1. Abraham DA, Narasimhan U, Mahalingam VT, Krishnan M, Ganesan RM, Goh KW, Tan CS, Ming LC, Ardianto C. Estimation of Plasma Concentration of L-Carnosine and its Correlation with Core Symptoms of Autism Spectrum Disorder Children: A Pilot Clinical Trial. Front Biosci (Landmark Ed). 2024; 29(10): 365.

BACKGROUND: Literature indicates that L-carnosine may be deficient in autism spectrum disorder (ASD) children. The aim of the present study was to estimate the level of L-carnosine in plasma and correlate it with the Autism Treatment Evaluation Checklist (ATEC) and Childhood Autism Rating Scale 2nd Edition, Standard Version (CARS2-ST) scores. To measure L-carnosine level, a bio-analytical method was developed using reverse phase high- liquid chromatography and validated as per International Conference on Harmonization guidelines. METHOD: Children were supplemented with L-carnosine (10-15 mg/kg) along with standard care therapies for 2 months. Before and after supplementation, scores on the ATEC, CARS2-ST, BEARS sleep screening tool, 6-item Gastrointestinal Severity Index, and Parental Stress Scale were evaluated, and L-carnosine was measured at the end of the trial. RESULTS: The calibration curve was linear in the range of 100-600 ng/mL (R(2) = 0.998). The level of L-carnosine quantified was 33.7 ± 0.2 ng/mL. There was no significant difference found in any of the outcome measures (p > 0.05). CONCLUSIONS: Despite the fact that L-carnosine is detectable in the blood, it was found to be ineffective in the management of ASD in children. CLINICAL TRIAL REGISTRATION: The study was registered in the Clinical Trial Registry-India, registration number: CTRI/2019/07/020102.

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2. Au Yeung TTW, Hui MMC, Kung KTF. An Empirical Qualitative Investigation into Psychosexual Development in and Sex Education for Autistic Youth: Insights from Autistic and Non-Autistic Young Adults. J Autism Dev Disord. 2024.

The present study was designed to examine autistic and non-autistic young adults’ lived experience in psychosexual development and sex education and to solicit recommendations on how to improve sex education programs. Participants included 10 autistic young adults and 10 non-autistic young adults aged 18 to 24 years. The two groups were matched for sex and education level. One-on-one semi-structured interviews were conducted. Participants’ responses were analyzed using comparative interpretative phenomenological analysis. Four superordinate themes emerged: (1) « Who am I as a sexual being »; (2) Making sense of psychosexual development; (3) Sources of information; and (4) « Dear developers of sex education programs ». Most autistic participants shared feelings of intense anxiety about romantic and sexual relationships, in part due to anticipated difficulties in social communication. Interestingly, although interview questions mostly focused on sex and adolescence, issues surrounding romantic relationships and their links to current self-concept were prominent themes in many autistic participants’ responses, suggesting that autism-friendly sex education programs need to address issues related to romance and should target not only adolescents but also young adults. Also, autistic participants learned from peer interactions within the autistic community, highlighting the importance of facilitating peer exchanges and continuous learning beyond completing a program. Regarding delivery format, autistic participants valued concreteness and a mixed-sex small-group setting, and recommended using visual cues, real life examples, and role play. Autistic individuals have unmet psychosexual educational needs. Further research may consider their needs, lived experience, and recommendations when developing new autism-friendly sex education programs.

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3. Bryers A, Hawkes CA, Parkin E, Dawson N. Progress towards understanding risk factor mechanisms in the development of autism spectrum disorders. Biochem Soc Trans. 2024; 52(5): 2047-58.

Autism spectrum disorders (ASD) are a heterogenous set of syndromes characterised by social impairment and cognitive symptoms. Currently, there are limited treatment options available to help people with ASD manage their symptoms. Understanding the biological mechanisms that result in ASD diagnosis and symptomatology is an essential step in developing new interventional strategies. Human genetic studies have identified common gene variants of small effect and rare risk genes and copy number variants (CNVs) that substantially increase the risk of developing ASD. Reverse translational studies using rodent models based on these genetic variants provide new insight into the biological basis of ASD. Here we review recent findings from three ASD associated CNV mouse models (16p11.2, 2p16.3 and 22q11.2 deletion) that show behavioural and cognitive phenotypes relevant to ASD. These models have identified disturbed excitation-inhibition neurotransmitter balance, evidenced by dysfunctional glutamate and GABA signalling, as a key aetiological mechanism. These models also provide emerging evidence for serotoninergic neurotransmitter system dysfunction, although more work is needed to clarify the nature of this. At the brain network level, prefrontal cortex (PFC) dysfunctional connectivity is also evident across these models, supporting disturbed PFC function as a key nexus in ASD aetiology. Overall, published data highlight the utility and valuable insight gained into ASD aetiology from preclinical CNV mouse models. These have identified key aetiological mechanisms that represent putative novel therapeutic targets for the treatment of ASD symptoms, making them useful translational models for future drug discovery, development and validation.

