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Background: Very large sample sizes are often needed to capture heterogeneity in autism, necessitating data sharing across multiple studies with diverse assessment instruments. In these cases, data harmonization can be a critical tool for deriving a single dataset for analysis. This can be done through computational approaches that enable the conversion of scores across various instruments. To this end, our study examined the use of analytical approaches for mapping scores on two measures of adaptive functioning, namely predicting the scores on the vineland adaptive behavior scales II (VABS) from the scores on the adaptive behavior assessment system II (ABAS). Methods: Data from the province of Ontario neurodevelopmental disorders network were used. The dataset included scores VABS and the ABAS for 720 participants (autism n = 547, 433 male, age: 11.31 ± 3.63 years; neurotypical n = 173, 95 male, age: 12.53 ± 4.05 years). Six regression approaches (ordinary least squares (OLS) linear regression, ridge regression, ElasticNet, LASSO, AdaBoost, random forest) were used to predict VABS total scores from the ABAS scores, demographic variables (age, sex), and phenotypic measures (diagnosis; core and co-occurring features; IQ; internalizing and externalizing symptoms). Results: The VABS scores were significantly higher than the ABAS scores in the autism group, but not the neurotypical group (median difference: 8, 95% CI = (7,9)). The difference was negatively associated with age (beta = -1.2 ± 0.12, t = -10.6, p < 0.0001). All estimators demonstrated similar performance, with no statistically significant differences in mean absolute error (MAE) values across estimators (MAE range: 4.96–6.91). The highest contributing features to the prediction model were ABAS composite score, diagnosis, and age. Limitations: This study has several strengths, including the large sample. We did not examine the conversion of domain scores across the two measures of adaptive functioning and suggest this as a future area of investigation. Conclusion: Overall, our results supported the feasibility of harmonization. Our results suggest that a linear regression model trained on the ABAS composite score, the ABAS raw domain scores, and age, sex, and diagnosis would provide an acceptable trade-off between accuracy, parsimony, and data collection and processing complexity. [ABSTRACT FROM AUTHOR]

Objectives: Attention‐deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental condition and is characterized by inattention, hyperactivity, and impulsivity. Research suggests that some populations, such as females and individuals with high intelligence quotients may be a risk for late ADHD diagnosis and subsequent treatment. Our goal is to advance our understanding of ADHD diagnosis, by examining (1) how child sex and cognitive abilities together are related to the age of diagnosis and (2) whether symptom presentation, current internalizing and externalizing symptoms, and demographic factors are related to age of diagnosis. Methods: Our analyses contained children who completed the required tests (N = 568) from a pre‐existing dataset of 1380 children with ADHD from the Province of Ontario Neurodevelopmental Disorders (POND) Network (pond‐network.ca). First, we conducted a moderation analysis with sex as the predictor, cognitive abilities as the moderator, and age of diagnosis as the outcome. Second, we conducted correlation analyses examining how symptom presentation, current internalizing and externalizing symptoms, and demographic factors are related to age of diagnosis. Results: Higher IQ was related to a later age of diagnosis. Higher hyperactive–impulsive symptoms and externalizing symptoms were related to an earlier age of diagnosis. Internalizing symptoms were trend associated with a later age of diagnosis in girls. Higher socioeconomic status and non‐White maternal ethnicity were related to later age of diagnosis. Conclusions: IQ, sex, ADHD symptomology, internalizing symptoms, externalizing symptoms, and socio‐demographic factors affect the age of diagnosis. [ABSTRACT FROM AUTHOR]

With brain structure and function undergoing complex changes throughout childhood and adolescence, age is a critical consideration in neuroimaging studies, particularly for those of individuals with neurodevelopmental conditions. However, despite the increasing use of large, consortium‐based datasets to examine brain structure and function in neurotypical and neurodivergent populations, it is unclear whether age‐related changes are consistent between datasets and whether inconsistencies related to differences in sample characteristics, such as demographics and phenotypic features, exist. To address this, we built models of age‐related changes of brain structure (regional cortical thickness and regional surface area; N = 1218) and function (resting‐state functional connectivity strength; N = 1254) in two neurodiverse datasets: the Province of Ontario Neurodevelopmental Network and the Healthy Brain Network. We examined whether deviations from these models differed between the datasets, and explored whether these deviations were associated with demographic and clinical variables. We found significant differences between the two datasets for measures of cortical surface area and functional connectivity strength throughout the brain. For regional measures of cortical surface area, the patterns of differences were associated with race/ethnicity, while for functional connectivity strength, positive associations were observed with head motion. Our findings highlight that patterns of age‐related changes in the brain may be influenced by demographic and phenotypic characteristics, and thus future studies should consider these when examining or controlling for age effects in analyses. [ABSTRACT FROM AUTHOR]

Irritability is a common, impairing, and potentially multifaceted manifestation of psychopathology. We designed The Irritability and Dysregulation of Emotion Scale (TIDES-13) to determine whether various expressions of irritability in children and youth form multiple subdimensions with distinct correlates. We administered parent-report (n = 3875, mean age = 8.9) and youth self-report (n = 579, mean age = 15.1) versions of TIDES-13 in a population and community-based sample. We conducted exploratory/confirmatory factor analyses and regression analyses to examine the dimensionality of TIDES-13 and the associations of the scale with age, gender, anxiety, depression, ODD, ADHD traits, and the Affective Reactivity Index (ARI). A higher-order model with a global irritability dimension and four subdimensions, including proneness to anger (PA), internalized negative emotional reactivity (iNER), externalized negative emotional reactivity (eNER), and reactive aggression (RA), showed good to excellent fit in both parent-report and self-report. The global irritability dimension showed excellent internal reliability (⍵Total; parent-report = 0.97, ⍵Total; self-report = 0.95), explained a majority of the item variance (⍵Hierarchical; parent-report = 0.94, ⍵Hierarchical; self-report = 0.90), and was moderately correlated with the ARI (rparent = 0.68, rself = 0.77). Subdimensions PA, eNER, and RA were negatively associated with age in males, whereas iNER was positively associated with age in females. Traits of ODD and ADHD were associated primarily with the global irritability dimension, whereas iNER was strongly associated with anxiety and depression traits over and above the global irritability dimension. Our results support a unidimensional interpretation of irritability in a population sample. However, limited evidence of specific behavioral, age, and sex correlates with particular irritability subdimensions may warrant further investigation. [ABSTRACT FROM AUTHOR]

