Pubmed du 22/10/19

mardi 22 octobre 2019

1. Bracken MB. SSRIs and autism : interpreting an umbrella review. Lancet Psychiatry ;2019 (Nov) ;6(11):893.

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2. Dajani D, Burrows C, Nebel MB, Mostofsky S, Gates K, Uddin LQ. Parsing heterogeneity in autism spectrum disorder and attention-deficit/hyperactivity disorder with individual connectome mapping. Brain Connect ;2019 (Oct 21)

Traditional diagnostic systems for neurodevelopmental disorders define diagnostic categories that are heterogeneous in behavior and underlying neurobiological alterations. The goal of this study was to parse heterogeneity in a core executive function, cognitive flexibility, in children with a range of abilities (N=132 ; children with autism spectrum disorder [ASD], attention deficit/hyperactivity disorder [ADHD], and typically developing [TD] children) using directed functional connectivity profiles derived from resting-state fMRI data. Brain regions activated in response to a cognitive flexibility task in adults were used to guide region-of-interest (ROI) selection to estimate individual connectivity profiles in this study. We expected to find subgroups of children who differed in their network connectivity metrics and symptom measures. Unexpectedly, we did not find a stable or valid subgrouping solution, which suggests that categorical models of the neural substrates of cognitive flexibility in children may be invalid. Exploratory analyses revealed dimensional associations between network connectivity metrics and ADHD symptomatology and executive function ability across the entire sample. Results shed light on the validity of conceptualizing the neural substrates of cognitive flexibility categorically in children. Ultimately, this work may provide a foundation for the development of a revised nosology focused on neurobiological substrates as an alternative to traditional symptom-based classification systems.

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3. Ferguson A, Vigil DC. A comparison of the ASD experience of low-SES hispanic and non-hispanic white parents. Autism Res ;2019 (Oct 22)

This study compared the experiences of Hispanic families, who were primarily of Mexican heritage, and non-Hispanic White families from the United States both from low socioeconomic status (SES) backgrounds having a child with a diagnosis of Autism Spectrum Disorder (ASD). The Centers for Disease Control and Prevention (CDC) reports that Hispanic children are diagnosed with ASD 2 years later than non-Hispanic White children [Baio et al., MMWR Surveillance Summaries 2018:67(SS-6) : 1-23]. However, there has been limited investigation in exploring how SES might impact both diagnosis and experience. A survey of basic demographic information and a qualitative survey were used for this study. Basic demographic information obtained included SES, parent educational level, age of diagnosis of the children, religious affiliation, and marital status. Hour-long interviews were conducted to gather information about the personal experiences of these families relating to diagnoses and treatment. Comparative results of basic demographic information showed no difference in age of diagnosis between the two groups when SES was controlled. Although SES was controlled, the non-Hispanic White families had a higher education level and were slightly wealthier. Qualitatively, similarities included family support, doctor response to parent concerns, and acceptance of diagnosis by family members and friends. Differences included religious views, acceptance of diagnosis, knowledge of developmental milestones, and finding resources. Most significantly, the findings indicate no difference in the age of diagnosis of ASD between the Hispanic and non-Hispanic White children, which could be attributed to increased awareness and having access to a proactive parent organization. Autism Res 2019, 00 : 1-11. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : This study showed that Hispanic and Non-Hispanic White children from poor backgrounds got a diagnosis of Autism Spectrum Disorder (ASD) at the same age. Results show differences in religious views, acceptance of diagnosis, knowledge of milestones, and finding resources. This might be because people are more aware of ASD today and Hispanic families were involved with an active parent organization.

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4. Fiore M, Barone R, Copat C, Grasso A, Cristaldi A, Rizzo R, Ferrante M. Metal and essential element levels in hair and association with autism severity. J Trace Elem Med Biol ;2019 (Sep 25):126409.

