1. Baldridge D, Kaster L, Sancimino C, Srivastava S, Molholm S, Gupta A, Oh I, Lanzotti V, Grewal D, Riggs ER, Savatt JM, Hauck R, Sveden A, Constantino JN, Piven J, Gurnett CA, Chopra M, Hazlett H, Payne PRO. The Brain Gene Registry: a data snapshot. J Neurodev Disord. 2024; 16(1): 17.

Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment Protocol (RNAP), which include cognitive, neurologic, and neuropsychiatric assessments, as well as assessments for attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Co-enrollment of BGR participants in the Clinical Genome Resource’s (ClinGen’s) GenomeConnect enables display of variant information in ClinVar. The BGR currently contains data on 479 participants who are 55% male, 6% Asian, 6% Black or African American, 76% white, and 12% Hispanic/Latine. Over 200 genes are represented in the BGR, with 12 or more participants harboring variants in each of these genes: CACNA1A, DNMT3A, SLC6A1, SETD5, and MYT1L. More than 30% of variants are de novo and 43% are classified as variants of uncertain significance (VUSs). Mean standard scores on cognitive or developmental screens are below average for the BGR cohort. EHR data reveal developmental delay as the earliest and most common diagnosis in this sample, followed by speech and language disorders, ASD, and ADHD. BGR data has already been used to accelerate gene-disease validity curation of 36 genes evaluated by ClinGen’s BGR Intellectual Disability (ID)-Autism (ASD) Gene Curation Expert Panel. In summary, the BGR is a resource for use by stakeholders interested in advancing translational research for brain genes and continues to recruit participants with clinically reported variants to establish a rich and well-characterized national resource to promote research on neurodevelopmental disorders.

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2. Batouli SAH, Razavi F, Sisakhti M, Oghabian Z, Ahmadzade H, Tehrani Doost M. Examining the Dominant Presence of Brain Grey Matter in Autism During Functional Magnetic Resonance Imaging. Basic Clin Neurosci. 2023; 14(5): 585-604.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with symptoms appearing from early childhood. Behavioral modifications, special education, and medicines are used to treat ASD; however, the effectiveness of the treatments depends on early diagnosis of the disorder. The primary approach in diagnosing ASD is based on clinical interviews and valid scales. Still, methods based on brain imaging could also be possible diagnostic biomarkers for ASD. METHODS: To identify the amount of information the functional magnetic resonance imaging (fMRI) reveals on ASD, we reviewed 292 task-based fMRI studies on ASD individuals. This study is part of a systematic review with the registration number CRD42017070975. RESULTS: We observed that face perception, language, attention, and social processing tasks were mainly studied in ASD. In addition, 73 brain regions, nearly 83% of brain grey matter, showed an altered activation between the ASD and normal individuals during these four tasks, either in a lower or a higher activation. CONCLUSION: Using imaging methods, such as fMRI, to diagnose and predict ASD is a great objective; research similar to the present study could be the initial step.

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3. Bhandari K, Kanodia H, Donato F, Caroni P. Selective vulnerability of the ventral hippocampus-prelimbic cortex axis parvalbumin interneuron network underlies learning deficits of fragile X mice. Cell Rep. 2024; 43(5): 114124.

High-penetrance mutations affecting mental health can involve genes ubiquitously expressed in the brain. Whether the specific patterns of dysfunctions result from ubiquitous circuit deficits or might reflect selective vulnerabilities of targetable subnetworks has remained unclear. Here, we determine how loss of ubiquitously expressed fragile X mental retardation protein (FMRP), the cause of fragile X syndrome, affects brain networks in Fmr1y/- mice. We find that in wild-type mice, area-specific knockout of FMRP in the adult mimics behavioral consequences of area-specific silencing. By contrast, the functional axis linking the ventral hippocampus (vH) to the prelimbic cortex (PreL) is selectively affected in constitutive Fmr1y/- mice. A chronic alteration in late-born parvalbumin interneuron networks across the vH-PreL axis rescued by VIP signaling specifically accounts for deficits in vH-PreL theta-band network coherence, ensemble assembly, and learning functions of Fmr1y/- mice. Therefore, vH-PreL axis function exhibits a selective vulnerability to loss of FMRP in the vH or PreL, leading to learning and memory dysfunctions in fragile X mice.

