1. New Autism Genes Identified in Largest Study to Date. American journal of medical genetics Part A. 2023; 191(1): 8-9.

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2. Anderson-Chavarria M, Turner J. Searching for the ‘Trigger’: An ethnographic analysis of parental beliefs regarding autism causation and vaccination in Puerto Rico. Vaccine. 2022.

This study examines the personal beliefs held by parents of autistic children in Puerto Rico regarding the cause of their child’s autism and how these beliefs may influence parental vaccination decision-making. This study seeks to contribute towards diversifying the autism literature by focusing on an autism community living in a relatively lower income, resource-deficit context. These findings expand our understandings of how parents of autistic children may perceive vaccines and how these perceptions are informed by various sources of knowledge. This ethnographic research study was conducted between May 2017 and August 2019. Methods included 350+ hours of participant-observation and semi-structured interviewing of 35 Puerto Rican parents of autistic children. 32 of these 35 parents interviewed believed autism to be the result of genetic risks that are ‘triggered’ by an unknown environmental factor. Suggested ‘triggers’ included various environmental contaminants and vaccinations. The subject of vaccination came up in every interview; 18 interviewed parents did not believe vaccines ‘triggered’ autism, 3 parents attributed their child’s autism entirely to vaccines, while 14 considered vaccines to be one of several possible ‘triggers’. It is important to note that no parents interviewed perceived vaccinations to be inherently or universally harmful. Rather, they perceived vaccinations to be one of many possible ‘triggers’ for a child predisposed to develop autism. In some cases, this perception prompted parents to oppose mandatory vaccination policies on the island. Parents shared nuanced, complex understandings of autism causation that may carry implications for COVID-19 vaccine uptake within the Puerto Rican autistic community.

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3. Davidovitch M, Gazit S, Patalon T, Leitner Y, Rotem RS. Late diagnosis of autism spectrum disorder-Journey, parents’ concerns, and sex influences. Autism research : official journal of the International Society for Autism Research. 2022.

Despite increasing awareness for diagnosing autism spectrum disorder (ASD) and initiating treatments early in life, many children and adolescents continue to be diagnosed at a relatively older age. Focusing on children who first received an ASD diagnosis at age six or older, this study aimed to describe the symptoms that parents reported when ASD was diagnosed, follow the patients’ clinical trajectory prior to receiving the diagnosis, and describe differences in symptoms and prior diagnoses between males and females cases. We included 258 children (205 males and 53 females) who were first diagnosed with autism at age 6-18 in 2017-2018. We retrieved demographic information, neurologic and developmental symptoms, diagnoses, and medications dispensing history from the children’s electronic medical charts. The data indicated that prior diagnoses of language delays and attention deficit hyperactivity disorder were common among children with a late ASD diagnosis. Two thirds of the children were prescribed one or more medications to treat psychosocial and behavioral conditions before receiving a late ASD diagnosis. Difficulties in social relationships with peers were the leading reported symptoms by parents at the time of ASD diagnosis. Across these different domains, some differences were found between males and females, including a somewhat higher cognitive level in males, who were also more likely to present aggressive behavior.

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4. Demchick BB, Flanagan J, Li CY, Cassidy R, Golding J. Early Indicators of Autism in Infants: Development of the IMES Screening Tool. OTJR : occupation, participation and health. 2022: 15394492221134910.

We developed the Infant, Motor, and Engagement Scale (IMES) to address the public health goal of early identification of autism spectrum disorder (ASD). The IMES is a screening tool that assesses quality of infants’ interaction with people and objects during early play. We aimed to examine the IMES’ preliminary psychometric properties and its value in discriminating between infants later diagnosed with ASD and typically developing infants. We used the IMES to score retrospective home videos of 15 male infants, 7 who were later diagnosed with autism. We examined interrater reliability using Cohen’s Kappa, internal consistency with Cronbach’s alpha and content validity through expert review. Preliminary data support validity and reliability of the IMES for early identification for infants at 6 to 9 months. With further research, the IMES has the potential to identify at risk infants at a young age that may have long-term impact on child and family outcomes.

