A reading of stereotypy in autism through the concept of iteration

Objective:Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) are neurodevelopmental disorders with overlapping symptomatology and shared genetic makeup. Numerous previous studies have investigated ASD and ADHD using resting state functional networks. One functional network of particular interest is the Default Mode Network (DMN), as it has been shown to be abnormal in several mental disorders. Previous studies have investigated the DMN in ASD and ADHD separately but reported mixed trends of increased and decreased functional connectivity (FC) in the DMN in ASD and increased FC in ADHD. Additionally, little studies have investigated executive and attentional network dysfunction in the DMN for ASD and ADHD populations. To better understand the shared characteristics between ASD and ADHD, this study analyzed the DMN FC in children with ASD and ADHD.Participants and Methods:Archival datasets from Autism Brain Imaging Data Exchange (ABIDE)-I and ADHD-200 datasets were used, with 33 ADHD, 35 ASD, and 32 typically developing (TD) males (ages = 7-17 years). After applying a standard pre-processing pipeline, 11 regions of interest (ROIs) from the Dosenbach-160 atlas were examined with 55 ROI pairs generated for the 100 subjects.Results:Significant differences were noted between ASD-ADHD groups in attentional networks and executive functioning networks. Specifically, significant Group x VIQ interactions were noted for FC between the following pairs of regions: medial prefrontal cortex - ventromedial prefrontal cortex, anterior cingulate cortex -ventromedial prefrontal cortex, inferior temporal lobe - ventromedial prefrontal cortex, angular -ventromedial prefrontal cortex, angular -anterior cingulate cortex, inferior temporal lobe -ventrolateral prefrontal cortex, angular -superior frontal lobe, and intraparietal sulcus -superior frontal lobe. In the above FC pairs, FC in ADHD was negatively correlated with VIQ, with no correlation for ASD and positive correlation for TD. Previous literature has indicated that ADHD individuals demonstrate increased executive functioning deficits compared to ASD individuals. This study provides evidence at a neural level for these findings by demonstrating decreased FC trends in ADHD in attentional and executive functioning networks compared to ASD individuals. Group and VIQ main effects demonstrated mixed patterns across the three groups, as well as shared decreased FC in attention/executive networks for both ASD and ADHD groups.Conclusions:In summary, this study found similar findings from previous studies regarding mixed connectivity patterns, as well as shared dysfunction between ASD and ADHD groups. These results help in solidifying the theory that ASD and ADHD share clinical and neural patterns which need to be examined further. Future directions include utilizing more ASD+ADHD comorbid individuals in studies comparing ASD and ADHD FC trends as well as seeking to further understand the neuropsychological and neuroimaging profiles in ASD and ADHD.

Previous studies have shown that immunological factors are involved in the pathogenesis of autism spectrum disorders (ASDs). However, this research has been conducted almost exclusively in Western contexts, and only a handful of studies on immune measures have been conducted in Asian populations, such as Chinese populations. The present study examined whether immunological abnormalities are associated with cognitive deficits and problem behaviors in Chinese children with ASD and whether these children show different immunological profiles. Thirteen typically developing (TD) children and 22 children with ASD, aged 6–17 years, participated voluntarily in the study. Executive functions and short-term memory were measured using neuropsychological tests, and behavioral measures were assessed using parent ratings. The children were also assessed on immunological measures, specifically, the levels of cytokines and chemokines in the blood serum. Children with ASD showed greater deficits in cognitive functions, as well as altered levels of immunological measures, including CCL2, CCL5, and CXCL9 levels, compared to TD children, and the cognitive functions and associated behavioral deficits of children with ASD were significantly associated with different immunological measures. The children were further sub-classified into ASD with only autistic features (ASD-only) or ASD comorbid with attention deficit hyperactivity disorder (ASD + ADHD). The comorbidity results showed that there were no differences between the two groups of ASD children in any of the cognitive or behavioral measures. However, the results pertaining to immunological measures showed that the children with ASD-only and ASD + ADHD exhibited distinct cytokine and chemokine profiles and that abnormal immunologic function was associated with cognitive functions and inattention/hyperactivity symptoms. These results support the notion that altered immune functions may play a role in the selective cognitive and behavioral symptoms of ASD.

