1. Aishworiya R, Chin HL, Savulescu J. Should newborn genetic testing for autism be introduced?. J Med Ethics;2024 (Dec 3)

This manuscript provides a review of the potential role of newborn genetic testing for autism, and whether the state has an inherent responsibility to facilitate and subsidise this. This is situated within the broader construct of benefits and limitations of genetic testing currently. Potential benefits of such presymptomatic genetic testing include facilitating earlier diagnosis and access to appropriate intervention which can improve the treatment outcome for the child and indirectly benefit caregivers and society by reducing the care needs of the child and adult in future. However, there are several limitations to newborn genetic testing including the variable penetrance of ‘autism-risk’ genes, marked phenotypic heterogeneity of autism, real-world limitations in access to treatment, potential psychological harm to caregivers and financial considerations. We hence argue for facilitation of diagnostic genetic testing instead, especially for parents who seek to have greater understanding of recurrence likelihoods, related to reproductive decision-making. Facilitation of such testing can be in the form of both financial subsidies and infrastructural elements including availability of testing facilities and trained healthcare personnel for individualised pregenetic and postgenetic test counselling.

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2. Beaglehole B, Thwaites B, Kew B, Mulder R. The changing doctor-patient relationship in psychiatry: observations on recent trends in autism, attention-deficit hyperactivity disorder, gender dysphoria and mental distress. Br J Psychiatry;2024 (Dec 4):1-3.

This editorial highlights increasing prevalence and treatment rates of apparently disparate disorders. We ask whether cross-disorder factors including greater mental health literacy, social media and a shift to psychiatric explanations for distress contribute to these trends. We highlight a consequence: the changing doctor-patient relationship and its impacts.

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3. Buehler R, Ansorge U, Silani G. Social attention in the wild – fixations to the eyes and autistic traits during a naturalistic interaction in a healthy sample. Sci Rep;2024 (Dec 3);14(1):30102.

Attention to social stimuli is a key component of social behavior and facilitates the development of fundamental social skills. Studies investigating social attention in neurotypical or neurodiverse populations have often relied on screen-based experiments using static images or videos, which lack the sensory richness and reciprocity present in real-life social interactions. This can possibly be attributed to the challenges one encounters when creating naturalistic experiments, such as dealing with dynamically moving areas of interest (AOIs), which require either time-intensive manual coding or restraining of participants. Here, we present findings from an experimental paradigm using unrestrained mobile eye-tracking and a face detection algorithm (MTCNN) to measure fixation rates during a semi-structured, face-to-face interview. Data from N = 62 healthy adult participants was analyzed for gaze behavior and related to participants’ autistic traits. We observed a significant negative correlation between fixation rates on the eye region averaged over the entire interaction and scores on the autism spectrum quotient (AQ) (r = -0.14), indicating participants with high autistic traits fixated less frequently on the eye region. We also compared different types of interview questions (open vs. closed) to explore whether the reduction in fixation rates was more pronounced for specific time intervals during the interview. Lastly, we discuss both possibilities for extensions as well as limitations of the presented paradigm that could serve as inspiration for future research.

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4. Cao W, Li H, Luo J. Prefrontal cortical circuits in social behaviors: an overview. J Zhejiang Univ Sci B;2024 (Nov 15);25(11):941-955.

Social behaviors are fundamental and intricate functions in both humans and animals, governed by the interplay of social cognition and emotions. A noteworthy feature of several neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia (SCZ), is a pronounced deficit in social functioning. Despite a burgeoning body of research on social behaviors, the precise neural circuit mechanisms underpinning these phenomena remain to be elucidated. In this paper, we review the pivotal role of the prefrontal cortex (PFC) in modulating social behaviors, as well as its functional alteration in social disorders in ASD or SCZ. We posit that PFC dysfunction may represent a critical hub in the pathogenesis of psychiatric disorders characterized by shared social deficits. Furthermore, we delve into the intricate connectivity of the medial PFC (mPFC) with other cortical areas and subcortical brain regions in rodents, which exerts a profound influence on social behaviors. Notably, a substantial body of evidence underscores the role of N-methyl-D-aspartate receptors (NMDARs) and the proper functioning of parvalbumin-positive interneurons within the mPFC for social regulation. Our overarching goal is to furnish a comprehensive understanding of these intricate circuits and thereby contribute to the enhancement of both research endeavors and clinical practices concerning social behavior deficits.

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5. Cheung HK, Tang YC, Yu HS. Validity and reliability of the Spence Children’s Anxiety Scale – parent version among Hong Kong children with various psychiatric disorders. East Asian Arch Psychiatry;2024 (Sep);34(3):51-57.

BACKGROUND: Anxiety disorders are among the most common mental health problems in childhood. Early detection and treatment are essential. We aimed to determine the psychometric properties of the Spence Children’s Anxiety Scale – parent version (SCAS-P) in children with various psychiatric disorders in Hong Kong. METHODS: Children aged 6 to 12 years and their parents or guardians were recruited by convenience sampling from the child and adolescent psychiatry specialist out-patient clinic at Queen Mary Hospital. The parents or guardians were asked to complete the SCAS-P, the Diagnostic Interview Schedule for Children version IV (DISC-IV) anxiety module, the Screen for Child Anxiety Related Emotional Disorders parent version (SCARED-P), and the Child Behavior Checklist (CBCL). RESULTS: In total, 135 child-parent pairs were included. The median age of the children (78 male and 57 female) was 10 (range, 8-11) years. The children had various psychiatric diagnoses; 43.7% had attention deficit hyperactivity disorder and 41.4% had autism spectrum disorder. In addition, 57 (42.2%) children were diagnosed by a psychiatrist with at least one anxiety disorder (based on the DISC-IV anxiety module). The median SCAS-P score was 36.0; it was higher in children with anxiety disorder (n = 57) than in children without anxiety disorder (n = 78) [46.0 vs 28.5, p < 0.001]. The internal consistency of the SCAS-P was high (Cronbach's alpha = 0.938). Convergent validity of the SCAS-P was confirmed with the SCARED-P and CBCL subscales of internalising and anxiety, whereas divergent validity of the SCAS-P was confirmed with the CBCL subscales of externalising, aggression, and delinquency. Test-retest reliability of the SCAS-P was good (intraclass correlation coefficient = 0.90). The SCAS-P had satisfactory criterion validity for any anxiety disorder (area under the curve [AUC] = 0.77), obsessive compulsive disorder (AUC = 0.76), social anxiety disorder (AUC = 0.70), separation anxiety disorder (AUC = 0.81), generalised anxiety disorder (AUC = 0.82), and physical injury fears (AUC = 0.86). CONCLUSION: The SCAS-P has satisfactory validity and reliability in screening anxiety disorders among children with various psychiatric disorders. In a busy clinic setting, we recommend using the total SCAS-P score to screen anxiety among children with psychiatric disorders.

