1. Bhalla S, Mehan S. 4-hydroxyisoleucine mediated IGF-1/GLP-1 signalling activation prevents propionic acid-induced autism-like behavioural phenotypes and neurochemical defects in experimental rats. Neuropeptides. 2022; 96: 102296.

Autism is a neuropsychiatric disorder characterized by a neurotransmitter imbalance that impairs neurodevelopment processes. Autism development is marked by communication difficulties, poor socio-emotional health, and cognitive impairment. Insulin-like growth factor-1 (IGF-1) and glucagon-like growth factor-1 (GLP-1) are responsible for regular neuronal growth and homeostasis. Autism progression has been linked to dysregulation of IGF-1/GLP-1 signalling. 4-hydroxyisoleucine (HI), a pharmacologically active amino acid produced from Trigonella foenum graecum, works as an insulin mimic and has neuroprotective properties. The GLP-1 analogue liraglutide (LRG) was employed in our investigation to compare the efficacy of 4-HI in autism prevention. The current study explores the protective effects of 4-HI 50 and 100 mg/kg orally on IGF-1/GLP-1 signalling activation in a PPA-induced experimental model of autism. Propionic acid (PPA) injections to rats by intracerebroventricular (ICV) route for the first 11 days of the experiment resulted in autism-like neurobehavioral, neurochemical, gross morphological, and histopathological abnormalities. In addition, we investigated the dose-dependent neuroprotective effects of 4-HI on the levels of several neurotransmitters and neuroinflammatory cytokines in rat brain homogenate and blood plasma. Neuronal apoptotic and anti-oxidant cellular markers were also studied in blood plasma and brain homogenate samples. Furthermore, the luxol fast blue (LFB) staining results demonstrated significant demyelination in the brains of PPA-induced rats reversed by 4-HI treatment. Rats were assessed for spontaneous locomotor impairments, neuromuscular coordination, stress-like behaviour, learning, and memory to assess neurobehavioral abnormalities. The administration of 4-HI and LRG significantly reversed the behavioural, gross and histological abnormalities in the PPA-treated rat brains. After treatment with 4-HI and LRG, LFB-stained photomicrographs of PPA-treated rats’ brains demonstrated the recovery of white matter loss. Our findings indicate that 4-HI protects neurons in rats with autism by enhancing the IGF-1 and GLP-1 protein levels.

Lien vers le texte intégral (Open Access ou abonnement)

2. Campi E, Choi E, Chen YJ, Holland CM, Bristol S, Sideris J, Crais ER, Watson LR, Baranek GT. Sensory Reactivity of Infants at Elevated Likelihood of Autism and Associations with Caregiver Responsiveness. Journal of autism and developmental disorders. 2022: 1-10.

Infants at elevated likelihood of developing autism display differences in sensory reactivity, especially hyporeactivity, as early as 7 months of age, potentially contributing to a developmental cascade of autism symptoms. Caregiver responsiveness, which has been linked to positive social communication outcomes, has not been adequately examined with regard to infant sensory reactivity. This study examined the multiplicative impact of infant sensory hypo- and hyperreactivity on caregiver responsiveness to sensory reactivity and regulation cues in 43 infants at elevated likelihood of autism. Sensory hyperreactivity was found to moderate the association between sensory hyporeactivity and caregiver responsiveness, such that caregivers of infants with moderately high sensory hypo- and hyperreactivity demonstrated higher responsiveness.

Lien vers le texte intégral (Open Access ou abonnement)

3. Chan AJS, Engchuan W, Reuter MS, Wang Z, Thiruvahindrapuram B, Trost B, Nalpathamkalam T, Negrijn C, Lamoureux S, Pellecchia G, Patel RV, Sung WWL, MacDonald JR, Howe JL, Vorstman J, Sondheimer N, Takahashi N, Miles JH, Anagnostou E, Tammimies K, Zarrei M, Merico D, Stavropoulos DJ, Yuen RKC, Fernandez BA, Scherer SW. Genome-wide rare variant score associates with morphological subtypes of autism spectrum disorder. Nature communications. 2022; 13(1): 6463.

