| 1. |
- Achermann, Sheila, et al.
(författare)
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Parents' experiences from participating in an infant sibling study of autism spectrum disorder
- 2020
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Ingår i: Research in Autism Spectrum Disorders. - : Elsevier BV. - 1750-9467 .- 1878-0237. ; 69
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Tidskriftsartikel (refereegranskat)abstract
- Background:Prospective longitudinal studies of infant siblings of children with autism spectrum disorder (ASD) play an important role in advancing our knowledge about early developmental pathways in ASD. Despite this clear benefit, currently little is known about potential risks or disadvantages for participating families. As a first step in addressing this issue, we asked parents about their experiences from participating in an infant sibling study.Method:Eighty-eight families responded to a questionnaire examining parents' experiences from participating in an infant sibling study. The questions assessed parents' satisfaction with the study, the child's perceived satisfaction, and the parents' motivation for participating. The study included parents of two groups, (1) infants with an older sibling diagnosed with ASD (HR, high risk, n = 43) and (2) infants with no familial history of ASD (LR, low risk, n = 21).Results:The results indicated that parents are generally positive about study participation and few disadvantages were reported. This pattern was mirrored when splitting parents' responses into the two groups. There was no indication for group differences between parents of infants at high risk and low risk for ASD.Conclusion:Our findings present a first step into understanding parents' experiences from participating in an infant sibling study. Most parents were satisfied with participation in the study and only few disadvantages were reported. Our results have implications for ethical discussions about benefits and risks regarding infant sibling studies in various fields.
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| 2. |
- Afsharnejad, Bahareh, et al.
(författare)
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KONTAKT (R) social skills group training for Australian adolescents with autism spectrum disorder : a randomized controlled trial
- 2022
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Ingår i: European Child and Adolescent Psychiatry. - : Springer. - 1018-8827 .- 1435-165X. ; 31, s. 1695-1713
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Tidskriftsartikel (refereegranskat)abstract
- While there is a large body of evidence drawn from randomised controlled trials supporting the efficacy of SSGT in autistic adolescents, the control arms of these studies are almost exclusively treated either as usual or waitlist. Addressing this limitation, 90 verbal autistic adolescents (70% male) aged 12-17 years (M = 13.77, SD = 1.6) with IQ > 70 participated in this pragmatic two-armed randomised controlled trial design study evaluating the efficacy of sixteen 90-min sessions of SSGT KONTAKT (R) (n = 46) in comparison to a manualised interactive group cooking programme (n = 44) of equal dosage controlling for the potentially confounding effects of exposure to a social group context. The primary outcome was the adolescents' progress towards achieving their personally meaningful social goals at follow-up. Secondary outcomes were changes in autistic traits, quality of life, facial emotion recognition skills, social anxiety, and loneliness. Assessments were conducted at baseline, post intervention and 12-week follow-up. The interaction between time point and group allocation was investigated through a random-effects regression model (linear mixed model) to examine changes in the dependent outcomes. While intention-to-treat analysis (N = 90) demonstrated that both SSGT (ES = 1.36, p < .001) and active control (ES = 1.10, p < .001) groups made progress towards their personally meaningful social goals at follow-up, KONTAKT (R) participants demonstrated greater progress in social goal attainment than their peers in the active control group (ES = 0.35, p = .04). Findings suggest that KONTAKT (R) is efficacious in supporting autistic adolescents to achieve their personally meaningful social goals compared to other prosocial group activities.
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| 3. |
- Bloomfield, Madeleine, et al.
(författare)
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European Autism GEnomics Registry (EAGER): protocol for a multicentre cohort study and registry
- 2024
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Ingår i: BMJ OPEN. - 2044-6055. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and participants' genetic profiles.Methods and analysis EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will be given a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent to the study to access pre-existing clinical data. Participants will be added to the EAGER registry and data will be shared externally through established AIMS-2-TRIALS mechanisms.Ethics and dissemination To date, EAGER has received full ethical approval for 11 out of the 13 sites in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023), Spain (HCB/2023/0038, PIC-164-22), Sweden (Dnr 2023-06737-01), Ireland (230907) and Italy (CET_62/2023, CEL-IRCCS OASI/24-01-2024/EM01, EM 2024-13/1032 EAGER). Findings will be disseminated via scientific publications and conferences but also beyond to participants and the wider community (eg, the AIMS-2-TRIALS website, stakeholder meetings, newsletters).
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| 4. |
- Bolte, Sven, et al.