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4. Doherty M, Chown N, Martin N, Shaw SCK. Autistic psychiatrists’ experiences of recognising themselves and others as autistic: a qualitative study. BJPsych Open. 2024; 10(6): e183.

BACKGROUND: Diagnosis of autism falls under the remit of psychiatry. Recognition that psychiatrists could be autistic is recent. Psychiatrists are the second largest specialty group in Autistic Doctors International, a peer support group for autistic doctors. AIMS: To explore the experiences of autistic psychiatrists in relation to recognising themselves and others as autistic. METHOD: This was a qualitative study using loosely structured interviews and an interpretive phenomenological analysis. RESULTS: Eight autistic senior psychiatrists based in the UK participated. One had a childhood diagnosis, two had been diagnosed in adulthood and the remainder self-identified as autistic as adults. Recognition of autism followed diagnosis of their children or encounters with autistic patients. Barriers to self-recognition included lack of autism training, the deficit-based diagnostic criteria and stereotypical views of autism. Recognising that they were autistic led to the realisation that many colleagues were also likely to be autistic, particularly in neurodevelopmental psychiatry. All participants reported the ability to quickly recognise autistic patients and to develop a good rapport easily, once they were aware of their own autistic identity. Difficulties recognising patients as autistic occurred before self-recognition when they shared autistic characteristics and experiences. ‘If we don’t recognise ourselves as autistic how on earth can we diagnose patients accurately?’ CONCLUSIONS: Autistic psychiatrists face multiple barriers to recognising that they are autistic. Lack of self-recognition may impede diagnostic accuracy with autistic patients. Self-recognition and disclosure by autistic psychiatrists may be facilitated by reframing the traditional deficit-based view of autism towards a neurodiversity-affirmative approach, with consequent benefits for autistic patients.

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5. Eisfeldt J, Higginbotham EJ, Lenner F, Howe J, Fernandez BA, Lindstrand A, Scherer SW, Feuk L. Resolving complex duplication variants in autism spectrum disorder using long-read genome sequencing. Genome Res. 2024.

Rare or de novo structural variation, primarily in the form of copy number variants, is detected in 5%-10% of autism spectrum disorder (ASD) families. While complex structural variants involving duplications can generally be detected using microarray or short-read genome sequencing (GS), these methods frequently fail to characterize breakpoints at nucleotide resolution, requiring additional molecular methods for validation and fine-mapping. Here, we use Oxford Nanopore Technologies PromethION long-read GS to characterize complex genomic rearrangements (CGRs) involving large duplications that segregate with ASD in five families. In total, we investigated 13 CGR carriers and were able to resolve all breakpoint junctions at nucleotide resolution. While all breakpoints were identified, the precise genomic architecture of one rearrangement remained unresolved with three different potential structures. The findings in two families include potential fusion genes formed through duplication rearrangements, involving IL1RAPL1-DMD and SUPT16H-CHD8 In two of the families originating from the same geographical region, an identical rearrangement involving ANK2 was identified, which likely represents a founder variant. In addition, we analyze methylation status directly from the long-read data, allowing us to assess the activity of rearranged genes and regulatory regions. Investigation of methylation across the CGRs reveals aberrant methylation status in carriers across a rearrangement affecting the CREBBP locus. In aggregate, our results demonstrate the utility of nanopore sequencing to pinpoint CGRs associated with ASD in five unrelated families, and highlight the importance of a gene-centric description of disease-associated complex chromosomal rearrangements.

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6. Garikipati A, Ciobanu M, Singh NP, Barnes G, Dinenno FA, Geisel J, Mao Q, Das R. Parent-Led Applied Behavior Analysis to Impact Clinical Outcomes for Individuals on the Autism Spectrum: Retrospective Chart Review. JMIR Pediatr Parent. 2024; 7: e62878.

