1. Alnahdi G. Enhancing the quality of life of mothers of children with intellectual disabilities or Autism: The role of disability-specific support. Res Dev Disabil;2024 (Jun 12);151:104780.

BACKGROUND: A holistic approach considering the physical, emotional, and social dimensions of living with a disability is essential for developing effective support systems, policies, and interventions. The quality of life of individuals with disabilities is interrelated with the well-being of their families making family quality of life (FQOL) a crucial aspect of study. AIMS: This study explores the effects of support on FQOL among Saudi Arabian families with children diagnosed with intellectual disabilities or autism, from the perspectives of 269 mothers. METHODS AND PROCEDURES: Through a survey, we examined how disability-related support correlates with FQOL, emphasizing the need for personalized support systems. We employed multiple regression analysis to assess the impact of various factors on FQOL, including the type and severity of disability, family income, and marital status. OUTCOMES AND RESULTS: The findings revealed that disability-related support is a significant predictor of FQOL, highlighting its critical role in enhancing the well-being of families. CONCLUSIONS AND IMPLICATIONS: This study contributes to the scarce regional literature, and underscores the importance of inclusive social policies tailored to the diverse needs of families with disabilities.

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2. Asta L, Di Bella T, La Fauci Belponer F, Bruschetta M, Martines S, Basile E, Boncoddo M, Bellomo F, Cucinotta F, Ricciardello A, Turriziani L, Colombi C, Banchelli F, Cuoghi Costantini R, D’Amico R, Persico AM. Cognitive, behavioral and socio-communication skills as predictors of response to Early Start Denver Model: a prospective study in 32 young children with Autism Spectrum Disorder. Front Psychiatry;2024;15:1358419.

INTRODUCTION: The effectiveness of early interventions in young autistic children is well established, but there is great interindividual variability in treatment response. Predictors of response to naturalistic developmental behavioral interventions (NDBI), like the Early Start Denver Model (ESDM), are needed. METHODS: We conducted an exploratory study to prospectively seek predictors of response in 32 young children treated with ESDM after receiving an ASD diagnosis. All children were less than 39 months old (mean age: 29.7 mo), and received individualized ESDM for nine months. Tests were administered at the beginning, after 4 months, and at the end of treatment. RESULTS: Four children (12.5%) were « strong responders », 8 children (25.0%) were « moderate responders », and 20 children (62.5%) were « poor responders ». A more favorable response to ESDM was significantly predicted by higher PEP-3 Expressive Language, Receptive Language, Cognitive Verbal/Preverbal, Visuo-Motor Imitation scores, higher GMDS-ER Personal/Social, and VABS-II Communication scores, by lower ADI-R C restricted/stereotypic behaviors, and by joint attention level. DISCUSSION: Most predictors showed a linear association with increasing response to ESDM, but GMDS-ER Personal-Social and joint attention level predicted strong response, while PEP-3 receptive language equally predicted moderate or strong response. Although larger samples will be necessary to reach definitive conclusions, in conjunction with prior reports our findings begin providing information able to assist clinicians in choosing the most appropriate treatment program for young autistic children.

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3. Dakopolos A, Condy E, Smith E, Harvey D, Kaat AJ, Coleman J, Riley K, Berry-Kravis E, Hessl D. Developmental associations between cognition and adaptive behavior in intellectual and developmental disability. J Neurodev Disord;2024 (Jun 13);16(1):31.