(författare)
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Challenges and Inequalities of Opportunities in European Psychiatry Research The Example of Psychodiagnostic Tool Availability in Research on Early Autism Identification
- 2018
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Ingår i: European Journal of Psychological Assessment. - : Hogrefe Publishing Group. - 1015-5759 .- 2151-2426. ; 34:4, s. 270-277
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Tidskriftsartikel (refereegranskat)abstract
- Europe is diverse in terms of economy, cultures, socio-demography, and languages. A crucial aspect of psychiatric research is the availability of standardized screening, diagnostic, and characterization instruments. We fine-mapped the accessibility of 14 clinical scales and cognitive tests for the assessment of early childhood Autism Spectrum Disorder (ASD; e.g., ADOS, ADI-R, SCQ, SRS, CHAT, MESL) within 21 European countries. These tools are essential for internationally competitive early ASD detection research. We identified a considerable variation not only in the availability, but also psychometric standardization, and formal distribution of the instruments between the countries, privileging English speaking, high-income, and highly populated European countries. Absence of country-specific standardization was a problem across many countries, independent of income and size. Findings demonstrate, on a concrete level, the challenges in creating equal early ASD identification research opportunities in Europe, and the need for increased funding for instrument development and validation. We discuss the reasons, implications, and consequences of this inequity and ways of reducing it.
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| 5. |
- Bolte, Sven, et al.
(författare)
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Infants at risk for autism : a European perspective on current status, challenges and opportunities
- 2013
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Ingår i: European Child and Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 22:6, s. 341-348
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Tidskriftsartikel (refereegranskat)abstract
- Currently, autism cannot be reliably diagnosed before the age of 2 years, which is why longitudinal studies of high-risk populations provide the potential to generate unique knowledge about the development of autism during infancy and toddlerhood prior to symptom onset. Early autism research is an evolving field in child psychiatric science. Key objectives are fine mapping of neurodevelopmental trajectories and identifying biomarkers to improve risk assessment, diagnosis and treatment. ESSEA (Enhancing the Scientific Study of Early Autism) is a COST (European Cooperation in Science and Technology) Action striving to create a European collaboration to enhance the progress of the discovery and treatment of the earliest signs of autism, and to establish European practice guidelines on early identification and intervention by bringing together European expertise from cognitive neuroscience and clinical sciences. The objective of this article is to clarify the state of current European research on at-risk autism research, and to support the understanding of different contexts in which the research is being conducted. We present ESSEA survey data on ongoing European high-risk ASD studies, as well as perceived challenges and opportunities in this field of research. We conclude that although high-risk autism research in Europe faces several challenges, the existence of several key factors (e.g., new and/or large-scale autism grants, availability of new technologies, and involvement of experienced research groups) lead us to expect substantial scientific and clinical developments in Europe in this field during the next few years.
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| 6. |
- de Schipper, Elles, et al.
(författare)
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Towards an ICF core set for ADHD : a worldwide expert survey on ability and disability
- 2015
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Ingår i: European Child and Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 24:12, s. 1509-1521
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Tidskriftsartikel (refereegranskat)abstract
- This is the second in a series of four empirical studies designed to develop International Classification of Functioning, Disability and Health (ICF and Children and Youth version, ICF-CY) core sets for attention deficit hyperactivity disorder (ADHD). The objective of this stage was to gather the opinions from international experts on which ability and disability concepts were considered relevant to functioning in ADHD. An email-based survey was carried out amongst international experts in ADHD. Relevant functional ability and disability concepts were extracted from their responses and linked to the ICF/-CY categories by two independent researchers using a standardised linking procedure. 174 experts from 11 different disciplines and 45 different countries completed the survey. Meaningful concepts identified in their responses were linked to 185 ICF/-CY categories. Of these, 83 categories were identified by at least 5 % of the experts and considered the most relevant to ADHD: 30 of these were related to Body functions (most identified: attention functions, 85 %), 30 to Activities and Participation (most identified: school education, 52 %), 20 to Environmental factors (most identified: support from immediate family, 61 %), and 3 to Body structures (most identified: structure of brain, 83 %). Experts also provided their views on particular abilities related to ADHD, naming characteristics such as high-energy levels, flexibility and resiliency. Gender differences in the expression of ADHD identified by experts pertained mainly to females showing more internalising (e.g. anxiety, low self-esteem) and less externalising behaviours (e.g. hyperactivity), leading to a risk of late- and under-diagnosis in females. Results indicate that the impact of ADHD extends beyond the core symptom domains, into all areas of life and across the lifespan. The current study in combination with three additional preparatory studies (comprehensive scoping review, focus groups, clinical study) will provide the scientific basis to define the ADHD ICF/-CY core sets for multi-purpose use in basic and applied research and every day clinical practice.
