75.1%; phrase speech: 91.4%), and 19.4% reported developmental regression. At the time of the survey, persisting deficits in expressive language (19.4%) and peer interactions (14.0%) were reported in conjunction with behavioral problems (ADHD: 30.2%; anxiety: 11.0%). In multivariate logistic regression, ASD severity was associated with parental consanguinity, gestational diabetes, delay in walking, and developmental regression. CONCLUSIONS: ASD prevalence in Qatar is consistent with recent international studies. The methods employed in this study should help designing comparable surveys in the region. We estimated that 187,000 youths under age 20 have ASD in Gulf countries. This figure should assist in planning health and educational services for a young, fast-growing population.

Early Predictors of Trajectories of Tobacco Use Level from Adolescence to Young Adulthood: A 16-Year Follow-Up of the TEMPO Cohort Study (1999-2015).

PURPOSE: Individual and family characteristics early on in life are associated with adolescent smoking; however, their role with regard to long-term tobacco smoking trajectories into young adulthood is not well-known, which is what we set out to study using data from a longitudinal community-based cohort. METHODS: We used data from 2,025 youths in France (12-26 years at baseline, 16 years of follow-up), participating in the longitudinal TEMPO cohort study. First, we modeled smoking trajectories from adolescence onwards using Group-Based Trajectory Modeling, by using the declared consumption of cigarettes at different ages. Second, among trajectories of smokers, associations with individual and family characteristics in childhood and adolescence were studied using multinomial logistic regression. RESULTS: We observed 5 smoking trajectories: non-smokers (62.3%), 3 groups of persistent smokers with different levels of tobacco use (low, intermediate, high), and a group characterized by high-level smoking followed by cessation. Among participants who were lifetime smokers (n = 763), the trajectory of tobacco use was associated with early substance use initiation, academic attainment, grade retention, and parental smoking. Early tobacco and cannabis use initiation predicted high-level tobacco use, whether it persisted (OR 2.29, 95% CI 1.23-4.28) or not (OR 2.99, 95% CI 1.59-5.63). Grade retention and parental smoking predicted persistent smoking of intermediate (respectively OR 1.53, 95% CI 1.03-1.92; OR 1.74, 95% CI 1.03-2.92) or high level use (respectively OR 1.74, 95% CI 1.07-2.85; OR 1.70, 95% CI 0.91-3.18). Poor academic attainment predicted all 3 smoking trajectories, especially persistent high-level smoking (no high school degree: OR 5.29, 95% CI 1.65-16.97, vocational degree: OR 1.94, 95% CI 0.99-3.80). CONCLUSIONS: Tobacco smoking trajectories from adolescence to adulthood are associated with early substance use initiation, parental smoking, and academic difficulties.

Testing Syndromes of Psychopathology in Parent and Youth Ratings Across Societies.

As societies become increasingly diverse, mental health professionals need instruments for assessing emotional, behavioral, and social problems in terms of constructs that are supported within and across societies. Building on decades of research findings, multisample alignment confirmatory factor analyses tested an empirically based 8-syndrome model on parent ratings across 30 societies and youth self-ratings across 19 societies. The Child Behavior Checklist for Ages 6-18 and Youth Self-Report for Ages 11-18 were used to measure syndromes descriptively designated as Anxious/Depressed, Withdrawn/Depressed, Somatic Complaints, Social Problems, Thought Problems, Attention Problems, Rule-Breaking Behavior, and Aggressive Behavior. For both parent ratings (N = 61,703) and self-ratings (N = 29,486), results supported aggregation of problem items into 8 first-order syndromes for all societies (configural invariance), plus the invariance of item loadings (metric invariance) across the majority of societies. Supported across many societies in both parent and self-ratings, the 8 syndromes offer a parsimonious phenotypic taxonomy with clearly operationalized assessment criteria. Mental health professionals in many societies can use the 8 syndromes to assess children and youths for clinical, training, and scientific purposes.

Developmental functioning and symptom severity influence age of diagnosis in Canadian preschool children with autism.