BACKGROUND : Autism Spectrum Disorder (ASD) is a complex disorder with heterogeneous etiology and wide clinical severity which supports the needs of recognizing biological and clinical features in patient subsets. The present study aimed to understand possible associations between the hair levels of metals and essential elements and some specific features of ASD measured by the Autism Diagnostic Observation Schedule (ADOS) that represents the gold-standard instrument to objectively confirm ASD diagnosis. METHODS : A cross-sectional study was performed in the province of Catania (Sicily, South Italy). Forty-eight subjects with ASD (70.8% male), aged from 2 to 17 years were studied. Metals (Li, Be, Al, Ni, As, Mo, Cd, Hg, U, Pb) and essential trace elements (Cr, Co, Mn, Zn, Cu, Se) were quantified in hair by inductively coupled plasma mass spectrometry analysis. Participants were characterized by measuring the severity of autism symptoms and cognitive levels. RESULTS : A significant and positive correlation was found between hair metal burden (lead, aluminum, arsenic and cadmium levels) and severity of ASD symptoms (social communication deficits and repetitive, restrictive behaviors). Hair zinc level were inversely related with age while there was a negative, significant association between hair zinc level and severity of autistic symptoms (defective functional play and creativity and increase of stereotyped behavior). Lead, molybdenum and manganese hair levels were inversely correlated with cognitive level (full intelligence quotient) in ASD individuals. CONCLUSIONS : The present study suggests the importance to combine metallomics analysis with pertinent disease features in ASD to identify potential environmental risk factors on an individual level possibly in the early developmental period.

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5. Geisler D. Educational Case : Fragile X Syndrome with Size Mosaicism. Acad Pathol ;2019 (Jan-Dec) ;6:2374289519877550.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies : Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

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6. Hrdlicka M, Sanda J, Urbanek T, Kudr M, Dudova I, Kickova S, Pospisilova L, Mohaplova M, Maulisova A, Krsek P, Kyncl M, Blatny M, Komarek V. Diffusion Tensor Imaging And Tractography In Autistic, Dysphasic, And Healthy Control Children. Neuropsychiatr Dis Treat ;2019 ;15:2843-2852.

Background : Diffusion tensor imaging (DTI) is a powerful tool for investigating brain anatomical connectivity. The aim of our study was to compare brain connectivity among children with autism spectrum disorders (ASD), developmental dysphasia (DD), and healthy controls (HC) in the following tracts : the arcuate fasciculus (AF), inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF). Methods : Our sample consisted of 113 children with a mean age 8.7+/-2.2 years (77 boys, 36 girls), divided into three subgroups : ASD (n=39), DD (n=36), and HC (n=38). The International Classification of Diseases, 10th ed. was used to make clinical diagnoses. DTI images were collected using a 1.5 T Phillips Achieva MR imaging system. Results : Detailed analyses of fractional anisotropy (FA) revealed significant differences among the ASD, DD, and HC groups in the left AF (p=0.014) and right AF (p=0.001), the left IFOF (p<0.001) and right IFOF (p<0.001), the left ILF (p<0.001) and right ILF (p<0.001), but not in the UF. Post-hoc analyses revealed three patterns of FA differences among the groups : (1) in the right AF, right IFOF, and right ILF, FA was significantly lower in the ASD group compared to the DD and HC groups ; however, there was no difference in FA between DD and HC ; (2) in the left AF and left IFOF, FA was significantly lower in the ASD than in the HC group, but there were no differences between DD vs HC nor DD vs ASD ; and (3) in the left ILF, no difference in FA was seen between ASD and DD, but FA in both was significantly lower than in the HC. Conclusion : Microstructural white matter properties differed between ASD vs DD and HC subjects. The tract where FA impairment in ASD and DD subjects was the most similar was the left ILF.

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7. Kim JY, Fusar-Poli P, Shin JI. SSRIs and autism : interpreting an umbrella review - Authors’ reply. Lancet Psychiatry ;2019 (Nov) ;6(11):893-894.