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4. Bove M, Palmieri MA, Santoro M, Agosti LP, Gaetani S, Romano A, Dimonte S, Costantino G, Sikora V, Tucci P, Schiavone S, Morgese MG, Trabace L. Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism. Transl Psychiatry. 2024; 14(1): 193.

Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking. To this aim, preclinical studies can be really helpful to longitudinally study behavioural alterations resembling human symptoms and to investigate the underlying neurobiological correlates. In this regard, the BTBR T(+) Itpr3(tf)/J (BTBR) mice are an inbred mouse strain that exhibits a pattern of behaviours well resembling human ASD-like behavioural features. In this study, the BTBR mice model was used to investigate neurochemical and biomolecular alterations, regarding Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), together with GABAergic, glutamatergic, cholinergic, dopaminergic and noradrenergic neurotransmissions and their metabolites in four different brain areas, i.e. prefrontal cortex, hippocampus, amygdala and hypothalamus. In our results, BTBR strain reported decreased noradrenaline, acetylcholine and GABA levels in prefrontal cortex, while hippocampal measurements showed reduced NGF and BDNF expression levels, together with GABA levels. Concerning hypothalamus, no differences were retrieved. As regarding amygdala, we found reduced dopamine levels, accompanied by increased dopamine metabolites in BTBR mice, together with decreased acetylcholine, NGF and GABA levels and enhanced glutamate content. Taken together, our data showed that the BTBR ASD model, beyond its face validity, is a useful tool to untangle neurotransmission alterations that could be underpinned to the heterogeneous ASD-like behaviours, highlighting the crucial role played by amygdala.

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5. Brusilovskiy E, Salzer MS, Pomponio Davidson A, Feeley C, Pfeiffer B. Using GPS and Self-Report Data to Examine the Relationship Between Community Mobility and Community Participation Among Autistic Young Adults. Am J Occup Ther. 2024; 78(3).

IMPORTANCE: Community participation of autistic adults is important for health and well-being. Many clinical efforts and interventions aim to enhance community participation in this population. OBJECTIVE: To empirically examine the relationship between community participation and community mobility. DESIGN: A randomized controlled trial using data from baseline and 4- to 6-wk follow-up. SETTING: Community organizations serving autistic adults in Philadelphia. PARTICIPANTS: Sixty-three autistic young adults with data on community mobility and participation from a prior study on public transportation use. OUTCOMES AND MEASURES: Participants were tracked with GPS-enabled cell phones over a 2-wk period. A spatiotemporal data mining algorithm was used to compute the total number of destinations, nonhome destinations, unique destinations, percentage of time spent outside the home, and median daily activity space area from the GPS data. The Temple University Community Participation measure was used to collect self-report data in 21 different areas, and total amount, breadth, and sufficiency of participation were calculated. RESULTS: Moderate and statistically significant associations were found between community mobility and participation variables at baseline and follow-up. However, changes in community mobility were not related to changes in community participation. CONCLUSION: Health policymakers and providers should consider community mobility as a factor that can affect community participation in autistic individuals. Plain-Language Summary: Lower levels of community participation among autistic young adults affect health outcomes and overall quality of life. Community mobility is often a barrier to community participation. An understanding of the relationship between community mobility and community participation can lead to occupational therapists tailoring specific interventions and policies that support autistic young adults to engage in important life activities within the community.

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6. Carter S, Lin JC, Chow T, Martinez MP, Qiu C, Feldman RK, McConnell R, Xiang AH. Preeclampsia Onset, Days to Delivery, and Autism Spectrum Disorders in Offspring: Clinical Birth Cohort Study. JMIR Public Health Surveill. 2024; 10: e47396.