Defining different genetic subtypes of autism spectrum disorder (ASD) can enable the prediction of developmental outcomes. Based on minor physical and major congenital anomalies, we categorize 325 Canadian children with ASD into dysmorphic and nondysmorphic subgroups. We develop a method for calculating a patient-level, genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD have a significantly higher GRVS compared to those with nondysmorphic ASD (P = 0.03). Using the polygenic transmission disequilibrium test, we observe an over-transmission of ASD-associated common variants in nondysmorphic ASD probands (P = 2.9 × 10(-3)). These findings replicate using WGS data from 442 ASD probands with accompanying morphology data from the Simons Simplex Collection. Our results provide support for an alternative genomic classification of ASD subgroups using morphology data, which may inform intervention protocols.

Lien vers le texte intégral (Open Access ou abonnement)

4. Díaz-Agea JL, Macías-Martínez N, Leal-Costa C, Girón-Poves G, García-Méndez JA, Jiménez-Ruiz I. What can be improved in learning to care for people with autism? A qualitative study based on clinical nursing simulation. Nurse education in practice. 2022; 65: 103488.

AIM/OBJECTIVE: The aim of this study was to identify the main patterns of errors that 4th year nursing students made in simulated clinical practice with scenarios of care for people with Autism Spectrum Disorder (ASD). BACKGROUND: Clinical simulation currently plays a major role in the training of nursing students and provides the participants with the opportunity to practice and develop their clinical sills with a pediatric patient diagnosed with ASD. DESIGN: A retrospective longitudinal qualitative study was performed. METHODS: Content analysis of the existing debriefing records from a period of 7 academic years (2016-2022) was carried out. The scenario was simulated by a standardized patient diagnosed with ASD, with 23 groups of nursing students. RESULTS: The results showed different patterns of errors. These patterns were grouped into 1 main category (weaknesses) and 5 major subcategories: clinical, communication, knowledge about ASD, emotions, and behavior towards parents. The most repeated errors were excessive use of verbal communication, abundant stimuli, low demand for information from primary caregivers, low demand for information about the child’s emotions and interests, and a lack of knowledge of the profile of the child with ASD. CONCLUSION: From the findings of this study, we can highlight the lack of training that students received on the practical approach for providing care to these individuals. It has also been inferred in this study that clinical simulation is a tool that favors reflection and experiential learning for students when they are faced with caring for people with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

5. Green J. Autism as emergent and transactional. Frontiers in psychiatry. 2022; 13: 988755.

The current epistemology of autism as a phenotype derives from the consistency of historical accounts and decades of work within the tradition of descriptive epidemiology, culminating in current categorical descriptions within DSM and ICD nosologies and the concept of « prototypical autism. » The demonstrated high heritability of this phenotype has led to an essentialist theory of autism as a biological entity and the concerted search within the developmental brain and genetic science for discrete biological markers. This search has not revealed simple markers explaining autistic outcomes and has led to moves towards a more dimensional account. This article proposes an alternative transactional approach. It proposes to understand autistic states as an emergent property within a complex developmental system; as the neurodivergent brain, and mind and body, encounter their social and physical environment within early development. Key evidence in support of this approach comes from random allocation intervention trials based on such transactional development theory, both in the infancy pre-diagnostic prodrome and the early post-diagnostic period. In replicated evidence, these intervention trials show that a targeted alteration in the quality of social transactional environment available for the child leads to significant, predictable, and sustained alterations in the outcome dimensional autistic phenotype over time; and further, in one prodromal trial, to a significant reduction in later categorical classification status. The inference from this evidence is that the prototypical autistic phenotype is to a degree malleable with a changed experienced social environment and that it is emergent from its constituent traits. Such a transactional approach enlarges our notion of the phenotype and brings the study of autism within mainstream individual difference developmental science. It challenges essentialist views, for instance as to intrinsic autistic « social avoidance » or theory of mind empathy deficits, integrates dimensional and categorical perspectives, and is consistent with the lived experience of autistic people and their advocacy for improved understanding within a social model.