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6. Choi A, Kim B, Labriola E, Wiest A, Wang Y, Smith J, Shin H, Jin X, An I, Hong J, Antila H, Thomas S, Bhattarai JP, Beier K, Ma M, Weber F, Chung S. Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism. iScience;2024 (Dec 20);27(12):111285.

Sleep disturbances are prevalent in children with autism spectrum disorder (ASD). Strikingly, sleep problems are positively correlated with the severity of ASD symptoms, such as memory impairment. However, the neural mechanisms underlying sleep disturbances and cognitive deficits in ASD are largely unexplored. Here, we show that non-rapid eye movement sleep (NREMs) is fragmented in the 16p11.2 deletion mouse model of ASD. The degree of sleep fragmentation is reflected in an increased number of calcium transients in the activity of locus coeruleus noradrenergic (LC-NE) neurons during NREMs. In contrast, optogenetic inhibition of LC-NE neurons and pharmacological blockade of noradrenergic transmission using clonidine consolidate sleep. Furthermore, inhibiting LC-NE neurons restores memory. Finally, rabies-mediated screening of presynaptic neurons reveals altered connectivity of LC-NE neurons with sleep- and memory-regulatory regions in 16p11.2 deletion mice. Our findings identify a crucial role of the LC-NE system in regulating sleep stability and memory in ASD.

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7. Choi JW, Oh J, Bennett DH, Kannan K, Tancredi DJ, Miller M, Schmidt RJ, Shin HM. Corrigendum to ‘Gestational exposure to organophosphate esters and autism spectrum disorder and other non-typical development in a cohort with elevated familial likelihood’ [Environ. Res. 263 (2024) 120141]. Environ Res;2024 (Dec 2):120492.

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8. Day M, Wood C, Corker E, Freeth M. Understanding the barriers to hiring autistic people as perceived by employers in the United Kingdom. Autism;2024 (Dec 4):13623613241301493.

In the United Kingdom, autistic adults struggle more to find jobs than non-autistic adults, which is a big concern to the government. To help more autistic people get jobs, hiring processes need to be better. By understanding what employers find challenging about hiring autistic people, we can come up with solutions to improve autistic people’s employment chances. A survey of 1212 employers and employees who hire people was conducted to find out what affects employers’ decisions to hire autistic people. Most people said they were open to hiring autistic applicants. This was particularly true for younger employers and men. People who had hired autistic people before were more likely to intend to do so again. However, key barriers to hiring were (1) not knowing enough about autism and (2) problems with how hiring is usually done in organisations. Employers also reported worrying about whether autistic employees would fit in at work, their productivity and the need for better training and changes to hiring methods. Our results indicate that it is important to educate employers about autism and make hiring practices more inclusive.

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9. Dorsey SG, Mocci E, Lane MV, Krueger BK. Rapid effects of valproic acid on the fetal brain transcriptome: implications for brain development and autism. Transl Psychiatry;2024 (Dec 4);14(1):482.

There is an increased incidence of autism among the children of women who take the anti-epileptic, mood-stabilizing drug, valproic acid (VPA) during pregnancy; moreover, exposure to VPA in utero causes autistic-like symptoms in rodents and non-human primates. Analysis of RNA-seq data obtained from E12.5 fetal mouse brains 3 hours after VPA administration to the pregnant dam revealed that VPA rapidly and significantly increased or decreased the expression of approximately 7,300 genes. No significant sex differences in VPA-induced gene expression were observed. Expression of 399 autism risk genes was significantly altered by VPA as was expression of 258 genes that have been reported to modulate fetal brain development but are not otherwise linked to autism. Expression of genes associated with intracellular signaling pathways, neurogenesis, and excitation-inhibition balance as well as synaptogenesis, neuronal fate determination, axon and dendritic development, neuroinflammation, circadian rhythms, and epigenetic modulation of gene expression was dysregulated by VPA. Notably, at least 40 genes that are known to regulate embryonic neurogenesis were dysregulated by VPA. The goal of this study was to identify mouse genes that are: (a) significantly up- or downregulated by VPA in the fetal brain and (b) associated with autism and/or known to play a role in embryonic neurodevelopmental processes, perturbation of which has the potential to alter brain connectivity and, consequently behavior, in the adult. The genes meeting these criteria provide potential targets for future hypothesis-driven studies to elucidate the proximal causes of errors in brain connectivity underlying neurodevelopmental disorders such as autism.

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10. Drye M, Banarjee C, Perry L, Viggiano A, Irvin D, Messinger D. Children’s social preference for teachers versus peers in autism inclusion classrooms: An objective perspective. Autism Res;2024 (Dec 3)

In inclusive preschools, children with autism spectrum disorder (ASD) and other developmental disabilities (DD) are less socially engaged with peers than are typically developing (TD) children. However, there is limited objective information describing how children with ASD engage with teachers, or how teacher engagement compares to engagement with peers. We tracked over 750 hours’ worth of children’s (N = 77; N(ASD) = 24, N(DD) = 23, N(TD) = 30; M(age) = 43.98 months) and teachers’ (N = 12) locations and orientations across eight inclusion preschool classrooms to quantify child-teacher and child-peer social preference. Social approach velocity and time in social contact were computed for each child and compared across social partners to index children’s preference for teachers over peers. Children with ASD approached teachers–but not peers-more quickly than children with TD, and children with ASD were approached more quickly by teachers and more slowly by peers than children with TD. Children with ASD spent less time in social contact with peers and did not differ from children with TD in their time in social contact with teachers. Overall, children with ASD showed a greater preference for approaching, being approached by, and being in social contact with teachers (relative to peers) than children with TD. No significant differences emerged between children with DD and children with TD. In conclusion, children with ASD exhibited a stronger preference for engaging with teachers over peers, re-emphasizing the need for classroom-based interventions that support the peer interactions of children with ASD.

