Pubmed du 14/07/23

Pubmed du jour

1. Almasoud H, Ain G. Corrigendum to « Parental perspectives on autism services in Saudi Arabia: Decade comparison (2011-2021) » [Res. Dev. Disabil. 137 (2023) 104485]. Res Dev Disabil;2023 (Jul 14):104572.

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2. Derbyshire E, Maes M. The Role of Choline in Neurodevelopmental Disorders-A Narrative Review Focusing on ASC, ADHD and Dyslexia. Nutrients;2023 (Jun 25);15(13)

Neurodevelopmental disorders appear to be rising in prevalence, according to the recent Global Burden of Disease Study. This rise is likely to be multi-factorial, but the role of certain nutrients known to facilitate neurodevelopment should be considered. One possible contributing factor could be attributed to deficits in choline intake, particularly during key stages of neurodevelopment, which includes the first 1000 days of life and childhood. Choline, a key micronutrient, is crucial for optimal neurodevelopment and brain functioning of offspring. The present narrative review discusses the main research, describing the effect of choline in neurodevelopmental disorders, to better understand its role in the etiology and management of these disorders. In terms of findings, low choline intakes and reduced or altered choline status have been reported in relevant population subgroups: pregnancy (in utero), children with autism spectrum disorders, people with attention deficit hyperactivity disorder and those with dyslexia. In conclusion, an optimal choline provision may offer some neuronal protection in early life and help to mitigate some cognitive effects in later life attributed to neurodevelopmental conditions. Research indicates that choline may act as a modifiable risk factor for certain neurodevelopmental conditions. Ongoing research is needed to unravel the mechanisms and explanations.

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3. Friedman NR, Watkins L, Barnard-Brak L, Barber A, White SW. De-implementation of Low-Value Practices for Autism Spectrum Disorder. Clin Child Fam Psychol Rev;2023 (Jul 14)

Due to a variety of factors, Autism Spectrum Disorder (ASD) has long been tethered to use of low-value practice (LVP), arguably moreso than any other psychiatric or neurodevelopmental condition. Although dissemination of empirically supported treatments (EST) for autistic individuals has expanded markedly over the past decade, there has not been concomitant reduction in the use of LVP. It is critical that clinicians and scientists not only promote the implementation of EST, but also facilitate the de-implementation (abandonment and/or divestment) of ineffective or harmful practices. In this review, we describe a data-driven approach that can be used to identify LVP, drawing from established criteria for identification of evidence-based treatments (e.g., APA Division 12, National Clearinghouse on Autism Evidence and Practice; SAMHSA), as well as broader considerations such as social validity, cost, and parsimony. Herein, a data-based approach to LVP identification is proposed with a goal of improving quality of service access. Within an implementation science framework, we identify specific facilitators that sustain LVP use, and recommendations for subsequent de-implementation strategies are offered.

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4. Godler DE, Inaba Y, Bui MQ, Francis D, Skinner C, Schwartz CE, Amor DJ. Defining the 3’Epigenetic Boundary of the FMR1 Promoter and Its Loss in Individuals with Fragile X Syndrome. Int J Mol Sci;2023 (Jun 27);24(13)

This study characterizes the DNA methylation patterns specific to fragile X syndrome (FXS) with a full mutation (FM > 200 CGGs), premutation (PM 55-199 CGGs), and X inactivation in blood and brain tissues at the 3′ boundary of the FMR1 promoter. Blood was analyzed from 95 controls and 462 individuals (32% males) with FM and PM alleles. Brain tissues (62% males) were analyzed from 12 controls and 4 with FXS. There was a significant increase in intron 1 methylation, extending to a newly defined 3′ epigenetic boundary in the FM compared with that in the control and PM groups (p < 0.0001), and this was consistent between the blood and brain tissues. A distinct intron 2 site showed a significant decrease in methylation for the FXS groups compared with the controls in both sexes (p < 0.01). In all female groups, most intron 1 (but not intron 2 sites) were sensitive to X inactivation. In all PM groups, methylation at the 3' epigenetic boundary and the proximal sites was significantly decreased compared with that in the control and FM groups (p < 0.0001). In conclusion, abnormal FMR1 intron 1 and 2 methylation that was sensitive to X inactivation in the blood and brain tissues provided a novel avenue for the detection of PM and FM alleles through DNA methylation analysis.