BACKGROUND: Intellectual and developmental disabilities (IDDs) are associated with both cognitive challenges and difficulties in conceptual, social, and practical areas of living, commonly referred to as adaptive behavior (DSM-5). Although cross-sectional associations between intelligence or cognition and adaptive behavior have been reported in IDD populations, no study to date has examined whether developmental changes in cognition contribute to or track with changes in adaptive behavior. The present study sought to examine associations of longitudinal developmental change in domains of cognition (NIH Toolbox Cognition Battery, NIHTB-CB) and adaptive behavior domains (Vineland Adaptive Behavior Scales-3; VABS-3) including Socialization, Communication, and Daily Living Skills (DLS) over a two year period in a large sample of children, adolescents and young adults with IDD. METHODS: Three groups were recruited, including those with fragile X syndrome, Down syndrome, and other/idiopathic intellectual disability. Eligible participants (n = 263) included those who were between 6 and 26 years (m(age) = 15.52, sd = 5.17) at Visit 1, and who had a diagnosis of, or suspected intellectual disability (ID), including borderline ID, with a mental age of at least 3.0 years. Participants were given cognitive and adaptive behavior assessments at two time points over a two year period (m = 2.45 years, range = 1.27 to 5.56 years). In order to examine the association of developmental change between cognitive and adaptive behavior domains, bivariate latent change score (BLCS) models were fit to compare change in the three cognitive domains measured by the NIHTB-CB (Fluid Cognition, Crystallized Cognition, Total Cognition) and the three adaptive behavior domains measured by the VABS-3 (Communication, DLS, and Socialization). RESULTS: Over a two year period, change in cognition (both Crystallized and Total Composites) was significantly and positively associated with change in daily living skills. Also, baseline cognition level predicted growth in adaptive behavior, however baseline adaptive behavior did not predict growth in cognition in any model. CONCLUSIONS: The present study demonstrated that developmental changes in cognition and adaptive behavior are associated in children and young adults with IDD, indicating the potential for cross-domain effects of intervention. Notably, improvements in DLS emerged as a primary area of adaptive behavior that positively related to improvements in cognition. This work provides evidence for the clinical, « real life » meaningfulness of changes in cognition detected by the NIHTB-CB in IDD, and provides empirical support for the NIHTB-CB as a fit-for-purpose performance-based outcome measure for this population.

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4. Deng S, Tan S, Guo C, Liu Y, Li X. Impaired effective functional connectivity in the social preference of children with autism spectrum disorder. Front Neurosci;2024;18:1391191.

BACKGROUND: The medial prefrontal cortex (mPFC), amygdala (Amyg), and nucleus accumbens (NAc) have been identified as critical players in the social preference of individuals with ASD. However, the specific pathophysiological mechanisms underlying this role requires further clarification. In the current study, we applied Granger Causality Analysis (GCA) to investigate the neural connectivity of these three brain regions of interest (ROIs) in patients with ASD, aiming to elucidate their associations with clinical features of the disorder. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from the ABIDE II database, which included 37 patients with ASD and 50 typically developing (TD) controls. The mPFC, Amyg, and NAc were defined as ROIs, and the differences in fractional amplitude of low-frequency fluctuations (fALFF) within the ROIs between the ASD and TD groups were computed. Subsequently, we employed GCA to investigate the bidirectional effective connectivity between the ROIs and the rest of the brain. Finally, we explored whether this effective connectivity was associated with the social responsiveness scale (SRS) scores of children with ASD. RESULTS: The fALFF values in the ROIs were reduced in children with ASD when compared to the TD group. In terms of the efferent connectivity from the ROIs to the whole brain, the ASD group exhibited increased connectivity in the right cingulate gyrus and decreased connectivity in the right superior temporal gyrus. Regarding the afferent connectivity from the whole brain to the ROIs, the ASD group displayed increased connectivity in the right globus pallidus and decreased connectivity in the right cerebellar Crus 1 area and left cingulate gyrus. Additionally, we demonstrated a positive correlation between effective connectivity derived from GCA and SRS scores. CONCLUSION: Impairments in social preference ASD children is linked to impaired effective connectivity in brain regions associated with social cognition, emotional responses, social rewards, and social decision-making. This finding further reveals the potential neuropathological mechanisms underlying ASD.

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5. Duan K, Eyler L, Pierce K, Lombardo MV, Datko M, Hagler DJ, Taluja V, Zahiri J, Campbell K, Barnes CC, Arias S, Nalabolu S, Troxel J, Ji P, Courchesne E. Differences in regional brain structure in toddlers with autism are related to future language outcomes. Nat Commun;2024 (Jun 13);15(1):5075.

Language and social symptoms improve with age in some autistic toddlers, but not in others, and such outcome differences are not clearly predictable from clinical scores alone. Here we aim to identify early-age brain alterations in autism that are prognostic of future language ability. Leveraging 372 longitudinal structural MRI scans from 166 autistic toddlers and 109 typical toddlers and controlling for brain size, we find that, compared to typical toddlers, autistic toddlers show differentially larger or thicker temporal and fusiform regions; smaller or thinner inferior frontal lobe and midline structures; larger callosal subregion volume; and smaller cerebellum. Most differences are replicated in an independent cohort of 75 toddlers. These brain alterations improve accuracy for predicting language outcome at 6-month follow-up beyond intake clinical and demographic variables. Temporal, fusiform, and inferior frontal alterations are related to autism symptom severity and cognitive impairments at early intake ages. Among autistic toddlers, brain alterations in social, language and face processing areas enhance the prediction of the child’s future language ability.