Lien vers le texte intégral (Open Access ou abonnement)

6. Hogan AL, Winston M, Barstein J, Losh M. Slower Peak Pupillary Response to Emotional Faces in Parents of Autistic Individuals. Frontiers in psychology. 2022; 13: 836719.

BACKGROUND: Atypical autonomic arousal has been consistently documented in autism spectrum disorder (ASD) and is thought to contribute to the social-communication phenotype of ASD. Some evidence suggests that clinically unaffected first-degree relatives of autistic individuals may also show subtle differences in indices of autonomic arousal, potentially implicating heritable pathophysiological mechanisms in ASD. This study examined pupillary responses in parents of autistic individuals to investigate evidence that atypical autonomic arousal might constitute a subclinical physiological marker of ASD heritability within families of autistic individuals. METHODS: Pupillary responses to emotional faces were measured in 47 ASD parents and 20 age-matched parent controls. Macro-level pupillary responses (e.g., mean, peak, latency to peak) and dynamic pupillary responses over the course of the stimulus presentation were compared between groups, and in relationship to subclinical ASD-related features in ASD parents. A small ASD group (n = 20) and controls (n = 17) were also included for exploratory analyses of parent-child correlations in pupillary response. RESULTS: Parents of autistic individuals differed in the time course of pupillary response, exhibiting a later primary peak response than controls. In ASD parents, slower peak response was associated with poorer pragmatic language and larger peak response was associated with poorer social cognition. Exploratory analyses revealed correlations between peak pupillary responses in ASD parents and mean and peak pupillary responses in their autistic children. CONCLUSION: Differences in pupillary responses in clinically unaffected parents, together with significant correlations with ASD-related features and significant parent-child associations, suggest that pupillary responses to emotional faces may constitute an objective physiological marker of ASD genetic liability, with potential to inform the mechanistic underpinnings of ASD symptomatology.

Lien vers le texte intégral (Open Access ou abonnement)

7. Janz P, Bainier M, Marashli S, Schoenenberger P, Valencia M, Redondo RL. Neurexin1α knockout rats display oscillatory abnormalities and sensory processing deficits back-translating key endophenotypes of psychiatric disorders. Translational psychiatry. 2022; 12(1): 455.

Neurexins are presynaptic transmembrane proteins crucial for synapse development and organization. Deletion and missense mutations in all three Neurexin genes have been identified in psychiatric disorders, with mutations in the NRXN1 gene most strongly linked to schizophrenia (SZ) and autism spectrum disorder (ASD). While the consequences of NRXN1 deletion have been extensively studied on the synaptic and behavioral levels, circuit endophenotypes that translate to the human condition have not been characterized yet. Therefore, we investigated the electrophysiology of cortico-striatal-thalamic circuits in Nrxn1α^-/- rats and wildtype littermates focusing on a set of translational readouts, including spontaneous oscillatory activity, auditory-evoked oscillations and potentials, as well as mismatch negativity-like (MMN) responses and responses to social stimuli. On the behavioral level Nrxn1α^-/- rats showed locomotor hyperactivity. In vivo freely moving electrophysiology revealed pronounced increases of spontaneous oscillatory power within the gamma band in all studied brain areas and elevation of gamma coherence in cortico-striatal and thalamocortical circuits of Nrxn1α^-/- rats. In contrast, auditory-evoked oscillations driven by chirp-modulated tones showed reduced power in cortical areas confined to slower oscillations. Finally, Nrxn1α^-/- rats exhibited altered auditory evoked-potentials and profound deficits in MMN-like responses, explained by reduced prediction error. Despite deficits for auditory stimuli, responses to social stimuli appeared intact. A central hypothesis for psychiatric and neurodevelopmental disorders is that a disbalance of excitation-to-inhibition is underlying oscillatory and sensory deficits. In a first attempt to explore the impact of inhibitory circuit modulation, we assessed the effects of enhancing tonic inhibition via δ-containing GABA_A receptors (using Gaboxadol) on endophenotypes possibly associated with network hyperexcitability. Pharmacological experiments applying Gaboxadol showed genotype-specific differences, but failed to normalize oscillatory or sensory processing abnormalities. In conclusion, our study revealed endophenotypes in Nrxn1α^-/- rats that could be used as translational biomarkers for drug development in psychiatric disorders.