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5. Kalfiřt L, Su CT, Fu CP, Lee SD, Yang AL. Motor Skills, Heart Rate Variability, and Arterial Stiffness in Children with Autism Spectrum Disorder. Healthcare (Basel);2023 (Jun 30);11(13)

The prevalence of autism spectrum disorder (ASD) among children has been recently increasing. The severity of symptoms greatly varies between individuals with ASD, ranging from relatively mild to extremely severe. It is important to have a clearer understanding of the possible adverse consequences resulting from this disorder, such as delayed motor development, autonomic dysregulation, and arterial stiffness. Thus, the objective of this study was to investigate differences in motor skills, heart rate variability (HRV), and arterial stiffness between children with ASD and typically developing children. In this study, the school-aged children with mild symptoms of ASD (n = 17, 11.1 ± 1.0 years old) and typically developing peers (n = 15, 11.0 ± 0.5 years old) were recruited. Motor skills, HRV, and arterial stiffness were measured in these two groups. Motor skills were evaluated by the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition. Moreover, HRV was measured through a short-term recording using the Polar heart rate monitor, and arterial stiffness was assessed by non-invasive computerized oscillometry. Compared with the typically developing group, children with ASD displayed significant deficits in some areas of motor skills, including manual coordination, strength and agility, and total motor composite. Moreover, children with ASD exhibited significantly reduced HRV, including time- and frequency-domain measures. However, the results did not demonstrate any statistically significant differences in arterial stiffness between the groups. Our findings demonstrated the presence of motor skill deficits and autonomic dysregulation in children with ASD.

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6. Lax E, Do Carmo S, Enuka Y, Sapozhnikov DM, Welikovitch LA, Mahmood N, Rabbani SA, Wang L, Britt JP, Hancock WW, Yarden Y, Szyf M. Methyl-CpG binding domain 2 (Mbd2) is an epigenetic regulator of autism-risk genes and cognition. Transl Psychiatry;2023 (Jul 13);13(1):259.

The Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment. However, its exact role in neurodevelopment and brain function is mostly unknown. Here we show that Mbd2-deficiency in mice (Mbd2-/-) results in deficits in cognitive, social and emotional functions. Mbd2 binds regulatory DNA regions of neuronal genes in the hippocampus and loss of Mbd2 alters the expression of hundreds of genes with a robust down-regulation of neuronal gene pathways. Further, a genome-wide DNA methylation analysis found an altered DNA methylation pattern in regulatory DNA regions of neuronal genes in Mbd2-/- mice. Differentially expressed genes significantly overlap with gene-expression changes observed in brains of Autism Spectrum Disorder (ASD) individuals. Notably, downregulated genes are significantly enriched for human ortholog ASD risk genes. Observed hippocampal morphological abnormalities were similar to those found in individuals with ASD and ASD rodent models. Hippocampal Mbd2 knockdown partially recapitulates the behavioral phenotypes observed in Mbd2-/- mice. These findings suggest that Mbd2 is a novel epigenetic regulator of genes that are associated with ASD in humans. Mbd2 loss causes behavioral alterations that resemble those found in ASD individuals.

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7. Lotan M, Zwilling M, Romano A. Psychometric Values of a New Scale: The Rett Syndrome Fear of Movement Scale (RSFMS). Diagnostics (Basel);2023 (Jun 23);13(13)

(1) Background: One of the characteristics associated with Rett syndrome (RTT) is a fear of movement (FOM). Despite the grave consequences on health, function, and the caregiver’s burden associated with bradykinesia accompanying FOM, there is no specific FOM assessment tool for RTT. (2) Objective: To construct and assess the psychometric values of a scale evaluating FOM in RTT (Rett syndrome fear of movement scale-RSFMS). (3) Methods: Twenty-five girls aged 5-33, including a research group (N = 12 individuals with RTT) and control group (N = 13 typically developing girls at equivalent ages). The Pain and Discomfort Scale (PADS) and Facial Action Coding System (FACS) assessed the participants’ behavior and facial expressions in rest and movement situations. (4) Results: Significant behavioral differences were recorded in these rest and movement situations within the research groups using the RSFMS (p = 0.003), FACS (p = 0.002) and PADS (p = 0.002). No differences in reactions were found within the control group. The new scale, RSFMS, was found to show a high inter- and intra-rater reliability (r = 0.993, p < 0.001; r = 0.958, p < 0.001; respectively), good internal consistency (α = 0.77), and high accuracy (94.4%). (5) Conclusions: The new scale for measuring FOM in RTT, the RSFMS, was validated using the FACS and PADS. The RSFMS was found to be a tool that holds excellent psychometric values. The new scale can help clinicians working with individuals with RTT to plan appropriate management strategies for this population.

