1. Albers J, Kraja G, Eller D, Eck K, McBrian D, Bain JM. Assessing the Feasibility of Using the Ketogenic Diet in Autism Spectrum Disorder. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2022.

Evidence demonstrating efficacy of dietary interventions for autism spectrum disorder (ASD) remains inconsistent. Recent research on the ketogenic diet (KD) for the treatment of ASD has suggested benefit. Children with ASD often demonstrate ritualized food specific behaviors, taste and texture aversions, and an increased prevalence of food restrictions and allergies. There is a need to investigate how these features contribute to initiation and adherence of the KD. Two surveys were administered to assess the feasibility of utilizing the KD for ASD. First, paper surveys were given to caregivers of children presenting to outpatient neurology clinics. Next, experienced clinicians were recruited and surveyed online using Redcap. χ(2) analysis was used to compare ASD and non ASD caregiver responses. Descriptive metrics were used to present clinician responses. Responses to each question were evaluated individually. This article is protected by copyright. All rights reserved.

Lien vers le texte intégral (Open Access ou abonnement)

2. Alusi G, Berry-Kravis E, Nelson D, Orefice LL, Booker SA. Emerging Therapeutic Strategies for Fragile X Syndrome: Q&A. ACS chemical neuroscience. 2022; 13(24): 3544-6.

Understanding how best to treat aspects of Fragile X syndrome has the potential to improve the quality of life of affected individuals. Such an effective therapy has, as yet, remained elusive. In this article, we ask those researching or affected by Fragile X syndrome their views on the current state of research and from where they feel the most likely therapy may emerge.

Lien vers le texte intégral (Open Access ou abonnement)

3. 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.

Lien vers le texte intégral (Open Access ou abonnement)

4. Antezana L, Coffman MC, DiCriscio AS, Richey JA. Effects of nonsocial and circumscribed interest images on neural mechanisms of emotion regulation in autistic adults. Frontiers in behavioral neuroscience. 2022; 16: 1057736.

INTRODUCTION: Emotion dysregulation is commonly reported among autistic individuals. Prior work investigating the neurofunctional mechanisms of emotion regulation (ER) in autistic adults has illustrated alterations in dorsolateral prefrontal cortex (dlPFC) activity, as well as concurrent atypical patterns of activation in subcortical regions related to affect during cognitive reappraisal of social images. Whereas most research examining ER in autism has focused on regulation of negative emotions, the effects of regulating positive emotions has been generally understudied. This is surprising given the relevance of positive motivational states to understanding circumscribed interests (CI) in autism. METHODS: Accordingly, the purpose of this study was to use fMRI with simultaneous eye-tracking and pupillometry to investigate the neural mechanisms of ER during passive viewing and cognitive reappraisal of a standardized set of nonsocial images and personalized (self-selected) CI images. RESULTS: The autistic group demonstrated comparatively reduced modulation of posterior cingulate cortex (PCC) activation during cognitive reappraisal of CI images compared to viewing of CI, although no eye-tracking/pupillometry differences emerged between-groups. Further, the autistic group demonstrated increased PCC connectivity with left lateral occipital and right supramarginal areas when engaging in cognitive reappraisal vs. viewing CI. DISCUSSION: In autistic adults, CI may be differentially modulated via PCC. Considering the documented role of the PCC as a core hub of the default mode network, we further postulate that ER of CI could potentially be related to self-referential cognition.

Lien vers le texte intégral (Open Access ou abonnement)

5. Byström K, Wrangsjö B, Grahn P. COMSI(®)-A Form of Treatment That Offers an Opportunity to Play, Communicate and Become Socially Engaged through the Lens of Nature-A Single Case Study about an 8-Year-Old Boy with Autism and Intellectual Disability. International journal of environmental research and public health. 2022; 19(24).

