1. Alcocer Alkureishi L, Hageman JR. Caring for Children with Autism. Pediatr Ann;2024 (Jan);53(1):e1-e2.

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2. Columna L, Haegele JA, Barry A, Prieto L. « I Can Do It »: Perceived Competence of Parents of Autistic Children After Participating in a Physical Activity Intervention. J Phys Act Health;2024 (Jan 9):1-8.

BACKGROUND: Autistic children can benefit from physical activity (PA) in a variety of ways. However, autistic children tend not to meet PA recommendations and, consequently, may not experience the associated benefits. Parental PA support can facilitate PA participation among autistic children, but parents of autistic children may lack the skills to help their child engage in PA. Few studies, to date, have examined the outcomes of parent-mediated PA interventions for autistic children. The purpose of this study was to explore parents’ perceived behavioral control (PBC) to support their autistic children in PA after their participation in a PA intervention. METHODS: The theory of planned behavior served as the framework for this descriptive-qualitative investigation. Fifteen parents (each with 1 autistic child in the intervention) participated in semistructured interviews (3 wk after the intervention), which were transcribed and then analyzed using thematic line-by-line analysis. RESULTS: Three themes characterized the changes to parents’ PBC after completing the PA intervention. Those themes were: (1) I learned by son! (2) You are my coach! and (3) I can do it! CONCLUSIONS: The results showed that by participating in a parent-mediated PA intervention, parents experienced improved confidence and awareness of their child’s abilities, thus enhancing their PBC. Future research is needed to examine how these improvements in PBC may influence the actual PA behaviors of autistic children.

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3. Dell’Osso L, Nardi B, Bonelli C, Amatori G, Pereyra MA, Massimetti E, Cremone IM, Pini S, Carpita B. Autistic Traits as Predictors of Increased Obsessive-Compulsive Disorder Severity: The Role of Inflexibility and Communication Impairment. Brain Sci;2024 (Jan 9);14(1)

Due to similar manifestations, some authors have proposed a potential correlation between autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD). This link has long been recognized and debated, with some authors arguing that these disorders frequently occur comorbid but distinct while others believe they are part of the same spectrum. The aim of our study was to explore the prevalence and correlates of autistic traits in 55 OCD patients and 55 matched controls and to assess possible autistic dimensions predictive of higher OCD symptoms. All participants were assessed with the Obsessive-Compulsive Spectrum-Short Version (OBS-SV) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). The OCD group scored significantly higher in both questionnaires. Total OBS-SV scores and domains were significantly correlated with all AdAS Spectrum domains and total score. The AdAS Spectrum total, Verbal Communication and Inflexibility and adherence to routine domain scores were significant positive predictors of higher OBS-SV scores. Lastly, when two clusters of subjects (high and low autism) were determined, Inflexibility and adherence to routine domain presented the greatest influence in forming the clusters. Our findings support the association between OCD and autistic traits in the adult population, supporting the hypothesis of a neurodevelopmental basis for these psychiatric conditions.

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4. Dinstein I, Solomon S, Zats M, Shusel R, Lottner R, Gershon BB, Meiri G, Menashe I, Shmueli D. Large increase in ASD prevalence in Israel between 2017 and 2021. Autism Res;2024 (Jan 9)

Accurate estimation of annual changes in autism spectrum disorders (ASD) prevalence is critical for planning the expansion of diagnostic, education, and intervention services at an adequate rate. Previous studies from Israel have reported that ASD prevalence among 8-year-old children has increased from estimates of 0.3% in 2008 to 0.65% in 2015 and 1.3% in 2018. Here, we analyzed data acquired from the National Insurance Institute of Israeli (NII), a governmental organization that approves and monitors all ASD children who receive welfare services in Israel, and Clalit Health Services (CHS), the largest Health Maintenance Organization in Israel that provides health services to ~52% of the population. Data from both sources included annual data files from 2017 to 2021 containing the number of ASD cases per year of birth for 1-17-year-old children. This allowed us to estimate annual ASD prevalence among 3.5 million children born between 2000 and 2020 in Israel. Both data sources revealed a nearly two-fold increase in ASD prevalence among 1-17-year-old children from 2017 to 2021. Estimated prevalence rates differed across age groups with 2-3-year-old (day-care) children increasing from 0.27% to 1.19% (>4 fold change), 4-6-year-old (pre-school) children increasing from 0.8% to 1.83%, and 8-year-old children increasing from 0.82% to 1.56% in NII data. These results demonstrate that autism prevalence continues to increase in Israel with a shift towards diagnosis at earlier ages. These findings highlight the challenge facing health and education service providers in meeting the needs of a rapidly growing autism population.

