1. Begum-Ali J, Gossé LK, Mason L, Pasco G, Charman T, Johnson MH, Jones EJH. Infant sleep predicts trajectories of social attention and later autism traits. J Child Psychol Psychiatry;2023 (Mar 29)

BACKGROUND: Children with neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often experience sleep disturbances, but little is known about when these sleep differences emerge and how they relate to later development. METHODS: We used a prospective longitudinal design in infants with a family history of ASD and/or ADHD to examine infant sleep and its relation to trajectories of attention and later neurodevelopmental disorders. We formed factors of Day and Night Sleep from parent-reported measures (including day/night sleep duration, number of naps in the day, frequency of night awakenings and sleep onset problems). We examined sleep in 164 infants at 5-, 10- and 14-months with/without a first-degree relative with ASD and/or ADHD who underwent a consensus clinical assessment for ASD at age 3. RESULTS: By 14-months, infants with a first-degree relative with ASD (but not ADHD) showed lower Night Sleep scores than infants with no family history of ASD; lower Night Sleep scores in infancy were also associated with a later ASD diagnosis, decreased cognitive ability, increased ASD symptomatology at 3-years, and developing social attention (e.g., looking to faces). We found no such effects with Day Sleep. CONCLUSIONS: Sleep disturbances may be apparent at night from 14-months in infants with a family history of ASD and also those with later ASD, but were not associated with a family history of ADHD. Infant sleep disturbances were also linked to later dimensional variation in cognitive and social skills across the cohort. Night Sleep and Social Attention were interrelated over the first 2 years of life, suggesting that this may be one mechanism through which sleep quality influences neurodevelopment. Interventions targeted towards supporting families with their infant’s sleep problems may be useful in this population.

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2. Black MH, Greenwood DL, Hwa JCC, Pivac J, Tang J, Clarke PJF. What Are You Worried About? Content and Extent of Worry in Autistic Adults. J Autism Dev Disord;2023 (Mar 29):1-15.

Autistic adults commonly experience anxiety and worry, although knowledge on how worry presents and the content, extent, and experiences among autistic adults is limited. A convergent parallel mixed-methods approach was used to explore the presentation and experiences of worry in autistic and non-autistic adults. Quantitative surveys were used to compare the content and extent of worry in autistic adults to non-autistic adults, with semi-structured interviews also conducted with autistic adults to gain a deeper understanding of the experiences, impacts and content of worry in autistic adults. Findings indicated that autistic adults demonstrated clinically significant levels of worry which were substantially higher than non-autistic adults. Autistic adults described worry as a cycle of negative thoughts impacting their daily life. Findings indicate that autistic adults may worry more than non-autistic adults, impacting on participation in activities of daily living, sleep, and mental health.

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3. Blume J, Dhanasekara CS, Kahathuduwa CN, Mastergeorge AM. Central Executive and Default Mode Networks: An Appraisal of Executive Function and Social Skill Brain-Behavior Correlates in Youth with Autism Spectrum Disorder. J Autism Dev Disord;2023 (Mar 29)

Atypical connectivity patterns have been observed for individuals with autism spectrum disorders (ASD), particularly across the triple-network model. The current study investigated brain-behavior relationships in the context of social skills and executive function profiles for ASD youth. We calculated connectivity measures from diffusion tensor imaging using Bayesian estimation and probabilistic tractography. We replicated prior structural equation modeling of behavioral measures with total default mode network (DMN) connectivity to include comparisons with central executive network (CEN) connectivity and CEN-DMN connectivity. Increased within-CEN connectivity was related to metacognitive strengths. Our findings indicate behavior regulation difficulties in youth with ASD may be attributable to impaired connectivity between the CEN and DMN and social skill difficulties may be exacerbated by impaired within-DMN connectivity.

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4. Colomar L, San José Cáceres A, Álvarez-Linera J, González-Peñas J, Huertas Patón A, Martín de Blas D, Polo Arrondo AP, Solís A, Jones E, Parellada M. Role of cortical excitatory/inhibitory imbalance in autism spectrum disorders from a symptom severity trajectories framework: a study protocol. BMC Psychiatry;2023 (Mar 29);23(1):213.

