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

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

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

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

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

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

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

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

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

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

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

Pharmacoresistant partial-onset epilepsy misdiagnosed as panic disorder: a case report.

The clinical differentiation between simple partial epileptic seizures of temporal lobe origin and panic attacks is often difficult on clinical grounds alone, because both conditions are characterized by common symptomatology which includes the feeling of fear, autonomic system dysfunction, disorientation and alternation of the level of consciousness when these conditions evolve clinically. The symptoms stem from common pathophysiologic and anatomic substrates of these two conditions, localized in the limbic system, especially the amygdala. We present the case of a young woman who had a febrile seizure in childhood and subsequent episodes of fear accompanied by tremor and possible alteration of consciousness followed by headache. These spells were diagnosed as panic attacks during her teenage years and she was given Clobazam in order to suppress them. The patient responded well for several years without attacks but her symptoms reappeared following discontinuation of her medication in order to conceive. At that time a detailed history was taken from her spouse and further clinical evaluation raised the suspicion of seizures especially due to the fact that her spells were characterized by alteration of consciousness; she was therefore referred for additional investigations which included admission to a monitoring unit for epilepsy. Long-term video-EEG recording revealed the presence of simple partial seizures with secondary generalization confirming the clinical impression. She was subsequently treated with antiepileptic medications; however the patient's condition worsened to the point where she became pharmacoresistant having failed several antiepileptic drug trials in monotherapy or combination. An MRI scan of the brain revealed the presence of right-sided mesial temporal sclerosis, a known consequence of febrile seizures. Her seizures were nocturnal tonic-clonic and gradually worsened to the point of occurring during most nights. She was therefore referred for a presurgical evaluation which confirmed that the epileptic focus was associated with the area of mesial temporal sclerosis. The epileptic focus was successfully removed from the right anterior temporal lobe and since then she remained free of seizures whereas, in addition, the presumed symptoms of panic attacks also resolved. This case indicates the occasional difficulty in diagnosing simple partial seizures and how it may be confused with psychiatric conditions. Therefore, the treating physician, especially the psychiatrist, should remain vigilant when treating cases of panic attacks, especially when they present with either atypical symptomatology, such as the case described, or when they do not respond to appropriately chosen treatment; such cases may warrant referral for further investigation.

Amyloidosis: review and imaging findings.

Amyloidosis is a collection of pathophysiologically related disease entities caused by the extracellular deposition of abnormal fibrillar proteins called amyloid. The accumulation of amyloid may be systemic, involving many organs, or localized manifesting as infiltration of individual organs, or in the form of a focal, tumorlike lesion. Amyloidosis may develop in the setting of underlying conditions, usually chronic inflammatory diseases, in which case it is termed secondary, or it may involve no underlying disease and thus be primary or idiopathic. Amyloid infiltration leads to pathology through the disruption of normal tissue structure and function or through cytotoxic effects of intermediate forms of protein aggregates. Clinical manifestations of the disease vary and are nonspecific, increasing the need of imaging during the investigation of the disease. Imaging findings are diverse and not pathognomonic; however, combined with the patient's clinical history they can raise the suspicion of amyloidosis and direct toward its confirmation by biopsy. Radiologists should be familiar with the appearance of amyloidosis in various modalities to aid the early identification of the disease and direct toward prompt treatment planning. Such knowledge would provide the radiologist with an opportunity to contribute to patient care and aid reducing the high morbidity and mortality of the disease.

Language impairment and early social competence in preschoolers with autism spectrum disorders: a comparison of DSM-5 profiles.

Children with autism spectrum disorder (ASD) and structural language impairment (LI) may be at risk of more adverse social-developmental outcomes. We examined trajectories of early social competence (using the Vineland-II) in 330 children aged 2-4 years recently diagnosed with ASD, and compared 3 subgroups classified by: language impairment (ASD/LI); intellectual disability (ASD/ID) and ASD without LI or ID (ASD/alone). Children with ASD/LI were significantly more socially impaired at baseline than the ASD/alone subgroup, and less impaired than those with ASD/ID. Growth in social competence was significantly slower for the ASD/ID group. Many preschool-aged children with ASD/LI at time of diagnosis resembled "late talkers" who appeared to catch up linguistically. Children with ASD/ID were more severely impaired and continued to lag further behind.

Treatment of a man with a mild learning disability who was sexually assaulted whilst in prison.

The aim of this study is to describe the psychological effects on a man with a mild learning disability who was sexually assaulted whilst in prison, and the treatment which was carried out. J. suffered Post-Traumatic Stress Disorder (PTSD), as defined in DSM-III-R, combined with associated features of depression and anxiety. Treatment involved imaginal exposure to the assault, followed by systematic desensitization to the traumatic experience of imprisonment preceding the assault. Activities were also carried out to develop J.'s self-esteem, coping strategies and anxiety management. The successful outcome of treatment is discussed in relation to models of emotional processing. Some discrepancies between scores on self-evaluation questionnaires and behavioural observations raise issues concerning the best way of assessing treatment outcome for people with learning disabilities.