BACKGROUND: Maternal preeclampsia is associated with a risk of autism spectrum disorders (ASD) in offspring. However, it is unknown whether the increased ASD risk associated with preeclampsia is due to preeclampsia onset or clinical management of preeclampsia after onset, as clinical expectant management of preeclampsia allows pregnant women with this complication to remain pregnant for potentially weeks depending on the onset and severity. Identifying the risk associated with preeclampsia onset and exposure provides evidence to support the care of high-risk pregnancies and reduce adverse effects on offspring. OBJECTIVE: This study aimed to fill the knowledge gap by assessing the ASD risk in children associated with the gestational age of preeclampsia onset and the number of days from preeclampsia onset to delivery. METHODS: This retrospective population-based clinical cohort study included 364,588 mother-child pairs of singleton births between 2001 and 2014 in a large integrated health care system in Southern California. Maternal social demographic and pregnancy health data, as well as ASD diagnosis in children by the age of 5 years, were extracted from electronic medical records. Cox regression models were used to assess hazard ratios (HRs) of ASD risk in children associated with gestational age of the first occurrence of preeclampsia and the number of days from first occurrence to delivery. RESULTS: Preeclampsia occurred in 16,205 (4.4%) out of 364,588 pregnancies; among the 16,205 pregnancies, 2727 (16.8%) first occurred at <34 weeks gestation, 4466 (27.6%) first occurred between 34 and 37 weeks, and 9012 (55.6%) first occurred at ≥37 weeks. Median days from preeclampsia onset to delivery were 4 (IQR 2,16) days, 1 (IQR 1,3) day, and 1 (IQR 0,1) day for those first occurring at <34, 34-37, and ≥37 weeks, respectively. Early preeclampsia onset was associated with greater ASD risk (P=.003); HRs were 1.62 (95% CI 1.33-1.98), 1.43 (95% CI 1.20-1.69), and 1.23 (95% CI 1.08-1.41), respectively, for onset at <34, 34-37, and ≥37 weeks, relative to the unexposed group. Within the preeclampsia group, the number of days from preeclampsia onset to delivery was not associated with ASD risk in children; the HR was 0.995 (95% CI 0.986-1.004) after adjusting for gestational age of preeclampsia onset. CONCLUSIONS: Preeclampsia during pregnancy was associated with ASD risk in children, and the risk was greater with earlier onset. However, the number of days from first preeclampsia onset to delivery was not associated with ASD risk in children. Our study suggests that ASD risk in children associated with preeclampsia is not increased by expectant management of preeclampsia in standard clinical practice. Our results emphasize the need to identify effective approaches to preventing the onset of preeclampsia, especially during early pregnancy. Further research is needed to confirm if this finding applies across different populations and clinical settings.

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7. Catalano F, Santorelli D, Astegno A, Favaretto F, D’Abramo M, Del Giudice A, De Sciscio ML, Troilo F, Giardina G, Di Matteo A, Travaglini-Allocatelli C. Conformational and dynamic properties of the KH1 domain of FMRP and its fragile X syndrome linked G266E variant. Biochim Biophys Acta Proteins Proteom. 2024: 141019.

The Fragile X messenger ribonucleoprotein (FMRP) is a complex, multi-domain protein involved in interactions with various macromolecules, including proteins and coding/non-coding RNAs. The three KH domains (KH0, KH1 and KH2) within FMRP are recognized for their roles in mRNA binding. In the context of Fragile X syndrome (FXS), over-and-above CGG triplet repeats expansion, three specific point mutations have been identified, each affecting one of the three KH domains ((R138)QKH0, (G266)EKH1, and (I304N)KH2) resulting in the expression of non-functional FMRP. This study aims to elucidate the molecular mechanism underlying the loss of function associated with the (G266E)KH1 pathological variant. We investigate the conformational and dynamical properties of the isolated KH1 domain and the two KH1 site-directed mutants (G266E)KH1 and (G266A)KH1. Employing a combined in vitro and in silico approach, we reveal that the (G266E)KH1 variant lacks the characteristic features of a folded domain. This observation provides an explanation for functional impairment observed in FMRP carrying the G266E mutation within the KH1 domain, as it renders the domain unable to fold properly. Molecular Dynamics simulations suggest a pivotal role for residue 266 in regulating the structural stability of the KH domains, primarily through stabilizing the α-helices of the domain. Overall, these findings enhance our comprehension of the molecular basis for the dysfunction associated with the (G266E)KH1 variant in FMRP.

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8. Cheng HHL, Chau A, Chan H, Seto J, Wong H, So J, Leung YW, Wong AV, Cheung TCK. Employment needs of and barriers for Chinese youth and young adults with Autism Spectrum Conditions in Ontario, Canada. Res Dev Disabil. 2024; 149: 104729.