BACKGROUND: Autism spectrum disorder (ASD) can have traits that impact multiple domains of functioning and quality of life, which can persevere throughout life. To mitigate the impact of ASD on the long-term trajectory of an individual’s life, it is imperative to seek early and adequate treatment via scientifically validated approaches, of which applied behavior analysis (ABA) is the gold standard. ABA treatment must be delivered via a behavior technician with oversight from a board-certified behavior analyst. However, shortages in certified ABA therapists create treatment access barriers for individuals on the autism spectrum. Increased ASD prevalence demands innovations for treatment delivery. Parent-led treatment models for neurodevelopmental conditions are effective yet underutilized and may be used to fill this care gap. OBJECTIVE: This study reports findings from a retrospective chart review of clinical outcomes for children that received parent-led ABA treatment and intends to examine the sustained impact that modifications to ABA delivery have had on a subset of patients of Montera, Inc. dba Forta (« Forta »), as measured by progress toward skill acquisition within multiple focus areas (FAs). METHODS: Parents received ≥40 hours of training in ABA prior to initiating treatment, and patients were prescribed focused (<25 hours/week) or comprehensive (>25-40 hours/week) treatment plans. Retrospective data were evaluated over ≥90 days for 30 patients. The clinical outcomes of patients were additionally assessed by age (2-5 years, 6-12 years, 13-22 years) and utilization of prescribed treatment. Treatment encompassed skill acquisition goals; to facilitate data collection consistency, successful attempts were logged within a software application built in-house. RESULTS: Improved goal achievement success between weeks 1-20 was observed for older age, all utilization, and both treatment plan type cohorts. Success rates increased over time for most FAs, with the exception of executive functioning in the youngest cohort and comprehensive plan cohort. Goal achievement experienced peaks and declines from week to week, as expected for ABA treatment; however, overall trends indicated increased skill acquisition success rates. Of 40 unique combinations of analysis cohorts and FAs, 20 showed statistically significant positive linear relationships (P<.05). Statistically significant positive linear relationships were observed in the high utilization cohort (communication with P=.04, social skills with P=.02); in the fair and full utilization cohorts (overall success with P=.03 for the fair utilization cohort and P=.001 for the full utilization cohort, and success in emotional regulation with P<.001 for the fair utilization cohort and P<.001 for the full utilization cohort); and in the comprehensive treatment cohort (communication with P=.001, emotional regulation with P=.045). CONCLUSIONS: Parent-led ABA can lead to goal achievement and improved clinical outcomes and may be a viable solution to overcome treatment access barriers that delay initiation or continuation of care.

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7. Gaynor C, Chen Y, Tager-Flusberg H. Concurrent predictors of behavioral inflexibility in minimally verbal and verbal autistic children. Autism Res. 2024.

Behavioral inflexibility (BI) refers to the rigid and inflexible patterns of behaviors that are a core aspect of autism. Few studies have investigated BI in autism separately from other restricted and repetitive behaviors (RRBs). The present study used a relatively new measure, the behavioral inflexibility scale (BIS; Lecavalier, L., Bodfish, J., Harrop, C., Whitten, A., Jones, D., Pritchett, J., Faldowski, R., & Boyd, B. (2020). Autism Research, 13(3), 489-499), to examine the relationship of BI and variables that are both core symptoms in autism as well as symptoms associated with cooccurring mental health conditions, atypical sensory experiences, and adaptive functioning in a sample of 87 children with autism. Additionally, we aimed to understand how these relationships may be related to autistic individuals’ verbal status: minimally verbal (MV) or verbal. Results revealed that anxiety, attention deficit/hyperactive, depressive, oppositional defiance problems, and sensory differences were all significantly correlated with BI in the MV group. In contrast, only anxiety, depressive, and oppositional defiance problems were significantly correlated with BI in the verbal group. Linear regression analyses showed that oppositional defiance problems and atypical sensory experiences explained a significant proportion of the variance of BI in the MV group, whereas only depressive problems were significant in the verbal group after accounting for other mental health conditions. Overall, our findings demonstrate that multiple aspects of psychopathology are significantly related to BI and can have broader implications for interventions and mental health care in autistic children.

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8. Grosvenor LP, Croen LA, Lynch FL, Marafino BJ, Maye M, Penfold RB, Simon GE, Ames JL. Autism Diagnosis Among US Children and Adults, 2011-2022. JAMA Netw Open. 2024; 7(10): e2442218.