BACKGROUND: Early diagnosis of autism spectrum disorder (ASD) is essential in most Canadian jurisdictions to access interventions that improve long-term child outcomes. Our main objective was to identify factors associated with timing of ASD diagnosis in five provinces across Canada. METHODS: Factors influencing age of diagnosis were assessed in the analyses of an inception cohort of children diagnosed with ASD between ages 2 and 5 years. We examined bivariate associations and using a series of multiple variable regression models, evaluated the unique contributions of developmental functioning, ASD symptoms and demographic variables. Children with known genetic abnormalities, or severe sensory or motor impairments interfering with assessment were excluded. RESULTS: Participants were 421 children (84.6% boys). The mean age of diagnosis was 38.2 months (SD=8.7), an average of 19 months after parents identified initial concerns. Factors associated with later diagnosis included more advanced language and cognitive skills, and higher levels of restricted repetitive behaviour symptoms. Child sex and family demographics were not associated with age of diagnosis. In regression analyses, language and cognitive skills accounted for 6.8% of variance in age of diagnosis and ASD symptoms contributed an additional 5.5%. Provincial site accounted for 4.0% of variance in age of diagnosis, independent of developmental skills and ASD symptoms. INTERPRETATION: Diagnosis of ASD occurred, on average, 19 months after parents' initial concerns. Language and cognitive skills, symptom severity and provincial site accounted for variation in age of ASD diagnosis in this Canadian cohort. Variable presentation across the developmental continuum must be considered in planning assessment services to ensure timely ASD diagnosis so that outcomes can be improved. Policy and practice leadership is also needed to reduce interprovincial variability.

Editorial: The rising prevalence of autism.

The first autism surveys were simple head counts of children already diagnosed with a severe autism phenotype and residing in small, circumscribed geographical areas. Prevalence was low, ranging from 0.4 to 2/1,000 in the 1960's and 1970's. Today, the methodology of surveys has become more complex; studies include large populations, multiple sites, stratified samples and rely on intricate sets of screening activities followed by some form of diagnostic confirmation procedures. Yet, and as surprising as it may be, there is no standardization of autism survey methodology. Each survey has unique design features that reflect the local educational and health services infrastructure and current social policies for children with disabilities, they include or not parents, teachers and subjects with Autism Spectrum Disorder (ASD), and rely on variable screening and diagnostic instruments and methods. As such, prevalence differences between studies are hazardous to evaluate and whether observed discrepancies are due to method factors or true differences in population parameters, cannot be determined.

Special Editorial: Open science and the Journal of Child Psychology & Psychiatry - next steps?

The JCPP works at the cutting edge of clinical science to publish ground-breaking research across the full range of topics in the field of child psychology and psychiatry. As JCPP editors, who are also active researchers in our own right, we are conscious of the threat posed to our field by what has come to be known as the reproducibility crisis - the fact that many published findings, initially trumpeted as important developments in the field, cannot be replicated and are therefore likely to be spurious (Nature Human Behaviour, 1, 2017, 21). The JCPP is conscious of its responsibility to play its part in addressing this issue as best it can. The roots of the problem are complex and its causes multifaceted. As one part of its response, the JCPP embraces the principles of open science and encourage preregistration of study protocols. Furthermore, we are working towards implementing new systems to promote preregistration with the hope of increasing scientific transparency and accountability and reducing the risks of selective reporting and posthoc rationalisation of findings (Journal of Child Psychology & Psychiatry, 59, 2018, 1).

Prevalence and Correlates of Autism Spectrum Disorders in Quebec: Prévalence et corrélats des troubles du spectre de l'autisme au Québec.