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5. Dückert S, Bart S, Gewohn P, König H, Schöttle D, Konnopka A, Rahlff P, Erik F, Vogeley K, Schulz H, David N, Peth J. Health-related quality of life in family caregivers of autistic adults. Front Psychiatry;2023;14:1290407.

INTRODUCTION: Family members of autistic individuals often provide support for their autistic relative throughout the lifespan which can lead to massive burden themselves. Reduced health-related Quality of Life (HRQoL) in family caregivers is assumed; however, only a handful studies on the HRQoL of family caregivers providing care to adult relatives exist as opposed to autistic children. Thus, the current study aimed to (i) investigate the current state of physical and mental HRQoL of family caregivers of autistic adults compared to the general population, and (ii) examine caregiver-related (e.g., age, subjective caregiver burden) and care recipient-related variables (e.g., symptom severity, utilization of formal services) explaining variance in the caregivers’ HRQoL. METHODS: N = 149 family caregivers completed a nationwide online survey, including the Short-Form Health Survey (SF-8) in order to assess the HRQoL. T-tests were used to compare the HRQoL of family caregivers with the general population. Bivariate correlational and multiple linear regression analyses were conducted in order to identify predictors explaining variance in family caregivers’ HRQoL. RESULTS: Family caregivers of autistic adults reported significantly lower physical (M = 46.71, SD = 8.72, Cohen’s d = 0.42) and mental HRQoL (M = 40.15, SD = 11.28, Cohen’s d = 1.35) compared to the general population. Multiple linear regression with the mental HRQoL as the outcome showed a significant model (F(11, 95) = 5.53, p < .001, adj. R(2) = .32) with increased subjective burden explaining most of the variance in mental HRQoL (ß = .32, GDW = .141, p < .001). Multiple linear regression analysis with the outcome physical HRQoL did not reveal a statistically significant model (F(11,95) = 1.09, p = .38). However, bivariate analyses also showed a positive correlation with the subjective caregiver burden (r= .20, p < .05). DISCUSSION: Findings highlight the need to consider HRQoL (and caregiver burden) of family caregivers of autistic adults in several healthcare settings to monitor a potential comprised health status in early stages, with the long-term goal to improve family caregivers' HRQoL.

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6. Ghamari R, Tahmaseb M, Sarabi-Jamab A, Etesami SA, Mohammadzadeh A, Alizadeh F, Tehrani-Doost M. Association of verbal and non-verbal theory of mind abilities with non-coding variants of OXTR in youth with autism spectrum disorder and typically developing individuals: a case-control study. BMC Psychiatry;2024 (Jan 8);24(1):30.