BACKGROUND: There is considerable evidence reporting an excitatory/inhibitory (E/I) cortical imbalance in autism spectrum disorders (ASD). However, previous findings on the direction of this imbalance and its relationship to ASD symptomatology are heterogeneous. Some factors contributing to these mixed results might be the methodological differences between studies assessing the E/I ratio and the intrinsic variability within the autistic spectrum. Studying the evolution of ASD symptoms and the factors that modulate it might help to explain and reduce this variability. Here we present a study protocol to explore the longitudinal role of E/I imbalance in ASD symptoms, combining different approaches to measure the E/I ratio and using the trajectories of symptom severity as a framework. METHODS: This observational two time-point prospective study assesses the E/I ratio and the evolution of the behavioural symptoms in a sample of at least 98 participants with ASD. Participants are enrolled at 12 to 72 months of age and followed from 18 to 48 months after. A comprehensive battery of tests is applied to evaluate ASD clinical symptoms. The E/I ratio is approached from electrophysiology, magnetic resonance, and genetics. We will calculate the individual change for the main ASD symptoms and, based on that, we will define the trajectories of symptom severity. Then, we will investigate the correlation between measures of excitation/inhibition balance and autistic symptomatology cross-sectionally, as well as the ability of these measurements to predict changes in symptoms over time. DISCUSSION: This study presents a robust multisystemic approach to the E/I imbalance theory in autism and its relation to divergent symptom trajectories. That setting will allow us to relate and compare the neurobiological information coming from different sources and its impact on behavioural symptoms while accounting for the high variability in ASD. The findings derived from this study could contribute to the ASD biomarkers research and might provide valuable evidence for the development of more personalized treatments in ASD.

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5. Cope EC, Wang SH, Waters RC, Gore IR, Vasquez B, Laham BJ, Gould E. Activation of the CA2-ventral CA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice. Nat Commun;2023 (Mar 29);14(1):1750.

Mutation or deletion of the SHANK3 gene, which encodes a synaptic scaffolding protein, is linked to autism spectrum disorder and Phelan-McDermid syndrome, conditions associated with social memory impairments. Shank3B knockout mice also exhibit social memory deficits. The CA2 region of the hippocampus integrates numerous inputs and sends a major output to the ventral CA1 (vCA1). Despite finding few differences in excitatory afferents to the CA2 in Shank3B knockout mice, we found that activation of CA2 neurons as well as the CA2-vCA1 pathway restored social recognition function to wildtype levels. vCA1 neuronal oscillations have been linked to social memory, but we observed no differences in these measures between wildtype and Shank3B knockout mice. However, activation of the CA2 enhanced vCA1 theta power in Shank3B knockout mice, concurrent with behavioral improvements. These findings suggest that stimulating adult circuitry in a mouse model with neurodevelopmental impairments can invoke latent social memory function.

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6. de Belen RA, Pincham H, Hodge A, Silove N, Sowmya A, Bednarz T, Eapen V. Eye-tracking correlates of response to joint attention in preschool children with autism spectrum disorder. BMC Psychiatry;2023 (Mar 29);23(1):211.

BACKGROUND: A number of differences in joint attention behaviour between children with autism spectrum disorder (ASD) and typically developing (TD) individuals have previously been documented. METHOD: We use eye-tracking technology to assess response to joint attention (RJA) behaviours in 77 children aged 31 to 73 months. We conducted a repeated-measures analysis of variance to identify differences between groups. In addition, we analysed correlations between eye-tracking and clinical measures using Spearman’s correlation. RESULTS: The children diagnosed with ASD were less likely to follow gaze compared to TD children. Children with ASD were less accurate at gaze following when only eye gaze information was available, compared to when eye gaze with head movement was observed. Higher accuracy gaze-following profiles were associated with better early cognition and more adaptive behaviours in children with ASD. Less accurate gaze-following profiles were associated with more severe ASD symptomatology. CONCLUSION: There are differences in RJA behaviours between ASD and TD preschool children. Several eye-tracking measures of RJA behaviours in preschool children were found to be associated with clinical measures for ASD diagnosis. This study also highlights the construct validity of using eye-tracking measures as potential biomarkers in the assessment and diagnosis of ASD in preschool children.