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8. King BH. Fluoxetine and Repetitive Behaviors in Children and Adolescents With Autism Spectrum Disorder. Jama ;2019 (Oct 22) ;322(16):1557-1558.

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9. Leboucher A, Bermudez-Martin P, Mouska X, Amri EZ, Pisani DF, Davidovic L. Fmr1-Deficiency Impacts Body Composition, Skeleton, and Bone Microstructure in a Mouse Model of Fragile X Syndrome. Front Endocrinol (Lausanne) ;2019 ;10:678.

Fragile X syndrome (FXS) is a neurodevelopmental disorder associated with intellectual disability, hyperactivity, and autism. FXS is due to the silencing of the X-linked FMR1 gene. Murine models of FXS, knock-out (KO) for the murine homolog Fmr1, have been generated, exhibiting CNS-related behavioral, and neuronal anomalies reminiscent of the human phenotypes. As a reflection of the almost ubiquitous expression of the FMR1 gene, FXS is also accompanied by physical abnormalities. This suggests that the FMR1-deficiency could impact skeletal ontogenesis. In the present study, we highlight that Fmr1-KO mice display changes in body composition with an increase in body weight, likely due to both increase of skeleton length and muscular mass along with reduced visceral adiposity. We also show that, while Fmr1-deficiency has no overt impact on cortical bone mineral density (BMD), cortical thickness was increased, and cortical eccentricity was decreased in the femurs from Fmr1-KO mice as compared to controls. Also, trabecular pore volume was reduced and trabecular thickness distribution was shifted toward higher ranges in Fmr1-KO femurs. Finally, we show that Fmr1-KO mice display increased physical activity. Although the precise molecular signaling mechanism that produces these skeletal and bone microstructure changes remains to be determined, our study warrants further investigation on the impact of FMR1-deficiency on whole-body composition, as well as skeletal and bone architecture.

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10. Marothi R, Csigo K, Keri S. Early-Stage Vision and Perceptual Imagery in Autism Spectrum Conditions. Front Hum Neurosci ;2019 ;13:337.

Autism spectrum conditions (ASC) are characterized by multifaceted alterations in visual perception and mental imagery. However, the interaction between early-stage visual perception and imagery has not been explored. We recruited 40 individuals with ASC and 20 neurotypical control volunteers to participate in a lateral masking task. Participants detected a luminance-contrast target pattern (Gabor patch) flanked by two collinear masks. The flanking masks inhibit target detection at small target-mask distances and facilitate target detection at intermediate target-mask distances. In the perceptual task, the masks appeared adjacent to the target. In the imagery task, participants imagined the masks immediately after seeing them. Results revealed that individuals with ASC characterized by exceptional visuoconstructional abilities (enhanced Block Design performance ; n = 20) showed weaker inhibition at small target-mask distances and stronger facilitation at intermediate target-mask distances relative to the controls. Visual imagery was markedly dampened in ASC regardless of the visuoconstructional abilities. At the behavioral level, these results indicate increased facilitation via lateral connections in the primary visual cortex (V1) of individuals with ASC who exhibit exceptional visuoconstructional abilities, together with less efficient mental imagery.

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11. McDaniel J, Woynaroski T, Keceli-Kaysili B, Watson LR, Yoder P. Vocal Communication With Canonical Syllables Predicts Later Expressive Language Skills in Preschool-Aged Children With Autism Spectrum Disorder. J Speech Lang Hear Res ;2019 (Oct 22):1-8.