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| 7. |
- Falck-Ytter, Terje, et al.
(författare)
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Lack of Visual Orienting to Biological Motion and Audiovisual Synchrony in 3-Year-Olds with Autism
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7, s. e68816-
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that children with autism orient towards audiovisual synchrony (AVS) rather than biological motion and that the opposite pattern is to be expected in typical development. Here, we challenge this notion by showing that 3-year-old neurotypical children orient to AVS and to biological motion in point-light displays but that 3-year-old children with autism orient to neither of these types of information. Thus, our data suggest that two fundamental mechanisms are disrupted in young children with autism: one that supports orienting towards others' movements and one that supports orienting towards multimodally specified events. These impairments may have consequences for socio-cognitive development and brain organization.
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| 8. |
- Li, Danyang, et al.
(författare)
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Rare variants in the outcome of social skills group training for autism
- 2022
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Ingår i: Autism Research. - : Wiley. - 1939-3792 .- 1939-3806. ; 15:3, s. 434-446
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Tidskriftsartikel (refereegranskat)abstract
- Exome sequencing has been proposed as the first-tier genetic testing in autism spectrum disorder (ASD). Here, we performed exome sequencing in autistic individuals with average to high intellectual abilities (N = 207) to identify molecular diagnoses and genetic modifiers of intervention outcomes of social skills group training (SSGT) or standard care. We prioritized variants of clinical significance (VCS), variants of uncertain significance (VUS) and generated a pilot scheme to calculate genetic scores of rare and common variants in ASD-related gene pathways. Mixed linear models were used to test the association between the carrier status of VCS/VUS or the genetic scores with intervention outcomes measured by the social responsiveness scale. Additionally, we combined behavioral and genetic features using a machine learning (ML) model to predict the individual response. We showed a rate of 4.4% and 11.3% of VCS and VUS in the cohort, respectively. Individuals with VCS or VUS had improved significantly less after standard care than non-carriers at post-intervention (β = 9.35; p = 0.036), while no such association was observed for SSGT (β = −2.50; p = 0.65). Higher rare variant genetic scores for synaptic transmission and regulation of transcription from RNA polymerase II were separately associated with less beneficial (β = 8.30, p = 0.0044) or more beneficial (β = −6.79, p = 0.014) effects after SSGT compared with standard care at follow-up, respectively. Our ML model showed the importance of rare variants for outcome prediction. Further studies are needed to understand genetic predisposition to intervention outcomes in ASD.
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| 9. |
- Lipsker, Camilla Wiwe, et al.
(författare)
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Prevalence of autism traits and attention-deficit hyperactivity disorder symptoms in a clinical sample of children and adolescents with chronic pain
- 2018
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Ingår i: Journal of Pain Research. - 1178-7090. ; 11, s. 2827-2836
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Recent research has suggested that autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) may be comorbid to pediatric chronic pain, but the empirical support is yet scarce. Therefore, the current study aimed to investigate the occurrence of traits and symptoms consistent with clinically significant ASD and ADHD in a group of children and adolescents with chronic debilitating pain and examine potential differences in pain and demographic variables between children with and without clinically significant traits and symptoms of ASD and ADHD. Patients and methods: This cross-sectional study included 146 parent-child dyads (102 girls, 111 mothers, children 8-17 years) consecutively referred to a tertiary pain clinic. Parents completed the Social Responsiveness Scale to assess autistic traits, and Conners-3 to measure symptoms of ADHD in their children. Children completed the Liibeck Pain Questionnaire to evaluate experienced pain. Results: Among children, 20 (13.7%) received scores consistent with clinically significant ASD and 29 (19.9%) received scores consistent with clinically significant ADHD, with a combined prevalence of clinically significant ASD/ADHD traits and symptoms of 26% of the total sample. Only 4.8% of children were previously diagnosed with either disorder. Among children with clinically significant ASD traits, girls were more prevalent, parents reported lower health, and the pain was more likely triggered by being in school. Among children with clinically significant ADHD symptoms, there were no gender differences and pain was more likely triggered by the family situation and new situations. No differences regarding pain intensity, duration, or frequency were found between children with and without clinically significant ASD traits or ADHD symptoms. Conclusion: Children with debilitating chronic pain, particularly girls, may present with an elevated risk of having a comorbid, possibly high-functioning, neurodevelopmental disorder. Results suggest that clinical assessment of pediatric chronic pain should include screening for neurodevelopmental disorders.
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| 10. |
- Mahdi, Soheil, et al.