This case study shows how an 8-year-old boy with autism and mild intellectual disability underwent positive psychological development in terms of play, social communication, and mentalization during a year and a half of group-based therapy using COMSI(®)-(COMmunication and Social Interaction). This eclectic treatment has a relational approach and is based on developmental psychology, knowledge of autism, and the impact of nature and animals on human health. The change in the child was been studied using both quantitative and qualitative methods. His general intellectual capacity was measured using the Wechler Preschool and Primary Scale of Intelligence, and his Mentalization Ability/Theory of Mind was assessed using three tests: Eva and Anna, Hiding the fruit and Kiki and the cat. Throughout the study period, change was documented with the help of the therapists’ process notes and the parents’ descriptions. The results show that support for the child comes from three different sources: nature, animals, and the therapists. Animals and nature form the basis for episodes of coordinated attention in conversation and play with therapists. The therapists’ approach used sensitivity and compliance with the child’s needs and focus of interest.

Lien vers le texte intégral (Open Access ou abonnement)

6. Collins BE, Neul JL. Rett Syndrome and MECP2 Duplication Syndrome: Disorders of MeCP2 Dosage. Neuropsychiatric disease and treatment. 2022; 18: 2813-35.

Rett syndrome (RTT) is a neurodevelopmental disorder caused predominantly by loss-of-function mutations in the gene Methyl-CpG-binding protein 2 (MECP2), which encodes the MeCP2 protein. RTT is a MECP2-related disorder, along with MECP2 duplication syndrome (MDS), caused by gain-of-function duplications of MECP2. Nearly two decades of research have advanced our knowledge of MeCP2 function in health and disease. The following review will discuss MeCP2 protein function and its dysregulation in the MECP2-related disorders RTT and MDS. This will include a discussion of the genetic underpinnings of these disorders, specifically how sporadic X-chromosome mutations arise and manifest in specific populations. We will then review current diagnostic guidelines and clinical manifestations of RTT and MDS. Next, we will delve into MeCP2 biology, describing the dual landscapes of methylated DNA and its reader MeCP2 across the neuronal genome as well as the function of MeCP2 as a transcriptional modulator. Following this, we will outline common MECP2 mutations and genotype-phenotype correlations in both diseases, with particular focus on mutations associated with relatively mild disease in RTT. We will also summarize decades of disease modeling and resulting molecular, synaptic, and behavioral phenotypes associated with RTT and MDS. Finally, we list several therapeutics in the development pipeline for RTT and MDS and available evidence of their safety and efficacy.

Lien vers le texte intégral (Open Access ou abonnement)

7. Demerdzieva A, Pop-Jordanova N. An Overview of Pediatric Approaches to Child with Developmental Delay Especially if There is Suspicion of ASD in First Few Years of Life. Prilozi (Makedonska akademija na naukite i umetnostite Oddelenie za medicinski nauki). 2022; 43(3): 43-53.

To be a pediatrician means that one encounters many serious childhood health problems and one finds many ways to help families cope with these problems. Symptoms in children can be discrete, and the responsibility of the pediatrician to distinguish normal development from pathological. We are facing a new era in the developmental assessment of children. A cluster of neurodevelopmental disorders includes ASD (autism spectrum disorder) and ADHD (attention deficit hyperactivity disorder). Parents often do not recognize the problem on time. Generally, their first concern is speech delay, leading to the suspicion of hearing problems. Therefore, it is very important to obtain objective anamnestic information and for the child to undergo a careful physical examination, a neurophysiological assessment, and metabolic and genetic testing. The etiology usually is multifactorial: genetic, epigenetic, and non-genetic factors act in combination through various paths. Most children seem to have typical neurodevelopment during first their year. It was found that approximately one-third of children with ASD lose some skills during the preschool period, usually speech related, but sometimes also non-verbal communication, social or play skills. In conclusion we must say that it is very important to recognize the early signs of ASD and any kind of other developmental delay and to start with early intervention. Clinical pediatricians tend to correlate clinical manifestations and biological underpinnings related to neurodevelopmental disorder, especially ASD. Therefore, better treatment possibilities are needed.

Lien vers le texte intégral (Open Access ou abonnement)

8. Derguy C, Aubé B, Rohmer O, Loyal D. Evaluation of teachers’ knowledge and attitudes regarding the school inclusion of autistic children: Validation of a brief assessment toolkit. The British journal of educational psychology. 2022.