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6. Ford A, Walum H, Brice B, Patel H, Kunnikuru S, Jones W, Berman GJ, Shultz S. Caregiver greeting to infants under 6 months already reflects emerging differences in those later diagnosed with autism. Proc Biol Sci;2024 (Jun);291(2024):20232494.

As infants develop, caregivers adjust their behaviour to scaffold their infant’s emerging skills, such that changes in infants’ social abilities are expected to elicit changes in caregiver behaviour. We examined whether changes in the probability of infant-directed caregiving behaviour-specifically, greeting, a ubiquitous signal used by caregivers to initiate reciprocal interactions-differ between infant-caregiver dyads with an infant later diagnosed with autism and dyads with a neurotypically developing infant during infants’ first 6 months. Using longitudinal data from 163 dyads, we found that caregivers in autism dyads (n = 40) used greeting less and at later infant ages than caregivers with a neurotypically developing infant (neurotypical dyads, n = 83). Caregivers in dyads with infants at elevated familial genetic likelihood for autism who did not receive an autism diagnosis (EL-non-autism dyads, n = 40) showed no differences in greeting compared with neurotypical dyads. Socioeconomic status partially mediated the difference between autism and neurotypical dyads. These findings show that autism and socioeconomic status were associated with the mutually adapted dynamics of dyadic interaction beginning in the first postnatal weeks. Importantly, differences in caregiver greeting observed in autism dyads are not interpreted as suboptimal behaviour from caregivers but rather indicate how early emerging social differences related to autism, years before overt features are present, may alter social learning opportunities elicited by the infant.

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7. Freeman M, Fakhori N, Monteil D. Progressive spasticity and developmental delay in an infant with a CTNNB1 mutation. BMJ Case Rep;2024 (Jun 13);17(6)

We present an infant referred to Developmental Paediatrics for delays, slow growth, hypotonia, esotropia and spasticity. Over the course of 2 months, the infant’s exam progressed, demonstrating worsening spasticity and tonal changes in the setting of a normal brain MRI with acquired microcephaly. Genetic testing demonstrated a pathogenic CTNNB1 nonsense mutation. Following the discovery of the underlying cause for the child’s clinical picture, the child was evaluated by therapeutic services and neurology, which was initially only available via asynchronous telehealth, due to a resource limited area. Cerebral palsy is a nonprogressive neurodevelopmental disorder and, when associated with developmental delay, qualifies for further genetic investigation into the underlying aetiology. Genetic testing recommendations exist for developmental delay, but there is no current algorithm regarding testing for cerebral palsy. Education and clear guidelines on genetic testing allow for better prognostication and potential treatment in cases of cerebral palsy, especially when associated with other disorders.

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8. Gao L, Wang Z, Long Y, Zhang X, Su H, Yu Y, Hong J. Autism spectrum disorders detection based on multi-task transformer neural network. BMC Neurosci;2024 (Jun 13);25(1):27.

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders that cause people difficulties in social interaction and communication. Identifying ASD patients based on resting-state functional magnetic resonance imaging (rs-fMRI) data is a promising diagnostic tool, but challenging due to the complex and unclear etiology of autism. And it is difficult to effectively identify ASD patients with a single data source (single task). Therefore, to address this challenge, we propose a novel multi-task learning framework for ASD identification based on rs-fMRI data, which can leverage useful information from multiple related tasks to improve the generalization performance of the model. Meanwhile, we adopt an attention mechanism to extract ASD-related features from each rs-fMRI dataset, which can enhance the feature representation and interpretability of the model. The results show that our method outperforms state-of-the-art methods in terms of accuracy, sensitivity and specificity. This work provides a new perspective and solution for ASD identification based on rs-fMRI data using multi-task learning. It also demonstrates the potential and value of machine learning for advancing neuroscience research and clinical practice.

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9. Gonzalez Ramirez C, Salvador SG, Patel RKR, Clark S, Miller NW, James LM, Ringelberg NW, Simon JM, Bennett J, Amaral DG, Burette AC, Philpot BD. Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey. Front Neuroanat;2024;18:1410791.