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7. Guneykaya D, Ugursu B, Logiacco F, Popp O, Almut Feiks M, Meyer N, Wendt S, Semtner M, Cherif F, Gauthier C, Madore C, Yin Z, Çınar Ö, Arslan T, Gerevich Z, Mertins P, Butovsky O, Kettenmann H, Wolf SA. Sex-Specific Microglia State in the Neuroligin-4 Knock-Out Mouse Model of Autism Spectrum Disorder. Brain Behav Immun;2023 (Mar 29)

Neuroligin-4 (NLGN4) loss-of-function mutations are associated with monogenic heritable autism spectrum disorder (ASD) and cause alterations in both synaptic and behavioral phenotypes. Microglia, the resident CNS macrophages, are implicated in ASD development and progression. Here we studied the impact of NLGN4 loss in a mouse model, focusing on microglia phenotype and function in both male and female mice. NLGN4 depletion caused lower microglia density, less ramified morphology, reduced response to injury and purinergic signaling specifically in the hippocampal CA3 region predominantly in male mice. Proteomic analysis revealed disrupted energy metabolism in male microglia and provided further evidence for sexual dimorphism in the ASD associated microglial phenotype. In addition, we observed impaired gamma oscillations in a sex-dependent manner. Lastly, estradiol application in male NLGN4(-/-) mice restored the altered microglial phenotype and function. Together, these results indicate that loss of NLGN4 affects not only neuronal network activity, but also changes the microglia state in a sex-dependent manner that could be targeted by estradiol treatment.

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8. Hardiansyah I, Nyström P, Taylor MJ, Bölte S, Ronald A, Falck-Ytter T. Global motion processing in infants’ visual cortex and the emergence of autism. Commun Biol;2023 (Mar 28);6(1):339.

Autism is a heritable and common neurodevelopmental condition, with behavioural symptoms typically emerging around age 2 to 3 years. Differences in basic perceptual processes have been documented in autistic children and adults. Specifically, data from many experiments suggest links between autism and alterations in global visual motion processing (i.e., when individual motion information is integrated to perceive an overall coherent pattern). Yet, no study has investigated whether a distinctive organization of global motion processing precede the emergence of autistic symptoms in early childhood. Here, using a validated infant electroencephalography (EEG) experimental paradigm, we first establish the normative activation profiles for global form, global motion, local form, and local motion in the visual cortex based on data from two samples of 5-month-old infants (total n = 473). Further, in a sample of 5-month-olds at elevated likelihood of autism (n = 52), we show that a different topographical organization of global motion processing is associated with autistic symptoms in toddlerhood. These findings advance the understanding of neural organization of infants’ basic visual processing, and its role in the development of autism.

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9. Kato Y, Shirai R, Ohbuchi K, Oizumi H, Yamamoto M, Miyata W, Iguchi T, Mimaki Y, Miyamoto Y, Yamauchi J. Hesperetin Ameliorates Inhibition of Neuronal and Oligodendroglial Cell Differentiation Phenotypes Induced by Knockdown of Rab2b, an Autism Spectrum Disorder-Associated Gene Product. Neurol Int;2023 (Mar 10);15(1):371-391.

Autism spectrum disorder (ASD) is a central nervous system (CNS) neurodevelopmental disorder that includes autism, pervasive developmental disorder, and Asperger’s syndrome. ASD is characterized by repetitive behaviors and social communication deficits. ASD is thought to be a multifactorial disorder with a range of genetic and environmental factors/candidates. Among such factors is the rab2b gene, although it remains unclear how Rab2b itself is related to the CNS neuronal and glial developmental disorganization observed in ASD patients. Rab2 subfamily members regulate intracellular vesicle transport between the endoplasmic reticulum and the Golgi body. To the best of our knowledge, we are the first to report that Rab2b positively regulates neuronal and glial cell morphological differentiation. Knockdown of Rab2b inhibited morphological changes in N1E-115 cells, which are often used as the neuronal cell differentiation model. These changes were accomplished with decreased expression levels of marker proteins in neuronal cells. Similar results were obtained for FBD-102b cells, which are used as the model of oligodendroglial cell morphological differentiation. In contrast, knockdown of Rab2a, which is another Rab2 family member not known to be associated with ASD, affected only oligodendroglial and not neuronal morphological changes. In contrast, treatment with hesperetin, a citrus flavonoid with various cellular protective effects, in cells recovered the defective morphological changes induced by Rab2b knockdown. These results suggest that knockdown of Rab2b inhibits differentiation in neuronal and glial cells and may be associated with pathological cellular phenotypes in ASD and that hesperetin can recover their phenotypes at the in vitro level at least.