Lien vers le texte intégral (Open Access ou abonnement)

8. Kaba D, Çelik ZY. 3q29 microdeletion syndrome associated with developmental delay and pulmonary stenosis: a case report. The Turkish journal of pediatrics. 2022; 64(5): 925-31.

BACKGROUND: 3q29 microdeletion syndrome (OMIM 609425), first described in 2005, is a rare copy number variation (CNV), accompanied by various neurodevelopmental and psychiatric problems. Phenotypic features of the syndrome have not been fully characterized due to the new definition and rarity. Facial dysmorphology, musculoskeletal anomalies, cardiovascular abnormalities, gastrointestinal abnormalities, and dental abnormalities can be seen. CASE: A 28-month-old male patient was brought to the child and adolescent psychiatry clinic with a complaint of speech delay. He had mild dysmorphic symptoms. He was also sensitive to voice and often covered his ears. Balloon valvuloplasty was performed on the postnatal 28th day due to severe pulmonary stenosis. While karyotype was found to be normal, in array-Comparative genomic hybridization (aCGH), copy loss was detected in the long arm of chromosome 3 (arr[hg19] 3q29[196,209,689-197,601,344]x1), which contains approximately 1.4 Mb harboring 30 genes. Genetic counseling was given to the family of the patient who was diagnosed with 3q29 microdeletion syndrome. CONCLUSIONS: In conclusion, we present 3q29 microdeletion syndrome with global developmental delay (GDD), dysmorphic face, hyperacusis, scoliosis, and severe pulmonary stenosis. Performing genetic analysis in patients with developmental delay and congenital heart disease (CHD) for which the cause cannot be explained will prevent these rare diseases from being missed, and the characteristics of the diseases will be better characterized with the reported cases.

Lien vers le texte intégral (Open Access ou abonnement)

9. Lavallée A, Dumitriu D. Low Risk of Neurodevelopmental Impairment in the COVID-19 Generation Should Not Make Researchers Complacent. JAMA network open. 2022; 5(10): e2238958.

Lien vers le texte intégral (Open Access ou abonnement)

10. Lu M, Pang F, Wang R, Liu Y, Peng T. The association between autistic traits and excessive smartphone use in Chinese college students: The chain mediating roles of social interaction anxiety and loneliness. Research in developmental disabilities. 2022; 131: 104369.

This study draws upon a large sample of Chinese college students to examine the chain mediating roles of social interaction anxiety and loneliness in the relation between autistic traits and excessive smartphone use. To test our hypothesis that social interaction anxiety and loneliness mediate the relation between autistic traits and excessive smartphone use, we recruited a sample of 1103 college students and asked them to complete an assessment that measured the degrees of autistic traits, social interaction anxiety, loneliness, and excessive smartphone use. The results showed significant correlations among these variables. More autistic traits, which are correlated with higher levels of social interaction anxiety and higher levels of loneliness, were found to be associated with excessive smartphone use. In conclusion, this study highlights the need for screening for excessive smartphone use among college students who demonstrate autistic traits. Social interaction anxiety and loneliness show great potential in screening for excessive smartphone use among college students with high levels of autistic traits. We discuss the practical implications of the findings and directions for future study.

Lien vers le texte intégral (Open Access ou abonnement)

11. Mungmunpuntipantip R, Wiwanitkit V. COVID-19 Vaccines for Children with Developmental Disabilities: Correspondence. Journal of developmental and behavioral pediatrics : JDBP. 2022.

Lien vers le texte intégral (Open Access ou abonnement)

12. Naples AJ, Foss-Feig JH, Wolf JM, Srihari VH, McPartland JC. Predictability modulates neural response to eye contact in ASD. Molecular autism. 2022; 13(1): 42.