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11. Garcia-Cabau C, Bartomeu A, Tesei G, Cheung KC, Pose-Utrilla J, Picó S, Balaceanu A, Duran-Arqué B, Fernández-Alfara M, Martín J, De Pace C, Ruiz-Pérez L, García J, Battaglia G, Lucas JJ, Hervás R, Lindorff-Larsen K, Méndez R, Salvatella X. Mis-splicing of a neuronal microexon promotes CPEB4 aggregation in ASD. Nature;2024 (Dec 4)

The inclusion of microexons by alternative splicing occurs frequently in neuronal proteins. The roles of these sequences are largely unknown, and changes in their degree of inclusion are associated with neurodevelopmental disorders(1). We have previously shown that decreased inclusion of a 24-nucleotide neuron-specific microexon in CPEB4, a RNA-binding protein that regulates translation through cytoplasmic changes in poly(A) tail length, is linked to idiopathic autism spectrum disorder (ASD)(2). Why this microexon is required and how small changes in its degree of inclusion have a dominant-negative effect on the expression of ASD-linked genes is unclear. Here we show that neuronal CPEB4 forms condensates that dissolve after depolarization, a transition associated with a switch from translational repression to activation. Heterotypic interactions between the microexon and a cluster of histidine residues prevent the irreversible aggregation of CPEB4 by competing with homotypic interactions between histidine clusters. We conclude that the microexon is required in neuronal CPEB4 to preserve the reversible regulation of CPEB4-mediated gene expression in response to neuronal stimulation.

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12. Gogate A, Kaur K, Khalil R, Bashtawi M, Morris MA, Goodspeed K, Evans P, Chahrour MH. The genetic landscape of autism spectrum disorder in an ancestrally diverse cohort. NPJ Genom Med;2024 (Dec 4);9(1):62.

Autism spectrum disorder (ASD) comprises neurodevelopmental disorders with wide variability in genetic causes and phenotypes, making it challenging to pinpoint causal genes. We performed whole exome sequencing on a modest, ancestrally diverse cohort of 195 families, including 754 individuals (222 with ASD), and identified 38,834 novel private variants. In 68 individuals with ASD (~30%), we identified 92 potentially pathogenic variants in 73 known genes, including BCORL1, CDKL5, CHAMP1, KAT6A, MECP2, and SETD1B. Additionally, we identified 158 potentially pathogenic variants in 120 candidate genes, including DLG3, GABRQ, KALRN, KCTD16, and SLC8A3. We also found 34 copy number variants in 31 individuals overlapping known ASD loci. Our work expands the catalog of ASD genetics by identifying hundreds of variants across diverse ancestral backgrounds, highlighting convergence on nervous system development and signal transduction. These findings provide insights into the genetic underpinnings of ASD and inform molecular diagnosis and potential therapeutic targets.

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13. Jyothi BN, Angel S, Ravi Kumar CP, Tamhankar PM. Child with KBG syndrome. BMJ Case Rep;2024 (Dec 4);17(12)

We report a male child with developmental delay, microcephaly and facial dysmorphism in the form of a turri-brachycephaly-shaped skull, triangular face, posteriorly rotated lop ears, thick bushy eyebrows, synophrys, long deep philtrum and prominent incisors. The mobile application Face2Gene was used to screen the patient’s facial photographs for known syndromes. The application suggested a high likelihood of KBG syndrome. Exome sequencing confirmed this by identifying a heterozygous pathogenic known mutation p.Tyr1406Ter in the ANKRD11 gene. Thus, the diagnosis of KBG syndrome was suggested only by the Face2Gene application, and the confirmation required DNA testing such as exome sequencing analysis.

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14. Lam XR, Cheng LJ, Leo CSY, Toh ZA, He HG. Global prevalence of depression in caregivers of children with autism: A systematic review and meta-analysis. J Pediatr Nurs;2024 (Dec 2)

PROBLEM: Depression is reported as the most common disorder among caregivers, especially for caregivers of children with autism. However, limited systematic reviews have investigated the prevalence of depressive symptoms among these caregivers. This systematic review and meta-analysis aim to synthesize the prevalence of global depressive symptoms among caregivers of children with autism and identify associated factors. ELIGIBILITY CRITERIA: Articles were limited to English language and reported on the prevalence of depressive symptoms among formal or informal caregivers, aged 18 or older, of children with ASD, with no publication year restrictions. SAMPLE: A total of 40 included studies involving 13,853 caregivers of children with autism were included. RESULTS: Meta-analysis of 40 included studies involving 13,853 caregivers of children with autism showed a pooled prevalence estimate of 45 % (95 % CI: 39.0-51.0). Depressive symptoms were most prevalent in European studies, with a rate of 54 % (N: 980), closely followed by the Eastern Mediterranean region at 53 % (N:1071). The South-East Asia and Western Pacific region exhibited a prevalence of 40 % (N: 5719), while the Americas reported a rate of 38 % (N: 6083). CONCLUSION: This review presents compelling evidence of a high global prevalence rate of 45 % for depressive symptoms among caregivers of children with ASD. IMPLICATIONS: To enhance nursing support for caregivers of children with ASD, specific interventions are needed. Nurses should integrate mental health screenings into regular check-ups, link caregivers to community resources, and receive specialized training. Promoting respite care and collaborating with stakeholders can further address caregiver stress and mental health stigma.