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10. Knight EJ, Freedman EG, Myers EJ, Berruti AS, Oakes LA, Cao CZ, Molholm S, Foxe JJ. Severely Attenuated Visual Feedback Processing in Children on the Autism Spectrum. J Neurosci;2023 (Mar 29);43(13):2424-2438.

Individuals on the autism spectrum often exhibit atypicality in their sensory perception, but the neural underpinnings of these perceptual differences remain incompletely understood. One proposed mechanism is an imbalance in higher-order feedback re-entrant inputs to early sensory cortices during sensory perception, leading to increased propensity to focus on local object features over global context. We explored this theory by measuring visual evoked potentials during contour integration as considerable work has revealed that these processes are largely driven by feedback inputs from higher-order ventral visual stream regions. We tested the hypothesis that autistic individuals would have attenuated evoked responses to illusory contours compared with neurotypical controls. Electrophysiology was acquired while 29 autistic and 31 neurotypical children (7-17 years old, inclusive of both males and females) passively viewed a random series of Kanizsa figure stimuli, each consisting of four inducers that were aligned either at random rotational angles or such that contour integration would form an illusory square. Autistic children demonstrated attenuated automatic contour integration over lateral occipital regions relative to neurotypical controls. The data are discussed in terms of the role of predictive feedback processes on perception of global stimulus features and the notion that weakened « priors » may play a role in the visual processing anomalies seen in autism.SIGNIFICANCE STATEMENT Children on the autism spectrum differ from typically developing children in many aspects of their processing of sensory stimuli. One proposed mechanism for these differences is an imbalance in higher-order feedback to primary sensory regions, leading to an increased focus on local object features rather than global context. However, systematic investigation of these feedback mechanisms remains limited. Using EEG and a visual illusion paradigm that is highly dependent on intact feedback processing, we demonstrated significant disruptions to visual feedback processing in children with autism. This provides much needed experimental evidence that advances our understanding of the contribution of feedback processing to visual perception in autism spectrum disorder.

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11. Kreis I, Zhang L, Mittner M, Syla L, Lamm C, Pfuhl G. Aberrant uncertainty processing is linked to psychotic-like experiences, autistic traits, and is reflected in pupil dilation during probabilistic learning. Cogn Affect Behav Neurosci;2023 (Mar 28)

Aberrant belief updating due to misestimation of uncertainty and an increased perception of the world as volatile (i.e., unstable) has been found in autism and psychotic disorders. Pupil dilation tracks events that warrant belief updating, likely reflecting the adjustment of neural gain. However, whether subclinical autistic or psychotic symptoms affect this adjustment and how they relate to learning in volatile environments remains to be unraveled. We investigated the relationship between behavioral and pupillometric markers of subjective volatility (i.e., experience of the world as unstable), autistic traits, and psychotic-like experiences in 52 neurotypical adults with a probabilistic reversal learning task. Computational modeling revealed that participants with higher psychotic-like experience scores overestimated volatility in low-volatile task periods. This was not the case for participants scoring high on autistic-like traits, who instead showed a diminished adaptation of choice-switching behavior in response to risk. Pupillometric data indicated that individuals with higher autistic- or psychotic-like trait and experience scores differentiated less between events that warrant belief updating and those that do not when volatility was high. These findings are in line with misestimation of uncertainty accounts of psychosis and autism spectrum disorders and indicate that aberrancies are already present at the subclinical level.