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Neurodevelopmental conditions can be associated with decreased health-related quality of life; however, the predictors of these outcomes remain largely unknown. We characterized the predictors of health-related quality of life (HRQoL) in a sample of neurodiverse children and youth. We used a cross-sectional subsample from the Province of Ontario Neurodevelopmental Disorders Network (POND) consisting of those children and young people in the POND dataset with complete study data (total n = 615; 31% female; age: 11.28 years ± 2.84 years). Using a structural equation model, we investigated the effects of demographics (age, sex, socioeconomic status), core features (Social Communication Questionnaire, Toronto Obsessive Compulsive Scale, Strengths and Weaknesses of attention deficit/hyperactivity disorder (ADHD)-symptoms and Normal Behavior), co-occurring symptoms (Child Behaviour Checklist), and adaptive functioning (Adaptive Behaviour Assessment System) on HRQoL (KINDL). A total of 615 participants had complete data for this study (autism = 135, ADHD = 273, subthreshold ADHD = 7, obsessive–compulsive disorder (OCD) = 38, sub-threshold OCD = 1, neurotypical = 161). Of these participants, 190 (31%) identified as female, and 425 (69%) identified as male. The mean age was 11.28 years ± 2.84 years. Health-related quality of life was negatively associated with co-occurring symptoms (B = − 0.6, SE = 0.20, CI (− 0.95, − 0.19), p = 0.004)) and age (B = − 0.1, SE = 0.04, CI (− 0.19, − 0.01), p = 0.037). Fewer co-occurring symptoms were associated with higher socioeconomic status (B = − 0.5, SE = − 0.05, CI (− 0.58, − 0.37), p < 0.001). This study used a cross-sectional design. Given that one's experiences, needs, supports, and environment and thus HrQoL may change significantly over the lifespan and a longitudinal analysis of predictors is needed to capture these changes. Future studies with more diverse participant groups are needed. These results demonstrate the importance of behavioural and sociodemographic characteristics on health-related quality of life across neurodevelopmental conditions. [ABSTRACT FROM AUTHOR]

Objective: To examine the theoretical and empirical contribution of Joe Biederman and his colleagues to the understanding of executive function (EF) and ADHD. Method: We searched PubMed for references to EF in Biederman's publications and conducted a narrative review of this literature. Results: In 50 or more papers using neuropsychological tests, rating scales and measures of mind wandering, Biederman demonstrated that EF are evident in ADHD and closely linked to its underlying neurobiological and genetic risk. He argued that EF need to be monitoring to ensure comprehensive assessment and treatment, but could not be used as a diagnostic proxy. Conclusion: Biederman built an innovative and impressive collaboration to address the issue of EF in ADHD. His work shows a commitment to understanding of EF in order to improve patient care. Biederman laid down a roadmap for research in ADHD and EF for the rest of the field to follow. [ABSTRACT FROM AUTHOR]

Children and adolescents with externalizing disorders are at risk for suicidal ideation or behavior. Factors that put them at risk could be symptoms related or facilitated by their environment. We evaluated the links of symptoms profiles with suicidality, and the effects of family relationship characteristics on these links. Latent profile analysis was used to subgroup participants referred for ADHD assessment (n = 1249, aged 6–17) based on their externalizing and internalizing symptoms. Self- and parent-reported child suicidal ideation (S–SI, P-SI), and parent-reported self-harm behavior (P-SHB) were compared across profiles. The moderating effects of parent-reported marital conflict and parenting practices were examined. A four-profile model showed optimal fit. Participants of the Low Symptoms profile followed by the Inattentive-Hyperactive/Impulsive profile showed lower P-SI compared to those of the Irritable-Defiant and the Conduct Problems profiles. Low Symptoms participants also reported lower S–SI compared to those of the Inattentive-Hyperactive/Impulsive and the Irritable-Defiant profiles. Participants of the Irritable-Defiant and the Conduct Problems profiles had higher P-SHB compared to the Low Symptoms and the Inattentive-Hyperactive/Impulsive participants. Dysregulated marital conflict practices were associated with greater increase in P-SI in all profiles compared to the Low Symptoms profile. Aggressive marital conflict practices were associated with increased P-SHB in the Conduct Problems profile compared to the Inattentive-Hyperactive/Impulsive profile. Children and adolescents with irritability and defiance symptoms with or without conduct problems show higher risk for suicidal ideation and behavior compared to those with ADHD symptoms alone. Dysregulated and aggressive marital conflict practices might pose additional suicidality risk in children and adolescents with disruptive behavior. [ABSTRACT FROM AUTHOR]

Background: Anxiety disorders are the most common psychiatric problems among Canadian youth and typically have an onset in childhood or adolescence. They are characterized by high rates of relapse and chronicity, often resulting in substantial impairment across the lifespan. Genetic factors play an important role in the vulnerability toward anxiety disorders. However, genetic contribution to anxiety in youth is not well understood and can change across developmental stages. Large-scale genetic studies of youth are needed with detailed assessments of symptoms of anxiety disorders and their major comorbidities to inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Methods: The Genetic Architecture of Youth Anxiety (GAYA) study is a Pan-Canadian effort of clinical and genetic experts with specific recruitment sites in Calgary, Halifax, Hamilton, Toronto, and Vancouver. Youth aged 10–19 (n = 13,000) will be recruited from both clinical and community settings and will provide saliva samples, complete online questionnaires on demographics, symptoms of mental health concerns, and behavioural inhibition, and complete neurocognitive tasks. A subset of youth will be offered access to a self-managed Internet-based cognitive behavioral therapy resource. Analyses will focus on the identification of novel genetic risk loci for anxiety disorders in youth and assess how much of the genetic risk for anxiety disorders is unique or shared across the life span. Discussion: Results will substantially inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Given that the GAYA study will be the biggest genomic study of anxiety disorders in youth in Canada, this project will further foster collaborations nationally and across the world. [ABSTRACT FROM AUTHOR]

Sensory processing abilities are highly variable within and across people diagnosed with autism and attention-deficit/hyperactivity disorder (ADHD). This study examined the transdiagnostic nature of sensory processing abilities, and their association with features of autism and ADHD, in a large sample of autistic people (n = 495) and people with ADHD (n = 461). Five similar data-driven sensory phenotypes characterized sensory processing abilities, and showed similar patterns of association with features of autism and ADHD, across both diagnostic groups. These results demonstrate the transdiagnostic nature of sensory processing abilities, while contributing to a growing body of literature that suggests the autism and ADHD diagnostic labels have poor explanatory power. [ABSTRACT FROM AUTHOR]

Objective: To evaluate if children and adolescents with a diagnosis of ASD or ADHD have distinct executive function (EF) profiles. Methods: Peer-reviewed articles comparing ASD, ADHD, and typically developing individuals under 19 years of age were identified. The domains evaluated were: working memory, response inhibition, planning, cognitive flexibility, attention, processing speed, and visuospatial abilities. Results: Fifty-eight articles met inclusion criteria. Analyses were performed on 45 performance metrics from 24 individual tasks. No differences in EF were found between individuals diagnosed with ASD and ADHD. Individuals diagnosed with ASD and ADHD exhibited worse performance in attention, flexibility, visuospatial abilities, working memory, processing speed, and response inhibition than typically developing individuals. Groups did not differ in planning abilities. Conclusion: Children and adolescents with ASD and ADHD have similar EF profiles. Further research is needed to determine if comorbidity accounts for the commonality in executive dysfunction between each disorder. [ABSTRACT FROM AUTHOR]