BACKGROUND: The ability to attribute mental states to others is called theory of mind (ToM) and is a substantial component of social cognition. This ability is abnormally developed in individuals with autism spectrum disorder (ASD). Several studies over the past decade have identified the oxytocin receptor gene (OXTR) and its variants as promising components for explaining the molecular mechanisms underlying Theory of Mind (ToM). The main aim of this study is to examine the association between rs2268498 and rs53576, two functional single nucleotide polymorphisms (SNPs), and verbal and non-verbal ToM in children and adolescents with ASD and a group of typically developing youth. METHODS: The study involved 44 children and adolescents with high-functioning ASD aged 8 to 18 years old and 44 TD individuals who were matched on age and sex. In all participants, blood samples were collected and rs2268498 and rs53576 were genotyped. Happe’s Strange Stories test and the moving shapes paradigm were used to measure verbal and non-verbal ToM in all participants. RESULTS: The results of permutation tests and logistic regression suggested that in TD group, rs2268498 AA carriers showed significant higher scores in variables representing verbal ToM (ToM stories and appropriateness score) whereas, in ASD group, rs53576 AA carriers exhibited significant better performance in parameters related to non-verbal ToM (ToM general rule and intentionality score). The results of hierarchical clustering in both groups support the findings by distinguishing between language-related and language-independent aspects of ToM. CONCLUSIONS: In the present study, we examined the association between rs2268498 and rs53576 and social functioning in individuals with ASD and TD group. We found preliminary evidence that rs2268498 and rs53576 are associated with ToM related abilities in healthy individuals as well as in autistic individuals. Accordingly, rs2268498 and rs53576 may play an important role in predicting ToM capabilities. It will be necessary to conduct further research to address the association of genetic variants with a deficit in ToM in individuals with ASD.

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7. Hsu CT, Sato W, Yoshikawa S. An investigation of the modulatory effects of empathic and autistic traits on emotional and facial motor responses during live social interactions. PLoS One;2024;19(1):e0290765.

A close relationship between emotional contagion and spontaneous facial mimicry has been theoretically proposed and is supported by empirical data. Facial expressions are essential in terms of both emotional and motor synchrony. Previous studies have demonstrated that trait emotional empathy enhanced spontaneous facial mimicry, but the relationship between autistic traits and spontaneous mimicry remained controversial. Moreover, previous studies presented faces that were static or videotaped, which may lack the « liveliness » of real-life social interactions. We addressed this limitation by using an image relay system to present live performances and pre-recorded videos of smiling or frowning dynamic facial expressions to 94 healthy female participants. We assessed their subjective experiential valence and arousal ratings to infer the amplitude of emotional contagion. We measured the electromyographic activities of the zygomaticus major and corrugator supercilii muscles to estimate spontaneous facial mimicry. Individual differences measures included trait emotional empathy (empathic concern) and the autism-spectrum quotient. We did not find that live performances enhanced the modulatory effect of trait differences on emotional contagion or spontaneous facial mimicry. However, we found that a high trait empathic concern was associated with stronger emotional contagion and corrugator mimicry. We found no two-way interaction between the autism spectrum quotient and emotional condition, suggesting that autistic traits did not modulate emotional contagion or spontaneous facial mimicry. Our findings imply that previous findings regarding the relationship between emotional empathy and emotional contagion/spontaneous facial mimicry using videos and photos could be generalized to real-life interactions.

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8. Işık-Uslu AE, Çetin Z. Early intervention service needs of mothers with a child diagnosed with autism spectrum disorder in Turkey: A qualitative study. J Pediatr Nurs;2024 (Jan 9)

BACKGROUND: Early intervention services play a crucial role in the prevention and management of Autism Spectrum Disorder (ASD). With the increasing prevalence of ASD, understanding the specific needs of mothers and their children is essential for the development of effective interventions and support systems. METHODS: This interview study examines the early intervention service needs of Turkish mothers with children aged 2-6 who have been diagnosed with ASD. Semi-structured in-depth interviews were conducted with nine mothers. Thematic analysis was carried out following the guidance and six steps procedures described by Braun and Clarke. FINDINGS: The study’s findings reveal six distinct themes that encompass the needs expressed by the participating mothers: 1) psychological support needs, 2) social support needs, 3) financial support needs, 4) strengthening the family, 5) government-based enhancement, and 6) the need for social awareness. DISCUSSION: The findings underscore the significance of comprehensive early intervention services tailored to address the needs of mothers. The stressors associated with the impact of ASD on families are highlighted, aligning with Guralnick’s framework. The findings emphasize the need for holistic intervention programs and stress the importance of collaborative relationships among parents, educators, and service providers. APPLICATION TO PRACTICE: The practical implications of this study benefit healthcare professionals, policymakers, educators, and stakeholders. The emphasis lies in aligning interventions with the ASD needs of both mothers and children, ultimately aiding in the development of effective policies and the enhancement of the quality of care for individuals with ASD in Turkey.