IMPORTANCE: An improved understanding of autism spectrum disorder (ASD) prevalence over time and across the lifespan can inform health care service delivery for the growing population of autistic children and adults. OBJECTIVE: To describe trends in the prevalence of ASD diagnoses using electronic records data from a large network of health systems in the US. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study examined annual diagnosis rates in health records of patients in US health systems from January 1, 2011, to December 31, 2022. Eligible individuals were included in the study sample for a given calendar year if they were enrolled in a participating health system for at least 10 months out of the year. Data were extracted from 12 sites participating in the Mental Health Research Network, a consortium of research centers embedded within large, diverse health care systems. MAIN OUTCOME AND MEASURES: Diagnoses of ASD were ascertained using International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) revision codes. Annual diagnosis rates were calculated as the number of unique members diagnosed, divided by the total members enrolled. RESULTS: A total of 12 264 003 members were enrolled in 2022 (2 359 359 children aged 0 to 17 years [19.2%]; 6 400 222 female [52.2%]; 93 002 American Indian or Alaska Native [0.8%], 1 711 950 Asian [14.0%], 952 287 Black or African American [7.8%], 2 971 355 Hispanic [24.2%], 166 144 Native Hawaiian or Pacific Islander [1.4%], and 6 462 298 White [52.7%]). The ASD diagnosis rate was greatest among 5-to-8-year-olds throughout the study period and increased by 175% among the full sample, from 2.3 per 1000 in 2011 to 6.3 per 1000 in 2022. The greatest relative increase in diagnosis rate from 2011 to 2022 occurred among 26-to-34-year-olds (450%) and increases were greater for female vs male individuals among children (305% [estimated annual percentage change (EAPC), 13.62 percentage points; 95% CI, 12.49-14.75 percentage points] vs 185% [EAPC, 9.63 percentage points; 95% CI, 8.54-10.72 percentage points], respectively) and adults (315% [EAPC, 13.73 percentage points; 95% CI, 12.61-14.86 percentage points] vs 215% [EAPC, 10.33 percentage points; 95% CI, 9.24-11.43 percentage points]). Relative increases were greater in racial and ethnic minority groups compared with White individuals among children, but not adults. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of children and adults in the US, ASD diagnosis rates increased substantially between 2011 and 2022, particularly among young adults, female children and adults, and children from some racial or ethnic minority groups. Diagnosis prevalence trends generated using health system data can inform the allocation of resources to meet the service needs of this growing, medically complex population.

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9. Khan H, Rihal V, Kaur A, Singh TG. Proposed Hypothesis of TWEAK/Fn14 Receptor Modulation in Autism Spectrum Disorder. CNS Neurol Disord Drug Targets. 2024.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a complex, multiple etiology that is marked by impaired social interaction, communication, and repetitive behaviour. There is presently no pharmaceutical treatment for the core symptoms of ASD, even though the prevalence of ASD is increasing worldwide. Treatment of autism spectrum disorder involves the interaction of numerous signalling pathways, such as the Wnt/beta-catenin pathway, probiotics and kynurenine pathway, PPAR pathway, PI3K-AKT-mTOR pathway, Hedgehog signaling pathway, etc. The scientific literature has revealed TWEAK/Fn14 to not be explored in the autism spectrum disorder. In vitro and in vivo, TWEAK can control a wide range of cellular responses. Recent research has revealed that TWEAK and Fn14 are expressed in the Central Nervous System (CNS) and upregulated in perivascular endothelial cells, astrocytes, neurons, and microglia in response to various stimuli, including cerebral ischemia. This upregulation is followed by cell death and an increase in Blood-brain Barrier (BBB) permeability. The study has revealed that Aurintricarboxylic Acid (ATA) acts as an agent that suppresses TWEAK/Fn14 signaling. Similarly, from the discussion, it has been emphasized that the proposed molecular TWEAK/Fn14 signalling pathway can be considered as a therapeutic approach in the management of autism spectrum disorder.

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10. Klila H, Giuliani F. [Autism spectrum disorder in woman and application of current recommendations]. Rev Med Suisse. 2024; 20(893): 2011-4.

The concept of autism has led to the inclusion of increasingly heterogeneous and atypical individuals. Clinicians find it difficult to establish clear boundaries between autism, other psychiatric and/or neurodevelopmental disorders and atypical individuals, despite standardized instruments. What’s more, these standardized instruments have been built around the male phenotype, and do not allow for an accurate assessment of autism in women. Whatever the gender, the diagnosis is based on multiple, variable, disabling and persistent deficits. Finally, we’ll mention a few recommendations to help clinicians make a diagnosis or invoke the precautionary principle.

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11. Lapierre M, Elgbeili G, Laplante DP, O’Hara MW, D’Antono B, King S. Prenatal maternal subjective distress predicts higher autistic-like traits in offspring: The Iowa Flood Study. Dev Psychopathol. 2024: 1-13.