BACKGROUND: Teachers’ level of knowledge regarding autism and their attitudes towards inclusion are major levers for the successful schooling of autistic students. However, there are currently insufficient validated tools for evaluating these two concepts among teachers that are adapted to the French context and to the constraints of the classroom setting. AIMS: This study was designed to test both the validity of The Autism Knowledge Screening Scale (AKSS) and of the Autism Attitude Scale for Teachers (AAST) among French teachers. SAMPLE: Our final sample consisted of 307 French teachers (50.5% primary school teachers and 49.5% secondary school teachers). METHODS: First, confirmatory factor analyses were conducted to test the two initial factor structures and an exploratory factor analysis was conducted regarding the AKSS. Second, criterion validity was assessed for each of the two scales. RESULTS: Concerning knowledge of autism, a two-factor model (8 items) explaining 53% of the variance was observed. The first factor represented knowledge about aetiology and the second represented knowledge about symptoms. Concerning attitudes towards autism, a one-factor model (14 items) exhibited good model fit (χ (2) /df = 1.71, RMSEA = .048, AGFI = .979, SRMR = .068, CFI = .987, NNFI = .984). As expected, participants who were specialized teachers, had training, and a high degree of contact with autism had more knowledge (regarding aetiology but not regarding symptoms) and more positive attitudes. CONCLUSIONS: This study validated two quick-to-use tools for making an initial diagnosis of teachers’ knowledge and attitudes regarding the school inclusion of autistic children. The use of these tools could help to fine-tune the content of training programs for teachers and test their efficacy, particularly in France where the inclusion of autistic children is still far from international standards.

Lien vers le texte intégral (Open Access ou abonnement)

9. Elhefnawei DM, Mahmoud AH, Kadry MO, Al-Mokaddem AK, Badawy MA, El-Desouky MA. Calcium voltage-gated channel subunit alpha 1 C and glial fibrillary acidic protein signaling pathways as a selective biomarker in predicting the efficacy of liposomal loaded co-enzyme Q in the autistic rat model. Toxicology reports. 2023; 10: 17-26.

Autism spectrum disorder (ASD) is an extreme neuropsychotic disturbance with both environmental and genetic origins. Sodium propionate (PPA) a metabolic bioproduct of gut microbiota is well-thought-out as a successful autism animal model. Nevertheless, Liposomal drug delivery system possess the advantagous of biocompatibility, targeting organs, ability to carry large drug payloads and skipping macrophages for this purpose the current study was carried out to investigate the hypothesis that Calcium Voltage-Gated channel subunit alpha 1 C (CACNA1C) and glial fibrillary acidic protein (GFAP) signaling pathways crosstalk with the efficacy of Co-enzyme Q10 (Co-Q10) and liposomal loaded Co-enzyme Q10 (L Co-Q10) in PPA mediated autistic rat model. Autism was conducted by buffered PPA (500 mg/Kg b.wt) daily for 5 consecutive days subsequently treatment via Co-Q10 in a dose of (10 mg/kg b.wt) and L Co-Q10 (2 mg/kg b.wt) for four weeks then the autistic model was followed for signs of autism at different time intervals of (one, two and four weeks). The control, PPA intoxicated, and treated groups were subjected to behavioral tests (Y-Maze and open field), antioxidant analysis, gene expression analysis, and histological examination at different time intervals of the study. The results revealed that Co-Q10 and L Co-Q10 significantly elevated antioxidative stress biomarkers, comprising superoxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (TAC). In addition, they significantly ameliorated the oxidative stress biomarker malondialdehyde (MDA). Meanwhile, they significantly downregulated GFAP and CACNA1C mRNA gene expressions, Co-Q10 and LCo-Q10 showed improvement in almost brain regions post PPA histopathological alterations, even better results were manifested via LCo-Q10 groups. These results showed the superiority of LCo-Q10 over Co-Q10 in competing autism. In conclusion: The administration of anti-inflammatory and antioxidant agents such as Co-Q10 and L Co-Q10 may represent a promising strategy to counteract pathological behaviors in ASD model via targeting organs, increasing retention time, and reducing side effects.