BACKGROUND: Cultural-based literature focusing on Asian autistic immigrants living in Western countries is very limited. AIMS: The present study is a quality improvement exercise aiming to fill the gap by investigating the employment needs of and barriers for Chinese autistic youth and young adults in Ontario, Canada. METHODS & PROCEDURES: 71 individuals diagnosed with autism and 24 diagnosed with other mental illnesses, aged 12-29, participated in an online survey regarding their work readiness, work skills, interests, health and cultural concerns. Analyses were conducted to compare the autistic group and the mental health group. OUTCOMES & RESULTS: Results show that the autistic sample has inferior (1) work habits related skills, (2) work style related skills, (3) level of independence, (4) skills to perform routine daily activities, (5) interpersonal skills at work, and (6) ability to tolerate visual and moving stimuli in the work environment. It is also found that the autistic group has more symptoms of depression, anxiety, and autism than that of the non-autistic group. CONCLUSIONS & IMPLICATIONS: The study shed light into the unique needs and barriers of Chinese autistic young adults and the service gap in supporting their transition to employment.

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9. Chirica MG, Zhu Y, Mu W, Zhou H, Gong J, Chan RCK, Kwapil TR, Berenbaum H. Exploring phenotypic overlap across schizotypy and autism spectrum conditions in American and Chinese young adults. Schizophr Res. 2024; 267: 359-66.

Competing theories have been proposed to explain the considerable overlap in social-cognitive features and risk factors across schizotypy and autism spectrum conditions (ASCs). Six previous factor analyses have been reported in the literature, yet all have major limitations; evidence for the clear superiority of any of the competing theories is insufficient and warrants further investigation. The primary aim of the present research was to identify dimensions that cut across schizotypy and ASCs while addressing limitations of past research. Data were collected from three independent samples (n = 1006, 544, and 2469) in the U.S. and China using the Autism-Spectrum Quotient, the Schizotypal Personality Questionnaire, and the Wisconsin Schizotypy Scales. Exploratory factor analyses in Sample 1 identified an interpretable three-factor structure, which was replicated in Samples 2 and 3 using confirmatory factor analyses. We found consistent evidence for three dimensions (Aberrant Salience, Asociality, and Concrete Thinking) underlying schizotypy and ASCs. This three-dimension model is consistent with a common vulnerability model of schizotypy and ASCs. Implications of these findings for the schizotypy and ASCs literature are discussed.

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10. Darwish M, El Hajj R, Khayat L, Alaaeddine N. Stem Cell Secretions as a Potential Therapeutic Agent for Autism Spectrum Disorder: A Narrative Review. Stem Cell Rev Rep. 2024.

Autism spectrum disorder (ASD) is a neurodevelopmental illness characterized by impaired social interaction and restricted repetitive behaviors or interests. The rising prevalence of ASD diagnosis has triggered a surge in research into investigating the underlying neuropathological processes and finding new therapeutic approaches. ASD is characterized by neuroinflammation and dysregulation of neuro-immune cross-talk, which suggests that stem cell treatment might be a potential therapeutic approach. The beneficial and restorative effects of stem cells are mainly due to their paracrine activity, in which stem cells generate and release extracellular vesicles such as exosomes and distinct secreted non-vesicle soluble proteins, including, growth factors, chemokines, cytokines, and immunomodulatory molecules referred to as the Secretome. In this paper, we reviewed the existing research exploring the therapeutic potential of stem cell secretome focusing on their role in addressing ASD pathology. Furthermore, we proposed a comprehensive mechanism of action for stem cell secretions, encompassing the broader secretome as well as the specific contribution of exosomes, in alleviating ASD neuropathology. Across the reviewed studies, exosomes and secreted soluble factors of the transplanted stem cell demonstrate a potential efficacy in ameliorating autistic-like behaviors. The proposed mechanism of action involves the modulation of signaling pathways implicated in neuroinflammation, angiogenesis, cellular apoptosis, and immunomodulation.

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11. Davis TE, 3rd, Brennan J. Specific Phobia, Fear, and the Autism Spectrum in Children and Adolescents: Adapting OST for ASD. Clin Child Fam Psychol Rev. 2024.