Autism spectrum disorder prevalence more than quadrupled in the United States between 2000 and 2020. Ice storm-related prenatal maternal stress (PNMS) predicts autistic-like trait severity in children exposed early in gestation. The objective was to determine the extent to which PNMS influences the severity and trajectory of autistic-like traits in prenatally flood-exposed children at ages 4-7 years and to test moderation by sex and gestational timing. Soon after the June 2008 floods in Iowa, USA, 268 women pregnant during the disaster were assessed for objective hardship, subjective distress, and cognitive appraisal of the experience. When their children were 4, 5½, and 7 years old, mothers completed the Social Communication Questionnaire (SCQ) to assess their children’s autistic-like traits; 137 mothers completed the SCQ for at least one age. The final longitudinal multilevel model showed that the greater the maternal subjective distress, the more severe the child’s autistic-like traits, controlling for objective hardship. The effect of PNMS on rate of change was not significant, and there were no significant main effects or interactions involving sex or timing. Prenatal maternal subjective distress, but not objective hardship or cognitive appraisal, predicted more severe autistic-like traits at age 4, and this effect remained stable through age 7.

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12. Leisman G. Neurodiversity and Autism Spectrum Disorder: An Ostriches’ Head in the Sand?. J Integr Neurosci. 2024; 23(10): 186.

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13. Negi K, Saini V, Kumar S, Sharma U, Jacob NE. Stress Assessment in Parents of Children With Autism Spectrum Disorder: A Prospective Case-Control Study. Cureus. 2024; 16(9): e70438.

BACKGROUND: Autism spectrum disorder (ASD) is a disorder that is manageable but has no cure. Therefore, it is associated with parental stress, which is often not given importance. Early identification and holistic management of children with ASD are needed. METHODS: This prospective case-control study, conducted over 18 months, included 111 newly diagnosed autism cases (ages 2-9) from the Child Development Clinic at Shri Mahant Indiresh Hospital, Dehradun, India, diagnosed as per the International Clinical Epidemiology Network (INCLEN) criteria (DSM-V). Controls were 99 typically developing children from a well-baby clinic. Data collection involved administering the Autism Parenting Stress Scale and a predesigned questionnaire to both cases and controls. Parents with psychiatric or mental health issues were excluded. RESULTS: Parents of children with autism exhibited significantly higher stress scores compared to parents of typically developing children. In our study, out of a total of 210 subjects, 52.9% were diagnosed with autism, while 47.1% were controls. Cases were analyzed based on household and socioeconomic background. It was found that 94.6% of the cases showed significant stress levels. CONCLUSION: ASD significantly impacts parental stress, particularly among families from higher socioeconomic backgrounds and metropolitan areas. This study emphasizes the need for targeted support and interventions to address elevated stress levels and improve family dynamics, especially for parents of higher-functioning children.

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14. Phan JM, Dwyer P, Elsherif MM, Friedel E, Kapp SK. Oxytocin in autism: Rethinking treatment and research through a neurodivergent perspective. Psychoneuroendocrinology. 2024; 171: 107220.

This perspective piece addresses critical challenges in oxytocin-based interventions for autism, drawing on neurodivergent perspectives to highlight key issues in research relevance and inclusivity. Although oxytocin has been posited to modulate social and routinized behaviors in autistic individuals, empirical findings on its efficacy remain inconsistent. We argue that these behavioral targets may reflect neurotypical biases, often disregarding autistic individuals’ perspectives, thereby limiting intervention acceptability and efficacy. Past research has frequently excluded marginalized autistic populations, including individuals with intellectual disabilities or gender-diverse identities, exacerbating generalizability issues. This piece advocates for a reorientation of research objectives in autism, proposing a shift from modifying core autistic behaviors towards enhancing quality of life through participatory research. By integrating autistic perspectives into study design and outcome selection, researchers move away from deficit-oriented frameworks and instead prioritize socially valid outcomes, such as reducing anxiety and improving adaptive functioning. Further, the perspective piece critiques the reliance on animal models, which often lack translational validity due to autism’s complex social and communicative dimensions. In closing, we underscore the importance of inclusive, reproducible autism research practices that align with the lived experiences and priorities of autistic individuals. Embracing participatory research, alongside rigorous methodological adjustments, can foster advancements that effectively support the well-being of the autistic community.

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15. Salia S, Burke FF, Hinks ME, Randell AM, Matheson MA, Walling SG, Swift-Gallant A. Gut microbiota transfer from the preclinical maternal immune activation model of autism is sufficient to induce sex-specific alterations in immune response and behavioural outcomes. Brain Behav Immun. 2024; 123: 813-23.