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5. Giulivi C, Wang JY, Hagerman RJ. Artificial neural network applied to fragile X-associated tremor/ataxia syndrome stage diagnosis based on peripheral mitochondrial bioenergetics and brain imaging outcomes. Scientific reports. 2022; 12(1): 21382.

No proven prognosis is available for the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Artificial neural network analyses (ANN) were used to predict FXTAS progression using data from 127 adults (noncarriers and FMR1 premutation carriers with and without FXTAS) with five outcomes from brain MRI imaging and 22 peripheral bioenergetic outcomes from two cell types. Diagnosis accuracy by ANN predictions ranged from 41.7 to 86.3% (depending on the algorithm used), and those misclassified usually presented a higher FXTAS stage. ANN prediction of FXTAS stages was based on a combination of two imaging findings (white matter hyperintensity and whole-brain volumes adjusted for intracranial volume) and four bioenergetic outcomes. Those at Stage 3 vs. 0-2 showed lower mitochondrial mass, higher oxidative stress, and an altered electron transfer consistent with mitochondrial unfolded protein response activation. Those at Stages 4-5 vs. 3 had higher oxidative stress and glycerol-3-phosphate-linked ATP production, suggesting that targeting mGPDH activity may prevent a worse prognosis. This was confirmed by the bioenergetic improvement of inhibiting mGPDH with metformin in affected fibroblasts. ANN supports the prospect of an unbiased molecular definition in diagnosing FXTAS stages while identifying potential targets for personalized medicine.

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6. Laidi C, Neu N, Watilliaux A, Martinez-Teruel A, Razafinimanana M, Boisgontier J, Hotier S, d’Albis MA, Delorme R, Amestoy A, Holiga Š, Moal ML, Coupé P, Leboyer M, Houenou J, Rondi-Reig L, Paradis AL. Preserved navigation abilities and spatio-temporal memory in individuals with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2022.

Cerebellar abnormalities have been reported in autism spectrum disorder (ASD). Beyond its role in hallmark features of ASD, the cerebellum and its connectivity with forebrain structures also play a role in navigation. However, the current understanding of navigation abilities in ASD is equivocal, as is the impact of the disorder on the functional anatomy of the cerebellum. In the present study, we investigated the navigation behavior of a population of ASD and typically developing (TD) adults related to their brain anatomy as assessed by structural and functional MRI at rest. We used the Starmaze task, which permits assessing and distinguishing two complex navigation behaviors, one based on allocentric learning and the other on egocentric learning of a route with multiple decision points. Compared to TD controls, individuals with ASD showed similar exploration, learning, and strategy performance and preference. In addition, there was no difference in the structural or functional anatomy of the cerebellar circuits involved in navigation between the two groups. The findings of our work suggest that navigation abilities, spatio-temporal memory, and their underlying circuits are preserved in individuals with ASD.

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7. Louros SR, Seo SS, Maio B, Martinez-Gonzalez C, Gonzalez-Lozano MA, Muscas M, Verity NC, Wills JC, Li KW, Nolan MF, Osterweil EK. Excessive proteostasis contributes to pathology in fragile X syndrome. Neuron. 2022.

In fragile X syndrome (FX), the leading monogenic cause of autism, excessive neuronal protein synthesis is a core pathophysiology; however, an overall increase in protein expression is not observed. Here, we tested whether excessive protein synthesis drives a compensatory rise in protein degradation that is protective for FX mouse model (Fmr1(-/y)) neurons. Surprisingly, although we find a significant increase in protein degradation through ubiquitin proteasome system (UPS), this contributes to pathological changes. Normalizing proteasome activity with bortezomib corrects excessive hippocampal protein synthesis and hyperactivation of neurons in the inferior colliculus (IC) in response to auditory stimulation. Moreover, systemic administration of bortezomib significantly reduces the incidence and severity of audiogenic seizures (AGS) in the Fmr1(-/y) mouse, as does genetic reduction of proteasome, specifically in the IC. Together, these results identify excessive activation of the UPS pathway in Fmr1(-/y) neurons as a contributor to multiple phenotypes that can be targeted for therapeutic intervention.

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8. Pillai RLI, Covington M, Visintainer PF, Branch HJ. Association of autism with lead poisoning in an environmental health clinic. Pediatric research. 2022.