Fears and phobias are a common mental health concern for youth, and particularly for autistic youth. The following review briefly summarizes the extant literature on specific phobias and specific phobias in autistic youth. The evidence base is briefly highlighted pointing to the strong base behind behavioral and cognitive-behavioral treatments and techniques. A broad discussion of key evidence-based treatment findings is presented, leading up to the impactful work of Thomas H. Ollendick in researching Öst’s One-Session Treatment (OST) with children and adolescents. OST for child specific phobias is discussed, and particular emphasis is given to this treatment’s ongoing adaptation for use with youth on the autism spectrum.

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12. Ellingford RA, Tojo M, Basson MA, Andreae LC. Male-Dominant Effects of Chd8 Haploinsufficiency on Synaptic Phenotypes during Development in Mouse Prefrontal Cortex. ACS Chem Neurosci. 2024; 15(8): 1635-42.

CHD8 is a high penetrance, high confidence risk gene for autism spectrum disorder (ASD), a neurodevelopmental disorder that is substantially more prevalent among males than among females. Recent studies have demonstrated variable sex differences in the behaviors and synaptic phenotypes of mice carrying different heterozygous ASD-associated mutations in Chd8. We examined functional and structural cellular phenotypes linked to synaptic transmission in deep layer pyramidal neurons of the prefrontal cortex in male and female mice carrying a heterozygous, loss-of-function Chd8 mutation in the C57BL/6J strain across development from postnatal day 2 to adulthood. Notably, excitatory neurotransmission was decreased only in Chd8(+/-) males with no differences in Chd8(+/-) females, and the majority of alterations in inhibitory transmission were found in males. Similarly, analysis of cellular morphology showed male-specific effects of reduced Chd8 expression. Both functional and structural phenotypes were most prominent at postnatal days 14-20, a stage approximately corresponding to childhood. Our findings suggest that the effects of Chd8 mutation are predominantly seen in males and are maximal during childhood.

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13. Karagöz H, Akça Ö F, Yıldırım MS, Zamani AG, Oflaz MB. Comparison of MicroRNA Levels of 18-60-month-old Autistic Children with Those of Their Siblings and Controls. Clin Psychopharmacol Neurosci. 2024; 22(2): 322-32.

OBJECTIVE: The present study aims to compare the levels of 7 microRNAs (mi-RNAs) (mi-RNA-125b, mi-RNA-23a-3p, mi-RNA-146a-5p, mi-RNA-106a, mi-RNA-151a-3p, mi-RNA-28, mi-RNA-125a) in the blood of the preschool children with autism and those of their siblings with healthy controls, and to investigate the association between these mi-RNAs and the severity of autism, behavioral problems, and siblings’ autistic traits. METHODS: A total of 35 children diagnosed with autism spectrum disorder (ASD) at the ages of 18-60 months (patient group), 35 non-affected siblings of the ASD group (sibling group), and 30 control subjects (control group) were involved in the study. The severity of ASD was measured using the Childhood Autism Rating Scale and the Autism Behavior Checklist (ABC). The behavioral problems of the children with ASD were assessed with the Aberrant Behavior Checklist, and the autistic traits of the siblings were assessed using the Autism spectrum screening scale for children. RESULTS: mi-RNA-106a-5p, mi-RNA-151a-3p, and mi-RNA-28-3p were found to be expressed significantly lower in the patient group compared to the control group. There was a significant positive correlation between mi-RNA-23a and the sensory subscale of the ABC. mi-RNA-151a was significantly associated with sound sensitivity and mi-RNA-28 with echolalia. After controlling for age and sex, the differences between groups were disappeared. CONCLUSION: The present study examined mi-RNAs that have been reported as biomarkers in the literature. Although several symptom clusters are found to be related to certain mi-RNA expression levels, they were not found to be significant in discriminating the patient and healthy groups.

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14. Kurahashi H, Kunisawa K, Mouri A. Social Behavior in Animal Models of Autism Spectrum Disorder. Methods Mol Biol. 2024; 2794: 331-40.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and stereotyped, repetitive patterns of behaviors, limited interests, and cognitive impairment. Especially, social deficit has been considered a core feature of ASD. Because of the limitations of the experimental approach in humans, valid animal models are essential in an effort to identify novel therapeutics for social deficits in ASD. The genetic and environmental factors are clinically relevant to the pathophysiology of ASD. Epidemiological studies demonstrate environmental interventions such as prenatal exposure to valproic acid (VPA). Prenatal exposure to VPA represents a robust model of ASD exhibiting face, construct, and predictive validity. Here, we introduce protocols of the social interaction test and the three-chamber test for evaluating social deficits in mice prenatally exposed to VPA.