BACKGROUND: Deficits in establishing and maintaining eye-contact are early and persistent vulnerabilities of autism spectrum disorder (ASD), and the neural bases of these deficits remain elusive. A promising hypothesis is that social features of autism may reflect difficulties in making predictions about the social world under conditions of uncertainty. However, no research in ASD has examined how predictability impacts the neural processing of eye-contact in naturalistic interpersonal interactions. METHOD: We used eye tracking to facilitate an interactive social simulation wherein onscreen faces would establish eye-contact when the participant looked at them. In Experiment One, receipt of eye-contact was unpredictable; in Experiment Two, receipt of eye-contact was predictable. Neural response to eye-contact was measured via the N170 and P300 event-related potentials (ERPs). Experiment One included 23 ASD and 46 typically developing (TD) adult participants. Experiment Two included 25 ASD and 43 TD adult participants. RESULTS: When receipt of eye-contact was unpredictable, individuals with ASD showed increased N170 and increased, but non-specific, P300 responses. The magnitude of the N170 responses correlated with measures of sensory and anxiety symptomology, such that increased response to eye-contact was associated with increased symptomology. However, when receipt of eye-contact was predictable, individuals with ASD, relative to controls, exhibited slower N170s and no differences in the amplitude of N170 or P300. LIMITATIONS: Our ASD sample was composed of adults with IQ > 70 and included only four autistic women. Thus, further research is needed to evaluate how these results generalize across the spectrum of age, sex, and cognitive ability. Additionally, as analyses were exploratory, some findings failed to survive false-discovery rate adjustment. CONCLUSIONS: Neural response to eye-contact in ASD ranged from attenuated to hypersensitive depending on the predictability of the social context. These findings suggest that the vulnerabilities in eye-contact during social interactions in ASD may arise from differences in anticipation and expectation of eye-contact in addition to the perception of gaze alone.

Lien vers le texte intégral (Open Access ou abonnement)

13. Preethy S, Raghavan K, Ikewaki N, Abraham SJ. Qualitative Evaluation of α-Synuclein – A Critical Step in Unraveling the Complexities of Autism Spectrum Disorder. Medical principles and practice : international journal of the Kuwait University, Health Science Centre. 2022.

α-synuclein is a widely studied biomarker in neurodevelopmental disorders such as autism spectrum disorder (ASD) and neurodegenerative diseases (termed synucleinopathies), including Alzheimer’s disease (AD), Parkinson’s disease (PD), dementia with Lewy bodies (DLBs), and multiple system atrophy. There are conflicting reports on the levels of α-synuclein in children with ASD compared to normal matched controls, with some reporting increased plasma levels and others decreased levels. Al-Mazidi, S., et al have reported that plasma Levels of α-synuclein in ASD is an indicator of disease severity. We go a step further in extrapolating that it is more important to qualitatively evaluate the α-synuclein based on its conformation for better understanding of disease mechanisms and planning treatment strategies. This is inferred from studies that have reported increase in plasma levels of α-synuclein in ASD after supplementation with beta glucans with beneficial effects on sleep and behaviour pattern in these children.

Lien vers le texte intégral (Open Access ou abonnement)

14. Rooney T, Stern YS, Hampton LH, Grauzer J, Hobson A, Levin A, Jones MK, Kaat AJ, Roberts MY. Screening for Autism in 2-Year-Old Children: The Application of the Systematic Observation of Red Flags to the Screening Tool for Autism in Toddlers and Young Children. American journal of speech-language pathology. 2022; 31(6): 2759-69.

PURPOSE: A multimeasure approach was developed to capitalize on the strengths of two screening measures: the Screening Tool for Autism in Toddlers and Young Children (STAT), an observational measure of social communication, and the Systematic Observation of Red Flags (SORF), a checklist including restricted and repetitive behavior (RRB) items. This approach offers a novel method of identifying autism in toddlers. METHOD: This was a retrospective study of data collected from a multidisciplinary diagnostic program for 24- to 36-month-olds with developmental delays. Raters with autism expertise but naïve to diagnoses applied the SORF to STAT videos. Psychometrics were derived for the SORF on STAT observations and a multiple-measure approach that used a Least Absolute Shrinkage and Selection Operator modeling framework to construct a STAT-SORF RRB Hybrid, retaining SORF RRB items based on individual predictive abilities. RESULTS: The SORF alone correctly classified 84% of the sample (84% sensitivity and 86% specificity). The STAT-SORF RRB Hybrid model, which retained four SORF RRB items, correctly classified 90% of a validation sample (95% sensitivity and 75% specificity). CONCLUSION: These findings highlight the potential utility of using multiple autism identification tools and regression-based scoring to establish presumptive eligibility and facilitate early access to autism interventions.