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9. Kojovic N, Cekic S, Castañón SH, Franchini M, Sperdin HF, Sandini C, Jan RK, Zöller D, Ben Hadid L, Bavelier D, Schaer M. Unraveling the developmental dynamic of visual exploration of social interactions in autism. Elife;2024 (Jan 9);13

Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.

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10. Mishra BR, Biswas T, Chakraborty R, Bhoi R, Ranjan R, Pattojoshi A. Maintenance Electroconvulsive Therapy in Autism Spectrum Disorder With Comorbid Psychosis Presenting With Recurrent Pharmaco-Resistant Catatonia: A Case Report. J ect;2023 (Dec 29)

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11. O’Hagan B, Augustyn M, Amgott R, White J, Hardesty I, Bangham C, Ursitti A, Foster S, Chandler A, Greece J. Using normalization process theory to inform practice: evaluation of a virtual autism training for clinicians. Front Health Serv;2023;3:1242908.

BACKGROUND: There is growing demand for developmental and behavioral pediatric services including autism evaluation and care management. Clinician trainings have been found to result in an increase of knowledge and attitudes. This study utilizes Normalization Process theory (NPT) to evaluate a clinician training program and its effects on practice. METHODS: The year-long virtual training program about autism screening and care management included didactic portions and case presentations. Focus groups and interviews were conducted with primary care clinicians (n = 10) from community health centers (n = 6) across an urban area five months post-training. Transcripts were deductively coded using NPT to uncover barriers to implementation of autism screening and care, benefits of the training program, and areas for future training. RESULTS: Participants were motivated by the benefits of expanding and improving support for autistic patients but noted this effort requires effective collaboration within a complex network of care providers including clinicians, insurance agencies, and therapy providers. Although there were support that participants could provide to families there were still barriers including availability of behavior therapy and insufficient staffing. Overall, participants positively viewed the training and reported implementing new strategies into practice. CONCLUSION: Despite the small sample size, application of NPT allowed for assessment of both training delivery and implementation of strategies, and identification of recommendations for future training and practice sustainability. Follow-up focus groups explored participants’ practice five months post-program. Variations in participants’ baseline experience and context at follow-up to enable application of skills should be considered when using NPT to evaluate clinician trainings.

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12. Ong LT, Fan SWD. Morphological and Functional Changes of Cerebral Cortex in Autism Spectrum Disorder. Innov Clin Neurosci;2023 (Oct-Dec);20(10-12):40-47.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by early-onset impairments in socialization, communication, repetitive behaviors, and restricted interests. ASD exhibits considerable heterogeneity, with clinical presentations varying across individuals and age groups. The pathophysiology of ASD is hypothesized to be due to abnormal brain development influenced by a combination of genetic and environmental factors. One of the most consistent morphological parameters for assessing the abnormal brain structures in patients with ASD is cortical thickness. Studies have shown changes in the cortical thickness within the frontal, temporal, parietal, and occipital lobes of individuals with ASD. These changes in cortical thickness often correspond to specific clinical features observed in individuals with ASD. Furthermore, the aberrant brain anatomical features and cortical thickness alterations may lead to abnormal brain connectivity and synaptic structure. Additionally, ASD is associated with cortical hyperplasia in early childhood, followed by a cortical plateau and subsequent decline in later stages of development. However, research in this area has yielded contradictory findings regarding the cortical thickness across various brain regions in ASD.

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13. Peralta-Marzal LN, Rojas-Velazquez D, Rigters D, Prince N, Garssen J, Kraneveld AD, Perez-Pardo P, Lopez-Rincon A. A robust microbiome signature for autism spectrum disorder across different studies using machine learning. Sci Rep;2024 (Jan 8);14(1):814.