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15. Mabondzo A, van de Kamp J, Mercimek-Andrews S. Dodecyl creatine ester therapy: from promise to reality. Cell Mol Life Sci. 2024; 81(1): 186.

Pathogenic variants in SLC6A8, the gene which encodes creatine transporter SLC6A8, prevent creatine uptake in the brain and result in a variable degree of intellectual disability, behavioral disorders (e.g., autism spectrum disorder), epilepsy, and severe speech and language delay. There are no treatments to improve neurodevelopmental outcomes for creatine transporter deficiency (CTD). In this spotlight, we summarize recent advances in innovative molecules to treat CTD, with a focus on dodecyl creatine ester, the most promising drug candidate.

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16. Moum SJ, Gadde JA. Beyond the AJR: Updates on the Glymphatic System, Perivascular Spaces, and Autism During Infancy. AJR Am J Roentgenol. 2024.

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17. Newman BT, Jacokes Z, Venkadesh S, Webb SJ, Kleinhans NM, McPartland JC, Druzgal TJ, Pelphrey KA, Van Horn JD. Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder. PLoS One. 2024; 19(4): e0301964.

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.

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18. Øverland E, Hauge Å L, Orm S, Øie MG, Skogli EW, Pellicano E, Andersen PN. « I have to charge my social battery »: Perspectives from autistic young adults on Quality of Life. Autism. 2024: 13623613241245578.

In this study we have asked a group of autistic young adults to describe what is important for their quality of life. The 14 participants (aged 21-29 years) were recruited from a 10-year follow-up study of autistic people. During interviews, our participants described the importance of having relationships with family, friends and pets. Having meaningful activities and being able to immerse themselves in particular interests was also reported to be important for a good quality of life. Interests had also guided their choice of what to study and what to do for work. They also spoke of how communication problems with professionals, bullying and sensory and emotional overload could have a negative impact on quality of life. Future interventions should focus on how professionals can help autistic people to connect to people/animals and meaningful activities, as the participants described this as important for having a good quality of life. These findings may be helpful in enhancing how passions and interests can be seen as opportunities for both academic and work careers for autistic people. Future research and interventions should also look at the communication barriers between autistic people and professionals, and how two-way understanding can be improved.

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19. Prato A, Saia F, Ferrigno M, Finocchiaro V, Barone R, Rizzo R. Sensory phenomena in children with Tourette syndrome or autism spectrum disorder. Front Psychiatry. 2024; 15: 1338234.

BACKGROUND: Tourette syndrome (TS) and autism spectrum disorder (ASD) are two neurodevelopmental disorders with an onset before the age of 18 years. TS patients frequently reported atypical sensory phenomena (SP). Sensory processing abnormalities are also particularly frequent in ASD individuals. OBJECTIVES: Considering the higher rate of atypical sensory behaviours in both neurodevelopmental disorders, in the present study we analysed sensory experiences in patients with ASD and in patients with TS. METHODS: We enrolled patients with a primary diagnosis of TS or ASD. All participants were assessed for primary diagnosis and associated comorbidities. The presence of sensory behaviours was investigated using the University of Sao Paulo’s Sensory Phenomena Scale (USP-SPS). RESULTS: SP were significantly more represented in the ASD-group versus TS-group, except for sound just-right perceptions and energy to released. ASD participants presented higher mean scores in all fields of USP-SPS severity scale respect on TS patients and healthy controls. The USP-SPS total score had significant positive correlations with the CYBOCS and MASC total scores in the TS cohort. In the ASD group, the USP-SPS total score was significantly negative correlated with the total IQ and marginally positive correlated with ADOS total score. CONCLUSION: SP are a frequently reported characteristic both of ASD and TS. Future studies are needed to better evaluate the differences on their phenomenology in patients with TS and ASD.