OBJECTIVE: To estimate the prevalence, comorbidities, and service use of people with autism spectrum disorders (ASDs) based on data from Quebec Integrated Chronic Diseases Surveillance System (QICDSS). METHODS: We included all residents up to age 24 eligible for health plan coverage who were in Quebec for at least 1 day from January 1, 1996, to March 31, 2015. To be considered as having an ASD, an individual had to have had at least 1 physician claim or hospital discharge abstract from 2000 to 2015 indicating one of the following ASD diagnosis codes: ICD-9 codes 299.0 to 299.9 or their ICD-10 equivalents. RESULTS: The QICDSS shows that the prevalence of ASD has risen steadily over the past decade to approximately 1.2% ( n = 16,940) of children and youths aged 1 to 17 years in 2014 to 2015. The same prevalence was obtained using Ministry of Education data. Common medical comorbidities included congenital abnormalities of the nervous system, particularly in the first year of life. Psychiatric comorbidity was much more highly prevalent, especially common mental disorders like anxiety and attention-deficit/hyperactivity disorder. Children and youths with ASDs made on average 2.3 medical visits per year compared with 0.2 in the general population. Between 18 and 24 years old, the mental health needs of individuals with ASDs were met less by medical specialists and more by general practitioners. CONCLUSION: Information derived from this database could support and monitor development of better medical services coordination and shared care to meet the continuous and changing needs of patients and families over time.

Comparison of Two Tools to Assess Sensory Features in Children With Autism Spectrum Disorder.

OBJECTIVE: This article documents the convergent validity of the Sensory Profile (SP) and the Sensory Processing Measure (SPM)-Home Form for children with autism spectrum disorder (ASD). METHO: . Parents of 34 children with ASD between ages 5 and 8 yr filled out both measures. Through correlations, χ² tests, and levels of agreement between classifications, the results for the SP and the SPM-Home Form were compared. RESULTS: The raw scores were correlated for some sensory domains (hearing, vision, touch, and proprioception) and for social functioning. The classifications showed a significant level of agreement for most scales (κs = .247-.589, p ≤ .05) and for the total scores (κ = .324, p ≤ .01). CONCLUSION: This study provides further evidence of convergent validity between both tools. The SPM-Home Form identifies more children with ASD who present with sensory features for every domain measured by both tools.

Joint trajectories of internalizing and externalizing problems in preschool children with autism spectrum disorder.

The co-occurring development of internalizing and externalizing problems were examined in an inception cohort of 392 children diagnosed with autism spectrum disorder at age 3 who were assessed on four occasions. Results indicated that internalizing and externalizing problems were stable over time and highly comorbid. Joint trajectory analysis suggested that 13% of the sample followed a dual high-risk trajectory. High risk was not found to be associated with intellectual ability or autism spectrum disorder symptom severity but was linked to lower income and gender: more girls than boys were found in the high/stable internalizing problems trajectory. The results suggest that 1 in 4 preschoolers followed a trajectory of internalizing or externalizing problems (or a combination of the two) that could be characterized as clinically elevated.

Temporal Trends in the Prevalence and Incidence of Diagnosed ADHD in Children and Young Adults between 1999 and 2012 in Canada: A Data Linkage Study.

OBJECTIVE: There is a need for the routine monitoring of treated attention-deficit hyperactivity disorder (ADHD) for timely policy making. The objective is to report and assess over a decade the prevalence and incidence of diagnosed ADHD in Canada. METHODS: Administrative linked patient data from the provinces of Manitoba, Ontario, Quebec, and Nova Scotia were obtained from the same sources as the Canadian Chronic Diseases Surveillance Systems to assess the prevalence and incidence of a primary physician diagnosis of ADHD ( ICD-9 and ICD-10 codes: 314, F90.x) for consultations in outpatient and inpatient settings (Med-Echo in Quebec, the Canadian Institute of Health Information Discharge Abstract Database in the 3 other provinces, plus the Ontario Mental Health Reporting System). Dates of service, diagnosis, and physician specialty were retained. The estimates were presented in yearly brackets between 1999-2000 and 2011-2012 by age and sex groups. RESULTS: The prevalence of ADHD between 1999 and 2012 increased in all provinces and for all groups. The prevalence was approximately 3 times higher in boys than in girls, and the highest prevalence was observed in the 10- to 14-year age group. The incidence increased between 1999 and 2012 in Manitoba, Quebec, and Nova Scotia but remained stable in Ontario. Incident cases were more frequently diagnosed by general practitioners followed by either psychiatrists or paediatricians depending on the province. CONCLUSION: The prevalence and incidence of diagnosed ADHD did not increase similarly across all provinces in Canada between 1999 and 2012. Over half of cases were diagnosed by a general practitioner.