Autism spectrum disorder (ASD) is a highly complex neurodevelopmental disorder characterized by deficits in sociability and repetitive behaviour, however there is a great heterogeneity within other comorbidities that accompany ASD. Recently, gut microbiome has been pointed out as a plausible contributing factor for ASD development as individuals diagnosed with ASD often suffer from intestinal problems and show a differentiated intestinal microbial composition. Nevertheless, gut microbiome studies in ASD rarely agree on the specific bacterial taxa involved in this disorder. Regarding the potential role of gut microbiome in ASD pathophysiology, our aim is to investigate whether there is a set of bacterial taxa relevant for ASD classification by using a sibling-controlled dataset. Additionally, we aim to validate these results across two independent cohorts as several confounding factors, such as lifestyle, influence both ASD and gut microbiome studies. A machine learning approach, recursive ensemble feature selection (REFS), was applied to 16S rRNA gene sequencing data from 117 subjects (60 ASD cases and 57 siblings) identifying 26 bacterial taxa that discriminate ASD cases from controls. The average area under the curve (AUC) of this specific set of bacteria in the sibling-controlled dataset was 81.6%. Moreover, we applied the selected bacterial taxa in a tenfold cross-validation scheme using two independent cohorts (a total of 223 samples-125 ASD cases and 98 controls). We obtained average AUCs of 74.8% and 74%, respectively. Analysis of the gut microbiome using REFS identified a set of bacterial taxa that can be used to predict the ASD status of children in three distinct cohorts with AUC over 80% for the best-performing classifiers. Our results indicate that the gut microbiome has a strong association with ASD and should not be disregarded as a potential target for therapeutic interventions. Furthermore, our work can contribute to use the proposed approach for identifying microbiome signatures across other 16S rRNA gene sequencing datasets.

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14. Peyre H, Peries M, Madieu E, David A, Picot MC, Pickles A, Baghdadli A. Association of difficulties in motor skills with longitudinal changes in social skills in children with autism spectrum disorder: findings from the ELENA French Cohort. Eur Child Adolesc Psychiatry;2024 (Jan 8)

Developmental coordination disorder is a frequently co-occurring condition with autism spectrum disorder (ASD). Several cross-sectional studies have reported that children with difficulties in motor skills have a higher severity of ASD symptoms. This study aims to examine the association of difficulties in motor skills with longitudinal changes in social skills in children with ASD. Participants were drawn from the ELENA cohort, a French longitudinal cohort of children with ASD. Motor skills were assessed using the Movement Assessment Battery for Children at baseline, while social skills were measured using the Autism Diagnostic Observation Schedule (ADOS-2) and the Vineland Adaptive Behavior Scales (VABS-II) at both the baseline and a follow-up assessment conducted 3 years later. A composite score of social skills was created at baseline and at both time points. Linear regression models were performed to assess the association between difficulties in motor skills and changes in social skills, considering potential confounders such as IQ, age, and gender. The sample included 162 children with ASD. Children with difficulties in global motor skills (N = 114) showed less favorable trajectories in social skills compared to those without motor difficulties. The results were consistent when examining the ADOS-2 and the VABS-II separately. This study provides evidence for the negative impact of difficulties in motor skills on the longitudinal development of social skills in children with ASD. Interventions targeting motor difficulties may have broader benefits, extending beyond motor function to improve socialization.

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15. Saponaro S, Lizzi F, Serra G, Mainas F, Oliva P, Giuliano A, Calderoni S, Retico A. Deep learning based joint fusion approach to exploit anatomical and functional brain information in autism spectrum disorders. Brain Inform;2024 (Jan 9);11(1):2.