Lien vers le texte intégral (Open Access ou abonnement)

10. Garrido D, Carballo G. Linguistic and motor profiles in preschool and school-age children with an older sibling with autism spectrum disorder. Journal of child language. 2022: 1-19.

This study examines receptive-expressive language, gross-fine motor skills, and IQ abilities in 78 children, 43 children with an older sibling with autism spectrum disorder (Sibs-ASD) and 35 children with an older sibling with typical development, ranging from 4 to 11 years of age. Depending on age, both groups were divided in preschool and school groups. The results show that more than 76% of Sibs-ASD performed at least one language and/or motor skill under 25th percentile. Significant differences were described at preschool stage in three aspects: grammatical comprehension, ball skills, and global motor skills. At school age, significant differences were found in two aspects: expressive language, and ball skills. Some differences seem to decrease over time; meanwhile others seem to increase; and others remain stable. Thus, it seems that vulnerability continues in unaffected Sibs-ASD and suggest that this population may benefit from continued screening and monitoring into the preschool and school-age stages.

Lien vers le texte intégral (Open Access ou abonnement)

11. Kaiser FMP, Gruenbacher S, Oyaga MR, Nio E, Jaritz M, Sun Q, van der Zwaag W, Kreidl E, Zopf LM, Dalm V, Pel J, Gaiser C, van der Vliet R, Wahl L, Rietman A, Hill L, Leca I, Driessen G, Laffeber C, Brooks A, Katsikis PD, Lebbink JHG, Tachibana K, van der Burg M, De Zeeuw CI, Badura A, Busslinger M. Correction: Biallelic PAX5 mutations cause hypogammaglobulinemia, sensorimotor deficits, and autism spectrum disorder. The Journal of experimental medicine. 2023; 220(1).

Lien vers le texte intégral (Open Access ou abonnement)

12. Norris JE, DeStefano LA, Schmitt LM, Pedapati EV, Erickson CA, Sweeney JA, Ethridge LE. Hemispheric Utilization of Alpha Oscillatory Dynamics as a Unique Biomarker of Neural Compensation in Females with Fragile X Syndrome. ACS chemical neuroscience. 2022; 13(23): 3389-402.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a trinucleotide expansion on the FMR1 gene and characterized by intellectual disability, sensory hypersensitivity, executive function difficulties, and social anxiety. Recently, efforts to define neural biomarkers for FXS have highlighted disruptions to power in the alpha frequency band; however the dynamic mechanisms supporting these findings are poorly understood. The current study aimed to explore the temporal and hemispheric dynamics supporting alpha phenotypes in FXS and their relationship with neural phenotypes related to auditory processing using electroencephalography during an auditory evoked task. Adolescents and adults (N = 36) with FXS and age/sex matched typically developing controls (N = 40) completed an auditory chirp task. Frontal alpha power in the prestimulus period was decomposed into « bursts » using percentile thresholding, then assessed for number of bursts per second (burst count) and burst length. Data were compared across left and right hemispheres to assess lateralization of neural activity. Individuals with FXS showed more differences in alpha power compared to TDC primarily in the right hemisphere. Notably, alpha hemisphere outcomes in males with FXS were driven by the number of times they entered a dynamically relevant period of alpha (burst count) rather than length of time spent in alpha. Females with FXS showed reduced burst counts but remained in sustained high alpha states for longer periods of time. Length of time spent in alpha may reflect a modulatory or compensatory mechanism capable of recovering sensory processing abilities in females with FXS resulting in a less severe clinical presentation. Right hemisphere abnormalities may impact sensory processing differences between males and females with FXS. The relationship between alpha burst length, count, sex, and hemisphere may shed light on underlying mechanisms for previously observed alpha power abnormalities in FXS and their variation by sex.