Despite significant disruption to school during the COVID-19 pandemic, research on the impact on children is sparse. This study examines in-person and virtual learning contexts and the impact of school format on mental health (MH). Children and adolescents were recruited from community and clinical settings. Parents and children completed prospective online surveys about school experiences (November 2020) and MH symptoms (February/March 2021), including school format and activities. Standardized measures of depression, anxiety, inattention, and hyperactivity were collected. Hierarchical regression analyses tested associations between school format and MH. Children (N = 1011; aged 6–18 years) attending school in-person (n = 549) engaged in high levels of participation in COVID-19 health measures and low levels of social learning activities. Learning online in high school was associated with greater MH symptoms (B = -2.22, CI[-4.32,-.12] to B = -8.18, CI[-15.59,-.77]). Children with no previous MH condition that attended school virtually experienced a similar magnitude of MH symptoms as those with previous MH conditions. However, children who attended school in a hybrid in-person format, with no previous MH condition, experienced less hyperactivity as same-age peers with prior MH problems (B = -8.08, CI[1.58,14.58]). Children's learning environments looked very different compared to before the pandemic. Removing children from school environments and limiting opportunities that support their MH, such as social learning activities, is problematic. Efforts to address the learning contexts to protect the mental health of children are needed. [ABSTRACT FROM AUTHOR]

The ability to recognize emotions evident in people's faces contributes to social functioning and might be affected by ADHD and irritability. Given their high co-occurrence, we examined the relative contribution of ADHD and irritability to facial emotion recognition (FER). We hypothesized that irritability but not ADHD traits would predict increased likelihood of misrecognizing emotions as negative, and that FER performance would explain the association of ADHD and irritability traits with social skills. FER was measured using the Reading the Mind in the Eyes Test (RMET) in children (6–14 years old) referred for ADHD assessment (n = 304) and healthy controls (n = 128). ADHD, irritability and social skills were measured using parent ratings. We used repeated measure logistics regression, comparing the effects across emotion valence of images (i.e., neutral/positive/negative). High irritability but not ADHD diagnosis predicted lower RMET accuracy. ADHD traits predicted lower RMET accuracy in younger but not older participants, whereas irritability predicted poorer accuracy at all ages. ADHD traits predicted lower RMET accuracy across all emotion valences, whereas irritability predicted increased probability of misrecognizing neutral and positive but not negative emotions. Irritability did not increase the probability for erroneously recognizing emotions as negative. ADHD and irritability traits fully explained the association between RMET and social skills. ADHD and irritability traits might impact the ability to identify emotions portrayed in faces. However, irritability traits appear to selectively impair recognition of neutral and positive but not negative emotions. ADHD and irritability are important when examining the link between FER and social difficulties. [ABSTRACT FROM AUTHOR]

Neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), attention‐deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD) are thought to arise in part from the disruption in the excitatory/inhibitory balance of gamma‐aminobutyric acid (GABA) and glutamate in the brain. Recent evidence has shown the involvement of the cerebellum in cognition and affect regulation, and cerebellar atypical function or damage is reported frequently in NDDs. Magnetic resonance spectroscopy studies have reported decreases in GABA in cortical brain areas in the NDDs, however, GABA levels in the cerebellum have not been examined. To determine possible group effects, we used a MEGA‐PRESS acquisition to investigate GABA+ levels in a cerebellar voxel in 343 individuals (aged 2.5–22 years) with ASD, ADHD, OCD and controls. Using a mixed effects model, we found no significant differences between groups in GABA+ concentration. Our findings suggest that cerebellar GABA+ levels do not differentiate NDD groups. Lay Summary: Neurochemical balance, particularly the neurotransmitter gamma‐amino butyric acid (GABA), plays an important role in the presentation of neurodevelopmental disorders (NDD). The cerebellum is a part of the brain involved in the control of cognitive and emotional processes and often affected in NDDs. We examined whether there were atypical GABA+ levels in the cerebellum of people with different NDDs. Despite the importance of cerebellar function in the NDDs, we found no differences between their GABA+ levels and those of typically developing participants. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity (ADHD) and autism spectrum (ASD) disorders are commonly co-occurring conditions characterized by neurocognitive impairments. Few studies have directly compared neurocognitive profiles in ADHD and ASD and fewer still have controlled for comorbidity of ADHD and ASD. All direct comparisons have been in clinic samples, leaving the question of generalizability of results unaddressed. We compared neurocognitive performance in clinically ascertained ASD (n = 261) and ADHD (n = 423) cases and controls (n = 162), 6.0–17.9 years of age. We also compared ASD (n = 190) and ADHD (n = 926) cases ascertained in the community with controls (n = 14,842) of similar age. Using the stop-signal task (SST), we measured response inhibition (stop-signal reaction time–SSRT), sustained attention (defined as reaction time variability–RTV), and reaction time (RT). We controlled for comorbidity using ADHD and ASD trait scores and categorically-defined ADHD. Compared with controls, both clinic ADHD and ASD had significantly longer SSRT and RTV than controls and did not differ from each other. ADHD traits accounted for neurocognitive impairment in ASD, but not vice versa. There were no group differences for RT. Similar patterns of neurocognitive impairment were observed in the community sample. In the largest direct comparison of ADHD and ASD to date, we found impaired response inhibition and sustained attention in both disorders. However, neurocognitive impairment in ASD was almost completely accounted for by comorbid ADHD. Results generalized in the community sample indicating that referral bias alone did not drive results. Response inhibition and sustained attention likely play a role in ADHD and ASD. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) have considerable overlap, supporting the need for a dimensional framework that examines neurodevelopmental domains which cross traditional diagnostic boundaries. In the following study, we use factor analysis to deconstruct the ASD–ADHD phenotype into its underlying phenotypic domains and test for measurement invariance across adaptive functioning, age, gender and ASD/ADHD clinical diagnoses. Methods: Participants included children and youth (aged 3–20 years) with a clinical diagnosis of ASD (n = 727) or ADHD (n = 770) for a total of 1,497 participants. Parents of these children completed the Social Communication Questionnaire (SCQ), a measure of autism symptoms, and the Strengths and Weaknesses of ADHD and Normal Behaviour (SWAN) questionnaire, a measure of ADHD symptoms. An exploratory factor analysis (EFA) was performed on combined SCQ and SWAN items. This was followed by a confirmatory factor analysis (CFA) and tests of measurement invariance. Results: EFA revealed a four‐factor solution (inattention, hyperactivity/impulsivity, social‐communication, and restricted, repetitive, behaviours and interests (RRBI)) and a CFA confirmed good model fit. This solution also showed good model fit across subgroups of interest. Conclusions: Our study shows that a combined ASD–ADHD phenotype is characterized by two latent ASD domains (social communication and RRBIs) and two latent ADHD domains (inattention and hyperactivity/impulsivity). We established measurement invariance of the derived measurement model across adaptive functioning, age, gender and ASD/ADHD diagnoses. [ABSTRACT FROM AUTHOR]