BACKGROUND: The integration of the information encoded in multiparametric MRI images can enhance the performance of machine-learning classifiers. In this study, we investigate whether the combination of structural and functional MRI might improve the performances of a deep learning (DL) model trained to discriminate subjects with Autism Spectrum Disorders (ASD) with respect to typically developing controls (TD). MATERIAL AND METHODS: We analyzed both structural and functional MRI brain scans publicly available within the ABIDE I and II data collections. We considered 1383 male subjects with age between 5 and 40 years, including 680 subjects with ASD and 703 TD from 35 different acquisition sites. We extracted morphometric and functional brain features from MRI scans with the Freesurfer and the CPAC analysis packages, respectively. Then, due to the multisite nature of the dataset, we implemented a data harmonization protocol. The ASD vs. TD classification was carried out with a multiple-input DL model, consisting in a neural network which generates a fixed-length feature representation of the data of each modality (FR-NN), and a Dense Neural Network for classification (C-NN). Specifically, we implemented a joint fusion approach to multiple source data integration. The main advantage of the latter is that the loss is propagated back to the FR-NN during the training, thus creating informative feature representations for each data modality. Then, a C-NN, with a number of layers and neurons per layer to be optimized during the model training, performs the ASD-TD discrimination. The performance was evaluated by computing the Area under the Receiver Operating Characteristic curve within a nested 10-fold cross-validation. The brain features that drive the DL classification were identified by the SHAP explainability framework. RESULTS: The AUC values of 0.66±0.05 and of 0.76±0.04 were obtained in the ASD vs. TD discrimination when only structural or functional features are considered, respectively. The joint fusion approach led to an AUC of 0.78±0.04. The set of structural and functional connectivity features identified as the most important for the two-class discrimination supports the idea that brain changes tend to occur in individuals with ASD in regions belonging to the Default Mode Network and to the Social Brain. CONCLUSIONS: Our results demonstrate that the multimodal joint fusion approach outperforms the classification results obtained with data acquired by a single MRI modality as it efficiently exploits the complementarity of structural and functional brain information.

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16. Vacy K, Thomson S, Moore A, Eisner A, Tanner S, Pham C, Saffrey R, Mansell T, Burgner D, Collier F, Vuillermin P, O’Hely M, Boon WC, Meikle P, Burugupalli S, Ponsonby AL. Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years: a prospective birth cohort study. EBioMedicine;2024 (Jan 9);100:104949.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental conditions with early life origins. Alterations in blood lipids have been linked to ADHD and ASD; however, prospective early life data are limited. This study examined (i) associations between the cord blood lipidome and ADHD/ASD symptoms at 2 years of age, (ii) associations between prenatal and perinatal predictors of ADHD/ASD symptoms and cord blood lipidome, and (iii) mediation by the cord blood lipidome. METHODS: From the Barwon Infant Study cohort (1074 mother-child pairs, 52.3% male children), child circulating lipid levels at birth were analysed using ultra-high-performance liquid chromatography-tandem mass spectrometry. These were clustered into lipid network modules via Weighted Gene Correlation Network Analysis. Associations between lipid modules and ADHD/ASD symptoms at 2 years, assessed with the Child Behavior Checklist, were explored via linear regression analyses. Mediation analysis identified indirect effects of prenatal and perinatal risk factors on ADHD/ASD symptoms through lipid modules. FINDINGS: The acylcarnitine lipid module is associated with both ADHD and ASD symptoms at 2 years of age. Risk factors of these outcomes such as low income, Apgar score, and maternal inflammation were partly mediated by higher birth acylcarnitine levels. Other cord blood lipid profiles were also associated with ADHD and ASD symptoms. INTERPRETATION: This study highlights that elevated cord blood birth acylcarnitine levels, either directly or as a possible marker of disrupted cell energy metabolism, are on the causal pathway of prenatal and perinatal risk factors for ADHD and ASD symptoms in early life. FUNDING: The foundational work and infrastructure for the BIS was sponsored by the Murdoch Children’s Research Institute, Deakin University, and Barwon Health. Subsequent funding was secured from the Minderoo Foundation, the European Union’s Horizon 2020 research and innovation programme (ENDpoiNTs: No 825759), National Health and Medical Research Council of Australia (NHMRC) and Agency for Science, Technology and Research Singapore [APP1149047], The William and Vera Ellen Houston Memorial Trust Fund (via HOMER Hack), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O’Brien Memorial Asthma Foundation, the Our Women Our Children’s Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Ilhan Food Allergy Foundation, Geelong Medical and Hospital Benefits Association, Vanguard Investments Australia Ltd, the Percy Baxter Charitable Trust, and Perpetual Trustees.