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9. Schmitt LM, Li J, Liu R, Horn PS, Sweeney JA, Erickson CA, Pedapati EV. Altered frontal connectivity as a mechanism for executive function deficits in fragile X syndrome. Molecular autism. 2022; 13(1): 47.

BACKGROUND: Fragile X syndrome (FXS) is the leading inherited monogenic cause of intellectual disability and autism spectrum disorder. Executive function (EF), necessary for adaptive goal-oriented behavior and dependent on frontal lobe function, is impaired in individuals with FXS. Yet, little is known how alterations in frontal lobe neural activity is related to EF deficits in FXS. METHODS: Sixty-one participants with FXS (54% males) and 71 age- and sex-matched typically-developing controls (TDC; 58% males) completed a five-minute resting state electroencephalography (EEG) protocol and a computerized battery of tests of EF, the Test of Attentional Performance for Children (KiTAP). Following source localization (minimum-norm estimate), we computed debiased weighted phase lag index (dWPLI), a phase connectivity value, for pairings between 18 nodes in frontal regions for gamma (30-55 Hz) and alpha (10.5-12.5 Hz) bands. Linear models were generated with fixed factors of group, sex, frequency, and connection. Relationships between frontal connectivity and EF variables also were examined. RESULTS: Individuals with FXS demonstrated increased gamma band and reduced alpha band connectivity across all frontal regions and across hemispheres compared to TDC. After controlling for nonverbal IQ, increased error rates on EF tasks were associated with increased gamma band and reduced alpha band connectivity. LIMITATIONS: Frontal connectivity findings are limited to intrinsic brain activity during rest and may not generalize to frontal connectivity during EF tasks or everyday function. CONCLUSIONS: We report gamma hyper-connectivity and alpha hypo-connectivity within source-localized frontal brain regions in FXS compared to TDC during resting-state EEG. For the first time in FXS, we report significant associations between EF and altered frontal connectivity, with increased error rate relating to increased gamma band connectivity and reduced alpha band connectivity. These findings suggest increased phase connectivity within gamma band may impair EF performance, whereas greater alpha band connectivity may provide compensatory support for EF. Together, these findings provide important insight into neurophysiological mechanisms of EF deficits in FXS and provide novel targets for treatment development.

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10. Singh AP, Jain VS, Yu JJ. Diffusion radiomics for subtyping and clustering in autism spectrum disorder: A preclinical study. Magnetic resonance imaging. 2023; 96: 116-25.

Autism spectrum disorder (ASD) is a highly prevalent, heterogenous neurodevelopmental disorder. Neuroimaging methods such as functional, structural, and diffusion MRI have been used to identify candidate imaging biomarkers for ASD, but current findings remain non-specific and likely arise from the heterogeneity present in ASD. To account for this, efforts to subtype ASD have emerged as a potential strategy for both the study of ASD and advancement of tailored behavioral therapies and therapeutics. Towards these ends, to improve upon current neuroimaging methods, we propose combining biologically sensitive neurite orientation dispersion and density index (NODDI) diffusion MR imaging with radiomics image processing to create a new methodological approach that, we hypothesize, can sensitively and specifically capture neurobiology. We demonstrate this method can sensitively distinguish differences between four genetically distinct rat models of ASD (Fmr1, Pten, Nrxn1, Disc1). Further, we demonstrate diffusion radiomic analyses hold promise for subtyping in ASD as we show unsupervised clustering of NODDI radiomic data generates clusters specific to the underlying genetic differences between the animal models. Taken together, our findings suggest the unique application of radiomic analysis on NODDI diffusion MRI may have the capacity to sensitively and specifically disambiguate the neurobiological heterogeneity present in the ASD population.

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11. Tao J, Hao R, Guo YT, Zhang W. [Characteristics of visual function in children with autism complicated with mental retardation]. [Zhonghua yan ke za zhi] Chinese journal of ophthalmology. 2022; 58(12): 1051-7.