Angelman syndrome (AS) is a neurogenetic disorder caused by mutations or deletions in the maternally-inherited UBE3A allele, leading to a loss of UBE3A protein expression in neurons. The paternally-inherited UBE3A allele is epigenetically silenced in neurons during development by a noncoding transcript (UBE3A-ATS). The absence of neuronal UBE3A results in severe neurological symptoms, including speech and language impairments, intellectual disability, and seizures. While no cure exists, therapies aiming to restore UBE3A function-either by gene addition or by targeting UBE3A-ATS-are under development. Progress in developing these treatments relies heavily on inferences drawn from mouse studies about the function of UBE3A in the human brain. To aid translational efforts and to gain an understanding of UBE3A and UBE3A-ATS biology with greater relevance to human neurodevelopmental contexts, we investigated UBE3A and UBE3A-ATS expression in the developing brain of the rhesus macaque, a species that exhibits complex social behaviors, resembling aspects of human behavior to a greater degree than mice. Combining immunohistochemistry and in situ hybridization, we mapped UBE3A and UBE3A-ATS regional and cellular expression in normal prenatal, neonatal, and adolescent rhesus macaque brains. We show that key hallmarks of UBE3A biology, well-known in rodents, are also present in macaques, and suggest paternal UBE3A silencing in neurons-but not glial cells-in the macaque brain, with onset between gestational day 48 and 100. These findings support proposals that early-life, perhaps even prenatal, intervention is optimal for overcoming the maternal allele loss of UBE3A linked to AS.

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10. Haddon JE, Titherage D, Heckenast JR, Carter J, Owen MJ, Hall J, Wilkinson LS, Jones MW. Linking haploinsufficiency of the autism- and schizophrenia-associated gene Cyfip1 with striatal-limbic-cortical network dysfunction and cognitive inflexibility. Transl Psychiatry;2024 (Jun 14);14(1):256.

Impaired behavioural flexibility is a core feature of neuropsychiatric disorders and is associated with underlying dysfunction of fronto-striatal circuitry. Reduced dosage of Cyfip1 is a risk factor for neuropsychiatric disorder, as evidenced by its involvement in the 15q11.2 (BP1-BP2) copy number variant: deletion carriers are haploinsufficient for CYFIP1 and exhibit a two- to four-fold increased risk of schizophrenia, autism and/or intellectual disability. Here, we model the contributions of Cyfip1 to behavioural flexibility and related fronto-striatal neural network function using a recently developed haploinsufficient, heterozygous knockout rat line. Using multi-site local field potential (LFP) recordings during resting state, we show that Cyfip1 heterozygous rats (Cyfip1(+/-)) harbor disrupted network activity spanning medial prefrontal cortex, hippocampal CA1 and ventral striatum. In particular, Cyfip1(+/-) rats showed reduced influence of nucleus accumbens and increased dominance of prefrontal and hippocampal inputs, compared to wildtype controls. Adult Cyfip1(+/-) rats were able to learn a single cue-response association, yet unable to learn a conditional discrimination task that engages fronto-striatal interactions during flexible pairing of different levers and cue combinations. Together, these results implicate Cyfip1 in development or maintenance of cortico-limbic-striatal network integrity, further supporting the hypothesis that alterations in this circuitry contribute to behavioural inflexibility observed in neuropsychiatric diseases including schizophrenia and autism.

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11. Kakuszi B, Szuromi B, Tóth M, Bitter I, Czobor P. Alterations in resting-state gamma-activity is adults with autism spectrum disorder: A High-Density EEG study. Psychiatry Res;2024 (Jun 14);339:116040.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a wide range of symptoms that include deficits in social cognition and difficulties with social interactions. Neural oscillations in the EEG gamma band have been proposed as an important candidate neurobiological marker of higher order cognitive processes and social interactions. We investigated resting-state gamma-activity of patients with ASD (n=23) in order to delineate alterations as compared to typically developing (TD) subjects (n=24). EEG absolute power was examined in the gamma (30-100Hz) frequency band. We found significantly reduced spectral power across the entire gamma range in the ASD group. The decrease was most pronounced over the inferior-frontal and temporo-parietal junction areas. We also found a significant decrease in gamma-activity over the dorsolateral prefrontal cortex, especially in the left side. Since these brain areas have been associated with social functioning, the reduced gamma-activity in ASD may represent a cortical dysfunction that could underlie a diminished capacity to interpret socially important information, thereby interfering with social functioning. The alterations we found may lend support for an improved diagnosis. Furthermore, they can lead to focused therapies, by targeting the dysfunctional brain activity to improve social cognitive and interaction abilities that are compromised in ASD.