The gut microbiome plays a vital role in health and disease, including neurodevelopmental disorders like autism spectrum disorder (ASD). ASD affects 4:1 males-to-females, and sex differences are apparent in gut microbiota composition among ASD individuals and in animal models of this condition, such as the maternal immune activation (MIA) mouse model. However, few studies have included sex as a biological variable when assessing the role of gut microbiota in mediating ASD symptoms. Using the MIA model of ASD, we assessed whether gut microbiota contributes to the sex differences in the presentation of ASD-like behaviors. Gut microbiota transplantation from MIA or vehicle/control male and female mice into healthy, otherwise unmanipulated, 4-week-old C57Bl/6 mice was performed for 6 treatments over 12 days. Colonization with male, but not female, MIA microbiota was sufficient to reduce sociability, decrease microbiota diversity and increase neuroinflammation with more pronounced deficits in male recipients. Colonization with both male and female donor microbiota altered juvenile ultrasonic vocalizations and anxiety-like behavior in recipients of both sexes, and there was an accompanied change in the gut microbiota and serum cytokine IL-4 and IL-7 levels of all recipients of MIA gut microbiota. In addition to the increases in gut microbes associated with pathological states, the female donor microbiota profile also had increases in gut microbes with known neural protective effects (e.g., Lactobacillus and Rikenella). These results suggest that gut reactivity to environmental insults, such as in the MIA model, may play a role in shaping the sex disparity in ASD development.

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16. Shahkar L, Lashkarbolouk N, Bigdeli N, Mazandarani M. Coinfection of pulmonary lophomoniasis, tuberculosis, and hydatid cyst in a pediatric autism patient: a case report and literature review. BMC Pediatr. 2024; 24(1): 689.

INTRODUCTION: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition marked by difficulties in social interaction, communication, and repetitive behaviors or restricted interests. Although research on the link between ASD and parasitic diseases is limited, immune deficiency and inflammation may contribute to the development of parasitic infections. CASE REPORT: We admitted a 14-year-old boy to the hospital who had a known history of ASD because he was presenting with respiratory symptoms, including cough and hemoptysis. During his time in the hospital, after conducting a series of tests and evaluations, we made a critical diagnosis of co-infection of lophomonas, tuberculosis, and hydatid cyst. In response to this diagnosis, we initiated a treatment plan that involved administering appropriate antibiotics as well as preparing for surgical intervention. CONCLUSION: This case report highlights the complexities and challenges of managing such a rare combination of co-infections with TB, pulmonary hydatid disease and lophomonas in a pediatric patient with underlying developmental considerations such as ASD.

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17. Shi Y, Gong Y, Guan Y, Tang J. Generation and discrimination of autism MRI images based on autoencoder. Front Psychiatry. 2024; 15: 1395243.

This study aims to explore an autoencoder-based method for generating brain MRI images of patients with Autism Spectrum Disorder (ASD) and non-ASD individuals, and to discriminate ASD based on the generated images. Initially, we introduce the research background of ASD and related work, as well as the application of deep learning in the field of medical imaging. Subsequently, we detail the architecture and training process of the proposed autoencoder model, and present the results of generating MRI images for ASD and non-ASD patients. Following this, we designed an ASD classifier based on the generated images and elucidated its structure and training methods. Finally, through analysis and discussion of experimental results, we validated the effectiveness of the proposed method and explored future research directions and potential clinical applications. This research offers new insights and methodologies for addressing challenges in ASD studies using deep learning technology, potentially contributing to the automated diagnosis and research of ASD.

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18. Smith-Young J, Pike A, Swab M, Chafe R. Parents’ and guardians’ experiences of barriers and facilitators in accessing autism spectrum disorder diagnostic services for their children: a qualitative systematic review. JBI Evid Synth. 2024.