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8. Moshe S, Oppenheim D, Slonim M, Hamburger L, Maccabi Y, Yirmiya N. Positive and challenging themes in parents’ perceptions of their relationships with their child with autism: Comparison between mothers and fathers. Autism;2023 (Jul 13):13623613231182513.

Most studies of how parents of children with autism see the parent-child relationship used questionnaires completed by the parents and focused on challenges. This study broadened the lens by interviewing parents using open-ended questions that provide an opportunity to raise challenging but also positive experiences. Seventy-five mother-father dyads were interviewed individually about their own and their spouses’ relationships with their preschooler, and we found nine relationship themes. In descending order, the themes mentioned most frequently by mothers were « Security and Closeness, » « Love, » and « Tenderness and Sensitivity, » and by fathers were « Pleasure in Joint Activities, » « Security and Closeness, » and « Guidance. » Positive themes were more common than challenging themes. Finally, more mothers mentioned the themes « Love, » « Tenderness and Sensitivity, » « High Involvement and Care, » and « Difficulties » than did fathers, whereas more fathers mentioned the themes « Guidance » and « Pleasure in Joint Activities » than did mothers. The findings portray a nuanced view of the parenting experience of mothers and fathers of preschoolers with autism.

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9. Peng P, Wang Q, Zhou Y, Hao Y, Chen S, Wu Q, Li M, Wang Y, Yang Q, Wang X, Liu Y, Ma Y, He L, Liu T, Zhang X. Autistic features in Chinese patients with chronic schizophrenia: Prevalence, clinical characteristics, and relationship with cognitive impairment. Asian J Psychiatr;2023 (Jul 11);87:103697.

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10. Pires S, Felgueiras P, Borges S, Jorge J. Autism Spectrum Disorder in Females and Borderline Personality Disorder: The Diagnostic Challenge. Cureus;2023 (Jun);15(6):e40279.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by pervasive deficits in communication and social interaction and patterns of repetitive, restrictive interests and/or stereotyped behaviors. Female sex/gender is not represented in the current conceptualization of ASD, and there is emerging evidence of a female phenotype. The etiology of ASD and borderline personality disorder (BPD) is not fully understood. Clinical observations suggest that ASD and BPD can overlap in clinical presentation and diagnostic characteristics, especially in female ASD cases. We report two clinical cases of two adolescent girls presenting overlap symptoms between ASD and BPD, raising questions about the female ASD phenotype and the potential misdiagnosis of ASD characteristics with BPD, as well as its impact on diagnosis and management. Diagnostic differentiation is crucial for targeted therapeutic interventions (psychopharmacological and psychosocial). Further studies are needed to enlighten the clinical similarities and diagnostic overlap between ASD females and BPD.

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11. Porter M, Sugden-Lingard S, Brunsdon R, Benson S. Autism Spectrum Disorder in Children with an Early History of Paediatric Acquired Brain Injury. J Clin Med;2023 (Jun 28);12(13)

Autism spectrum disorder (ASD) is a neurodevelopmental condition that arises from a combination of both genetic and environmental risk factors. There is a lack of research investigating whether early acquired brain injury (ABI) may be a risk factor for ASD. The current study comprehensively reviewed all hospital records at The Brain Injury Service, Kids Rehab at the Children’s Hospital at Westmead (Australia) from January 2000 to January 2020. Of the approximately 528 cases, 14 children with paediatric ABI were subsequently given an ASD diagnosis (2.7%). For this ASD sample, the mean age at the time of the ABI was 1.55 years, indicating a high prevalence of early ABI in this diagnostic group. The mean age of ASD diagnosis was, on average, 5 years later than the average ASD diagnosis in the general population. Furthermore, 100% of children had at least one medical comorbidity and 73% had three or more co-occurring DSM-5 diagnoses. Although based on a small data set, results highlight early paediatric ABI as a potential risk factor for ASD and the potential for a delayed ASD diagnosis following early ABI, with comorbidities possibly masking symptoms. This study was limited by its exploratory case series design and small sample size. Nonetheless, this study highlights the need for longitudinal investigation into the efficacy of early screening for ASD symptomatology in children who have sustained an early ABI to maximise potential intervention.