Alterations in the structural maturation of the amygdala subnuclei volumes are associated with anxiety behaviors in adults and children with neurodevelopmental and associated disorders. This study investigated the relationship between amygdala subnuclei volumes and anxiety in 233 children and adolescents (mean age = 11.02 years; standard deviation = 3.17) with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and children with obsessive compulsive disorder (OCD), as well as typically developing (TD) children. Parents completed the Child Behavior Checklist (CBCL), and the children underwent structural MRI at 3 T. FreeSurfer software was used to automatically segment the amygdala subnuclei. A general linear model revealed that children and adolescents with ASD, ADHD, and OCD had higher anxiety scores compared to TD children (p <.001). A subsequent interaction analysis revealed that children with ASD (B = 0.09, p <.0001) and children with OCD (B = 0.1, p <.0001) who had high anxiety had larger right central nuclei volumes compared with TD children. Similar results were obtained for the right anterior amygdaloid area. Amygdala subnuclei volumes may be key to identifying children with neurodevelopmental disorders or those with OCD who are at high risk for anxiety. Findings may inform the development of targeted behavioral interventions to address anxiety behaviors and to assess the downstream effects of such interventions. [ABSTRACT FROM AUTHOR]

Background: A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE). Methods: The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8–40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses. Results: When combining the studies in meta-analyses, results were significant for RTV (R 2 = 0.011, β = 0.088, p = 0.02) but not for CE (R 2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10). Conclusions: We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation. [ABSTRACT FROM AUTHOR]

The comorbidity of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) diagnoses is well established. An ASD diagnosis is associated with elevated ADHD traits and symptoms, as well as strengths in attention. In the ASD literature, attentional strengths have been described as maladaptive (e.g., hyperfocus), in contrast with positive portrayals in the typically developing population (e.g., flow). The objective of this study was to (1) compare profiles of attentional strengths and weaknesses in ASD and ADHD and (2) determine whether attentional strengths in ASD are associated with impairment, poorer cognitive flexibility, and perseveration/perfectionism. In a community sample of 5,744 children and youth, 131 children were reported as having a diagnosis of ASD (mean age 10.3 years) and 346 children were reported as having a diagnosis of ADHD (mean age 10.7 years). We used the Strengths and Weaknesses of Attention-Deficit/Hyperactivity-symptoms and Normal-behaviors (SWAN) rating scale to calculate attentional and hyperactive/impulse control strength and weakness counts and scores. The Autism-Spectrum Quotient Switching factor served as a measure of cognitive flexibility. Impairment was assessed with the Columbia Impairment Scale. We used the symmetry/ordering factor on the Toronto Obsessive-Compulsive Scale as a measure of perseveration/perfectionism. No differences were found between the ADHD and ASD groups in SWAN weakness scores, symptoms, or hyperactive/impulse control strengths; however, autistic children had higher rates of attentional strengths [odds ratio: 5.7, 95% CI (2.8, 11.6), p < 0.0001]. Post-hoc pairwise testing identified four attentional strengths with significantly higher rates in ASD than in ADHD. Attentional strength scores were not associated with impairment or poor cognitive flexibility, but predicted levels of perseveration/perfectionism. The effect of attentional strengths on impairment and cognitive flexibility did not differ between autistic and Control children, but the higher perseveration/perfectionism scores seen in ASD were not found in Control children. ASD is associated with a pattern of attentional strengths that is not found in ADHD Characterizing the full range of attentional abilities in autistic children may explain variability in outcomes such as quality-of-life indicators and identify protective factors, providing targets for strength-based behavioral interventions. The clinical and etiological implications of the subgroup of autistic children with attentional strengths require further investigation. [ABSTRACT FROM AUTHOR]

Objectifs Les confinements dans les provinces canadiennes ont malmené la santé mentale des enfants pendant la pandémie de COVID-19, et les enfants autistes y ont été particulièrement vulnérables. La présente étude visait à recenser les sous-groupes d'enfants autistes ayant des profils distincts de modification à leur santé mentale, afin de comprendre les facteurs propres aux enfants, aux parents et au système qui y sont associés et d'éclairer de futures interventions. Méthodologie Les chercheurs ont extrait les données d'une vaste cohorte ontarienne (n=1 570), dont faisaient partie 265 enfants autistes (âge moyen=10,9 ans, 76 % de sexe masculin). Ils ont utilisé l'analyse des nuées dynamiques pour répartir les profils de santé mentale distincts en six mesures (humeur, anxiété, symptômes de trouble obsessionnel-compulsif, irritabilité, inattention, hyperactivité) et ont examiné les différences entre les groupes. Ils ont également étudié les caractéristiques des enfants qui ont accédé à des services aigus en santé mentale. Résultats Le nombre optimal de grappes était fixé à deux. La première incluait ceux qui avaient éprouvé une détérioration de leur santé mentale dans les six mesures (61,3 %, intervalle de confiance à 95 %=54,9 à 67,4) et la seconde, les jeunes dont la santé mentale n'avait pas changé (38,7 %, intervalle de confiance à 95 %=32,6 à 45,1). Des facteurs étaient associés à la détérioration de la santé mentale des enfants : plus de symptômes internalisés préexistants et de forts taux de stress liés à la COVID-19. Les problèmes de santé mentale des parents et les facteurs propres aux systèmes, tels que la perte de soutien à l'apprentissage, l'accès aux médecins et les difficultés matérielles, étaient aussi liés à cette détérioration. L'accès à des services aigus en santé mentale découlait d'abord de l'insécurité financière et de la perte de services. Conclusions Plus de la moitié des enfants autistes ont éprouvé une détérioration de leur santé mentale, et les caractéristiques individuelles (troubles de santé mentale préexistants, stress lié à la COVID-19), parentales (santé mentale des parents) et systémiques (perte de services et difficultés matérielles) y étaient reliées, ce qui ouvrait la voie à des interventions cliniques et politiques multiniveaux. [ABSTRACT FROM AUTHOR]

Background: Neurocognitive impairments are common in OCD, although not well studied in children and youth with the disorder. Method: Using the stop‐signal task (SST), we measured response inhibition (stop‐signal reaction time—SSRT), sustained attention (reaction time variability—RTV), reaction time (RT), and performance monitoring (post‐error slowing—PES) in OCD cases and controls from two samples of children and youth. A Clinic OCD group (n = 171, aged 7–17 years) was recruited from a specialty clinic after rigorous assessment. A typically developing (Clinic TD, n = 157) group was enlisted through advertisement. A community OCD sample (Community OCD, n = 147) and controls (Community TD n = 13,832, aged 6‐17 years) were recruited at a science museum. We also identified a community group with high OCD traits without an OCD diagnosis (Community High Trait; n = 125). Results: Clinic OCD participants had longer SSRT and greater RTV than Clinic TD. These effects were greater in younger OCD participants and, for SSRT, in those on medication for OCD. The Community OCD group did not differ from Controls but was similar to the Clinic OCD group in ADHD and ASD comorbidity and medication usage. The Community High Trait group had longer SSRT and atypical PES suggesting that symptom severity predicts neurocognitive function. No group differences were found in RT. Conclusions: In the largest study of neurocognitive performance in children with OCD to date, we found impaired response inhibition and sustained attention in OCD participants in comparison to typically developing peers. Performance was worse in younger OCD participants. In the community sample, participants with high OCD trait scores but no OCD diagnosis had impaired response inhibition and error processing, suggesting that OCD might be under‐recognized. [ABSTRACT FROM AUTHOR]