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15. Li W, Song C, Hu L, Wu L, Zhu Z. Influence of parental education on the intelligence quotient profiles and socially adaptive behavior of school-age children with autism spectrum disorder in eastern China. J Zhejiang Univ Sci B;2024 (Feb 8);25(11):1009-1019.

Intelligence quotient (IQ) and adaptive behavior are the influencing factors of autism spectrum disorder (ASD) in children entering mainstream schools. This study explored the association between parental education level, IQ, and adaptive behavior in ASD groups. A total of 257 school-age ASD children were enrolled in our study from January 2017 to June 2021. Their parents completed a standard demographic form, including age at autism diagnosis, gender, school placement, and parents’ educational background. The Chinese version of the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) was completed by a certified assessor for each enrolled child. Parents were interviewed on adaptive behavior using the Chinese version of the Adaptive Behavior Assessment System, Second Edition (ABAS-II). The average IQ of school-age ASD children was 76.88 (standard deviation (SD)=22.62) and boys had higher IQ levels than girls. The IQ was positively correlated with age. The General Adaptive Composite (GAC) score was 82.47 (SD=15.86) and adaptive behavior did not increase with age. ASD children who attended mainstream schools had better adaptive behavior profiles than other children. The mother’s education level showed a significant correlation with the IQ and adaptive behavior of autistic children, while the father’s education level did not. Consequently, better training and support for parents may help autistic children enter mainstream schools, with adaptive training being the most urgently required skill for parents.

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16. Lio G, Corazzol M, Fadda R, Doneddu G, Sirigu A. A neuronal marker of eye contact spontaneously activated in neurotypical subjects but not in autistic spectrum disorders. Cortex;2024 (Nov 22);183:87-104.

Attention to faces and eye contact are key behaviors for establishing social bonds in humans. In Autism Spectrum Disorders (ASD), a disturbance in neurodevelopment, impaired face processing and gaze avoidance are key clinical features for ASD diagnosis. The biological alterations underlying these impairments are not yet clearly established. Using high-density electroencephalography coupled with multi-variate pattern classification and group blind source separation methods we searched for face- and-face components-related neural signals that could best discriminate visual processing of neurotypical subjects (N = 38) from ASD participants (N = 27). We isolated a face-specific neural signal in the superior temporal sulcus peaking at 240 msec after face-stimulus onset. A machine learning algorithm applied on the extracted neural component reached 74% decoding accuracy at the same latencies, discriminating the neurotypical population from ASD subjects in whom this signal was weak. By manipulating attention on different parts of the face, we also found that the power of the evoked signal in neurotypical subjects varied depending on the region observed: it was strong when the eye region fell on the fovea to decrease on regions further away and outside the stimulus face. Such face and face-components selective neural modulations were not found in ASD, although they did show typical early face-related P100 and N170 signals. These results show that specialized cortical mechanisms for face perception show higher responses for eyes when attention is focused on gaze and that these mechanisms may be particularly affected in autism spectrum disorders.

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17. Marcella B, Riccardo A, Franca C, Antea D, Mauro P, Giovanni M, Rosalia DM. Joint attention effect on irrelevant stimuli resistance in high functional autism and neurotypical adults. J Behav Ther Exp Psychiatry;2025 (Mar);86:102005.

BACKGROUND AND OBJECTIVES: Clinical practice reveals that individuals with autism characterized by the absence of cognitive impairment (High Functioning Autism-HFA) show difficulty in sharing attention with unfamiliar people. We hypothesized that this difficulty could affect cognitive control by selectively impairing stimulus-encoding or response-selection. METHODS: Twenty-one HFA and 23 neurotypical adults were involved in a two-phase study. The first phase was performed at home, through an online link; the second one was held four months later in our laboratory in the presence of two experimenters. A letter-flanker task was administered in both phases. In the Stimulus-Response (SR) conflict condition, the target and flankers were assigned to the same/different response keys. In the Stimulus-Stimulus (SS) conflict condition, the target and flankers were perceptually similar/dissimilar. Two mixed-ANOVAs were conducted on response times and accuracy with Phases (Home vs Lab), Groups (HFA, Neurotypical), SR conditions (congruent, incongruent, neutral) and SS conditions (congruent, incongruent) as factors. RESULTS: Results show that only HFAs’ inhibition ability was negatively affected by the experimenters’ presence compared to when they were alone, by reducing accuracy when dealing with an SS conflict. LIMITATIONS: The differences between the home-phase and lab-phase sessions require further elaboration to understanding the nature of social interaction during the lab session. CONCLUSIONS: These results suggest that, for HFA, the « at home » context, free from social and emotional pressure, allowed them to emphasize their detail-focused cognitive style.

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18. Ortiz-Cruz EE, Ayala-Guerrero F, Mateos-Salgado EL, Bernal-Hernández J, Carillo-Calvet HA, Jiménez-Andrade JL. Artificial neural network for evaluating sleep spindles and slow waves after transcranial magnetic stimulation in a child with autism. Neurocase;2024 (Oct);30(5):189-197.

Sleep spindles (SS) and slow waves (SW) serve as indicators of the integrity of thalamocortical connections, which are often compromised in individuals with autism spectrum disorder (ASD). Transcranial magnetic stimulation (TMS) can modulate brain activity associated with ASD. This study evaluated the effects of TMS on SS and SW in an 11-year-old male with ASD who received 17 sessions of TMS on the dorsolateral prefrontal cortex. Both SS and SW were detected before and after TMS and were analyzed using self-organizing maps (SOM). Using the SOM, a subset of SS and SW was identified that exhibited structural changes after TMS.

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19. Park JY, Jung NH. Developmental Characteristics of High-Risk Infants According to the Bayley Scales of Infant and Toddler Development-Third Edition. Child Care Health Dev;2025 (Jan);51(1):e70018.