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20. Sandin S, Yip BHK, Yin W, Weiss LA, Dougherty JD, Fass S, Constantino JN, Hailin Z, Turner TN, Marrus N, Gutmann DH, Sanders SJ, Christoffersson B. Examining Sex Differences in Autism Heritability. JAMA Psychiatry. 2024.

IMPORTANCE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder more prevalent in males than in females. The cause of ASD is largely genetic, but the association of genetics with the skewed sex ratio is not yet understood. To our knowledge, no large population-based study has provided estimates of heritability by sex. OBJECTIVE: To estimate the sex-specific heritability of ASD. DESIGN, SETTING, AND PARTICIPANTS: This was a population-based, retrospective analysis using national health registers of nontwin siblings and cousins from Sweden born between January 1, 1985, and December 31, 1998, with follow-up to 19 years of age. Data analysis occurred from August 2022 to November 2023. MAIN OUTCOMES AND MEASURES: Models were fitted to estimate the relative variance in risk for ASD occurrence owing to sex-specific additive genetics, shared environmental effects, and a common residual term. The residual term conceptually captured other factors that promote individual behavioral variation (eg, maternal effects, de novo variants, rare genetic variants not additively inherited, or gene-environment interactions). Estimates were adjusted for differences in prevalence due to birth year and maternal and paternal age by sex. RESULTS: The sample included 1 047 649 individuals in 456 832 families (538 283 males [51.38%]; 509 366 females [48.62%]). Within the entire sample, 12 226 (1.17%) received a diagnosis of ASD, comprising 8128 (1.51%) males and 4098 (0.80%) females. ASD heritability was estimated at 87.0% (95% CI, 81.4%-92.6%) for males and 75.7% (95% CI, 68.4%-83.1%) for females with a difference in heritability estimated at 11.3% (95% CI, 1.0%-21.6%). There was no support for shared environmental contributions. CONCLUSIONS AND RELEVANCE: These findings suggest that the degree of phenotypic variation attributable to genetic differences (heritability) differs between males and females, indicating that some of the underlying causes of the condition may differ between the 2 sexes. The skewed sex ratio in ASD may be partly explained by differences in genetic variance between the sexes.

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21. Stania M, Emich-Widera E, Kamieniarz-Olczak A, Kazek B, Swatowska-Wenglarczyk M, Juras G. Postural control before and after transitional locomotor tasks in children on the autism spectrum: A case-control study. Clin Biomech (Bristol, Avon). 2024; 115: 106251.

BACKGROUND: Instrumented measurements of postural control provide a more accurate insight into the motor development of children with autism. This study aimed to identify postural control deficits in autistic children during quiet standing before and after transient locomotor task. It was hypothesized that the parameters that characterize the trajectory of center of foot pressure (COP) displacement would be higher in autistic children compared to typically developing children. METHODS: Sixteen autistic children aged 6-10 but without a comorbidity diagnosis, were enrolled in the study group. The control group comprised 16 typically developing peers. The assessment of the transitional task comprised four different conditions: unperturbed and perturbed transition, stepping up, and stepping down tasks. Analysis of the COP signal was carried out for three distinct phases, i.e., phase 1 – quiet standing before step initiation, phase 2 – transit, and phase 3 – quiet standing until measurement completion. FINDINGS: The two-way ANOVA with a 2 × 4 factorial design (group × testing condition) revealed a group effect on all posturographic variables in the antero-posterior and medio-lateral directions of phase 1 and in the antero-posterior direction of phase 3. The Bonferroni post-hoc test showed the means of all those variables were significantly higher for the autistic than for typically developing children. Group allocation also had an effect on the time of transit and step length, which turned out to be significantly longer in autistic children compared to healthy peers. INTERPRETATION: Autistic children show increased postural sway before and after transitional locomotor tasks compared to typically developing children. The trial was prospectively registered in the Australian and New Zealand Clinical Trials Registry (no. ACTRN12621001113842; date registered: 23.08.2021).

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22. Tsompanidis A, Warrier V, Baron-Cohen S. Sex Differences in Autism Heritability and Likelihood: What’s in a Residual?. JAMA Psychiatry. 2024.

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23. Wadle SL, Ritter TC, Wadle TTX, Hirtz JJ. Topography and ensemble activity in auditory cortex of a mouse model of Fragile-X-Syndrome. eNeuro. 2024.