OBJECTIVE: The objectives of this review were to comprehensively identify the best available qualitative evidence about parents’ and guardians’ experiences of barriers and facilitators in accessing autism spectrum disorder (ASD) diagnostic services for their children; and to develop recommendations based on the review for addressing barriers to timely diagnosis and early intervention. INTRODUCTION: Early identification of ASD is a priority because the best chance for improving symptoms occurs through early and intensive intervention. A definitive ASD diagnosis is often a prerequisite for children to access publicly funded services, yet obtaining a diagnosis in itself can be stressful, frustrating, and time-consuming for many families. It is essential to understand the barriers and facilitators parents and guardians face in accessing ASD diagnostic services for their children. INCLUSION CRITERIA: This qualitative systematic review considered studies conducted worldwide that included parents and guardians of children up to 18 years of age who had accessed or who were attempting to access ASD diagnostic services for their children. METHODS: This review was conducted in accordance with the JBI methodology for systematic reviews of qualitative evidence. A literature search included CINAHL (EBSCOhost), CINAHL Plus (EBSCOhost), MEDLINE (EBSCOhost), APA PsycINFO (EBSCOhost), Social Services Abstracts (ProQuest), ERIC (EBSCOhost), and Embase. Gray literature sources included ProQuest Dissertations and Theses, Google Scholar, Google, OpenGrey, other online resources (government and organizational websites), and reference lists of retrieved records. No language, date, or country limits were applied to the searches. Retrieved records from the academic databases, gray literature, and reference lists of retrieved records were screened, with potentially relevant records examined in full against the inclusion criteria. Eligible studies were critically appraised for methodological quality and those included in this review were subjected to data extraction of descriptive details and study findings relevant to the review question. Study findings were synthesized and assigned confidence scores. All reviewers agreed upon the categories and finalized synthesized findings. RESULTS: The 36 included studies varied in qualitative research designs with high methodological quality. There were approximately 661 eligible participants, and 55 credible and unequivocal research findings. The research findings yielded 6 categories and 3 synthesized findings with moderate confidence scores. Parents’ and guardians’ ability to access ASD diagnostic services for their children is affected by i) encountering health care providers who actively listened to and addressed parents’ and guardians’ concerns instead of dismissing them, providing a sense of support and validation; ii) facing extended waiting times and associated financial burdens resulting in frustration and associated financial impact when delays occurred; and iii) encountering health care providers lacking specialized knowledge about ASD contributing to parents’ and guardians’ confusion due to inaccurate or conflicting diagnoses related to ASD comorbidities. CONCLUSION: Many parents described their journey in accessing ASD assessment and diagnostic services for their children as cumbersome. Parents’ and guardians’ experiences were affected by the level of perceived support by and knowledge of health care providers; confusion surrounding inaccurate/mixed diagnoses related to ASD; lengthy delays; and systemic and contextual barriers in navigating the pathway to ASD assessment and diagnosis that included socioeconomic and cultural disparities. REVIEW REGISTRATION: PROSPERO CRD42018100127.

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19. Subtirelu R, Writer M, Teichner E, Patil S, Indrakanti D, Werner T, Alavi A. Potential Neuroimaging Biomarkers for Autism Spectrum Disorder: A Comprehensive Review of MR Imaging, fMR Imaging, and PET Studies. PET Clin. 2024.

Autism spectrum disorder (ASD) is a characteristically heterogeneous disorder, as multiple neurodevelopmental disorders are characterized by similar symptomology and behavior. Research has shown that individuals with ASD benefit from early intervention; neuroimaging data may reveal information that cannot be obtained from traditional behavioral analysis. This review discusses the use of structural MR imaging, functional MR imaging (fMR imaging), and PET in the detection of ASD. Larger datasets, standardized methods of collection and analysis, and more robust meta-analyses are required to implement the observed biomarkers and improve the lives of patients living with AUD.

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20. Szabo A, O’Connell KS, Akkouh IA, Ueland T, Sønderby IE, Hope S, Røe AB, Dønnum MS, Sjaastad I, Steen NE, Ueland T, Sæther LS, Osete JR, Andreassen OA, Nærland T, Djurovic S. Elevated levels of peripheral and central nervous system immune markers reflect innate immune dysregulation in autism spectrum disorder. Psychiatry Res. 2024; 342: 116245.

BACKGROUND: Evidence suggests dysregulated immune functions in the pathophysiology of Autism spectrum disorder (ASD), although specific immune mechanisms are yet to be identified. METHODS: We assessed circulating levels of 25 immune/neuroinflammatory markers in a large ASD sample (n = 151) and matched controls (n = 72) using linear models. In addition, we performed global brain transcriptomics analyses of relevant immune-related genes. We also assessed the expression and function of factors and pathway elements of the inflammasome system in peripheral blood mononuclear cells (PBMC) isolated from ASD and controls using in vitro methods. RESULTS: We found higher circulating levels of IL-18 and adhesion factors (ICAM-1, MADCAM1) in individuals with ASD relative to controls. Consistent with this, brain levels of ICAM1 mRNA were also higher in ASD compared to controls. Furthermore, we found higher expression/activity of Caspase-1 and the inflammasome sensor NLRP3 in PBMCs in ASD, both at baseline and following inflammatory challenge. This corresponded with higher levels of secreted IL-18, IL-1β, and IL-8, as well as increased expression of adhesion factors following inflammasome activation in ASD PBMC cultures. Inhibition of the NLRP3-inflammasome rescued the observed immune phenotype in ASD in vitro. CONCLUSION: Our results suggest a role for inflammasome dysregulation in ASD pathophysiology.