BACKGROUND: The present study aimed to determine the developmental characteristics of high-risk infants with birth and perinatal risk factors according to gestational age using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) and to assess the clinical utility of the scale. METHODS: This study included 100 high-risk infants < 12 months' corrected age who presented to a hospital in Korea. Developmental levels of cognitive, language and motor scales were confirmed using Bayley-III and analysed by dividing the infants according to gestational age as follows: high-risk full-term, moderate-to-late preterm and very preterm. Collected data were analysed using descriptive statistics, frequency analysis, analysis of variance and chi-squared tests using SPSS version 24.0 (IBM Corp., Armonk, NY, USA). RESULTS: In terms of developmental characteristics according to gestational age, moderate-to-late preterm infants exhibited average levels in all cognitive, language and motor domains, while high-risk full-term infants and very preterm infants exhibited low average levels in all cognitive, language and motor domains. The three groups exhibited statistically significant differences in the language domain, and analysis of the relationship between gestational age and degree of developmental delay revealed significant differences, especially in expressive language. CONCLUSIONS: This study is meaningful in that it analysed the developmental characteristics of high-risk infants according to gestational age using Bayley-III. The Bayley-III test in high-risk infants < 12 months of age was useful for screening developmental delay; however, there is a need for careful follow-up and evaluation of the subsequent development process.

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20. Parvathy S, Basu B, Surya S, Jose R, Meera V, Riya PA, Jyothi NP, Sanalkumar R, Praz V, Riggi N, Nair BS, Gulia KK, Kumar M, Binukumar BK, James J. TLX3 regulates CGN progenitor proliferation during cerebellum development and its dysfunction can lead to autism. iScience;2024 (Dec 20);27(12):111260.

Tlx3, a master regulator of the fate specification of excitatory neurons, is primarily known to function in post-mitotic cells. Although we have previously identified TLX3 expression in the proliferating granule neuron progenitors (GNPs) of cerebellum, its primary role is unknown. Here, we demonstrate that the dysfunction of Tlx3 from the GNPs significantly reduced its proliferation through regulating anti-proliferative genes. Consequently, the altered generation of GNPs resulted in cerebellar hypoplasia, patterning defects, granule neuron-Purkinje ratio imbalance, and aberrant synaptic connections in the cerebellum. This altered cerebellar homeostasis manifested into a typical autism-like behavior in mice with motor, and social function disabilities. We also show the presence of TLX3 variants with uncharacterized mutations in human cases of autism spectrum disorder (ASD). Altogether, our study establishes Tlx3 as a critical gene involved in developing GNPs and that its deletion from the early developmental stage culminates in autism.

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21. Rea HM, Øien RA, Webb SJ, Bansal S, Strang JF, Nordahl-Hansen A. Gender Diversity, Gender Dysphoria/Incongruence, and the Intersection with Autism Spectrum Disorders: An Updated Scoping Review. J Autism Dev Disord;2024 (Dec 4)

In several ways, 2018 represents a global pivot point in research and care related to the intersection of gender diversity and autism, reflected by the increase in the number of studies on the intersection and broadening of topics. We conducted a scoping review of the literature published between September 2018 and January 2024 to summarize recent research in the field. We compared and contrasted research trends post September 2018 to research that was summarized in previous scoping reviews (Nordahl-Hansen et al. in J Autism Develop Disord 49:1745-1748, 2019; Øien et al. J Autism Develop Disord 48(12):4028-4037, 2018. https://doi.org/10.1007/s10803-018-3843-z ). We also summarized systematic reviews and meta-analyses published after 2018. Compared to previous reviews, we included more comprehensive search terms to focus on gender diversity broadly, rather than just gender dysphoria or gender identity disorder, and we included more detailed coding categories to uniquely identify shifts and continuities in research priorities over time. A total of 99 empirical research studies were published after August 2018 (the end of the search in the previous review) and through January 2024 on autism, gender diversity, and related topics were reviewed. There has been growth in the quantity and quality of studies on the intersection of autism and gender diversity, although methodological improvements are still needed and described in the current review. Future research should include more collaborations with stakeholders to set research priorities that are reflective of the communities being described.

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22. Ren X, Wang H, Lv X, Zhou Y, Fan Y, Yu Y, Turck CW, Chen Y, Lv L, Hu Y, Li H, Wang W, Qin D, Feng X, Hu X. Establishment of a standardized daily behavior collection and analysis system for brain disease models of rhesus and cynomolgus monkeys and its application in autism spectrum disorder. J Zhejiang Univ Sci B;2024 (Nov 15);25(11):972-995.

Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.

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23. Saferin N, Haseeb I, Taha AM, Beecroft SE, Pillai S, Neifer AE, Lakkuru R, Kistler BP, Nawor CN, Malik I, Hasan D, Carlson JA, Zade KK, Dressel SP, Carney EM, Shah R, Gautam S, Vergis J, Neifer KL, Johnson ZV, Gustison ML, Hall FS, Burkett JP. Folate prevents the autism-related phenotype caused by developmental pyrethroid exposure in prairie voles. bioRxiv;2024 (Dec 4)

Neurodevelopmental disorders (NDDs) have dramatically increased in prevalence to an alarming one in six children, and yet both causes and preventions remain elusive. Recent human epidemiology and animal studies have implicated developmental exposure to pyrethroid pesticides, one of the most common classes of pesticides in the US, as an environmental risk factor for autism and neurodevelopmental disorders. Our previous research has shown that low-dose chronic developmental pyrethroid exposure (DPE) changes folate metabolites in the adult mouse brain. We hypothesize that DPE acts directly on molecular targets in the folate metabolism pathway, and that high-dose maternal folate supplementation can prevent or reduce the biobehavioral effects of DPE. We exposed pregnant prairie vole dams chronically to vehicle or low-dose deltamethrin (3 mg/kg/3 days) with or without high-dose folate supplementation (methylfolate, 5 mg/kg/3 days). The resulting DPE offspring showed broad deficits in five behavioral domains relevant to neurodevelopmental disorders (including the social domain); increased plasma folate concentrations; and increased neural expression of SHMT1, a folate cycle enzyme. Maternal folate supplementation prevented most of the behavioral phenotypes (except for repetitive behaviors) and caused potentially compensatory changes in neural expression of FOLR1 and MTHFR, two folate-related proteins. We conclude that DPE causes neurodevelopmental disorder-relevant behavioral deficits; DPE directly alters aspects of folate metabolism; and preventative interventions targeting folate metabolism are effective in reducing, but not eliminating, the behavioral effects of DPE.