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12. Pu Y, An J, Mo X. Liquid Biopsy in Adverse Neurodevelopment of Children: Problems and Prospects. Methods Mol Biol;2023;2695:337-349.

Neurodevelopmental disorders in children have an important impact on the quality of life in the whole life cycle. Severe neurodevelopmental disorders will become a serious social and family burden and an important social and economic problem. The early and middle childhood is the critical period of children’s neurodevelopment. Early diagnosis of neurological disorders plays an important role in guiding children’s neurological development. Existing monitoring tools lack prenatal and even early assessment of children’s neurodevelopment, so reliable biomarkers are conducive to personalized care at an earlier stage. In this review, we will discuss different methods of neurodevelopmental monitoring at different times and the role and evaluation of liquid biopsy in neurodevelopmental monitoring.

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13. Sacrey LR, Zwaigenbaum L, Elshamy Y, Smith IM, Brian JA, Wass S. Comparative strengths and challenges on face-to-face and computer-based attention tasks in autistic and neurotypical toddlers. Autism Res;2023 (Jul 13)

The objectives were to compare patterns of visual attention in toddlers diagnosed with autism spectrum disorder (ASD) as compared to their sex- and age-matched neurotypical (NT) peers. Participants included 23 toddlers with ASD and 19 NT toddlers (mean age: 25.52 versus 25.21 months, respectively) assessed using computerized tasks to measure sustained attention, disengaging attention, and cognitive control, as well as an in-person task to assess joint attention. Toddlers in the ASD group showed increased looking durations on the sustained attention task, as well as reduced frequencies of responding to and initiating joint attention compared to NT peers, but showed no differences on tasks of disengaging attention and cognitive control. The results suggest that toddlers with ASD have attentional strengths that may provide a foundation for building attention, communicative, and ultimately, academic skills.

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14. Tarasi L, Martelli ME, Bortoletto M, di Pellegrino G, Romei V. Neural Signatures of Predictive Strategies Track Individuals Along the Autism-Schizophrenia Continuum. Schizophr Bull;2023 (Jul 14)

BACKGROUND AND HYPOTHESIS: Humans develop a constellation of different representations of the external environment, even in the face of the same sensory exposure. According to the Bayesian framework, these differentiations could be grounded in a different weight assigned to prior knowledge vs. new external inputs in predictive inference. Since recent advances in computational psychiatry suggest that autism (ASD) and schizophrenia (SSD) lie on the two diametric poles of the same predictive continuum, the adoption of a specific inferential style could be routed by dispositional factors related to autistic and schizotypal traits. However, no studies have directly investigated the role of ASD-SSD dimension in shaping the neuro-behavioral markers underlying perceptual inference. STUDY DESIGN: We used a probabilistic detection task while simultaneously recording EEG to investigate whether neurobehavioral signatures related to prior processing were diametrically shaped by ASD and SSD traits in the general population (n = 80). RESULTS: We found that the position along the ASD-SSD continuum directed the predictive strategies adopted by the individuals in decision-making. While proximity to the positive schizotypy pole was associated with the adoption of the predictive approach associated to the hyper-weighting of prior knowledge, proximity to ASD pole was related to strategies that favored sensory evidence in decision-making. CONCLUSIONS: These findings revealed that the weight assigned to prior knowledge is a marker of the ASD-SSD continuum, potentially useful for identifying individuals at-risk of developing mental disorders and for understanding the mechanisms contributing to the onset of symptoms observed in ASD and SSD clinical forms.

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15. Tataru C, Peras M, Rutherford E, Dunlap K, Yin X, Chrisman BS, DeSantis TZ, Wall DP, Iwai S, David MM. Topic modeling for multi-omic integration in the human gut microbiome and implications for Autism. Sci Rep;2023 (Jul 13);13(1):11353.