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21. Tan S, Zhang Q, Zhan R, Luo S, Han Y, Yu B, Muss C, Pingault V, Marlin S, Delahaye A, Peters S, Perne C, Kreiß M, Spataro N, Trujillo-Quintero JP, Racine C, Tran-Mau-Them F, Phornphutkul C, Besterman AD, Martinez J, Wang X, Tian X, Srivastava S, Urion DK, Madden JA, Saif HA, Morrow MM, Begtrup A, Li X, Jurgensmeyer S, Leahy P, Zhou S, Li F, Hu Z, Tan J, Xia K, Guo H. Monoallelic loss-of-function variants in GSK3B lead to autism and developmental delay. Mol Psychiatry. 2024.

De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de novo potential splicing-disrupting variants (PSDVs) in 5048 probands compared to 4090 unaffected siblings. We identified 55 genes with recurrent de novo PSDVs that were highly intolerant to variation. Forty-six of these genes have not been strongly implicated in ASD or other neurodevelopmental disorders previously, including GSK3B. Through international, multicenter collaborations, we assembled genotype and phenotype data for 15 individuals with GSK3B variants and identified common phenotypes including developmental delay, ASD, sleeping disturbance, and aggressive behavior. Using available single-cell transcriptomic data, we show that GSK3B is enriched in dorsal progenitors and intermediate forms of excitatory neurons in the developing brain. We showed that Gsk3b knockdown in mouse excitatory neurons interferes with dendrite arborization and spine maturation which could not be rescued by de novo missense variants identified from affected individuals. In summary, our findings suggest that PSDVs may play an important role in the genetic etiology of ASD and allow for the prioritization of new ASD candidate genes. Importantly, we show that genetic variation resulting in GSK3B loss-of-function can lead to a neurodevelopmental disorder with core features of ASD and developmental delay.

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22. Ye Q, Apsley AT, Hastings WJ, Etzel L, Newschaffer C, Shalev I. Parental age at birth, telomere length, and autism spectrum disorders in the UK Biobank cohort. Autism Res. 2024.

Older parental age at birth is associated with increased risk of autism spectrum disorders (ASD) in offspring. Independently, shorter telomere length (TL) has also been shown to be associated with ASD in children. However, older paternal age at birth, with or without controlling for maternal age, has been associated with longer TL, a seemingly contradictory finding. Here, we conducted a retrospective cohort study among participants in the UK Biobank to disentangle associations between leukocyte TL and ASD status in adults, and the potential moderation by parental age on adult offspring’s TL. Participants with ASD diagnosis (N = 87) with a mean age of 46.0 (SD 4.4) years were matched to participants without ASD diagnosis (N = 870) based on age, sex, ethnicity, education, household income, and assessment center. No statistically significant differences were seen in TL between participants with and without ASD when parental age at birth was not considered. However, there was a significant interaction between ASD diagnostic status and parental age on participants’ TL, such that older paternal or maternal age at birth was more strongly associated with longer TL in participants with ASD. This study suggests that the shortened TL observed in children with ASD in previous research may partially depend on parental age at birth. Future studies tracking TL attrition before ASD diagnosis are warranted to depict temporal associations and the interacting effects of parental age at birth and ASD status on TL across the lifespan.

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23. Zhang Y, Tang R, Hu ZM, Wang XH, Gao X, Wang T, Tang MX. Key Synaptic Pathology in Autism Spectrum Disorder: Genetic Mechanisms and Recent Advances. J Integr Neurosci. 2024; 23(10): 184.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and verbal communication, accompanied by symptoms of restricted and repetitive patterns of behavior or interest. Over the past 30 years, the morbidity of ASD has increased in most areas of the world. Although the pathogenesis of ASD is not fully understood, it has been associated with over 1000 genes or genomic loci, indicating the importance and complexity of the genetic mechanisms involved. This review focuses on the synaptic pathology of ASD and particularly on genetic variants involved in synaptic structure and functions. These include SHANK, NLGN, NRXN, FMR1, and MECP2 as well as other potentially novel genes such as CHD8, CHD2, and SYNGAP1 that could be core elements in ASD pathogenesis. Here, we summarize several pathological pathways supporting the hypothesis that synaptic pathology caused by genetic mutations may be the pathogenic basis for ASD.

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