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12. Keates N, Martin F, Waldock KE. Correction: Autistic People’s Perspectives on Functioning Labels and Associated Reasons, and Community Connectedness. J Autism Dev Disord;2024 (Jun 14)

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13. Kundu S, Sair H, Sherr EH, Mukherjee P, Rohde GK. Discovering the gene-brain-behavior link in autism via generative machine learning. Sci Adv;2024 (Jun 14);10(24):eadl5307.

Autism is traditionally diagnosed behaviorally but has a strong genetic basis. A genetics-first approach could transform understanding and treatment of autism. However, isolating the gene-brain-behavior relationship from confounding sources of variability is a challenge. We demonstrate a novel technique, 3D transport-based morphometry (TBM), to extract the structural brain changes linked to genetic copy number variation (CNV) at the 16p11.2 region. We identified two distinct endophenotypes. In data from the Simons Variation in Individuals Project, detection of these endophenotypes enabled 89 to 95% test accuracy in predicting 16p11.2 CNV from brain images alone. Then, TBM enabled direct visualization of the endophenotypes driving accurate prediction, revealing dose-dependent brain changes among deletion and duplication carriers. These endophenotypes are sensitive to articulation disorders and explain a portion of the intelligence quotient variability. Genetic stratification combined with TBM could reveal new brain endophenotypes in many neurodevelopmental disorders, accelerating precision medicine, and understanding of human neurodiversity.

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14. Lee SH, Jeon JJ, Lee WS, Lee S. Autoimmune connective tissue and dermatological diseases in children with autism spectrum disorder. J Invest Dermatol;2024 (Jun 11)

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15. Lynam A, Sweeney MR, Keenan L, McNally S. Autistic pupils’ experiences in primary and post-primary schools: A scoping review and consultation with autistic pupils in Ireland. Autism Dev Lang Impair;2024 (Jan-Dec);9:23969415241258705.

BACKGROUND AND AIMS: Autistic pupils have the right to be heard in matters concerning their education and to be active agents in shaping their school experiences. Despite this, educational policies and research have rarely included the voices of autistic children, failing to identify what they consider to be beneficial and meaningful in their own education. This study aimed to (i) summarise existing literature exploring autistic pupils’ experiences at school from their own perspectives and (ii) identify gaps for future research through a consultation with autistic pupils. METHODS: A scoping review was conducted to identify studies exploring first-person accounts of autistic pupils’ school experiences (primary and secondary; aged 4-18 years) published between 2005 and 2023. Thematic analysis was conducted to identify overarching thematic categories across the included studies. Review findings were discussed through a consultation with a Child and Youth Advisory Group (CYAG) comprised of autistic pupils in Ireland (N = 3), to seek feedback and inform a future research agenda. MAIN CONTRIBUTION: Thirty-six studies were included in the review and six themes were identified: Experiences of feeling misunderstood, of bullying and masking, of feeling excluded, of anxiety, of sensory needs in school, and of being overwhelmed during transitions. Consultation with the CYAG highlighted that these six themes were consistent with autistic pupils’ experiences but that reports of positive experiences were missing in the literature. CONCLUSIONS: This study identified several gaps in the literature on the school experiences of autistic pupils, based on both the scoping review and consultation with the CYAG. While the CYAG validated the themes identified in existing literature, there is a need for greater diversity in the samples included and increased focus on the potential positive aspects of the school experience. Implications. These findings have important research implications. In particular, further studies are needed with autistic pupils at primary school level, including those who are minimally or non-speaking, as well as ensuring pupils with positive school experiences are also represented. Findings also highlight the need for continued collaboration with autistic pupils themselves in matters concerning their education.

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16. Manning C. EXPRESS: Visual processing and decision-making in autism and dyslexia: Insights from cross-syndrome approaches. Q J Exp Psychol (Hove);2024 (Jun 14):17470218241264627.