Autism spectrum disorder (ASD) is a heterogeneous group of disorders which occurs with numerous medical conditions. In previous research, subtyping in ASD has been based mostly on cognitive ability and ASD symptom severity. The aim of the current study was to investigate whether specific medical conditions in ASD are associated with unique behavioral profiles. The medical conditions included in the study were macrocephaly, microcephaly, developmental regression, food selectivity, and sleep problems. The behavioral profile was composed of cognitive ability, adaptive skills, and autism severity, and was examined in each of the aforementioned medical conditions. The study population included 1224 participants, 1043 males and 181 females (M:F ratio = 5.8:1) with a mean age of 49.9 m (SD = 29.4) diagnosed with ASD using standardized tests. Groups with and without the specific medical conditions were compared on the behavioral measures. Developmental regression was present in 19% of the population and showed a more severe clinical presentation, with lower cognitive abilities, more severe ASD symptoms, and more impaired adaptive functioning. Microcephaly was observed in 6.3% of the population and was characterized by a lower cognitive ability and more impaired adaptive functioning in comparison to the normative head circumference (HC) group. Severe food selectivity was found in 9.8% and severe sleep problems in 5.1% of the ASD population. The food selectivity and sleep problem subgroups, both showed more severe autism symptoms only as described by the parents, but not per the professional assessment, and more impaired adaptive skills. Macrocephaly was observed in 7.9% of the ASD population and did not differ from the normative HC group in any of the examined behavioral measures. Based on these findings, two unique medical-behavioral subtypes in ASD that affect inherited traits of cognition and/or autism severity were suggested. The microcephaly phenotype occurred with more impaired cognition and the developmental regression phenotype with widespread, more severe impairments in cognition and autism severity. In contrast, severe food selectivity and sleep problems represent only comorbidities to ASD that affect functioning. Defining specific subgroups in ASD with a unique biological signature and specific behavioral phenotypes may help future genetic and neuroscience research.

Background: Autism spectrum disorder (ASD) is a multifactorial disorder resulting from genetic and nongenetic risk factors and their interaction. There is a paucity of data on the socioeconomic and demographic factors underlying ASD from India. Aim: The aim of this study was to evaluate the socioeconomic and demographic profile of ASD. Materials and Methods: Six hundred patients with behavioral complaints reporting to either psychiatric or pediatric outpatient departments were screened and validated as per Autism questionnaire (Childhood Autism Rating Scale [CARS]). Included patients were evaluated on socioeconomic and demographic scale the appropriate Child Behavior Checklist (CBCL). Results: Twenty-eight children out of 600 (4.66%) were found to have ASD. The average age at which parents first noticed symptoms was 16 months (range: 9–24 months). The mean age at first consultation for ASD symptoms was delayed for girls. A highly significant association between intelligence quotient (IQ) and a diagnosis of ASD was seen. The mean IQ of ASD patients (93.2 n = 28) was significantly lesser than either psychiatric diagnoses or no diagnosis. Even though all patients had an IQ >70, there were still 9/28 patients with a level 3 severity of ASD. A highly significant association between ASD diagnosis and CARS scores was seen. Out of the documented 26 presenting complaints, 17 were social impairment related and 9 related to repetitive patterns of behaviors. The clinical findings from the CBCL conform to a previously developed autism profile for CBCL. Conclusion: Children are taking longer than recommended for optimal outcome to receive a diagnosis. Girls were brought for consultation with the pediatrician later than the boys. Male preponderance in ASD with M: F ratio of 6:1 was highly significant. ASD was found higher in MSES and HSES families. Living in urban areas predicted higher severity. IQ was lesser than for other conditions in ASD.

Tuberous sclerosis complex (TSC) is highly associated with autism spectrum disorder (ASD). Objectives of the study were to characterize autistic features in young children with TSC. Participants included 138 children followed from ages 3 to 36 months with TSC from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network (TACERN), a multicenter, prospective observational study aimed at understanding the underlying mechanisms of ASD in TSC. Developmental and autism-specific assessments were administered, and a clinical diagnosis of ASD was determined for all participants at 36 months. Further analyses were performed on 117 participants with valid autism assessments based on nonverbal mental age greater than 15 months. Prevalence of clinical diagnosis of ASD at 36 months was 25%. Nearly all autistic behaviors on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and Autism Diagnostic Interview-Revised (ADI-R) were more prevalent in children diagnosed with ASD; however, autism-specific behaviors were also observed in children without ASD. Overall quality of social overtures, facial expressions, and abnormal repetitive interests and behaviors were characteristics most likely to distinguish children with ASD from those without an ASD diagnosis. Participants meeting ADOS-2 criteria but not a clinical ASD diagnosis exhibited intermediate developmental and ADOS-2 scores compared to individuals with and without ASD. ASD is highly prevalent in TSC, and many additional individuals with TSC exhibit a broad range of subthreshold autistic behaviors. Our findings reveal a broader autism phenotype that can be identified in young children with TSC, which provides opportunity for early targeted treatments. ANN NEUROL 2021;90:874-886.