Purpose We examined associations between vocal communication with canonical syllables and expressive language and then examined 2 potential alternative explanations for such associations. Method Specifically, we tested whether the associations remained when excluding canonical syllables in identifiable words and controlling for the number of communication acts. Participants included 68 preverbal or low verbal children with autism spectrum disorder (M age = 35.26 months). Results Vocal communication with canonical syllables and expressive language were concurrently and longitudinally associated with moderate to strong (R (2)s = .13-.70) and significant (ps < .001) effect sizes. Even when excluding spoken words from the vocal predictor and controlling for the number of communication acts, vocal communication with canonical syllables predicted expressive language. Conclusions The findings provide increased support for measuring vocal communication with canonical syllables and for examining a causal relation between vocal communication with canonical syllables and expressive language in children with ASD who are preverbal or low verbal. In future studies, it may be unnecessary to eliminate identifiable words when measuring vocal communication in this population. Following replication, vocal communication with canonical syllables may be considered when making intervention- planning decisions.

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12. Raatikainen V, Korhonen V, Borchardt V, Huotari N, Helakari H, Kananen J, Raitamaa L, Joskitt L, Loukusa S, Hurtig T, Ebeling H, Uddin LQ, Kiviniemi V. Dynamic lag analysis reveals atypical brain information flow in autism spectrum disorder. Autism Res ;2019 (Oct 22)

This study investigated whole-brain dynamic lag pattern variations between neurotypical (NT) individuals and individuals with autism spectrum disorder (ASD) by applying a novel technique called dynamic lag analysis (DLA). The use of 3D magnetic resonance encephalography data with repetition time = 100 msec enables highly accurate analysis of the spread of activity between brain networks. Sixteen resting-state networks (RSNs) with the highest spatial correlation between NT individuals (n = 20) and individuals with ASD (n = 20) were analyzed. The dynamic lag pattern variation between each RSN pair was investigated using DLA, which measures time lag variation between each RSN pair combination and statistically defines how these lag patterns are altered between ASD and NT groups. DLA analyses indicated that 10.8% of the 120 RSN pairs had statistically significant (P-value <0.003) dynamic lag pattern differences that survived correction with surrogate data thresholding. Alterations in lag patterns were concentrated in salience, executive, visual, and default-mode networks, supporting earlier findings of impaired brain connectivity in these regions in ASD. 92.3% and 84.6% of the significant RSN pairs revealed shorter mean and median temporal lags in ASD versus NT, respectively. Taken together, these results suggest that altered lag patterns indicating atypical spread of activity between large-scale functional brain networks may contribute to the ASD phenotype. Autism Res 2019. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY : Autism spectrum disorder (ASD) is characterized by atypical neurodevelopment. Using an ultra-fast neuroimaging procedure, we investigated communication across brain regions in adults with ASD compared with neurotypical (NT) individuals. We found that ASD individuals had altered information flow patterns across brain regions. Atypical patterns were concentrated in salience, executive, visual, and default-mode network areas of the brain that have previously been implicated in the pathophysiology of the disorder.

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13. Ramirez-Santana GM, Acosta-Rodriguez VM, Hernandez-Expostio S. A comparative study of language phenotypes in Autism Spectrum Disorder and Specific Language Impairment. Psicothema ;2019 (Nov) ;31(4):437-442.

BACKGROUND : Problems with communication and language are among the main characteristics of both Autism Spectrum Disorder (ASD) and Specific Language Impairment (SLI). The main objective of the present study was to analyze whether the two disorders have similar formal language profiles. METHOD : The study involved three groups of 20 students each, divided into ASD, SLI, and Control, of similar ages and IQ. The CELF-4 standardized test was administered to assess their language skills. RESULTS : No significant differences in language were found between the SLI and ASD groups, with no effect sizes. Differences were observed between the SLI and ASD groups when they were compared separately with the Control group, with a large effect size. CONCLUSIONS : There is an overlap in the linguistic profiles of children with SLI and children with ASD. Similarity is thus confirmed in comprehensive and expressive language, as well as in morphosyntactic and lexical-semantic production.

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14. Reddihough DS, Marraffa C, Mouti A, O’Sullivan M, Lee KJ, Orsini F, Hazell P, Granich J, Whitehouse AJO, Wray J, Dossetor D, Santosh P, Silove N, Kohn M. Effect of Fluoxetine on Obsessive-Compulsive Behaviors in Children and Adolescents With Autism Spectrum Disorders : A Randomized Clinical Trial. Jama ;2019 (Oct 22) ;322(16):1561-1569.