Background: Externalizing and internalizing behaviors contribute to clinical impairment in children with neurodevelopmental disorders (NDDs). Although associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in clinical and non-clinical pediatric samples, no previous study has examined whether similar shared associations are present across children with different NDDs. Methods: Multi-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6–18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive–compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging (DWI) and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (total n = 346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined. Results: No significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results. Conclusions: The current study provides evidence towards an absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with different primary NDD diagnoses and TDC. Different methodological approaches, including incorporation of multi-dimensional behavioral data (e.g., task-based fMRI) or clustering approaches may be needed to clarify complex brain-behavior relationships relevant to externalizing/internalizing behaviors in heterogeneous clinical NDD populations. [ABSTRACT FROM AUTHOR]

Measurements of response inhibition components of reactive inhibition and proactive inhibition within the stop-signal paradigm have been of particular interest to researchers since the 1980s. While frequentist nonparametric and Bayesian parametric methods have been proposed to precisely estimate the entire distribution of reactive inhibition, quantified by stop signal reaction times (SSRT), there is no method yet in the stop signal task literature to precisely estimate the entire distribution of proactive inhibition. We identify the proactive inhibition as the difference of go reaction times for go trials following stop trials versus those following go trials and introduce an Asymmetric Laplace Gaussian (ALG) model to describe its distribution. The proposed method is based on two assumptions of independent trial type (go/stop) reaction times and Ex-Gaussian (ExG) models. Results indicated that the four parametric ALG model uniquely describes the proactive inhibition distribution and its key shape features, and its hazard function is monotonically increasing, as are its three parametric ExG components. In conclusion, the four parametric ALG model can be used for both response inhibition components and its parameters and descriptive and shape statistics can be used to classify both components in a spectrum of clinical conditions. [ABSTRACT FROM AUTHOR]

Objectives Canadian province-wide lockdowns have challenged children's mental health (MH) during the COVID-19 pandemic, with autistic children being at particular risk. The purpose of our study was to identify sub-groups of autistic children with distinct mental health change profiles, to understand the child-, parent-, and system-specific factors associated with such profiles in order to ultimately inform future interventions. Methods Data were drawn from a large Canadian cohort (N=1,570) across Ontario, resulting in 265 autistic children (mean age=10.9 years, 76% male). K-means clustering analyses were employed to partition distinct MH profiles in six MH measures (mood, anxiety, OCD symptoms, irritability, inattention, hyperactivity) and group differences were examined with reference to the above factors. Additionally, we investigated the characteristics of children who accessed acute MH services. Results The optimal number of clusters was two; one included those experiencing MH deterioration across all six MH measures (61.3%, 95% confidence interval [CI]=54.9 to 67.4), and a second included youth that did not experience MH changes (38.7%, 95%CI=32.6 to 45.1). Child-specific factors associated with MH deterioration included higher pre-existing internalizing symptoms, high levels of COVID stress. Parental MH challenges and system-specific factors, such as the loss of learning supports, access to physicians and material deprivation, were also associated with MH deterioration. Access to acute MH services were primarily associated with financial insecurity and loss of services. Conclusions More than half of autistic children experienced MH deterioration, and person-specific (pre-existing MH, COVID related stress), parent-specific (Parent MH) and system-level (loss of services and material deprivation) characteristics were associated with such decline, providing clinical and policy opportunities for intervention at multiple levels. [ABSTRACT FROM AUTHOR]

Background: Atypical processing of unfamiliar, but less so familiar, stimuli has been described in Autism Spectrum Disorder (ASD), in particular in relation to face processing. We examined the construct of familiarity in ASD using familiar and unfamiliar songs, to investigate the link between familiarity and autism symptoms, such as repetitive behavior. Methods: Forty-eight children, 24 with ASD (21 males, mean age = 9.96 years ± 1.54) and 24 typically developing (TD) controls (21 males, mean age = 10.17 ± 1.90) completed a music familiarity task using individually identified familiar compared to unfamiliar songs, while magnetoencephalography (MEG) was recorded. Each song was presented for 30 s. We used both amplitude envelope correlation (AEC) and the weighted phase lag index (wPLI) to assess functional connectivity between specific regions of interest (ROI) and non-ROI parcels, as well as at the whole brain level, to understand what is preserved and what is impaired in familiar music listening in this population. Results: Increased wPLI synchronization for familiar vs. unfamiliar music was found for typically developing children in the gamma frequency. There were no significant differences within the ASD group for this comparison. During the processing of unfamiliar music, we demonstrated left lateralized increased theta and beta band connectivity in children with ASD compared to controls. An interaction effect found greater alpha band connectivity in the TD group compared to ASD to unfamiliar music only, anchored in the left insula. Conclusion: Our results revealed atypical processing of unfamiliar songs in children with ASD, consistent with previous studies in other modalities reporting that processing novelty is a challenge for ASD. Relatively typical processing of familiar stimuli may represent a strength and may be of interest to strength-based intervention planning. [ABSTRACT FROM AUTHOR]

This large cross-sectional study examined the impact of COVID-19 emergency measures on child/adolescent mental health for children/adolescents with and without pre-existing psychiatric diagnoses. Using adapted measures from the CRISIS questionnaire, parents of children aged 6–18 (N = 1013; 56% male; 62% pre-existing psychiatric diagnosis) and self-reporting children/adolescents aged 10–18 (N = 385) indicated changes in mental health across six domains: depression, anxiety, irritability, attention, hyperactivity, and obsessions/compulsions. Changes in anxiety, irritability, and hyperactivity were calculated for children aged 2–5 years using the Strengths and Difficulties Questionnaire. COVID-19 exposure, compliance with emergency measures, COVID-19 economic concerns, and stress from social isolation were measured with the CRISIS questionnaire. Prevalence of change in mental health status was estimated for each domain; multinomial logistic regression was used to determine variables associated with mental health status change in each domain. Depending on the age group, 67–70% of children/adolescents experienced deterioration in at least one mental health domain; however, 19–31% of children/adolescents experienced improvement in at least one domain. Children/adolescents without and with psychiatric diagnoses tended to experience deterioration during the first wave of COVID-19. Rates of deterioration were higher in those with a pre-exiting diagnosis. The rate of deterioration was variable across different age groups and pre-existing psychiatric diagnostic groups: depression 37–56%, anxiety 31–50%, irritability 40–66%, attention 40–56%, hyperactivity 23–56%, obsessions/compulsions 13–30%. Greater stress from social isolation was associated with deterioration in all mental health domains (all ORs 11.12–55.24). The impact of pre-existing psychiatric diagnosis was heterogenous, associated with deterioration in depression, irritability, hyperactivity, obsession/compulsions for some children (ORs 1.96–2.23) but also with improvement in depression, anxiety, and irritability for other children (ORs 2.13–3.12). Economic concerns were associated with improvement in anxiety, attention, and obsessions/compulsions (ORs 3.97–5.57). Children/adolescents with and without pre-existing psychiatric diagnoses reported deterioration. Deterioration was associated with increased stress from social isolation. Enhancing social interactions for children/adolescents will be an important mitigation strategy for current and future COVID-19 waves. [ABSTRACT FROM AUTHOR]