Autism spectrum disorder (ASD) is often associated with social communication impairments and specific sound processing deficits, for example problems in following speech in noisy environments. To investigate underlying neuronal processing defects located in the auditory neocortex (AC), we performed two-photon Ca(2+) imaging in FMR1 (Fragile X Messenger Ribonucleoprotein 1) knockout (KO) mice, a model for Fragile-X-Syndrome (FXS), the most common cause of hereditary ASD in humans. For primary AC (A1) and the anterior auditory field (AAF), topographic frequency representation was less ordered compared to control animals. We additionally analyzed ensemble AC activity in response to various sounds and found subfield-specific differences. In A1, ensemble correlations were lower in general, while in secondary AC (A2), correlations were higher in response to complex sounds, yet not to pure tones (PT). Furthermore, sound specificity of ensemble activity was decreased in AAF. Repeating these experiments one week later revealed no major differences regarding representational drift. Nevertheless, we found subfield- and genotype-specific changes in ensemble correlation values between the two times points, hinting at alterations in network stability in FMR1 KO mice. These detailed insights into AC networks activity and topography in FMR1 KO mice add to the understanding of auditory processing defects in FXS.Significance statement Communicative challenges often observed in people with autism spectrum disorder might be due to defects in cortical brain circuits responsible for sound analysis. To investigate these in detail, we used a mouse model of Fragile-X-Syndrome, which often is associated with autism spectrum disorder in humans. We found several alterations compared to control animals, including a less well-ordered topography of frequency analysis in auditory cortex. Furthermore, neuronal population activity patterns in response to various sounds were altered. This was also highly dependent on whether pure tones or complex sounds were presented. These data help to understand the causes of sound processing defects in Fragile-X-Syndrome.

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24. Walsh D, Brooks G, Naka M, Oxburgh G, Kyo A. Forensic interviews conducted with autistic adults in Japan: a review of the literature and directions for future research. Psychiatr Psychol Law. 2024; 31(2): 216-34.

The interviewing of victims, witnesses and suspects is important in helping resolve criminal investigations. In Japan, developments have recently occurred in the training of the police and their public prosecutors in these key tasks. Whilst literature exists on autism in Japan, studies examining police/public prosecutor interviews with autistic adults conducted in that country (and indeed, any other) remain scant. As elsewhere in the world, identification of those who manifest characteristics prevalent on the autism spectrum disorder (ASD) scale, has been found to be problematical to criminal justice professionals. To help address this deficit in understanding, we provide an overview of the literature concerning contemporary understanding of the challenges facing autistic adults as they attempt to reveal their verbal accounts, as well as suggested techniques when interviewing adults on the ASD scale during criminal investigations, offering lessons learned from research conducted around the world that provide potentially promising solutions for Japan.

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25. Winter AS, Yartel AK, Fountain C, Cheslack-Postava K, Zhang Y, Schieve LA, Kissin DM, Bearman P. The Role of Multiple Birth and Birth Complications in the Association Between Assisted Reproductive Technology Conception and Autism Diagnosis. Am J Epidemiol. 2024.

In recent decades, the use of assisted reproductive technology (ART) has increased rapidly. To assess the relationship between ART and autism diagnosis, we linked California birth records from 2000 through 2016 with contemporaneous records from the National ART Surveillance System (NASS) and autism caseload records from California’s Department of Developmental Services from 2000 through November 2019. All 95,149 birth records that were successfully linked to a NASS record, indicating an ART birth, were matched 1:1 using propensity scores to non-ART births. We calculated the hazard risk ratio (HRR) for autism diagnosis and the proportions of the relationship between ART conception and autism diagnosis mediated by multiple birth pregnancy and related birth complications. The HRR for autism diagnosis following ART compared with non-ART conception is 1.26 (95% CI, 1.17-1.35). Multiple birth, preterm birth, and Cesarean delivery jointly mediate 77.9% of the relationship between ART conception and autism diagnosis. Thus, increased use of single embryo transfer in the United States to reduce multiple births and related birth complications may be a strategy to address the risk of autism diagnosis among ART-conceived children.

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26. Yoo LJH, Stefanovic N, Watchorn RE. Atopic dermatitis and autism: tactile hypersensitivity impeding topical therapy use. Br J Dermatol. 2024; 190(5): 759-60.

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