Lien vers le texte intégral (Open Access ou abonnement)

15. Scheerer NE, Pourtousi A, Yang C, Ding Z, Stojanoski B, Anagnostou E, Nicolson R, Kelley E, Georgiades S, Crosbie J, Schachar R, Ayub M, Stevenson RA. Transdiagnostic Patterns of Sensory Processing in Autism and ADHD. Journal of autism and developmental disorders. 2022.

Sensory processing abilities are highly variable within and across people diagnosed with autism and attention-deficit/hyperactivity disorder (ADHD). This study examined the transdiagnostic nature of sensory processing abilities, and their association with features of autism and ADHD, in a large sample of autistic people (n = 495) and people with ADHD (n = 461). Five similar data-driven sensory phenotypes characterized sensory processing abilities, and showed similar patterns of association with features of autism and ADHD, across both diagnostic groups. These results demonstrate the transdiagnostic nature of sensory processing abilities, while contributing to a growing body of literature that suggests the autism and ADHD diagnostic labels have poor explanatory power.

Lien vers le texte intégral (Open Access ou abonnement)

16. Shivaswamy T, Souza RR, Engineer CT, McIntyre CK. Vagus Nerve Stimulation as a Treatment for Fear and Anxiety in Individuals with Autism Spectrum Disorder. Journal of psychiatry and brain science. 2022; 7(4).

Anxiety disorders affect a large percentage of individuals who have an autism spectrum disorder (ASD). In children with ASD, excessive anxiety is also linked to gastrointestinal problems, self-injurious behaviors, and depressive symptoms. Exposure-based cognitive behavioral therapies are effective treatments for anxiety disorders in children with ASD, but high relapse rates indicate the need for additional treatment strategies. This perspective discusses evidence from preclinical research, which indicates that vagus nerve stimulation (VNS) paired with exposure to fear-provoking stimuli and situations could offer benefits as an adjuvant treatment for anxiety disorders that coexist with ASD. Vagus nerve stimulation is approved for use in the treatment of epilepsy, depression, and more recently as an adjuvant in rehabilitative training following stroke. In preclinical models, VNS shows promise in simultaneously enhancing consolidation of extinction memories and reducing anxiety. In this review, we will present potential mechanisms by which VNS could treat fear and anxiety in ASD. We also discuss potential uses of VNS to treat depression and epilepsy in the context of ASD, and noninvasive methods to stimulate the vagus nerve.

Lien vers le texte intégral (Open Access ou abonnement)

17. Wilkinson EH, Britton TC, Hall SS. Examining Phenotypic Differences in Gaze Avoidance Between Autism Spectrum Disorder and Fragile X Syndrome. American journal on intellectual and developmental disabilities. 2022; 127(6): 435-54.

We examined potential phenotypic differences in eye gaze avoidance exhibited by boys with autism spectrum disorder (ASD) and boys with fragile X syndrome (FXS). In Study 1, the Eye Contact Avoidance Scale (ECAS) was administered to caregivers of boys aged 7-18 years with FXS (n = 148), ASD (n = 168), and mixed developmental disabilities (MDD; n = 128). In Study 2, subsets of boys with FXS (n = 31) and boys with ASD (n = 25) received a brief behavioral treatment probe to improve eye contact. Results showed that boys with FXS obtained significantly higher scores on the ECAS compared to boys with ASD and MDD. Exposure to the brief behavioral treatment probe resulted in significant decreases in scores for boys with FXS, but not for boys with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

18. Won H, Huguet G, Jacquemont S. Rare and common autism risk variants converge across 16p. Nature genetics. 2022; 54(11): 1587-8.

Lien vers le texte intégral (Open Access ou abonnement)