Importance : Selective serotonin receptor inhibitors are prescribed to reduce the severity of core behaviors of autism spectrum disorders, but their efficacy remains uncertain. Objective : To determine the efficacy of fluoxetine for reducing the frequency and severity of obsessive-compulsive behaviors in autism spectrum disorders. Design, Setting, and Participants : Multicenter, randomized, placebo-controlled clinical trial. Participants aged 7.5-18 years with autism spectrum disorders and a total score of 6 or higher on the Children’s Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorder (CYBOCS-PDD) were recruited from 3 tertiary health centers across Australia. Enrollment began November 2010 and ended April 2017. Follow-up ended August 2017. Interventions : Participants were randomized to receive fluoxetine (n = 75) or placebo (n = 71). Study medication was commenced at 4 or 8 mg/d for the first week, depending on weight, and then titrated to a maximum dose of 20 or 30 mg/d over 4 weeks. Treatment duration was 16 weeks. Main Outcomes and Measures : The primary outcome was the total score on the CYBOCS-PDD (scores range from 0-20 ; higher scores indicate higher levels of maladaptive behaviors ; minimal clinically important difference, 2 points) at 16 weeks postrandomization, analyzed with a linear regression model adjusted for stratification factors (site, age at baseline, and intellectual disability), with an additional prespecified model that included additional adjustment for baseline score, sex, communication level, and imbalanced baseline and demographic variables. Results : Among the 146 participants who were randomized (85% males ; mean age, 11.2 years), 109 completed the trial ; 31 in the fluoxetine group and 21 in the placebo group dropped out or did not complete treatment. The mean CYBOCS-PDD score from baseline to 16 weeks decreased in the fluoxetine group from 12.80 to 9.02 points (3.72-point decrease ; 95% CI, -4.85 to -2.60) and in the placebo group from 13.13 to 10.89 points (2.53-point decrease ; 95% CI, -3.86 to -1.19). The between-group mean difference at 16 weeks was -2.01 (95% CI, -3.77 to -0.25 ; P = .03) (adjusted for stratification factors), and in the prespecified model with further adjustment, it was -1.17 (95% CI, -3.01 to 0.67 ; P = .21). Conclusions and Relevance : In this preliminary study of children and adolescents with autism spectrum disorders, treatment with fluoxetine compared with placebo resulted in significantly lower scores for obsessive-compulsive behaviors at 16 weeks. Interpretation is limited by the high dropout rate, null findings of prespecified analyses that accounted for potentially confounding factors and baseline imbalances, and CIs for the treatment effect that included the minimal clinically important difference. Trial Registration : anzctr.org.au Identifier : ACTRN12608000173392.

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15. Tsilioni I, Patel AB, Pantazopoulos H, Berretta S, Conti P, Leeman SE, Theoharides TC. IL-37 is increased in brains of children with autism spectrum disorder and inhibits human microglia stimulated by neurotensin. Proc Natl Acad Sci U S A ;2019 (Oct 22) ;116(43):21659-21665.

Autism spectrum disorder (ASD) does not have a distinct pathogenesis or effective treatment. Increasing evidence supports the presence of immune dysfunction and inflammation in the brains of children with ASD. In this report, we present data that gene expression of the antiinflammatory cytokine IL-37, as well as of the proinflammatory cytokines IL-18 and TNF, is increased in the amygdala and dorsolateral prefrontal cortex of children with ASD as compared to non-ASD controls. Gene expression of IL-18R, which is a receptor for both IL-18 and IL-37, is also increased in the same brain areas of children with ASD. Interestingly, gene expression of the NTR3/sortilin receptor is reduced in the amygdala and dorsolateral prefrontal cortex. Pretreatment of cultured human microglia from normal adult brains with human recombinant IL-37 (1 to 100 ng/mL) inhibits neurotensin (NT)-stimulated secretion and gene expression of IL-1beta and CXCL8. Another key finding is that NT, as well as the proinflammatory cytokines IL-1beta and TNF increase IL-37 gene expression in cultured human microglia. The data presented here highlight the connection between inflammation and ASD, supporting the development of IL-37 as a potential therapeutic agent of ASD.