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24. Smith C, Lautarescu A, Charman T, Crosbie J, Schachar RJ, Iaboni A, Georgiades S, Nicolson R, Kelley E, Ayub M, Jones J, Arnold PD, Lerch JP, Anagnostou E, Kushki A. Harmonizing two measures of adaptive functioning using computational approaches: prediction of vineland adaptive behavior scales II (VABS-II) from the adaptive behavior assessment system II (ABAS-II) scores. Mol Autism;2024 (Dec 3);15(1):51.

BACKGROUND: Very large sample sizes are often needed to capture heterogeneity in autism, necessitating data sharing across multiple studies with diverse assessment instruments. In these cases, data harmonization can be a critical tool for deriving a single dataset for analysis. This can be done through computational approaches that enable the conversion of scores across various instruments. To this end, our study examined the use of analytical approaches for mapping scores on two measures of adaptive functioning, namely predicting the scores on the vineland adaptive behavior scales II (VABS) from the scores on the adaptive behavior assessment system II (ABAS). METHODS: Data from the province of Ontario neurodevelopmental disorders network were used. The dataset included scores VABS and the ABAS for 720 participants (autism n = 547, 433 male, age: 11.31 ± 3.63 years; neurotypical n = 173, 95 male, age: 12.53 ± 4.05 years). Six regression approaches (ordinary least squares (OLS) linear regression, ridge regression, ElasticNet, LASSO, AdaBoost, random forest) were used to predict VABS total scores from the ABAS scores, demographic variables (age, sex), and phenotypic measures (diagnosis; core and co-occurring features; IQ; internalizing and externalizing symptoms). RESULTS: The VABS scores were significantly higher than the ABAS scores in the autism group, but not the neurotypical group (median difference: 8, 95% CI = (7,9)). The difference was negatively associated with age (beta = -1.2 ± 0.12, t = -10.6, p < 0.0001). All estimators demonstrated similar performance, with no statistically significant differences in mean absolute error (MAE) values across estimators (MAE range: 4.96-6.91). The highest contributing features to the prediction model were ABAS composite score, diagnosis, and age. LIMITATIONS: This study has several strengths, including the large sample. We did not examine the conversion of domain scores across the two measures of adaptive functioning and suggest this as a future area of investigation. CONCLUSION: Overall, our results supported the feasibility of harmonization. Our results suggest that a linear regression model trained on the ABAS composite score, the ABAS raw domain scores, and age, sex, and diagnosis would provide an acceptable trade-off between accuracy, parsimony, and data collection and processing complexity.

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25. Song C, Han T, Hu L, Shao N, Wang Z, Jin Y, Chen T, Zhu Z. Early developmental levels of children with autism spectrum disorder with different adaptive behaviors: a retrospective analysis. J Zhejiang Univ Sci B;2024 (Nov 15);25(11):1031-1038.

The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (American Psychiatric Association, 2013) defines autism spectrum disorder (ASD) as a complex neurodevelopmental disorder that begins in early childhood and is accompanied by social communication deficits and repetitive stereotyped behaviors. According to the monitoring data released in 2021 in the United States, the prevalence of ASD in children was as high as 2.27%; that is, one in 44 children had autism (Maenneret al., 2021). China publicly reported this figure to be around 0.7% (Zhou et al., 2020). The current view is that children with ASD are generally impaired in their adaptation ability (McDonaldet al., 2016; Hodgeet al., 2021; Opertoet al., 2021). Adaptive behaviors comprise the conceptual, social, and practical skills that enable individuals to adapt to the environment, which play an important role in daily life (McDonald et al., 2019). « Adaptive behavior » was first described by Doll (1936). Subsequently, abnormalities in adaptive behavior were included in the criteria for intellectual disability for the first time (Heber, 1961). The American Association on Mental Retardation (AAMR) has refined and specified this term several times. Researchers hold different opinions on the structure of social adaptive capability. Greenspan and Granfield (1992) divided social adaptive capability into social understanding and social interaction. However, an increasing number of scholars considered that the concept of adaptive behaviors in children was constructed via multiple dimensions. The most representative one among them was the Vineland Adaptive Behavior Scales (VABS) proposed by Sparrow et al. (1984). This scale illustrates that adaptive behavior includes communication, daily living skills, socialization, and motor skills. Harrison and Oakland (2003) developed an Adaptive Behavior Assessment System (ABAS), by applying the theory of adaptive behavior proposed by AAMR and the American Association on Intellectual and Developmental Disabilities (AAIDD). This system shows that adaptive behavior has three adaptive composites, namely, conceptual composite (including communication, learning function, and self-management), social composite (including leisure and social skills), and practical composite (including community application, home living, health and safety, and self-care). As there are different requirements for the social adaptive capability of children from different cultural backgrounds and various regions, Chinese scholars have translated the Normal Development of Social Skills from Infant to Junior High School Children (S-M) scale compiled by Japanese scholars into Chinese, which is now widely used in China (Zhang et al., 1995). The impairment of adaptive function in children with ASD includes multiple dimensions, such as socialization, communication, and daily living skills (Kanne et al., 2011), and the degree of impairment can predict the prognosis and outcome in real life, including education acquisition and independent living ability (Farley et al., 2009). Therefore, adaptive behavioral capacity is considered to be a key intervention point that directly affects the individual and social outcomes of autistic children (Veenstra-VanderWeele et al., 2017; Bölte et al., 2019).

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26. Song C, Ma R, Ni W, Peng X, Li X, Shi R, Zhang Y, Yi L. Pupillometry reveals hyper-arousal in response to auditory stimuli in autistic children. J Zhejiang Univ Sci B;2024 (Nov 15);25(11):996-1008.