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17. Vernocchi P, Marangelo C, Guerrera S, Del Chierico F, Guarrasi V, Gardini S, Conte F, Paci P, Ianiro G, Gasbarrini A, Vicari S, Putignani L. Gut microbiota functional profiling in autism spectrum disorders: bacterial VOCs and related metabolic pathways acting as disease biomarkers and predictors. Front Microbiol;2023;14:1287350.

BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder. Major interplays between the gastrointestinal (GI) tract and the central nervous system (CNS) seem to be driven by gut microbiota (GM). Herein, we provide a GM functional characterization, based on GM metabolomics, mapping of bacterial biochemical pathways, and anamnestic, clinical, and nutritional patient metadata. METHODS: Fecal samples collected from children with ASD and neurotypical children were analyzed by gas-chromatography mass spectrometry coupled with solid phase microextraction (GC-MS/SPME) to determine volatile organic compounds (VOCs) associated with the metataxonomic approach by 16S rRNA gene sequencing. Multivariate and univariate statistical analyses assessed differential VOC profiles and relationships with ASD anamnestic and clinical features for biomarker discovery. Multiple web-based and machine learning (ML) models identified metabolic predictors of disease and network analyses correlated GM ecological and metabolic patterns. RESULTS: The GM core volatilome for all ASD patients was characterized by a high concentration of 1-pentanol, 1-butanol, phenyl ethyl alcohol; benzeneacetaldehyde, octadecanal, tetradecanal; methyl isobutyl ketone, 2-hexanone, acetone; acetic, propanoic, 3-methyl-butanoic and 2-methyl-propanoic acids; indole and skatole; and o-cymene. Patients were stratified based on age, GI symptoms, and ASD severity symptoms. Disease risk prediction allowed us to associate butanoic acid with subjects older than 5 years, indole with the absence of GI symptoms and low disease severity, propanoic acid with the ASD risk group, and p-cymene with ASD symptoms, all based on the predictive CBCL-EXT scale. The HistGradientBoostingClassifier model classified ASD patients vs. CTRLs by an accuracy of 89%, based on methyl isobutyl ketone, benzeneacetaldehyde, phenyl ethyl alcohol, ethanol, butanoic acid, octadecane, acetic acid, skatole, and tetradecanal features. LogisticRegression models corroborated methyl isobutyl ketone, benzeneacetaldehyde, phenyl ethyl alcohol, skatole, and acetic acid as ASD predictors. CONCLUSION: Our results will aid the development of advanced clinical decision support systems (CDSSs), assisted by ML models, for advanced ASD-personalized medicine, based on omics data integrated into electronic health/medical records. Furthermore, new ASD screening strategies based on GM-related predictors could be used to improve ASD risk assessment by uncovering novel ASD onset and risk predictors.

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18. Wang J, Zou L, Jiang P, Yao M, Xu Q, Hong Q, Zhu J, Chi X. Vitamin A ameliorates valproic acid-induced autism-like symptoms in developing zebrafish larvae by attenuating oxidative stress and apoptosis. Neurotoxicology;2024 (Jan 6)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive/stereotyped behaviors. Prenatal exposure to valproic acid (VPA) has been reported to induce ASD-like symptoms in human and rodents. However, the etiology and pathogenesis of ASD have not been well elucidated. This study aimed to explore the mechanisms underlying VPA-induced ASD-like behaviors using zebrafish model and investigated whether vitamin A could prevent VPA-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 25 and 50μM VPA from 4 to 96hours post fertilization (hpf) and the neurotoxicity was assessed. Our results showed that VPA affected the normal development of zebrafish larvae and induced ASD-like behaviors, including reduced locomotor activity, decreased distance near conspecifics, impaired social interaction and repetitive swimming behaviors. Exposure to VPA decreased the GFP signal in transgenic HuC:egfp zebrafish according to the negative effect of VPA on the expression of neurodevelopmental genes. In addition, VPA enhanced oxidative stress by promoting the production of reactive oxygen species (ROS) and hydrogen peroxide (H(2)O(2)) and inhibiting the activity of superoxide dismutase, then triggered apoptosis by upregulation of apoptotic genes. These adverse outcomes were mitigated by vitamin A, suggesting that vitamin A rescued VPA-induced ASD-like symptoms by inhibiting oxidative stress and apoptosis. Overall, this study identified vitamin A as a promising strategy for future therapeutic regulator of VPA-induced ASD-like behaviors.