Lien vers le texte intégral (Open Access ou abonnement)

13. Parellada M, Andreu-Bernabeu Á, Burdeus M, San José Cáceres A, Urbiola E, Carpenter LL, Kraguljac NV, McDonald WM, Nemeroff CB, Rodriguez CI, Widge AS, State MW, Sanders SJ. In Search of Biomarkers to Guide Interventions in Autism Spectrum Disorder: A Systematic Review. The American journal of psychiatry. 2022: appiajp21100992.

OBJECTIVE: The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials. METHODS: A systematic review of MEDLINE, Embase, and Scopus was conducted in April 2020. Seven criteria were applied to focus on original research that includes quantifiable response biomarkers measured alongside ASD symptoms. Interventional studies or human studies that assessed the correlation between biomarkers and ASD-related behavioral measures were included. RESULTS: A total of 5,799 independent records yielded 280 articles for review that reported on 940 biomarkers, 755 of which were unique to a single publication. Molecular biomarkers were the most frequently assayed, including cytokines, growth factors, measures of oxidative stress, neurotransmitters, and hormones, followed by neurophysiology (e.g., EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly heterogeneous, including in phenotypes, demographic characteristics, tissues assayed, and methods for biomarker detection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify biomarkers with large effect sizes. Reporting of individual-level values and summary statistics was inconsistent, hampering mega- and meta-analysis. Biomarkers assayed in multiple studies yielded mostly inconsistent results, revealing a « replication crisis. » CONCLUSIONS: There is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review highlights methodological imperatives for ASD biomarker research necessary to make definitive progress: consistent experimental design, correction for multiple comparisons, formal replication, sharing of sample-level data, and preregistration of study designs. Systematic « big data » analyses of multiple potential biomarkers could accelerate discovery.

Lien vers le texte intégral (Open Access ou abonnement)

14. Pehlivanidis A, Papanikolaou K. Theophrastus’s « Anaisthetos » (« The Obtuse Man »): the oldest « phenomenological » description of neurodevelopmental disorders in an adult. Psychiatrike = Psychiatriki. 2022; 33(4): 310-6.

Theophrastus (381-278 B.C.), was the first to adopt the term character for the description of distinct inner psychological and moral features of an individual. In his classic book ‘Characters’ in a simple style wording he analyses some of his contemporary individuals. The character « Αναίσθητος » (Anaisthetos) has been translated in English as « The Obtuse Man » and in Modern Greek both as « Αναίσθητος », meaning lack of appreciation and « Βραδύνους », meaning slowness of mind. Theophrastus’ description of this particular character is compatible with the co-occurrence in an adult of two Neurodevelopmental Disorders: the Attention-Deficit Hyperactivity Disorder (ADHD) and the Social Pragmatic Communication Disorder (SPCD), according to the 5th Diagnostic and Statistical Manual of Mental Disorders. Ten out of the twelve statements support the possible occurrence of ADHD while five of them the occurrence of SPCD. The description does not justify a diagnosis of an intellectual disability; therefore, we consider that in the Modern Greek vocabulary the original term «Αναίσθητος» (« Anaisthetos »), meaning lack of appreciation, is more accurately corresponding to this particular Theophrastus’s character than « Βραδύνους » (« Obtuse »), which indicates the presence of low intellectual capacities. Also the lack of repetitive and restrictive interests and behaviours excludes Autism Spectrum Disorder as a possible diagnosis. Minor psychiatric disorders and traits according to the Peripatic School were attributed to the lack of rational control over appetites and behavior. Accordingly, «Αναίσθητος» is a phenomenological description of a stigmatizing inappropriate social behavior and the only help that might give is in increasing self-awareness. In our contemporary clinical practice, though, the early recognition and appropriate treatment of Neurodevelopmental Disorders in affected individuals, leads to a better clinical care and may diminish stigmatization. The co-existence of these two disorders in a character in such a different historical context reinforces their validity as diagnostic constructs and provides an example of co-occurrence of Neurodevelopmental Disorders.