Impairments in emotional face processing are demonstrated by individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which is associated with altered emotion processing networks. Despite accumulating evidence of high rates of diagnostic overlap and shared symptoms between ASD and ADHD, functional connectivity underpinning emotion processing across these two neurodevelopmental disorders, compared to typical developing peers, has rarely been examined. The current study used magnetoencephalography to investigate whole-brain functional connectivity during the presentation of happy and angry faces in 258 children (5–19 years), including ASD, ADHD and typically developing (TD) groups to determine possible differences in emotion processing. Data-driven clustering was also applied to determine whether the patterns of connectivity differed among diagnostic groups. We found reduced functional connectivity in the beta band in ASD compared to TD, and a further reduction in the ADHD group compared to the ASD and the TD groups, across emotions. A group-by-emotion interaction in the gamma frequency band was also observed. Greater connectivity to happy compared to angry faces was found in the ADHD and TD groups, while the opposite pattern was seen in ASD. Data-driven subgrouping identified two distinct subgroups: NDD-dominant and TD-dominant; these subgroups demonstrated emotion- and frequency-specific differences in connectivity. Atypicalities in specific brain networks were strongly correlated with the severity of diagnosis-specific symptoms. Functional connectivity strength in the beta network was negatively correlated with difficulties in attention; in the gamma network, functional connectivity strength to happy faces was positively correlated with adaptive behavioural functioning, but in contrast, negatively correlated to angry faces. Our findings establish atypical frequency- and emotion-specific patterns of functional connectivity between NDD and TD children. Data-driven clustering further highlights a high degree of comorbidity and symptom overlap between the ASD and ADHD children. [ABSTRACT FROM AUTHOR]

Background: Many phenotypic studies have estimated the degree of comorbidity between Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), but few have examined the latent, or unobserved, structure of combined ASD and ADHD symptoms. This is an important perquisite toward better understanding the overlap between ASD and ADHD. Methods: We conducted a scoping review of studies that examined the factor or latent class structure of ASD and ADHD symptoms within the same clinical or general population sample. Results: Eight studies met final inclusion criteria. Four factor analysis studies found that ASD and ADHD domains loaded separately and one found that some ASD and ADHD domains loaded together. In the three latent class studies, there were evidence of profiles with high levels of co-occurring ASD and ADHD symptoms. Conclusions: Our scoping review provides some evidence of phenotypic overlap between ASD and ADHD at the latent, or unobserved, level, particularly when using a "person-centered" (latent class analysis) vs. a "variable-centered" (factor analysis) approach. [ABSTRACT FROM AUTHOR]

Objective: To summarize existing knowledge about the characteristics of attention problems secondary to traumatic brain injuries (TBI) of all severities in children. Methods: Computerized databases PubMed and PsychINFO and gray literature sources were used to identify relevant studies. Search terms were selected to identify original research examining new ADHD diagnosis or attention problems after TBI in children. Studies were included if they investigated any severity of TBI, assessed attention or ADHD after brain injury, investigated children as a primary or sub-analysis, and controlled for or excluded participants with preinjury ADHD or attention problems. Results: Thirty-nine studies were included in the review. Studies examined the prevalence of and risk factors for new attention problems and ADHD following TBI in children as well as behavioral and neuropsychological factors associated with these attention problems. Studies report a wide range of prevalence rates of new ADHD diagnosis or attention problems after TBI. Evidence indicates that more severe injury, injury in early childhood, or preinjury adaptive functioning problems, increases the risk for new ADHD and attention problems after TBI and both sexes appear to be equally vulnerable. Further, literature suggests that cases of new ADHD often co-occurs with neuropsychiatric impairment in other domains. Identified gaps in our understanding of new attention problems and ADHD include if mild TBI, the most common type of injury, increases risk and what brain abnormalities are associated with the emergence of these problems. Conclusion: This scoping review describes existing studies of new attention problems and ADHD following TBI in children and highlights important risk factors and comorbidities. Important future research directions are identified that will inform the extent of this outcome across TBI severities, its neural basis and points of intervention to minimize its impact. [ABSTRACT FROM AUTHOR]

Restricted interests and repetitive behaviors (RRBs) are core symptoms of autism spectrum disorder (ASD), and commonly occur in attention-deficit/hyperactivity disorder (ADHD). Little is known about how RRBs manifest in ADHD. We quantified and compared factor structures of RRBs in children with ASD (n = 634) or ADHD (n = 448), and related factors to sex and IQ. A four-factor solution emerged, including Stereotypy, Self-Injury, Compulsions, and Ritualistic/Sameness. Factor structures were equivalent across diagnoses, though symptoms were more severe in ASD. IQ negatively correlated with Stereotypy, Self-Injury, and Compulsions in ASD, and negatively correlated with Compulsions and Ritualistic/Sameness behaviors in ADHD. In ASD only, females exhibited higher Self-Injury. Thus, patterns of RRBs are preserved across ASD and ADHD, but severity and relationship with IQ differed. [ABSTRACT FROM AUTHOR]