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12. Mueller S, Decker L, Menge S, Ludolph AC, Freischmidt A. The Fragile X Protein Family in Amyotrophic Lateral Sclerosis. Mol Neurobiol;2023 (Mar 29)

The fragile X protein (FXP) family comprises the multifunctional RNA-binding proteins FMR1, FXR1, and FXR2 that play an important role in RNA metabolism and regulation of translation, but also in DNA damage and cellular stress responses, mitochondrial organization, and more. FMR1 is well known for its implication in neurodevelopmental diseases. Recent evidence suggests substantial contribution of this protein family to amyotrophic lateral sclerosis (ALS) pathogenesis. ALS is a highly heterogeneous neurodegenerative disease with multiple genetic and unclear environmental causes and very limited treatment options. The loss of motoneurons in ALS is still poorly understood, especially because pathogenic mechanisms are often restricted to patients with mutations in specific causative genes. Identification of converging disease mechanisms evident in most patients and suitable for therapeutic intervention is therefore of high importance. Recently, deregulation of the FXPs has been linked to pathogenic processes in different types of ALS. Strikingly, in many cases, available data points towards loss of expression and/or function of the FXPs early in the disease, or even at the presymptomatic state. In this review, we briefly introduce the FXPs and summarize available data about these proteins in ALS. This includes their relation to TDP-43, FUS, and ALS-related miRNAs, as well as their possible contribution to pathogenic protein aggregation and defective RNA editing. Furthermore, open questions that need to be addressed before definitively judging suitability of these proteins as novel therapeutic targets are discussed.

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13. Nitschke AS, do Valle HA, Vallance BA, Bickford C, Ip A, Lanphear N, Lanphear B, Weikum W, Oberlander TF, Hanley GE. Association between prenatal antibiotic exposure and autism spectrum disorder among term births: A population-based cohort study. Paediatr Perinat Epidemiol;2023 (Mar 28)

BACKGROUND: Prenatal antibiotic exposure induces changes in the maternal microbiome, which could influence the development of the infant’s microbiome-gut-brain axis. OBJECTIVES: We assessed whether prenatal antibiotic exposure is associated with an increased risk of autism spectrum disorder (ASD) in offspring born at term. METHODS: This population-based retrospective cohort study included everyone who delivered a live singleton-term infant in British Columbia, Canada between April 2000 and December 2014. Exposure was defined as filling antibiotic prescriptions during pregnancy. The outcome was an ASD diagnosis from the British Columbia Autism Assessment Network, with a follow-up to December 2016. To examine the association among pregnant individuals treated for the same indication, we studied a sub-cohort diagnosed with urinary tract infections. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios (HR). The analysis was stratified by sex, trimester, cumulative duration of exposure, class of antibiotic, and mode of delivery. We ran a conditional logistic regression of discordant sibling pairs to control for unmeasured environmental and genetic confounding. RESULTS: Of the 569,953 children included in the cohort, 8729 were diagnosed with ASD (1.5%) and 169,922 were exposed to prenatal antibiotics (29.8%). Prenatal antibiotic exposure was associated with an increased risk of ASD (HR 1.10, 95% confidence interval [CI] 1.05, 1.15), particularly for exposure during the first and second trimesters (HR 1.11, 95% CI 1.04, 1.18 and HR 1.09, 95% CI 1.03, 1.16, respectively), and exposure lasting ≥15 days (HR 1.13, 95% CI 1.04, 1.23). No sex differences were observed. The association was attenuated in the sibling analysis (adjusted odds ratio 1.04, 95% CI 0.92, 1.17). CONCLUSIONS: Prenatal antibiotic exposure was associated with a small increase in the risk of ASD in offspring. Given the possibility of residual confounding, these results should not influence clinical decisions regarding antibiotic use during pregnancy.

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14. Pagni BA, Hill E, Walsh MJM, Delaney S, Ogbeama D, Monahan L, Cook JR, Guerithault N, Dixon MV, Ballard L, Braden BB. Distinct and shared therapeutic neural mechanisms of mindfulness-based and social support stress reduction groups in adults with autism spectrum disorder. J Psychiatry Neurosci;2023 (Mar-Apr);48(2):E102-E114.