(författare)
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An international qualitative study of functioning in autism spectrum disorder using the World Health Organization international classification of functioning, disability and health framework
- 2018
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Ingår i: Autism Research. - : John Wiley & Sons. - 1939-3792 .- 1939-3806. ; 11:3, s. 463-475
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Tidskriftsartikel (refereegranskat)abstract
- This is the third in a series of four empirical studies designed to develop International Classification of Functioning, Disability and Health (ICF) Core Sets for Autism Spectrum Disorder (ASD). The present study aimed to describe functioning in ASD (as operationalized by the ICF) derived from the perspectives of diagnosed individuals, family members, and professionals. A qualitative study using focus groups and semi-structured interviews were conducted with 19 stakeholder groups (N = 90) from Canada, India, Saudi Arabia, South Africa, and Sweden. Meaningful concepts from the focus groups and individual interviews were linked to ICF categories using a deductive qualitative approach with standardized linking procedures. The deductive qualitative content analysis yielded meaningful functioning concepts that were linked to 110 ICF categories across all four ICF components. Broad variation of environmental factors and activities and participation categories were identified in this study, while body functions consisted mainly of mental functions. Body structures were sparsely mentioned by the participants. Positive aspects of ASD included honesty, attention to detail, and memory. The experiences provided by international stakeholders support the need to understand individuals with ASD in a broader perspective, extending beyond diagnostic criteria into many areas of functioning and environmental domains. This study is part of a larger systematic effort that will provide the basis to define ICF Core Sets for ASD, from which assessment tools can be generated for use in clinical practice, research, and health care policy making.
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| 11. |
- Nyström, Pär, et al.
(författare)
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Hypersensitive pupillary light reflex in infants at risk for autism
- 2015
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Post mortem brain tissue data and animal modeling work indicate cholinergic disruptions in autism. Moreover, the cholinergic system plays a key role in the early neurodevelopmental processes believed to be derailed early in life in individuals with the disorder. Yet, there is no data from human infants supporting a developmentally important role of this neurotransmitter system. Because the pupillary light reflex depends largely on cholinergic synaptic transmission, we assessed this reflex in a sample of infants at risk for autism as well as infants at low (average) risk. Methods: Ten-month-old infants with an older sibling with autism (n = 29, 16 females), and thus a genetic predisposition to developing the disorder themselves, were presented with white flashes on a computer monitor, and pupillary responses were captured using eye tracking. A control group matched on age and developmental level (n = 15, seven females) was also tested. Results: The siblings of children with autism had a faster and stronger pupillary light reflex compared to control infants. Baseline pupil diameter was equal in the two groups, ruling out tonic autonomic imbalance as an explanation for these differences. Conclusions: This study establishes that infant siblings of children with autism have hypersensitive pupillary light reflexes, a result which supports the view that altered sensory processing in infancy is associated with elevated autism risk. Moreover, the study indicates that individual differences in autism susceptibility are linked to differences in the cholinergic system during an early developmental period.
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| 12. |
- Nyström, Pär, 1975-, et al.
(författare)
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Responding to Other People's Direct Gaze : Alterations in Gaze Behavior in Infants at Risk for Autism Occur on Very Short Timescales
- 2017
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Ingår i: Journal of Autism and Developmental Disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 47:11, s. 3498-3509
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Tidskriftsartikel (refereegranskat)abstract
- Atypical gaze processing has been reported in children with autism spectrum disorders (ASD). Here we explored how infants at risk for ASD respond behaviorally to others' direct gaze. We assessed 10-month-olds with a sibling with ASD (high risk group; n = 61) and a control group (n = 18) during interaction with an adult. Eye-tracking revealed less looking at the adult in the high risk group during 300-1000 ms after the adult initiated direct gaze: a short alteration that is likely to go unnoticed by the naked eye. Data aggregated over longer segments (the traditional eye-tracking approach) showed no group differences. Although findings are limited by lack of outcome data, they are in line with theories linking atypical eye processing to the emergence of ASD.
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| 13. |
- Pokorny, Florian B., et al.