We examined the correlation between interviewer-administered Vineland Adaptive Behavior Scale II (VABS-II) and the parent-rated Adaptive Behavior Assessment System II (ABAS-II) questionnaire in 352 participants (ages 1.5–20.8 years) with autism spectrum disorder (ASD) to determine if ABAS could be used as a screen to reduce the number of VABS interviews. Corresponding domain scores between the two measures were highly correlated but scores were significantly lower on the ABAS-II. Screening with ABAS-II significantly reduced the number of VABS-II interviews required with little cost to overall accuracy. The ABAS-II provides a cost- and time-saving alternative to the VABS-II to rule out functional impairment; however, scores are not strictly comparable between the two measures. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that often involves impaired cognition, communication difficulties and restrictive, repetitive behaviors. ASD is extremely heterogeneous both clinically and etiologically, which represents one of the greatest challenges in studying the molecular underpinnings of ASD. While hundreds of ASD-associated genes have been identified that confer varying degrees of risk, no single gene variant accounts for >1% of ASD cases. Notably, a large number of ASD-risk genes function as epigenetic regulators, indicating potential epigenetic dysregulation in ASD. As such, we compared genome-wide DNA methylation (DNAm) in the blood of children with ASD (n = 265) to samples from age- and sex-matched, neurotypical controls (n = 122) using the Illumina Infinium HumanMethylation450 arrays. Results: While DNAm patterns did not distinctly separate ASD cases from controls, our analysis identified an epigenetically unique subset of ASD cases (n = 32); these individuals exhibited significant differential methylation from both controls than the remaining ASD cases. The CpG sites at which this subset was differentially methylated mapped to known ASD risk genes that encode proteins of the nervous and immune systems. Moreover, the observed DNAm differences were attributable to altered blood cell composition, i.e., lower granulocyte proportion and granulocyte-to-lymphocyte ratio in the ASD subset, as compared to the remaining ASD cases and controls. This ASD subset did not differ from the rest of the ASD cases in the frequency or type of high-risk genomic variants. Conclusion: Within our ASD cohort, we identified a subset of individuals that exhibit differential methylation from both controls and the remaining ASD group tightly associated with shifts in immune cell type proportions. This is an important feature that should be assessed in all epigenetic studies of blood cells in ASD. This finding also builds on past reports of changes in the immune systems of children with ASD, supporting the potential role of altered immunological mechanisms in the complex pathophysiology of ASD. The discovery of significant molecular and immunological features in subgroups of individuals with ASD may allow clinicians to better stratify patients, facilitating personalized interventions and improved outcomes. [ABSTRACT FROM AUTHOR]

Background: A decreased ability to inhibit a speeded motor response is a well-studied deficit in Attention Deficit Hyperactivity Disorder (ADHD), and has been proposed as an endophenotype. Inhibitory control has been assessed reliably with the Stop Signal Task (SST) and is associated with prior documented differences in regional brain function using f-MRI. Here, we advance on these findings by examining their structural connectivity and white matter integrity with the goal of identifying a network underlying a core cognitive deficit in ADHD. Methods: Healthy controls (N=16) and youth diagnosed with ADHD (N=60) were recruited through the Province of Ontario Neurodevelopmental Disorders Network (POND) and the Hospital for Sick Children. An f-MRI activation difference map was co-registered with each participant's white matter imaging data, representing the specific network nodes where ADHD youth diverged significantly from controls while performing the SST. Probabilistic tractography was applied from these nodes, and white matter integrity indices such as fractional anisotropy (FA) within the tracts of interest were contrasted between the groups and correlated with SST output measures, including the measure of inhibitory control, the stop signal reaction time (SSRT). Results: The tracts that connected the network nodes belonged primarily to the inferior fronto-occipital fasciculus (IFOF) and cingulum. ADHD subjects showed trend differences in FA compared to controls between right inferior frontal gyrus (IFG) and right superior temporal gyrus (P= 0.09), right IFG and right posterior cingulate (P= 0.01), right anterior cingulate to posterior cingulate (p= 0.08), and between left middle temporal gyrus (BA 39) and left posterior cingulate (P=0.02). A trend correlation was found between radial diffusivity within IFG to STG white matter (IFOF) and SSRT. Conclusions: We identified potential white matter tracts related to deficient inhibitory control, elucidating the brain mechanisms of an important cognitive deficit in ADHD. These findings could be integrated into future endophenotypic biomarker studies, incorporating altogether brain structure, function, and behavior for future studies of ADHD and other psychiatric conditions that exhibit this deficit. [ABSTRACT FROM AUTHOR]

Background: Hoarding, originally only considered a symptom of obsessive-compulsive disorder (OCD), is now categorized as a separate disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). We studied candidate serotonergic genes and the distinctness of hoarding in children and adolescents and hypothesized that unique gene variants would be associated with hoarding alone.Methods: We examined obsessive-compulsive (OC) traits, including hoarding, in a total of 5,213 pediatric participants in the community. We genotyped candidate serotonin genes (5-HTTLPR polymorphism in SLC6A4 for 2,018 individuals and single nucleotide polymorphisms [SNPs] across genes SLC6A4, HTR2A, and HTR1B for 4,711 individuals). In a previous study conducted by our group in the same sample, we identified a significant association between 5-HTTLPR and hoarding in males. In this study, we examined hoarding more closely by testing the association between serotonin gene variants and hoarding traits with and without other accompanying OC traits.Results: The [LG +S] variant in 5-HTTLPR was significantly associated with hoarding alone in males (p-value of 0.009). There were no significant findings for 5-HTTLPR in females. There were no significant findings after correction for multiple comparisons using SNP array data, but top SNP findings suggested that variation downstream of HTR1B may be implicated in hoarding alone in females.Conclusions: Our results suggest specific serotonin gene variants are associated with hoarding traits alone, differing between sexes. Top findings are in line with our former study, suggesting that individuals with hoarding alone were driving previous results. Our paper supports hoarding disorder's new designation. [ABSTRACT FROM AUTHOR]

Background: Although there is high co-occurrence between ASD and ADHD, the nature of this co-occurrence remains unclear. Our study aimed to examine the underlying relationship between ASD and ADHD symptoms in a combined sample of children with a primary clinical diagnosis of ASD or ADHD. Methods: Participants included children and youth (aged 3-20 years) with a clinical diagnosis of ASD (n = 303) or ADHD (n = 319) for a total of 622 participants. Parents of these children completed the social communication questionnaire (SCQ), a measure of autism symptoms, and the strengths and weaknesses of ADHD and normal behavior (SWAN) questionnaire, a measure of ADHD symptoms. A principal component analysis (PCA) was performed on combined SCQ and SWAN items, followed by a profile analysis comparing normalized component scores between diagnostic groups and gender. Results: PCA revealed a four-component solution (inattention, hyperactivity/impulsivity, social-communication, and restricted, repetitive, behaviors, and interests (RRBI)), with no overlap between SCQ and SWAN items in the components. Children with ASD had higher component scores in social-communication and RRBI than children with ADHD, while there was no difference in inattentive and hyperactive/impulsive scores between diagnostic groups. Males had higher scores than females in social-communication, RRBI, and hyperactivity/impulsivity components in each diagnostic group. Limitations: We did not formally assess children with ASD for ADHD using our research-criteria for ADHD, and vice versa. High rates of co-occurring ADHD in ASD, for example, may have inflated component scores in inattention and hyperactivity/impulsivity. A disadvantage with using single informant-based reports (i.e., parent-rated questionnaires) is that ASD and ADHD symptoms may be difficult to distinguish by parents, and may be interpreted differently between parents and clinicians. Conclusions: ASD and ADHD items loaded on separate components in our sample, suggesting that the measurement structure cannot explain the covariation between the two disorders in clinical samples. High levels of inattention and hyperactivity/impulsivity were seen in both ASD and ADHD in our clinical sample. This supports the need for a dimensional framework that examines neurodevelopmental domains across traditional diagnostic boundaries. Females also had lower component scores across social-communication, RRBI, and hyperactivity/impulsivity than males, suggesting that there may be gender-specific phenotypes related to the two conditions. [ABSTRACT FROM AUTHOR]