Lien vers le texte intégral (Open Access ou abonnement)

15. Saraf TS, McGlynn RP, Bhatavdekar OM, Booth RG, Canal CE. FPT, a 2-Aminotetralin, Is a Potent Serotonin 5-HT(1A), 5-HT(1B), and 5-HT(1D) Receptor Agonist That Modulates Cortical Electroencephalogram Activity in Adult Fmr1 Knockout Mice. ACS chemical neuroscience. 2022; 13(24): 3629-40.

There are no approved medicines for fragile X syndrome (FXS), a monogenic, neurodevelopmental disorder. Electroencephalogram (EEG) studies show alterations in resting-state cortical EEG spectra, such as increased gamma-band power, in patients with FXS that are also observed in Fmr1 knockout models of FXS, offering putative biomarkers for drug discovery. Genes encoding serotonin receptors (5-HTRs), including 5-HT(1A), 5-HT(1B), and 5-HT(1D)Rs, are differentially expressed in FXS, providing a rationale for investigating them as pharmacotherapeutic targets. Previously we reported pharmacological activity and preclinical neurotherapeutic effects in Fmr1 knockout mice of an orally active 2-aminotetralin, (S)-5-(2′-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (FPT). FPT is a potent (low nM), high-efficacy partial agonist at 5-HT(1A)Rs and a potent, low-efficacy partial agonist at 5-HT(7)Rs. Here we report new observations that FPT also has potent and efficacious agonist activity at human 5-HT(1B) and 5-HT(1D)Rs. FPT’s K(i) values at 5-HT(1B) and 5-HT(1D)Rs were <5 nM, but it had nil activity (>10 μM K(i)) at 5-HT(1F)Rs. We tested the effects of FPT (5.6 mg/kg, subcutaneous) on EEG recorded above the somatosensory and auditory cortices in freely moving, adult Fmr1 knockout and control mice. Consistent with previous reports, we observed significantly increased relative gamma power in untreated or vehicle-treated male and female Fmr1 knockout mice from recordings above the left somatosensory cortex (LSSC). In addition, we observed sex effects on EEG power. FPT did not eliminate the genotype difference in relative gamma power from the LSSC. FPT, however, robustly decreased relative alpha power in the LSSC and auditory cortex, with more pronounced effects in Fmr1 KO mice. Similarly, FPT decreased relative alpha power in the right SSC but only in Fmr1 knockout mice. FPT also increased relative delta power, with more pronounced effects in Fmr1 KO mice and caused small but significant increases in relative beta power. Distinct impacts of FPT on cortical EEG were like effects caused by certain FDA-approved psychotropic medications (including baclofen, allopregnanolone, and clozapine). These results advance the understanding of FPT’s pharmacological and neurophysiological effects.

Lien vers le texte intégral (Open Access ou abonnement)

16. 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.

Lien vers le texte intégral (Open Access ou abonnement)

17. Staton A, Dawson D, Moghaddam N, McGrath B. Specificity and sensitivity of the social communication questionnaire lifetime screening tool for autism spectrum disorder in a UK CAMHS service. Clinical child psychology and psychiatry. 2022: 13591045221137196.

INTRODUCTION: The Social Communication Questionnaire is used to identify children and young people (CYP) who may require formal ASD assessment. However, there is a paucity of research on its utility in Children and Adolescent Mental Health Services. This evaluation aimed to determine the sensitivity and specificity of the Social Communication Questionnaire (SCQ) in a UK, Midlands CAMHS service. METHOD: Forty young people (mean age 13.75 years) were screened using the caregiver reported SCQ before completing ‘gold standard’ assessment. RESULTS: The SCQ had a sensitivity of 80% and a specificity of 25.7%. ROC curve analysis indicated low diagnostic accuracy. Differences in predictive accuracy of SCQ and diagnostic standard were statistically significant (p < 0.0001). CONCLUSION: This evaluation builds on previous research suggesting that the SCQ may not be an efficient screening tool in CAMHS settings.

Lien vers le texte intégral (Open Access ou abonnement)

18. Talesh Jafadideh A, Mohammadzadeh Asl B. Structural filtering of functional data offered discriminative features for autism spectrum disorder. PloS one. 2022; 17(12): e0277989.