Atypical visual processing has been reported in developmental conditions like autism and dyslexia, and some accounts propose a causal role for visual processing in the development of these conditions. However, few studies make direct comparisons between conditions, or use sufficiently sensitive methods, meaning that it is hard to say whether atypical visual processing tells us anything specific about these conditions, or whether it reflects a more general marker of atypical development. Here I review findings from two computational modelling approaches (equivalent noise and diffusion modelling) and related electroencephalography (EEG) indices which we have applied to data from autistic, dyslexic and typically developing children to reveal how the component processes involved in visual processing and decision-making are altered in autism and dyslexia. The results identify both areas of convergence and divergence in autistic and dyslexic children’s visual processing and decision-making, with implications for influential theoretical accounts such as weak central coherence, increased internal noise and dorsal-stream vulnerability. In both sets of studies, we also see considerable variability across children in all three groups. To better understand this variability, and further understand the convergence and divergence identified between conditions, future studies would benefit from studying how the component processes reviewed here relate to transdiagnostic dimensions, which will also give insights into individual differences in visual processing and decision-making more generally.

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17. Meijsen J, Hu K, Krebs MD, Athanasiadis G, Washbrook S, Zetterberg R, Avelar ESRN, Shorter JR, Gådin JR, Bergstedt J, Howard DM, Ye W, Lu Y, Valdimarsdóttir UA, Ingason A, Helenius D, Plana-Ripoll O, McGrath JJ, Micali N, Andreassen OA, Werge TM, Fang F, Buil A. Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians. Nat Commun;2024 (Jun 13);15(1):5064.

Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

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18. Rippon G. Differently different?: A commentary on the emerging social cognitive neuroscience of female autism. Biol Sex Differ;2024 (Jun 13);15(1):49.

Autism is a neurodevelopmental condition, behaviourally identified, which is generally characterised by social communication differences, and restrictive and repetitive patterns of behaviour and interests. It has long been claimed that it is more common in males. This observed preponderance of males in autistic populations has served as a focussing framework in all spheres of autism-related issues, from recognition and diagnosis through to theoretical models and research agendas. One related issue is the near total absence of females in key research areas. For example, this paper reports a review of over 120 brain-imaging studies of social brain processes in autism that reveals that nearly 70% only included male participants or minimal numbers (just one or two) of females. Authors of such studies very rarely report that their cohorts are virtually female-free and discuss their findings as though applicable to all autistic individuals. The absence of females can be linked to exclusionary consequences of autism diagnostic procedures, which have mainly been developed on male-only cohorts. There is clear evidence that disproportionately large numbers of females do not meet diagnostic criteria and are then excluded from ongoing autism research. Another issue is a long-standing assumption that the female autism phenotype is broadly equivalent to that of the male autism phenotype. Thus, models derived from male-based studies could be applicable to females. However, it is now emerging that certain patterns of social behaviour may be very different in females. This includes a specific type of social behaviour called camouflaging or masking, linked to attempts to disguise autistic characteristics. With respect to research in the field of sex/gender cognitive neuroscience, there is emerging evidence of female differences in patterns of connectivity and/or activation in the social brain that are at odds with those reported in previous, male-only studies. Decades of research have excluded or overlooked females on the autistic spectrum, resulting in the construction of inaccurate and misleading cognitive neuroscience models, and missed opportunities to explore the brain bases of this highly complex condition. A note of warning needs to be sounded about inferences drawn from past research, but if future research addresses this problem of male bias, then a deeper understanding of autism as a whole, as well as in previously overlooked females, will start to emerge. Autism is a neurodevelopmental condition, behaviourally identified, which is generally characterised by social communication differences, and restrictive and repetitive patterns of behaviour and interests. It has long been claimed that it is more common in males, with oft-quoted ratios of 4M: 1F. This has been reflected in the development of diagnostic criteria for autism and, consequently, of measures of eligibility for autism research programmes, with females being (as is now emerging) disproportionately excluded.As outlined in this review, this issue has been particularly problematic in brain-based studies of autism. Many studies have only tested male autistic participants, or minimal numbers of autistic females. By default, sex differences were not examined. But the impression given by such research reports has commonly been that the findings would be applicable to all autistic individuals.Recent psychological and clinical research has shown that there are a significant number of autistic females who have been missed by traditional diagnostic practices. Their inclusion has increased their eligibility for autism research studies. With respect to brain research, it has become possible to devise studies with matched numbers of autistic females and males, and to replicate studies that have previously only tested males. Newly emerging findings from such studies are demonstrating that the ‘robust’ autism-related differences previously observed in autistic male-only cohorts do not fully generalise to autistic females.It will be necessary to exercise caution in drawing inferences from previous male-biased studies of the autistic brain. However, the identification and inclusion of previously excluded female autistic participants hopefully offers more accurate insights into this highly complex and heterogeneous condition. eng

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19. Sandoval SO, Méndez-Albelo NM, Xu Z, Zhao X. From wings to whiskers to stem cells: why every model matters in fragile X syndrome research. J Neurodev Disord;2024 (Jun 13);16(1):30.