The present study extends our previous work on characterizing the autistic behavior profile of boys with fragile X syndrome (FXS) who meet Diagnostic and Statistical Manual for Mental Disorders, 4th Edition criteria for autism spectrum disorder (ASD) into a longitudinal evaluation of ASD in FXS (FXS + ASD). Specifically, we aimed to determine the stability of the diagnosis and profile of ASD in FXS over time. Through regression models, we also evaluated which autistic and social behaviors and skills were correlates of diagnosis and autistic behavior severity (i.e., Autism Diagnostic Interview-Revised total scores). Finally, we assessed the evolution of cognitive parameters in FXS + ASD. A population of 56 boys (30-88 months at baseline) with FXS was evaluated using measures of autistic, social, and cognitive behaviors and skills at three yearly evaluations. We found that the diagnosis of ASD in FXS was relatively stable over time. Further emphasizing this stability, we found a set of behaviors and skills, particularly those related to peer relationships and adaptive socialization, that differentiated FXS + ASD from the rest of the FXS cohort (FXS + None) and contributed to autistic severity at all time points. Nevertheless, the general improvement in autistic behavior observed in FXS + ASD coupled with the concurrent worsening in FXS + None resulted in less differentiation between the groups over time. Surprisingly, FXS + ASD IQ scores were stable while FXS + None non-verbal IQ scores declined. Our findings indicate that ASD is a distinctive subphenotype in FXS characterized by deficits in complex social interaction, with similarities to ASD in the general population.

IntroductionAutism spectrum disorders (ASD) is a neurodevelopmental disorder that has been rarely diagnosed in Sub-Saharan Africa. Although a proportion of children do present features of ASD in the Democratic Republic of Congo (DRC), little is known about it prevalence. Often, the co-morbidities constitute the upfront symptoms and therefore may it recognition and management difficult, aggravating as such the prognosis. The present study therefore aimed at studying the clinical profile of autism spectrum disorder (ASD) and the associated morbidities among children and adolescents in outpatient clinics in Kinshasa, the Democratic Republic of Congo.MethodsWe conducted a cross sectional study in the three outpatients centers receiving patients referred for neurodevelopmental disorders in Kinshasa, DRC, from June 2008 to June 2010. A total of 450 subjects aged from 1-18 years old were referred and included in the study. The clinical diagnosis for ASD was made using the DSM-IV-R and the ADIR. Co-morbidities were identified using DSM-IV-R criteria together with an extensive clinical interview and observation. All patients were subject to an intellectual quotient evaluation and an electroencephalogram reporting.ResultsOf the 450 subjects referred, 120 (29.3%) received the diagnosis of ASD, with boys outnumbering girls (OR 3:1. The mean age was 7.9 years (SD 3.4) (p< 0.001). Intellectual disability (75.83 %) and epilepsy (72.50%) were the main co-morbidities significantly associated with autism (p< 0.001). It was also found that co-morbidities were most frequent in subjects with an IQ<70 (p=0.05).ConclusionASD is frequent among patients referred for neurodevelopmental disorders in the three outpatients’ centers for neurodevelopmental disorders in Kinshasa. Males seem to be more affected than female. The main co-morbidities were epilepsy and intellectual disabilities. Our findings suggest that it is important to screen for ASD and co-morbidities among all subjects referred for neurodevelopmental disorders and to undertake survey on ASD in various structures of rejected children from the society in Kinshasa DRC. This will help to identify and manage ASD and associated co-morbidities at an early stage for a better prognosis.

Risk factors and clinical profile of autism spectrum disorder in southern Brazil

Findings that a subgroup of children with an autism spectrum disorder (ASD) have linguistic capabilities that resemble specific language impairment (SLI) have led some authors to hypothesise that ASD and SLI have a shared aetiology. While considerable research has explored overlap in the language phenotypes of the two conditions, little research has examined possible overlap in cognitive characteristics. In this study, we explored nonword and sentence repetition performance, as well as performance on the Children's Embedded Figures Test (CEFT) for children with ASD or SLI. As expected, 'language impaired' children with ASD (ALI) and children with SLI performed worse than both 'language normal' ASD (ALN) and typically developing (TD) children on the nonword and sentence repetition tests. Further, the SLI children performed worse than all other groups on the CEFT. This finding supports distinct cognitive profiles in ASD and SLI and may provide further evidence for distinct aetiological mechanisms in the two conditions.

Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome

Tuberous sclerosis complex is a multisystem, chronic genetic condition characterized by systemic growth of benign tumors and often accompanied by epilepsy, autism spectrum disorders, and intellectual disability. Nonetheless, the neurodevelopmental phenotype of these patients is not often detailed. The authors describe 3 individuals with tuberous sclerosis complex who share common characteristics that can help to identify a distinct profile of autism spectrum disorder. These findings include typical cognitive development, expressive and pragmatic language deficits, and anxiety. The authors also describe features specific to tuberous sclerosis complex that require consideration before diagnosing an autism spectrum disorder. Identifying distinct profiles of autism spectrum disorder in tuberous sclerosis complex can help optimize treatment across the life span.

Dysregulation of the Ras MAPK signaling pathway is implicated in the pathogenesis of autism spectrum disorder (ASD). The RASopathies, a group of disorders caused by mutations of the Ras/MAPK pathway genes, share many overlapping clinical features. Studies suggest a high prevalence of ASD in the RASopathies, but detailed characterization of the ASD profile is lacking. The aim of this study was to compare the ASD symptom profile of three distinct RASopathies associated with both gain-of-function and loss-of-function mutations: neurofibromatosis type 1 (NF1), Noonan syndrome (NS), and cardiofaciocutaneous syndrome (CFC). Participants were drawn from existing databases if they had a diagnosis of a RASopathy, met the criteria for ASD, and were able to communicate verbally. We compared the phenotypic profile of NF1 + ASD (n = 48), NS + ASD (n = 11), and CFC + ASD (n = 7) on the Autism Diagnostic Inventory (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). We found subtle but non-significant group differences with higher levels of social impairments and lower restricted repetitive behaviors in the NF1 group as compared with the NS and CFC groups. We observed group differences in developmental milestones with most severe delays in CFC, followed by NS and NF1. Our results suggest that despite developmental differences, the ASD profile remains relatively consistent across the three RASopathies. Though our results need confirmation in larger samples, they suggest the possibility that treatment and mechanistic insights developed in the context of one RASopathy may be generalizable to others and possibly to non-syndromic ASD associated with dysregulation of Ras/MAPK pathway genes.

Investigating distinct and related contributions of Weak Central Coherence, Executive Dysfunction, and Systemizing theories to the cognitive profiles of children with Autism Spectrum Disorders and typically developing children

Autism spectrum disorders (ASDs) are associated with anomalies in time perception. In a perceptual simultaneity task, individuals with ASD demonstrate superior performance compared to typically developing (TD) controls. γ-activity, a robust marker of visual processing, is reportedly altered in ASD in response to a wide variety of tasks and these differences may be related to superior performance in perceptual simultaneity. Using time-frequency analysis, we assessed evoked γ-band phase-locking in magnetoencephalographic recordings of 16 ASD individuals and 17 age-matched TD controls. Individuals judged whether presented visual stimuli were simultaneous or asynchronous. We identified left frontal γ-activity in ASD, which was associated with a reduced perception of simultaneity. Where feature binding was observed at a neurophysiological level in parieto-occipital cortices in ASD in apparent simultaneity (asynchronous stimuli with short delay between them), this did not predict the correct behavioural outcome. These findings suggest distinct γ profiles in ASD associated with the perception of simultaneity.

RASopathies are associated with an increased risk of autism spectrum disorder (ASD). For neurofibromatosis type 1 (NF1) there is ample evidence for this increased risk, while for other RASopathies this association has been studied less. No specific ASD profile has been delineated so far for RASopathies or a specific RASopathy individually. We conducted a systematic review to investigate whether a specific RASopathy is associated with a specific ASD profile, or if RASopathies altogether have a distinct ASD profile compared to idiopathic ASD (iASD). We searched PubMed, Web of Science, and Open Grey for data about ASD features in RASopathies and potential modifiers. We included 41 articles on ASD features in NF1, Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Individuals with NF1, NS, CS, and CFC on average have higher ASD symptomatology than healthy controls and unaffected siblings, though less than people with iASD. There is insufficient evidence for a distinct ASD phenotype in RASopathies compared to iASD or when RASopathies are compared with each other. We identified several potentially modifying factors of ASD symptoms in RASopathies. Our systematic review found no convincing evidence for a specific ASD profile in RASopathies compared to iASD, or in a specific RASopathy compared to other RASopathies. However, we identified important limitations in the research literature which may also account for this result. These limitations are discussed and recommendations for future research are formulated.