While healthy gut microbiomes are critical to human health, pertinent microbial processes remain largely undefined, partially due to differential bias among profiling techniques. By simultaneously integrating multiple profiling methods, multi-omic analysis can define generalizable microbial processes, and is especially useful in understanding complex conditions such as Autism. Challenges with integrating heterogeneous data produced by multiple profiling methods can be overcome using Latent Dirichlet Allocation (LDA), a promising natural language processing technique that identifies topics in heterogeneous documents. In this study, we apply LDA to multi-omic microbial data (16S rRNA amplicon, shotgun metagenomic, shotgun metatranscriptomic, and untargeted metabolomic profiling) from the stool of 81 children with and without Autism. We identify topics, or microbial processes, that summarize complex phenomena occurring within gut microbial communities. We then subset stool samples by topic distribution, and identify metabolites, specifically neurotransmitter precursors and fatty acid derivatives, that differ significantly between children with and without Autism. We identify clusters of topics, deemed « cross-omic topics », which we hypothesize are representative of generalizable microbial processes observable regardless of profiling method. Interpreting topics, we find each represents a particular diet, and we heuristically label each cross-omic topic as: healthy/general function, age-associated function, transcriptional regulation, and opportunistic pathogenesis.

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16. Tsompanidis A, Blanken L, Broere-Brown ZA, van Rijn BB, Baron-Cohen S, Tiemeier H. Sex differences in placenta-derived markers and later autistic traits in children. Transl Psychiatry;2023 (Jul 13);13(1):256.

Autism is more prevalent in males and males on average score higher on measures of autistic traits. Placental function is affected significantly by the sex of the fetus. It is unclear if sex differences in placental function are associated with sex differences in the occurrence of autistic traits postnatally. To assess this, concentrations of angiogenesis-related markers, placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) were assessed in maternal plasma of expectant women in the late 1(st) (mean= 13.5 [SD = 2.0] weeks gestation) and 2(nd) trimesters (mean=20.6 [SD = 1.2] weeks gestation), as part of the Generation R Study, Rotterdam, the Netherlands. Subsequent assessment of autistic traits in the offspring at age 6 was performed with the 18-item version of the Social Responsiveness Scale (SRS). Associations of placental protein concentrations with autistic traits were tested in sex-stratified and cohort-wide regression models. Cases with pregnancy complications or a later autism diagnosis (n = 64) were also assessed for differences in placenta-derived markers. sFlt-1 levels were significantly lower in males in both trimesters but showed no association with autistic traits. PlGF was significantly lower in male pregnancies in the 1(st) trimester, and significantly higher in the 2(nd) trimester, compared to female pregnancies. Higher PlGF levels in the 2(nd) trimester and the rate of PlGF increase were both associated with the occurrence of higher autistic traits (PlGF-2(nd): n = 3469,b = 0.24 [SE = 0.11], p = 0.03) in both unadjusted and adjusted linear regression models that controlled for age, sex, placental weight and maternal characteristics. Mediation analyses showed that higher autistic traits in males compared to females were partly explained by higher PlGF or a faster rate of PlGF increase in the second trimester (PlGF-2(nd): n = 3469, ACME: b = 0.005, [SE = 0.002], p = 0.004). In conclusion, higher PlGF levels in the 2(nd) trimester and a higher rate of PlGF increase are associated with both being male, and with a higher number of autistic traits in the general population.

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17. Veronese S, Zoccante L, Smania N, Sbarbati A. Stretch marks: a visible expression of connective’s involvement in autism spectrum disorders. Front Psychiatry;2023;14:1155854.

In autism spectrum disorders (ASDs) in the pediatric population, skin manifestations are generally attributable to the concomitance of allergic forms or to accidental, self-inflicted or abusive lesions. However, clinical evidence has highlighted the presence of an increasing number of abdominal stretch marks, probably caused by the increase in the number of obesity cases in the pediatric population, in general, and therefore also among children with ASD. Stretch marks are often attributed to obesity, as they have an incidence of more than 50% in obese individuals. In the first part of this article we hypothesized that in addition to obesity there are other factors, such as a structural alteration on the skin in people with ASD, which can contribute/aggravate the phenomenon of stretch marks. Despite the high frequency with which stretch marks are found in children with ASD, this aspect has never been studied, the structure of the skin of children with ASD is not known. Furthermore, it is not known whether this structure is different from that of subjects without ASD. In the second part of the article, we hypothesized the mechanisms of the negative impact of simple abdominal stretch marks on the symptomatic picture of children with ASD. The presence of stretch marks, altered tactile perception, altered sensitivity to clothing fabrics can be a combination that influences development and determines negative consequences in the neurological picture of a child with ASD, as it is already known that the altered sensory perception in children with ASD contributes to the deterioration of social behavior. Furthermore, the presence of stretch marks may play a role in the postural and motor defects of children with ASD.