BACKGROUND: Mindfulness-based stress reduction (MBSR) alleviates depression and anxiety in adults with autism spectrum disorder (ASD); however, underlying therapeutic neural mechanisms and mindfulness-specific effects have yet to be elucidated. METHODS: We randomly assigned adults with ASD to MBSR or social support/education (SE). They completed questionnaires that assessed depression, anxiety, mindfulness traits, autistic traits and executive functioning abilities as well as a self-reflection functional MRI task. We used repeated-measures analysis of covariance (ANCOVA) to evaluate behavioural changes. To identify task-specific connectivity changes, we performed a generalized psychophysiological interactions (gPPI) functional connectivity (FC) analysis on regions of interest (ROIs; insula, amygdala, cingulum and prefrontal cortex [PFC]). We used Pearson correlations to explore brain-behaviour relationships. RESULTS: Our final sample included 78 adults with ASD – 39 who received MBSR and 39 who received SE. Mindfulness-based stress reduction uniquely improved executive functioning abilities and increased mindfulness traits, whereas both MBSR and SE groups showed reductions in depression, anxiety and autistic traits. Decreases specific to MBSR in insula-thalamus FC were associated with anxiety reduction and increased mindfulness traits, including the trait « nonjudgment; » MBSR-specific decreases in PFC-posterior cingulate connectivity correlated with improved working memory. Both groups showed decreased amygdala-sensorimotor and medial-lateral PFC connectivity, which corresponded with reduced depression. LIMITATIONS: Larger sample sizes and neuropsychological evaluations are needed to replicate and extend these findings. CONCLUSION: Together, our findings suggest that MBSR and SE are similarly efficacious for depression, anxiety and autistic traits, whereas MBSR produced additional salutary effects related to executive functioning and mindfulness traits. Findings from gPPI identified shared and distinct therapeutic neural mechanisms, implicating the default mode and salience networks. Our results mark an early step toward the development of personalized medicine for psychiatric symptoms in ASD and offer novel neural targets for future neurostimulation research. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04017793.

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15. Parvaiz R, Vindbjerg E, Crespi B, Happe F, Schalbroeck R, Al-Sayegh Z, Danielsen IM, Tonge B, Videbech P, Abu-Akel A. Protocol for the development and testing of the schiZotypy Autism Questionnaire (ZAQ) in adults: a new screening tool to discriminate autism spectrum disorder from schizotypal disorder. BMC Psychiatry;2023 (Mar 28);23(1):200.

BACKGROUND: Autism spectrum disorder (ASD) and schizotypal disorder (SD) both have a heterogenous presentation, with significant overlaps in symptoms and behaviour. Due to elevated recognition and knowledge of ASD worldwide, there is a growing rate of referrals from primary health professionals to specialised units. At all levels of assessment, the differential diagnostic considerations between ASD and SD exert major challenges for clinicians. Although several validated screening questionnaires exist for ASD and SD, none have differential diagnostic properties. Accordingly, in this study, we aim to develop a new screening questionnaire, the schiZotypy Autism Questionnaire (ZAQ), which provides a combined screening for both conditions, while also indicating the relative likelihood of each. METHODS: We aim to test 200 autistic patients and 100 schizotypy patients recruited from specialised psychiatric clinics and 200 controls from the general population (Phase 1). The results from ZAQ will be compared to the clinical diagnoses from interdisciplinary teams at specialised psychiatric clinics. After this initial testing phase, the ZAQ will be validated in an independent sample (Phase 2). CONCLUSIONS: The aim of the study is to investigate the discriminative properties (ASD vs. SD), diagnostic accuracy, and validity of the schiZotypy Autism Questionnaire (ZAQ). FUNDING: Funding was provided by Psychiatric Centre Glostrup, Copenhagen Denmark, Sofiefonden (Grant number: FID4107425), Trygfonden (Grant number:153588), Takeda Pharma. TRIAL REGISTRATION: Clinical Trials, NCT05213286, Registered 28 January 2022, clinicaltrials.gov/ct2/show/NCT05213286?cond = RAADS&draw = 2&rank = 1.