Fragile X syndrome (FXS) is caused by epigenetic silencing of the X-linked fragile X messenger ribonucleoprotein 1 (FMR1) gene located on chromosome Xq27.3, which leads to the loss of its protein product, fragile X messenger ribonucleoprotein (FMRP). It is the most prevalent inherited form of intellectual disability and the highest single genetic cause of autism. Since the discovery of the genetic basis of FXS, extensive studies using animal models and human pluripotent stem cells have unveiled the functions of FMRP and mechanisms underlying FXS. However, clinical trials have not yielded successful treatment. Here we review what we have learned from commonly used models for FXS, potential limitations of these models, and recommendations for future steps.

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20. Schendel D, Ejlskov L, Overgaard M, Jinwala Z, Kim V, Parner E, Kalkbrenner A, Ladd-Acosta C, Fallin MD, Xie S, Mortensen PB, Lee BK. 3-Generation Family Medical Histories of Mental, Neurologic, Cardiometabolic, Birth Defect, Asthma, Allergy, and Autoimmune Conditions Associated with Autism: an Open Source Catalogue of Findings. medRxiv;2024 (Jun 14)

The relatively few conditions and family members investigated in autism family health history limits etiologic understanding. For more comprehensive understanding and hypothesis-generation we produced an open-source catalogue of autism associations with family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions. All live births in Denmark, 1980-2012, of Denmark-born parents (1,697,231 births), and their 3-generation family members were followed through April 10, 2017 for each of 90 diagnoses (including autism), emigration or death. Adjusted hazard ratios (aHR) were estimated via Cox regression for each diagnosis-family member type combination, adjusting for birth year, sex, birth weight, gestational age, parental ages at birth, and number of family member types of index person; aHRs also calculated for sex-specific co-occurrence of each disorder. We obtained 6,462 individual family history aHRS across autism overall (26,840 autistic persons; 1.6% of births), by sex, and considering intellectual disability (ID); and 350 individual co-occurrence aHRS. Results are catalogued in interactive heat maps and down-loadable data files: https://ncrr-au.shinyapps.io/asd-riskatlas/ and interactive graphic summaries: https://public.tableau.com/views/ASDPlots_16918786403110/e-Figure5. While primarily for reference material or use in other studies (e.g., meta-analyses), results revealed considerable breadth and variation in magnitude of familial health history associations with autism by type of condition, family member type, sex of the family member, side of the family, sex of the index person, and ID status, indicative of diverse genetic, familial, and non-genetic autism etiologic pathways. Careful attention to sources of autism likelihood in family health history, aided by our open data resource, may accelerate understanding of factors underlying neurodiversity.

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21. Skaletski EC, Barry K, Dennis E, Donnelly R, Huerta C, Jones A, Schmidt K, Kabakov S, Ausderau KK, Li JJ, Travers BG. Correction: Sensorimotor Features and Daily Living Skills in Autistic Children With and Without ADHD. J Autism Dev Disord;2024 (Jun 14)

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22. Vinayagam R, Tanner C, Harley D, Karatela S, Brooker K. Correction to: « My Autism is Linked with Everything »: at the Crossroads of Autism and Diabetes. J Autism Dev Disord;2024 (Jun 14)

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23. Wang YC, Tai YM, Wu YY, Chiu YN, Tsai WC, Gau SS. A follow-up study of peer relationships in autistic and non-autistic youths: Mediating effects from autistic, emotional and behavioral symptoms. Res Dev Disabil;2024 (Jun 12);151:104768.