Objective: To explore the characteristics of visual function and eye diseases in children with autism spectrum disorder (ASD) and mental retardation. Methods: It was a cross-sectional study. Two hundred and ninety-two cases (584 eyes) of children with ASD combined with mental retardation from 7 special education schools in Chaoyang District of Beijing, including 235 males (80.48%) and 57 females (19.52%); The age ranged from 2 to 18 years old. Subjective far and near vision, near stereoacuity, objective vision, diopter, anterior segment and fundus were examined. In addition, 300 students with normal intelligence level, aged 2 to 18 years, were included as controls. LogMAR was used to record vision examination. Subjective, objective vision and diopter were examined. Mann Whitney U test or Kruskal Wallis H test was used for the data of children with different genders, different age. Results: Among 584 eyes of children with ASD and mental retardation, 272 eyes (47.22%) were ametropia, 260 eyes (45.14%) were astigmatism, 29 eyes (5.03%) were hyperopia, 10 eyes (1.74%) were myopia, and 47 eyes (8.16%) were amblyopia risk factors. Among 292 children, there were 20 cases of strabismus (6.85%), 3 cases of color weakness (1.03%), and 4 cases of external eye abnormalities (1.37%). Two hundred and eleven children completed near stereopsis examination, of which 54 (25.59%) were within 100″ and 157 (74.41%) were within 200″ to 900″. Two hundred and seventy-two eyes with ametropia, 157 eyes (57.72%) needed correction but did not. The median and quartile of subjective and objective logMAR visual acuity were 0.22(0.10, 0.35), 0.10(0.00, 0.22), respectively; There were no significant differences in far visual acuity, near visual acuity, objective visual acuity, diopter, and near stereoacuity between different genders of ASD children with mild or moderate mental retardation (all P>0.05); There was a statistically significant difference in ASD children with mild mental retardation at different age rangs (H=21.453, P<0.001). There was a statistically significant difference in subjective tests such as far visual acuity and near visual acuity, for children with moderate mental retardation (Z=-3.508, -4.503; P<0.001). There was no statistically significant difference in objective visual acuity, diopter and near stereo acuity(all P>0.05). There are 300 healthy children as the control group, with LogMar’s subjective far vision is 0.10(0.00, 0.22), and the objective vision is 0.00(0.00, 0.10), diopter 0.25 (-0.25, 0.50) D. Compared with healthy children, ASD children with mental retardation had a significant difference in subjective far vision and objective vision (Z=-8.527, -10.393; P<0.001). There was no significant difference in diopter (Z=-1.274, P=0.203). Conclusions: The subjective and objective visual acuity of children with ASD combined with mental retardation was lower than that of healthy children. The prevalence and uncorrected rate of refractive errors, strabismus, amblyopia and other eye diseases were significantly higher than those of healthy children. Their refractive errors were mainly astigmatism, and the rates of correction and treatment were low.

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12. Yang J, Shen Y, Tian Y, Peng J, Fu X, Li Y, Ou J. Investigating and comparing the psychometric properties of the Chinese Mandarin version of social responsiveness scale-2 and its shortened version in preschool-age children with autism spectrum disorder. Asian journal of psychiatry. 2022; 79: 103395.

We aimed to investigate and compare the psychometric properties of the Chinese Mandarin Social Responsiveness Scale-2 (SRS-2) and its shortened version. The study assessed 670 children with autism spectrum disorder (ASD) aged 30-54 months and 138 typical developmental (TD) children of the same age in mainland China. Our item reliability test revealed that only 36 items of the 65 items in the Chinese Mandarin SRS-2 (Preschool) met the reliability criteria. Moreover, the shortened version of SRS-2 (Preschool) with four subscales and 30 items maintained strong correlations (r = 0.961) with the Chinese Mandarin SRS-2 (Preschool), and demonstrated improved psychometric performance on the 4-week test-retest reliability (intraclass correlations was 0.70), internal consistency (Cronbach’s alpha 0.71-0.91), construct validity, and convergent validity with the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview-Revised, and Child Behavior Checklist. Receiver operating characteristics (ROC) analyses showed excellent and comparable discriminant validity of the shortened version with an area under the curve of 0.992. Our data suggested a cutoff ≥ 22.5 for the shortened version, with good accuracy in screening autism symptoms (sensitivity=96.9 %, specificity=94.2 %). Our findings demonstrated that the shortened version of SRS-2 (Preschool) was a reliable and valid instrument for identifying preschoolers with ASD in mainland China.

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