Atypical sensory responsivity is widely reported in autistic individuals and is related to elevated functional difficulties. Dynamically, altered initial responses and/or habituation rates could underlie their atypical averaged responses to repeated sensory stimuli. In this study we aimed to measure the arousal level in response to different types of auditory stimuli and the dynamic change of atypical arousal level using pupillometry in autistic children. In Experiment 1, 43 autistic children and 49 neurotypical (NT) children were asked to passively listen to a mild sound and an aversive sound repeatedly. In Experiment 2, 39 autistic children and 44 NT children who went through Experiment 1 listened to a gradually emerging non-startling sound and a suddenly emerging startling sound in a random order. We found that the autistic group showed hyper-arousal in response to the aversive sound and the startling sound as reflected by their larger change in pupil area. In comparison, these autistic children demonstrated normal arousal in response to the mild sound and the non-startling sound. Dynamically, the autistic group had a larger peak pupil area change than the NT group in the first trial and a normal habituation rate to the aversive sound. In summary, our results suggest hyper-arousal to aversive and startling stimuli and the role of larger initial responses in hyper-arousal in autism. Minimizing aversive and startling sensory stimuli or gradually increasing the volume of aversive auditory stimuli to allow autistic children to adapt using the principle of habituation is recommended to reduce the arousal level and problematic behaviors of autistic children.

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27. Su Q, Wong OWH, Lu W, Wan Y, Zhang L, Xu W, Li MKT, Liu C, Cheung CP, Ching JYL, Cheong PK, Leung TF, Chan S, Leung P, Chan FKL, Ng SC. Author Correction: Multikingdom and functional gut microbiota markers for autism spectrum disorder. Nat Microbiol;2024 (Dec 4)

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28. Sulek R, Edwards C, Monk R, Patrick L, Pillar S, Whitehouse AJ, Waddington H. ‘It depends entirely on the nature of those supports’: Community perceptions of the appropriateness of early support services for autistic children. Autism;2024 (Dec 4):13623613241302372.

We do not know much about what support services people think are okay for young autistic children. This study was a survey of 253 people. We asked autistic adults, parents, and professionals from Australia and New Zealand whether they thought it was okay to provide support services to autistic children. About half the people who shared their thoughts said it was okay to provide support services to autistic children and the other half said it depended on what the support service was like. They had three main ideas about whether support services were okay or not. The first one is that we should remember that these autistic children are children first, so we need to keep their childhood experiences in mind and let them have a say in decisions. The second is that we should not try to ‘fix’ the child, but instead, use supports that respect and understand the unique ways the child thinks. The final idea is that early, personalised help is good for autistic children and can make a positive difference in their lives. This study suggests that we should focus on what each child needs, think about how children can join in, and provide help in ways that respect autistic children.

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29. Tan P, Shen X, Zeng L, Weng X, Geng H. Pharmacotherapy for the core symptoms of autism spectrum disorder. J Zhejiang Univ Sci B;2024 (Nov 15);25(11):956-971.

Autism spectrum disorder (ASD) is a range of neurodevelopmental diseases characterized by social dysfunction and stereotypic behaviors. The etiology of ASD remains largely unexplored, resulting in a diverse array of described clinical manifestations and varying degrees of severity. Currently, there are no drugs approved by a supervisory organization that can effectively treat the core symptoms of ASD. Childhood and adolescence are crucial stages for making significant achievements in ASD treatment, necessitating the development of drugs specifically for these periods. Based on the drug targets and mechanisms of action, it can be found that atypical psychotropic medications, anti-inflammatory and antioxidant medications, hormonal medications, ion channel medications, and gastrointestinal medications have shown significant improvement in treating the core symptoms of ASD in both children and adolescents. In addition, comparisons of drugs within the same category regarding efficacy and safety have been made to identify better alternatives and promote drug development. While further evaluation of the effectiveness and safety of these medications is needed, they hold great potential for widespread application in the clinical treatment of the principal symptoms of ASD.

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30. Tromans SJ, Sawhney I, Odiyoor M, de Villiers J, McCarthy J, Boer H, Alexander R, Courtenay K, Wallace S, Gangadharan S, Roy A, Blake A, Purandare K, Iyer A, Laugharne R, Weisner V, Shankar R. Long-term segregation and seclusion for people with an intellectual disability and/or autism in hospitals: critique of the current state of affairs. Br J Psychiatry;2024 (Dec 4):1-8.

In November 2023, the Department of Health and Social Care published guidance, entitled ‘Baroness Hollins’ Final Report: My Heart Breaks – Solitary Confinement in Hospital Has no Therapeutic Benefit for People with a Learning Disability and Autistic People’. The report’s commendable analysis of the problems and identification of the areas where practice should be improved is unfortunately not matched by many of its recommendations, which appear to be contrary to evidence-based approaches. The concerns are wide-ranging, from the use of the term ‘solitary confinement’ for current long-term segregation (LTS) and seclusion, to presumption that all LTS and seclusion is bad, to holding clinicians (mainly psychiatrists) responsible for events beyond their locus of control. Importantly, there is a no guidance on how to practically deliver the recommendations in an evidence-based manner. This Feature critically appraises the report, to provide a comprehensive summary outlining potential positive impacts, identifying specific concerns and reflecting on best practice going forward.

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31. Whiting CC, Schoen SA, Bundy A, Lane SJ, Mailloux Z, Roley SS, May-Benson TA, Schaaf RC. Occupational Therapy Using Ayres Sensory Integration® in School-Based Practice: A Call to Action. Am J Occup Ther;2025 (Jan 1);79(1)

Challenges with processing and integrating sensory information affect children’s ability to successfully engage in their occupations at school and fully participate in the educational process. Occupational therapy using Ayres Sensory Integration® (ASI) is an evidence-based intervention for autistic children that has emerging evidence for children with idiopathic sensory integration differences. This article is a call to action for the occupational therapy profession to increase the use of ASI principles in school settings because it historically has been limited in its application. In this column, we respond to two main questions. First, is ASI necessary, essential, and inherently appropriate in school settings? Second, does ASI align with education laws and mandates? We present evidence showing that interventions to address sensory integration and processing function fall within the domain of school-based occupational therapy practitioners and provide examples for ways to use the principles of ASI across all the tiers of a multitiered system of supports. We also make recommendations for next steps that focus on best practices for implementing ASI in the academic setting and address concerns related to the feasibility of ASI in school-based practice within existing systemic and logistical constraints. As a result, occupational therapy practitioners will be empowered to advocate for use of ASI and its principles in the educational setting to proactively provide the support their students deserve.