(författare)
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Earlier Identification of Children with Autism Spectrum Disorder : An Automatic Vocalisation-based Approach
- 2017
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Ingår i: 18Th Annual Conference Of The International Speech Communication Association (INTERSPEECH 2017), Vols 1-6. - 9781510848764 ; , s. 309-313
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Konferensbidrag (refereegranskat)abstract
- Autism spectrum disorder (ASD) is a neurodevelopmental disorder usually diagnosed in or beyond toddlerhood. ASD is defined by repetitive and restricted behaviours, and deficits in social communication. The early speech-language development of individuals with ASD has been characterised as delayed. However, little is known about ASD-related characteristics of pre-linguistic vocalisations at the feature level. In this study. we examined pre-linguistic vocalisations of 10-month-old individuals later diagnosed with ASD and a matched control group of typically developing individuals (N = 20). We segmented 684 vocalisations from parent-child interaction recordings. All vocalisations were annotated and signal-analytically decomposed. We analysed ASD-related vocalisation specificities on the basis of a standardised set (eGeMAPS) of 88 acoustic features selected for clinical speech analysis applications. 54 features showed evidence for a differentiation between vocalisations of individuals later diagnosed with ASD and controls. In addition, we evaluated the feasibility of automated, vocalisation-based identification of individuals later diagnosed with ASD. We compared linear kernel support vector machines and a 1-layer bidirectional long short-term memory neural network. Both classification approaches achieved an accuracy of 75% for subject-wise identification in a subject-independent 3-fold cross-validation scheme. Our promising results may be an important contribution en-route to facilitate earlier identification of ASD.
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| 14. |
- Sanchez, Monica Siqueiros, et al.
(författare)
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Visual disengagement in young infants in relation to age, sex, SES, developmental level and adaptive functioning
- 2021
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Ingår i: Infant Behavior and Development. - : Elsevier. - 0163-6383 .- 1879-0453 .- 1934-8800. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Visual attention plays a key role in infants' interaction with the environment, and shapes their behavioral and brain development. As such, early problems with flexibly switching gaze from one stimulus to another (visual disengagement) have been hypothesized to lead to developmental difficulties (e.g. joint attention and social skills) over time. This study aimed to identify crosssectional associations between performance in the Gap task (gaze shift latencies and visual attention disengagement) and measures of development and adaptive behavior in conjunction to any sex or socioeconomic status effects in infancy. We measured visual attention disengagement in 436 5-month-old infants and calculated its association with cognitive developmental level, adaptive behaviours, socioeconomic status (SES) and biological sex. In the Gap task, participants must redirect their gaze from a central stimulus to an appearing peripheral stimulus. The three experimental conditions of the task (Gap, Baseline and Overlap) differ on the timepoint when the central stimuli disappears in relation to the appearance of the peripheral stimulus: 200 ms before the peripheral stimulus appears (Gap), simultaneously to its appearance (Baseline), or with peripheral stimulus offset (Overlap). The data from the experimental conditions showed the expected pattern, with average latencies being the shortest in the Gap and longest in the Overlap condition. Females were faster (p = .004) than males in the Gap condition, which could indicate that arousal-related effects differ as a function of biological sex. Infants from higher SES were slower (p =.031) in the Overlap condition compared to lower SES infants. This suggests that basic visual attention may differ by socio-cultural background, and should be considered when studying visual attention and its developmental correlates. We observed no significant association to concurrent developmental level or adaptive function. Given its large sample size, this study provides a useful reference for future studies of visual disengagement in early infancy.
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| 15. |
- Willfors, Charlotte, et al.
(författare)
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Symptoms of autism in Williams syndrome: a transdiagnostic approach
- 2024
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Ingår i: SCIENTIFIC REPORTS. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Williams syndrome (WS) is associated with atypical social communication and cognition reminiscent of the behaviours observed in autism. Nonetheless, WS also differs significantly from autism, such as regarding social motivation, which is typically enhanced in WS and reduced in autism. This study sought to examine the conditions' transdiagnostic similarities and differences for autistic symptoms and social functioning, and their developmental trajectories, by comparing individuals with WS (n = 24) and those diagnosed with idiopathic autism (n = 24) and attention deficit hyperactivity disorder (ADHD; n = 24), aged 9 to 53 years, on measures of autism, social functioning, IQ and cooccurring psychiatric conditions. Although only 12.5% in the WS group met the criteria for an autism diagnosis, a majority exhibited distinct difficulties within social communication, social cognition, repetitive behaviours, and atypical sensory reactivity resembling autism. Conversely, elevated social motivation and a high number of social initiatives accompany these characteristics. No group differences in the developmental trajectories of autism symptoms were found. Our results demonstrate that autistic behaviours are more frequent in individuals with WS, than in individuals with idiopathic ADHD, and emphasize the need for clinical management of these behaviours.
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| 16. |
- Zuffa, Simone, et al.
(författare)
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Early-life differences in the gut microbiota composition and functionality of infants at elevated likelihood of developing autism spectrum disorder
- 2023
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- 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 & gamma;-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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