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16. Pascual F, Camilli S, Lockey RF, Kolliputi N. Mind-Body Connection: Metabolite 4-Ethylphenyl Linked to Anxiety Behavior and Oligodendrocyte Modification in Autism Spectrum Disorder. Am J Physiol Gastrointest Liver Physiol;2023 (Mar 28)

The connection between byproducts of digestion in the gastrointestinal (GI) tract and neurocognitive disorders is an expanding area of research that has implications in autism spectrum disorder (ASD). Needham et al. (Needham et al., 2022) revealed that mice with elevated levels of 4-ethylphenyl sulfate (4EPS), a GI tract-derived metabolite previously found at increased levels in the plasma of individuals with ASD, had altered brain activity, anxiety-influenced behavior, and reduced myelination of neuronal axons. This is a monumental step forward in the study of gut-derived neuroactive compounds, like 4EPS, and advances the understanding of their role in modulating behavior and brain activity in neurocognitive disorders.

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17. Pelton MK, Crawford H, Bul K, Robertson AE, Adams J, de Beurs D, Rodgers J, Baron-Cohen S, Cassidy S. The role of anxiety and depression in suicidal thoughts for autistic and non-autistic people: A theory-driven network analysis. Suicide Life Threat Behav;2023 (Mar 28)

BACKGROUND: Autistic adults experience more frequent suicidal thoughts and mental health difficulties than non-autistic adults, but research has yet to explain how these experiences are connected. This study explored how anxiety and depression contribute to suicidal thoughts according to the Interpersonal Theory of Suicide for autistic and non-autistic adults. METHODS: Participants (autistic adults n = 463, 61% female; non-autistic n = 342, 64% female) completed online measures of anxiety, depression, thwarted belonging, and perceived burdensomeness. Network analysis explored whether: (i) being autistic is a risk marker for suicide; and (ii) pathways to suicidal thoughts are consistent for autistic and non-autistic adults. RESULTS: Being autistic connected closely with feeling like an outsider, anxiety, and movement, which connected to suicidal thoughts through somatic experiences, low mood, and burdensomeness. Networks were largely consistent for autistic and non-autistic people, but connections from mood symptoms to somatic and thwarted belonging experiences were absent for autistic adults. CONCLUSION: Autistic people experience more life stressors than non-autistic people leading to reduced coping, low mood, and suicidal thoughts. Promoting belonging, reducing anxiety, and understanding the role of movement could inform suicide prevention for autistic people. Research should accurately capture autistic lived experience when modeling suicide to ensure suicide prevention meets autistic needs.

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18. Pretzsch CM, Floris DL, Schäfer T, Bletsch A, Gurr C, Lombardo MV, Chatham CH, Tillmann J, Charman T, Arenella M, Jones E, Ambrosino S, Bourgeron T, Dumas G, Cliquet F, Leblond CS, Loth E, Oakley B, Buitelaar JK, Baron-Cohen S, Beckmann CF, Persico AM, Banaschewski T, Durston S, Freitag CM, Murphy DGM, Ecker C. Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism. Mol Psychiatry;2023 (Mar 29)

Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals’ adaptive skills naturally improve or remain stable, while others’ decrease. To pave the way for ‘precision-medicine’ approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6-30 years), with two assessment time points separated by ~12-24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful « Increasers », « No-changers », and « Decreasers » in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup’s neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences’ potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.

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19. Sadeghi S, Pouretemad HR, Badv RS, Brand S. Associations between Symptom Severity of Autism Spectrum Disorder and Screen Time among Toddlers Aged 16 to 36 Months. Behav Sci (Basel);2023 (Feb 27);13(3)