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32. Yuan G, Zhu Z, Guo H, Yang H, Zhang J, Zhang K, Zhang X, Lu X, Du J, Shi H, Jin G, Hao J, Sun Y, Su P, Zhang Z. Screen Time and Autism Spectrum Disorder: A Comprehensive Systematic Review of Risk, Usage, and Addiction. J Autism Dev Disord;2024 (Dec 3)

The relationship between autism spectrum disorder (ASD) and screen time (ST) has been extensively studied; but the evidence remains inconsistent, and a comprehensive quantitative synthesis of this association is lacking. This study aims to provide a robust quantitative assessment of the relationship between ASD and ST by consolidating and analyzing available evidence to offer a more precise understanding of this complex association. This systematic review followed PRISMA 2020 statement, and applied a quality assessment tool for quantitative studies to identity best available evidence. A comprehensive search was conducted in PubMed, Web of Science, Embase, and Scopus, covering literature published from January 1, 2006 to June 12, 2024. In total, 30 studies involving 356,666 participants met the inclusion criteria. The findings revealed a significant association between screen exposure in preschool children and the development of ASD, with a longer duration of screen exposure correlating with an increased likelihood of being diagnosed with autism. Furthermore, autistic people tend to have longer daily screen use and are at a higher risk of screen addiction compared to non-autistic individuals. These findings emphasize the importance of limiting ST for preschoolers and autistic people. However, the level of evidence supporting these conclusions is very low. Future studies should focus on controlling for confounding factors, using more objective measures, and further investigate the relationship between screen engagement styles (active or passive), screen use patterns (screen devices and content), and ASD.

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33. Zhao Y, Fan H, Zhang R, Zheng X. Factors associated with self-rated mental health in mothers of children and adolescents with autism spectrum disorder. J Zhejiang Univ Sci B;2024 (Nov 15);25(11):1020-1030.

The rising demand for child care is putting a strain on parents of children with autism spectrum disorder (ASD), particularly the mothers. This study investigated Chinese mothers of children with ASD and examined the factors associated with maternal mental health. An online national survey was completed by the parents of 5077 ASD children and adolescents aged 0‒17 years. A total of 28.0% of the mothers reported poor mental health status. Mothers with children aged 10‒13 years had a lower chance of having poor mental health status than mothers with children aged 0‒2 years (odds ratio (OR) 0.63, 95% confidence interval (CI) 0.43‒0.91). Mothers of children with high-functioning autism were less likely to have poor mental health status than those of children with low-functioning autism (OR 0.76, 95% CI 0.62‒0.94). Having children with comorbidities was related with a higher risk of poor mental status (OR 1.56, 95% CI 1.35‒1.81), as were having conflicts with other family members (OR 1.44, 95% CI 1.22‒1.70) and providing full-time care (OR 1.22, CI 1.06‒1.41). A higher-than-average family income was associated with lower risk of having poor mental health status (OR 0.70, 95% CI 0.58‒0.82). Factors related to the children and family, and providing full-time care, have a significant effect on mothers’ mental health status. Reducing obstacles to work and social interaction, as well as tackling the financial burden of raising an ASD child, may help improve the well-being of mothers.

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34. Zhu J, Liu H, Hu Y, Liu J, Dai C, Liang J, Cheng B, Tan M, Zhang Y, Cao Q, Lai X. Mechanistic insights into retinoic-acid treatment for autism in the improvement of social behavior: evidence from a multi omics study in rats. Neuropharmacology;2024 (Dec 4):110244.

BACKGROUND: Autism spectrum disorder (ASD) is a lifelong condition. It is characterized by complex etiologies, including disruptions in exogenous retinoic acid (RA) signaling, which may serve as an environmental risk factor. Targeting the RA pathway presents a promising therapeutic avenue, though the precise mechanisms remain to be elucidated. METHODS: Female Sprague-Dawley rats were treated with valproic acid (VPA) during pregnancy to induce an ASD model in their offspring. Some offspring received RA treatment postnatally. Social behavior and brain-functional connectivity were assessed using behavioral tests and functional magnetic resonance imaging (fMRI), respectively. Transcriptomics analysis and proteomics analysis of the hypothalamus identified differentially expressed genes (DEGs) and differentially expressed proteins (DEPs). These were intersected with ASD pathogenic genes (APGs) and ASD pathogenic proteins (APPs) to identify differentially expressed APGs (DE-APGs) and differentially expressed APPs (DE-APPs), which were validated by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Analyses of enrichment of signaling pathways were done using the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: RA treatment significantly improved social behaviors and revealed distinct patterns of hypo- and hyper-connectivity across various brain regions, with notable changes involving the hypothalamus and facial nerve. Differential analysis revealed 4165 DEGs (DEG 1) and 329 DEPs (DEP 1) between control and VPA groups, and 1610 DEGs (DEG 2) and 197 DEPs (DEP 2) between VPA and RA supplementation (RAS) groups. Twenty-two DE-APGs and five DE-APPs were identified, with key associations found between proteins such as Tbl1xr1 and Myo5a and >13 genes including Nrxn1, Cacna1e, and Gabrb2. Significant alterations in DE-APGs, including Grin2b, Nrxn1, Cacna1e, and Gabrb2, were confirmed via real-time RT-PCR and western blotting. In addition, 22 key signaling pathways were enriched in DEPs and DEGs. CONCLUSION: RA supplementation in ASD rats induced by VPA may ameliorate social deficits and modulated functional connectivity, especially in the hypothalamus and facial nerve regions. This suggests potential therapeutic benefits for neural circuitry dysregulation in ASD. Additionally, RA altered critical gene and protein expressions in hypothalamus, implicating its role in modulating key signaling pathways to mitigate social deficits in ASD. This study provides new insights into the molecular mechanisms of ASD and supports the development of novel therapeutic strategies.

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