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18. Zane E, Grossman RB. Analysis of Noun Phrase Ambiguity in Narratives Reveals Differences in Referential Establishment But Not Cohesion for Older Autistic Children. J Speech Lang Hear Res;2023 (Jul 14):1-19.

PURPOSE: Stories told by autistic narrators often contain relatively frequent use of ambiguous references. However, it remains unclear whether this ambiguity is driven by ambiguous character establishment (e.g., « Once upon a time, she/the girl… ») and/or ambiguous cohesion (e.g., « Two girls lived in a castle. She/The girl… »). In this study, we directly compared rates of each type of ambiguity within and between narratives told by autistic and non-autistic children, to determine which type of ambiguity is relatively more common in narratives told by autistic children. METHOD: Thirty-three 10- to 17-year-old autistic participants (n = 17) and non-autistic peers (n = 16), who were not statistically different in age, standardized language scores, and IQ scores (p > .8 for all), watched two short animated videos alone and then described the videos’ events to two listeners who were openly unfamiliar with the videos. We transcribed video recordings of narratives and coded all referential noun phrases (NPs) as either clear or ambiguous. We further categorized ambiguous NPs as either ineffective introduction or ineffective cohesion. RESULTS: Autistic children produced significantly higher rates of ambiguous establishment than non-autistic peers, whereas between-group comparisons’ rates of ambiguous cohesion were not statistically significant. CONCLUSIONS: Older children on the autism spectrum show differences in the way they introduce characters, selecting NP types that are only appropriate when their listener is already familiar with the referent. In contrast, once they have introduced characters, they show cohesive skills that are comparable to those of non-autistic peers. Findings support theories arguing that autistic children show differences in their application of social pragmatic principles (listener/context-specific pragmatic rules), whereas their use of linguistic pragmatics (context-independent rules) is similar to that of non-autistic peers.

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19. Zuffa S, Schimmel P, Gonzalez-Santana A, Belzer C, Knol J, Bölte S, Falck-Ytter T, Forssberg H, Swann J, Diaz Heijtz R. Early-life differences in the gut microbiota composition and functionality of infants at elevated likelihood of developing autism spectrum disorder. Transl Psychiatry;2023 (Jul 13);13(1):257.

Evidence from cross-sectional human studies, and preliminary microbial-based intervention studies, have implicated the microbiota-gut-brain axis in the neurobiology of autism spectrum disorder (ASD). Using a prospective longitudinal study design, we investigated the developmental profile of the fecal microbiota and metabolome in infants with (n = 16) and without (n = 19) a family history of ASD across the first 36 months of life. In addition, the general developmental levels of infants were evaluated using the Mullen Scales of Early Learning (MSEL) test at 5 and 36 months of age, and with ADOS-2 at 36 months of age. At 5 months of age, infants at elevated-likelihood of ASD (EL) harbored less Bifidobacterium and more Clostridium and Klebsiella species compared to the low-likelihood infants (LL). Untargeted metabolic profiling highlighted that LL infants excreted a greater amount of fecal γ-aminobutyric acid (GABA) at 5 months, which progressively declined with age. Similar age-dependent patterns were not observed in the EL group, with GABA being consistently low across all timepoints. Integrated microbiome-metabolome analysis showed a positive correlation between GABA and Bifidobacterium species and negative associations with Clostridium species. In vitro experiments supported these observations demonstrating that bifidobacteria can produce GABA while clostridia can consume it. At the behavioral level, there were no significant differences between the EL and LL groups at 5 months. However, at 36 months of age, the EL group had significantly lower MSEL and ADOS-2 scores compared to the LL group. Taken together, the present results reveal early life alterations in gut microbiota composition and functionality in infants at elevated-likelihood of ASD. These changes occur before any behavioral impairments can be detected, supporting a possible role for the gut microbiota in emerging behavioral variability later in life.

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