BACKGROUND: Little is known about how clinical features prospectively influence peer relationships in autistic populations. AIMS: This study investigated the clinical symptoms mediating the link between autism spectrum disorder (ASD) diagnosis and peer relationships at follow-up, i.e. the second time evaluation of this study. METHODS: The sample consisted of 366 autistic youths and 134 non-autistic comparisons. The autistic traits and emotional/behavioral problems were measured at baseline by Social Responsiveness Scale (SRS) and Child Behavior Checklist (CBCL). The interactions and problems with peers were assessed by the Social Adjustment Inventory for Children and Adolescents (SAICA) at follow-up. RESULTS: Each subscore of SRS and CBCL showed significant mediation effects. Multiple mediation analyses showed atypical social communication, social awareness problems, and delinquent behaviors mediated the link from ASD to less active peer interactions after controlling for sex, age, and IQ. Moreover, atypical social communication, social-emotional problems, and attention difficulties predicted problems with peers. After considering these mediation effects, the diagnosis of ASD still demonstrated a significantly direct effect on peer relationships at follow-up. CONCLUSIONS AND IMPLICATIONS: Our findings support that social-related autistic features, attention problems, and delinquent behaviors mediated a link between ASD and peer relationships. These mediators are potential measures for improving interactions and decreasing difficulties with peers in the autistic population.

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24. Zhang J, Guo J, Lu D, Cao Y. ASD-SWNet: a novel shared-weight feature extraction and classification network for autism spectrum disorder diagnosis. Sci Rep;2024 (Jun 13);14(1):13696.

The traditional diagnostic process for autism spectrum disorder (ASD) is subjective, where early and accurate diagnosis significantly affects treatment outcomes and life quality. Thus, improving ASD diagnostic methods is critical. This paper proposes ASD-SWNet, a new shared-weight feature extraction and classification network. It resolves the issue found in previous studies of inefficiently integrating unsupervised and supervised learning, thereby enhancing diagnostic precision. The approach utilizes functional magnetic resonance imaging to improve diagnostic accuracy, featuring an autoencoder (AE) with Gaussian noise for robust feature extraction and a tailored convolutional neural network (CNN) for classification. The shared-weight mechanism utilizes features learned by the AE to initialize the convolutional layer weights of the CNN, thereby integrating AE and CNN for joint training. A novel data augmentation strategy for time-series medical data is also introduced, tackling the problem of small sample sizes. Tested on the ABIDE-I dataset through nested ten-fold cross-validation, the method achieved an accuracy of 76.52% and an AUC of 0.81. This approach surpasses existing methods, showing significant enhancements in diagnostic accuracy and robustness. The contribution of this paper lies not only in proposing new methods for ASD diagnosis but also in offering new approaches for other neurological brain diseases.

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25. Zhang J, Weissenkampen JD, Kember RL, Grove J, Børglum AD, Robinson EB, Brodkin ES, Almasy L, Bucan M, Sebro R. Phenotypic and ancestry-related assortative mating in autism. Mol Autism;2024 (Jun 14);15(1):27.

BACKGROUND: Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in phenotypically defined autism subgroups [e.g., autism with and without intellectually disability (ID)]. It is also unclear what proportion of the phenotypic AM can be explained by the genetic similarity between parents of children with an autism diagnosis, and the consequences of AM on the genetic structure of the population. METHODS: To address these questions, we analyzed two family-based autism collections: the Simons Foundation Powering Autism Research for Knowledge (SPARK) (1575 families) and the Simons Simplex Collection (SSC) (2283 families). RESULTS: We found a similar degree of phenotypic and ancestry-related AM in parents of children with an autism diagnosis regardless of the presence of ID. We did not find evidence of AM for autism based on autism polygenic scores (PGS) (at a threshold of |r|> 0.1). The adjustment of ancestry-related AM or autism PGS accounted for only 0.3-4% of the fractional change in the estimate of the phenotypic AM. The ancestry-related AM introduced higher long-range linkage disequilibrium (LD) between single nucleotide polymorphisms (SNPs) on different chromosomes that are highly ancestry-informative compared to SNPs that are less ancestry-informative (D(2) on the order of 1 × 10(-5)). LIMITATIONS: We only analyzed participants of European ancestry, limiting the generalizability of our results to individuals of non-European ancestry. SPARK and SSC were both multicenter studies. Therefore, there could be ancestry-related AM in SPARK and SSC due to geographic stratification. The study participants from each site were unknown, so we were unable to evaluate for geographic stratification. CONCLUSIONS: This study showed similar patterns of AM in autism with and without ID, and demonstrated that the common genetic influences of autism are likely relevant to both autism groups. The adjustment of ancestry-related AM and autism PGS accounted for < 5% of the fractional change in the estimate of the phenotypic AM. Future studies are needed to evaluate if the small increase of long-range LD induced by ancestry-related AM has impact on the downstream analysis.

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