There is growing evidence that prevalence rates of autism spectrum disorder (ASD) are increasing. A number of factors appear to contribute to this increase, including excessive screen time. Screen time seems to be linked to the severity of the symptoms of ASD. Given this, the aim of the present cross-sectional study was to investigate the association between early screen time and ASD symptoms severity in the first 36 months of life. To this end, sixty-eight Iranian toddlers (mean age: 27.09 months; 22.1% females) with ASD were recruited. Parents completed the modified checklist for autism in toddlers (M-CHAT), the Repetitive Behavior Scale-Revised (RBS-R), and a lifestyle checklist. Next, parents rated children’s daily exposure to content specifically designed (foreground media) and not specifically designed (background media) for children, along with their daily exposure to social interaction. Per day, toddlers spent 5.12 h (±3.77) with foreground media, 3.72 h (±3.57) with background media, and 2.89 h (±2.74) in interaction with other people (parents). To test the hypotheses, we performed a series of Pearson’s correlations and multiple regression analyses. Toddlers’ higher severity scores for ASD symptoms were associated with longer foreground (r = 0.234, p = 0.001) and longer background (r = 0.180, p = 0.012) media duration, and with shorter duration of interaction with others (r = 0.192, p = 0.009). Toddlers spending 1 h more in foreground screen time and background screen time have 0.38 and 0.29 more units in the ASD symptom severity scale, respectively, while toddlers spending 1 h more in social interactions have 0.42 fewer units in the ASD symptom severity scale. The screen time and interaction duration are related to ASD symptoms severity of toddlers. The cross-sectional study design precludes causal associations, although bi-directional relationships appear plausible.

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20. Sun A, Wang J, Zhang J. Identifying autism spectrum disorder using edge-centric functional connectivity. Cereb Cortex;2023 (Mar 28)

Brain network analysis is an effective method to seek abnormalities in functional interactions for brain disorders such as autism spectrum disorder (ASD). Traditional studies of brain networks focus on the node-centric functional connectivity (nFC), ignoring interactions of edges to miss much information that facilitates diagnostic decisions. In this study, we present a protocol based on an edge-centric functional connectivity (eFC) approach, which significantly improves classification performance by utilizing the co-fluctuations information between the edges of brain regions compared with nFC to build the classification mode for ASD using the multi-site dataset Autism Brain Imaging Data Exchange I (ABIDE I). Our model results show that even using the traditional machine-learning classifier support vector machine (SVM) on the challenging ABIDE I dataset, relatively high performance is achieved: 96.41% of accuracy, 98.30% of sensitivity, and 94.25% of specificity. These promising results suggest that the eFC can be used to build a reliable machine-learning framework to diagnose mental disorders such as ASD and promote identifications of stable and effective biomarkers. This study provides an essential complementary perspective for understanding the neural mechanisms of ASD and may facilitate future investigations on early diagnosis of neuropsychiatric disorders.

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21. Wright B, Kingsley E, Cooper C, Biggs K, Bursnall M, Wang HI, Chater T, Coates E, Teare MD, McKendrick K, Gomez de la Cuesta G, Barr A, Solaiman K, Packham A, Marshall D, Varley D, Nekooi R, Parrott S, Ali S, Gilbody S, Le Couteur A. I-SOCIALISE: Results from a cluster randomised controlled trial investigating the social competence and isolation of children with autism taking part in LEGO(®) based therapy (‘Play Brick Therapy’) clubs in school environments. Autism;2023 (Mar 29):13623613231159699.

Autism is characterised by keen interests and differences in social interactions and communication. Activities that help autistic children and young people with social skills are commonly used in UK schools. LEGO(®) based therapy is a new activity that provides interesting and fun social opportunities for children and young people and involves building LEGO(®) models together. This study looked at LEGO(®) based therapy for the social skills of autistic children and young people in schools. It was a randomised controlled trial, meaning each school was randomly chosen (like flipping a coin) to either run LEGO(®) based therapy groups in school over 12 weeks and have usual support from school or other professionals, or only have usual support from school or other professionals. The effect of the LEGO(®) based therapy groups was measured by asking children and young people, their parents/guardians, and a teacher at school in both arms of the study to complete some questionnaires. The main objective was to see if the teacher’s questionnaire answers about the children and young people’s social skills changed between their first and second completions. The social skills of participants in the LEGO(®) based therapy groups were found to have improved in a small way when compared to usual support only. The study also found that LEGO(®) based therapy was not very costly for schools to run and parents/guardians and teachers said they thought it was good for their children and young people. We suggest further research into different potential benefits of LEGO(®) based therapy.

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