This study attempted to answer the question, « Can filtering the functional data through the frequency bands of the structural graph provide data with valuable features which are not valuable in unfiltered data »?. The valuable features discriminate between autism spectrum disorder (ASD) and typically control (TC) groups. The resting-state fMRI data was passed through the structural graph’s low, middle, and high-frequency band (LFB, MFB, and HFB) filters to answer the posed question. The structural graph was computed using the diffusion tensor imaging data. Then, the global metrics of functional graphs and metrics of functional triadic interactions were computed for filtered and unfiltered rfMRI data. Compared to TCs, ASDs had significantly higher clustering coefficients in the MFB, higher efficiencies and strengths in the MFB and HFB, and lower small-world propensity in the HFB. These results show over-connectivity, more global integration, and decreased local specialization in ASDs compared to TCs. Triadic analysis showed that the numbers of unbalanced triads were significantly lower for ASDs in the MFB. This finding may indicate the reason for restricted and repetitive behavior in ASDs. Also, in the MFB and HFB, the numbers of balanced triads and the energies of triadic interactions were significantly higher and lower for ASDs, respectively. These findings may reflect the disruption of the optimum balance between functional integration and specialization. There was no significant difference between ASDs and TCs when using the unfiltered data. All of these results demonstrated that significant differences between ASDs and TCs existed in the MFB and HFB of the structural graph when analyzing the global metrics of the functional graph and triadic interaction metrics. Also, these results demonstrated that frequency bands of the structural graph could offer significant findings which were not found in the unfiltered data. In conclusion, the results demonstrated the promising perspective of using structural graph frequency bands for attaining discriminative features and new knowledge, especially in the case of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

19. Wilson JE. Transcranial direct current stimulation for children with autism spectrum disorder: Implications for school-based settings. Developmental medicine and child neurology. 2022.

Lien vers le texte intégral (Open Access ou abonnement)

20. Wolstencroft J, Mandy W, Skuse D. Mental health and neurodevelopment in children and adolescents with Turner syndrome. Women’s health (London, England). 2022; 18: 17455057221133635.

OBJECTIVES: Turner syndrome (TS) is a rare sex chromosome aneuploidy, with an incidence of four in 10,000 new-born girls. TS is often associated with impaired social communication skills, but the extent to which these are attributable to Autism Spectrum Disorders (ASD) is uncertain. We made standardized assessments of the mental health and associated neurodevelopmental disorders in children and adolescents with TS and report on the prevalence of concurrent conditions. METHODS: Our sample comprised 127 girls with TS, 5-19 years of age. We obtained reports of their mental health from a combination of diagnostic interview (the Development and Wellbeing Assessment (DAWBA)), from the Strengths and Difficulties Questionnaire (SDQ) and from the Social Responsiveness Scale (SRS-2). Sources of information included parents, teachers and self-reports. The prevalence of mental health disorders in this sample was compared with age/sex matched national English data from typical controls. RESULTS: Most individuals with TS (83%) had experienced significant social communication difficulties and nearly one in four (23%) met diagnostic criteria for ASD on the DAWBA. One-third (34%) had at least one mental health or neurodevelopmental condition, and those girls with an ASD were at a greater risk of a co-occurring emotional disorder and/or attention deficit hyperactivity disorder (ADHD). CONCLUSION: Children and adolescents with TS are substantially more likely to meet criteria for ASD than their typically developing peers. Our finding has clinical implications for appropriate behavioural management from preschool through to adolescence.

Lien vers le texte intégral (Open Access ou abonnement)

21. Xiao L, Jiang S, Wang Y, Gao C, Liu C, Huo X, Li W, Guo B, Wang C, Sun Y, Wang A, Feng Y, Wang F, Sun T. Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model. Journal of translational medicine. 2022; 20(1): 570.

BACKGROUND: Until now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder. METHODS: VPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1 week. (Day 0-7). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20 day spatial learning and cognitive rigidity test using IntelliCage on day 11. RESULTS: Deep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation. CONCLUSIONS: Autism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted.

Lien vers le texte intégral (Open Access ou abonnement)