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16. van Leeuwen TM, van Petersen E, Burghoorn F, Dingemanse M, van Lier R. Autistic traits in synaesthesia : atypical sensory sensitivity and enhanced perception of details. Philos Trans R Soc Lond B Biol Sci ;2019 (Dec 9) ;374(1787):20190024.

In synaesthetes, specific sensory stimuli (e.g. black letters) elicit additional experiences (e.g. colour). Synaesthesia is highly prevalent among individuals with autism spectrum disorder (ASD), but the mechanisms of this co-occurrence are not clear. We hypothesized autism and synaesthesia share atypical sensory sensitivity and perception. We assessed autistic traits, sensory sensitivity and visual perception in two synaesthete populations. In Study 1, synaesthetes (N = 79, of different types) scored higher than non-synaesthetes (N = 76) on the Attention-to-detail and Social skills subscales of the autism spectrum quotient indexing autistic traits, and on the Glasgow Sensory Questionnaire indexing sensory hypersensitivity and hyposensitivity which frequently occur in autism. Synaesthetes performed two local/global visual tasks because individuals with autism typically show a bias towards detail processing. In synaesthetes, elevated motion coherence thresholds (MCTs) suggested reduced global motion perception, and higher accuracy on an embedded figures task suggested enhanced local perception. In Study 2, sequence-space synaesthetes (N = 18) completed the same tasks. Questionnaire and embedded figures results qualitatively resembled Study 1 results, but no significant group differences with non-synaesthetes (N = 20) were obtained. Unexpectedly, sequence-space synaesthetes had reduced MCTs. Altogether, our studies suggest atypical sensory sensitivity and a bias towards detail processing are shared features of synaesthesia and ASD. This article is part of the discussion meeting issue ’Bridging senses : novel insights from synaesthesia’.

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17. Wagels L, Schneider I, Menke S, Ponge AK, Kohn N, Schneider F, Habel U. Autism and Reactions to Provocation in a Social and Non-social Context. J Autism Dev Disord ;2019 (Oct 22)

Externalizing behaviors in individuals with autism spectrum disorder (ASD) are often either reduced or elevated compared to healthy controls (HCs). This study investigated the moderating role of context in ASD by comparing 32 individuals with ASD to 40 HCs during a social and a non-social provocation task. Compared to HCs, individuals with ASD showed similar externalizing behavior in the social context. In the non-social context reactions after provocation were enhanced relative to non-provoking situations. The findings implicate that the context is an important influencing variable when comparing individuals with ASD to HCs after being provoked. Impulsivity, trait aggression and empathy did not predict behavior in the ASD group but were partly related to observed behavior in HCs.

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18. Whiteley P, Carr K, Shattock P. Is Autism Inborn And Lifelong For Everyone ?. Neuropsychiatr Dis Treat ;2019 ;15:2885-2891.

Autism or autism spectrum disorder (ASD) is described as a lifelong condition with core behavioural symptoms appearing during infancy or early childhood. Genetic and other effects occurring during the earliest times of life are thought to play a significant contributory role to the presentation of autism, denoting that autism is typically seen as an innate or inborn condition. Such descriptions have, and continue to, define autism research and clinical practice. Inspection of the existing research literature, however, suggests that within the vast heterogeneity of autism, not everyone experiences autism in such a prescribed way. Various reports have observed the presentation of "acquired autism" following a period of typical development. Other findings have documented an abatement of clinically relevant autistic features and related comorbid pathology for some. Such reports offer important insights into the heterogeneity and complexity of autism.

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