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19. Warreman EB, Nooteboom LA, Leenen PJM, Geurts HM, Terry MB, Bos JHJ, Hak E, Hoek HW, van Rossum EFC, Vermeiren R, Ester WA. Metabolic syndrome in adults with autistic traits: associated psychological, behavioral, and biological factors in females and males – a PharmLines initiative. Front Psychiatry;2023;14:1303840.

BACKGROUND: While cardiovascular diseases is highly prevalent and an important cause of mortality in autistic adults, knowledge on their increased cardiovascular risk is limited. Hence, this study aimed to investigate psychological, behavioral, and physical factors associated with metabolic syndrome (MetS) in adults with autistic traits. METHODS: In total, 17,705 adults from the Lifelines Cohort were included and categorized using Autism Spectrum Quotient-10 sum-scores. The quartiles with highest (HQ-traits-group females: n = 2,635; males: n = 1803) and lowest levels of autistic traits (LQ-traits-group, n = idem) were analyzed. Using multivariable logistic regression, the associations between MetS and (self-reported and interviewed) psychological, behavioral, and physically measured factors in these stratified groups were investigated. RESULTS: Among females, MetS was more common in the HQ-traits-group than in the LQ-traits-group (10.0% versus 7.5%, p < 0.01), while this was not the case among males (HQ-traits-group 13.8% versus LQ-traits-group 13.1%, p = 0.52). In both the female and male HQ-traits-group, the presence of MetS was associated with poorer self-reported health, less daily physical activity, and altered leukocyte counts. CONCLUSION: These findings underline the relevance of adequate cardiovascular prevention in adults with higher levels of autistic traits. Future research could gain more insight into the relationship between cardiovascular risk and autistic traits in females, and into tailored cardiovascular prevention.

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20. Zaccarelli-Magalhães J, Manes M, Féba LS, Abreu GR, Flório JC, Ricci EL, Felício LF, Spinosa HS. Do Autistic and Depressed Rats Express the Same Type of Maternal Care?. Neuroscience;2024 (Jan 9);536:72-78.

Autism is a neurodevelopmental disorder that is more frequently diagnosed in men. Nevertheless, through current diagnostic tools, women have also been found to be affected by this disorder, but in different ways. Few studies have been conducted regarding unique periods of life, such as motherhood. Yet, extant literature has already described the existence of a comorbidity between autism and postpartum depression. Thus, this study aimed to compare the maternal care sphere between two animal models of these diseases. Lactating rats were subdivided into three groups (n = 8 animals/group): 1) control dams; 2) maternal separation (MS) dams, separated from their litter for 3 h daily from lactating day (LD) 2-12 for postpartum depression induction; and 3) valproic acid (VPA) dams, which were the pups of dams treated with 400 mg/kg of VPA (i.p.) on gestational day 12.5 for autism induction. Maternal care tests were performed during lactation and, after weaning, dams were euthanized for the analysis of dopaminergic system on the prefrontal cortex. The results showed an impairment of maternal care of MS dams and an improvement of VPA dams, as well as alterations on dopaminergic system that corroborates the behavior data. These findings indicate that VPA dams express better maternal care, even with cognitive and socialization difficulties. This is probably due to a hyper-focus, as opposed to MS dams, which mimic the maternal care dysfunction expressed by women with postpartum depression.

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