Background: Altered brain activity that has been observed in attention deficit hyperactivity disorder (ADHD) while performing cognitive control tasks like the stop signal task (SST) has generally been interpreted as reflecting either weak (under-active) or compensatory (over-active) versions of the same functions as in healthy controls. If so, then regional activities that correlate with the efficiency of inhibitory control (i.e. stop signal reaction time, SSRT) in healthy subjects should also correlate with SSRT in ADHD. Here we test the alternate hypothesis that BOLD (blood-oxygen-level-dependent) differences might instead reflect the redirection of neural processing resources normally used for task-directed inhibitory control, towards actively managing symptomatic behaviour. If so, then activities that correlate with SSRT in TD should instead correlate with inattentive and hyperactive symptoms in ADHD. Methods: We used fMRI (functional magnetic resonance imaging) in 14 typically developing (TD) and 14 ADHD adolescents performing the SST, and in a replication sample of 14 healthy adults. First, we identified significant group BOLD differences during all phases of activity in the SST (i.e. warning, response, reactive inhibition, error detection and post-error slowing). Next, we correlated these phases of activity with SSRT in TD and with SSRT, inattentive and hyperactive symptom scores in ADHD. We then identified whole brain significant correlations in regions of significant group difference in activity. Results: Only three regions of significant group difference were correlated with SSRT in TD and replication groups (left and right inferior frontal gyri (IFG) during error detection and hypothalamus during post-error slowing). Consistent with regions of altered activity managing symptomatic behaviour instead of task-directed behaviour, left IFG correlated with greater inattentive score, right IFG correlated with lower hyperactive score and hypothalamus correlated with greater inattentive score and oppositely correlated with SSRT compared to TD. Conclusions: Stimuli that elicit task-directed integration of neural processing in healthy subjects instead appear to be directing integrated function towards managing symptomatic behaviour in ADHD. The ability of the current approach to determine whether altered neural activities reflect comparable functions in ADHD and control groups has broad implications for the development and monitoring of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Serotonin system genes are commonly studied in obsessive‐compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive‐compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex. Methods: Obsessive‐compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive‐Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5‐HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4,HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores. Results: The [LG + S] variant in 5‐HTTLPR was significantly associated with hoarding in males (p‐value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5‐HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p‐value of 1.04e‐6 to 5.20e‐6). Conclusions: This represents the first genetic association study of OC trait dimensions in a community‐based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group. [ABSTRACT FROM AUTHOR]

Background: Social-communication difficulties, a hallmark of ASD, autism spectrum disorder (ASD) are often observed in attention – deficit/ hyperactivity disorder (ADHD), although are not part of its diagnostic criteria. Despite sex differences in the prevalence of ASD and ADHD, research examining how sex differences manifest in social and communication functions in these disorders remains limited, and findings are mixed. This study investigated potential sex differences with age in social adaptive function across these disorders, relative to controls. Method: One hundred fifteen youth with ASD, 172 youth with ADHD, and 63 typically developing controls (age range 7–13 years, 75% males) were recruited from the Province of Ontario Neurodevelopmental Disorder (POND) Network. Social adaptive function was assessed using the Adaptive Behavior Assessment System-Second Edition (ABAS-II). The proportions of adaptive behaviors present in each skill area were analyzed as a binomial outcome using logistic regression, controlling for age, and testing for an age-by-sex interaction. In an exploratory analysis, we examined the impact of controlling for core symptom severity on the sex effect. Results: Significant sex-by-age interactions were seen within ASD in the communication (p = 0.005), leisure (p = 0.003), and social skill areas (p < 0.0001). In all three areas, lower scores (indicating poorer function) were found in females compared to males at older ages despite females performing better at younger ages. There were significant differences in the sex-by-age interactions in the social and leisure domains between those with ASD and typically developing controls, with typically developing females showing better scores at older, compared to younger, ages. There were also significant differences in the sex-by-age interactions between ASD and ADHD on the social and leisure domains, as females with ADHD consistently scored higher on social skills than males across all ages, unlike those with ASD. Sex differences across age in the social domains for ADHD were similar to those in the typically developing group. Conclusion: Sex differences in social and communication skill areas were observed between ASD and ADHD, and typically developing controls, with females with ASD performing worse than males at older ages, despite an earlier advantage. These findings reinforce the need to take a developmental approach to understanding sex differences which may have diagnostic, prognostic, and treatment implications. [ABSTRACT FROM AUTHOR]

Background: Population‐based samples with valid, quantitative and genetically informative trait measures of psychopathology could be a powerful complement to case/control genetic designs. We report the convergent and predictive validity of the parent‐ and self‐report versions of the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scale (SWAN). We tested if SWAN scores were associated with ADHD diagnosis, ADHD polygenic risk, as well as traits and polygenic risk for disorders that co‐occur with ADHD: anxiety and obsessive‐compulsive disorder (OCD). Methods: We collected parent‐ and self‐report SWAN scores in a sample of 15,560 children and adolescents (6–17 years) recruited at a science museum (Spit for Science sample). We established age and sex norms for the SWAN. Sensitivity‐specificity analyses determined SWAN cut‐points that discriminated those with and without a reported ADHD diagnosis. These cut‐points were validated in a clinic sample (266 ADHD cases; 36 controls). Convergent validity was established using the Conners' parent‐ and self‐report scales. Using Spit for Science participants with genome‐wide data (n = 5,154), we tested if low, medium and high SWAN scores were associated with polygenic risk for ADHD, OCD and anxiety disorders. Results: Parent‐ and self‐report SWAN scores showed high convergent validity with Conners' scales and distinguished ADHD participants with high sensitivity and specificity in the Spit for Science sample. In a clinic sample, the Spit for Science cut‐points discriminated ADHD cases from controls with a sensitivity of 84% and specificity of 92%. High SWAN scores and scores above the Spit for Science cut‐points were significantly associated with polygenic risk for ADHD. SWAN scores were not associated with polygenic risk for OCD or anxiety disorders. Conclusions: Our study supports the validity of the parent‐ and self‐report SWAN scales and their potential in ADHD population‐based genetic research. [ABSTRACT FROM AUTHOR]

Adjusting speed to maintain fast and accurate performance is critical to goal-directed behavior. This study examined development of response time adjustments in the stop signal task in 13,709 individuals aged 6-17 years (49.0% Caucasian) across four trial types: correct and incorrect go, successful (stop-inhibit), and failed (stop-respond) trials. People sped more after correct than incorrect go responses and slowed more after failed than successful stop trials. Greater slowing after stop-respond but less slowing after stop-inhibit trials was associated with better response inhibition. Response time adjustments were evident in children as young as age 6, developed throughout childhood, and plateaued by age 10. Results were consistent with the predictions of the error detection and shifting goal priority hypotheses for adjustments. [ABSTRACT FROM AUTHOR]