1. Adebiyi E, Jennifer Christine MP. Temporal trends and regional variation of heart transplantation in children with intellectual and developmental disabilities. Pediatric transplantation. 2023: e14620.

BACKGROUND: Historically, intellectual and developmental disability (IDD) has been considered an important factor in choosing potential recipients of organ transplants among many transplant centers. This study evaluated the temporal changes at the national and regional levels in the proportion of heart transplantation in children with IDD. METHODS: Children younger than 19 years in the United Network for Organ Sharing (UNOS) database who received heart transplants from 2010 to 2021 were included in this study. The patients were grouped into only definitive intellectual disability, both definitive intellectual and motor disability, only definitive motor disability, and no developmental disability. Multinomial logistic regressions were used to examine the proportion of heart transplants in each category for the whole cohort and each geographic transplant region. RESULTS: There were 4273 pediatric heart transplant recipients included in the study. From 2010 to 2021, the percentages of pediatric heart transplants increased from 3.8% (95% CI, 0.01-0.05) to 5.8% (95% CI, 0.03-0.08) in children with only definitive intellectual disability (OR 0.07; 95% CI, 0.02-0.1, p(trend)  < .002), from 3.4% (95% CI, 0.01-0.05) to 6.6% (95% CI, 0.04-0.09) in children with both definitive intellectual disability and motor disability (OR 0.09; 95% CI, 0.05-0.13, p(trend)  < .001), and from 5.2% (95% CI, 0.02-0.07) to 8.3% (95% CI, 0.05-0.1) in children with only definitive motor disability (OR 0.06; 95% CI, 0.02-0.09, p(trend)  < .002). There were several regional differences in the proportion of children with intellectual and developmental disabilities who received heart transplants. CONCLUSION: There is increasing inclusion of children diagnosed with intellectual and developmental disabilities in heart transplantation. A review of the current allocation policies may address the marked geographic variations found in this study.

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2. Camia M, Scorza M, Lipparini A, Martorana L, Nardocci F, Padovani R, Rubichi S, Benassi E. Psychological health of mothers and siblings of children with autism spectrum disorders during COVID-19 pandemic: new evidence in Italian families. Acta bio-medica : Atenei Parmensis. 2023; 94(5): e2023199.

BACKGROUND AND AIM: Psychological challenges are well recognized in families with a child with Autism Spectrum Disorders (ASD). Instead, less is known about the effects of traumatic scenarios, such as COVID-19, on the psychological health of these families. The main aim of this research was to study the psychological health of both mothers and typically developing (TD) siblings of children with ASD during the COVID-19 pandemic. Second, we investigated the relationship between the mothers’ psychological resources and their children psychological well-being. METHODS: The sample included 52 mothers and their children: 15 with one child with ASD and at least one TD child (aged 4-14) (ASD-siblings group) and 37 with one or more TD child (aged 4-14) (TD control group). The data were collected through an online platform; four standardized questionnaires (GAD-7, BDI-II, CD-RISC 25 and CBCL) were administered. RESULTS: The analyses revealed more internalizing and total behavioral symptoms in the siblings of children with ASD, compared to TD control group. Regarding the mothers, we did not find differences in depression and anxious symptoms between the two groups. However, the results reported a lower level of resilience in the mothers of children with ASD relative to mothers of TD children. Finally, the psychological well-being of the TD children was associated with the level of mothers’ anxiety only in the ASD-siblings group. CONCLUSIONS: Overall, our data show that the COVID-19 outbreak may had been particularly challenging for families of children with ASD, and highlight the importance of intensifying psychological support to families.

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3. Chan V, Albaum CS, Khanlou N, Westra H, Weiss JA. Parent Involvement in Mental Health Treatment for Autistic Children: A Grounded Theory-Informed Qualitative Analysis. Child psychiatry and human development. 2023.

Cognitive behavior therapy (CBT) is an effective treatment for many autistic children experiencing mental health problems, and parents are particularly involved in their psychotherapy. This study presents a conceptual framework of successful parent involvement in CBT for autistic children. Seventeen therapists (94% female) and 11 mothers were interviewed about their involvement in a CBT program for autistic children ages 8-13 years. The conceptual framework depicts how parent involvement varies depending on child, parent, and environmental factors. Parents’ contributions to therapy were grouped into five main roles. Parents’ beliefs and attitudes toward therapy also influenced their involvement. This is the first study to empirically investigate how parents of autistic children contribute to the therapeutic process in CBT.

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4. Chen K, Zhuang W, Zhang Y, Yin S, Liu Y, Chen Y, Kang X, Ma H, Zhang T. Alteration of the large-scale white-matter functional networks in autism spectrum disorder. Cerebral cortex (New York, NY : 1991). 2023.

Autism spectrum disorder is a neurodevelopmental disorder whose core deficit is social dysfunction. Previous studies have indicated that structural changes in white matter are associated with autism spectrum disorder. However, few studies have explored the alteration of the large-scale white-matter functional networks in autism spectrum disorder. Here, we identified ten white-matter functional networks on resting-state functional magnetic resonance imaging data using the K-means clustering algorithm. Compared with the white matter and white-matter functional network connectivity of the healthy controls group, we found significantly decreased white matter and white-matter functional network connectivity mainly located within the Occipital network, Middle temporo-frontal network, and Deep network in autism spectrum disorder. Compared with healthy controls, findings from white-matter gray-matter functional network connectivity showed the decreased white-matter gray-matter functional network connectivity mainly distributing in the Occipital network and Deep network. Moreover, we compared the spontaneous activity of white-matter functional networks between the two groups. We found that the spontaneous activity of Middle temporo-frontal and Deep network was significantly decreased in autism spectrum disorder. Finally, the correlation analysis showed that the white matter and white-matter functional network connectivity between the Middle temporo-frontal network and others networks and the spontaneous activity of the Deep network were significantly correlated with the Social Responsiveness Scale scores of autism spectrum disorder. Together, our findings indicate that changes in the white-matter functional networks are associated behavioral deficits in autism spectrum disorder.

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5. Chen L, Xiong XY, Yao TT, Gui LN, Luo F, Du Y, Cheng Y. Blood exosome sensing via neuronal insulin-like growth factor-1 regulates autism-related phenotypes. Pharmacological research. 2023: 106965.

The development and progression of autism spectrum disorder (ASD) is characterized by multiple complex molecular events, highlighting the importance of the prefrontal brain regions in this process. Exosomes are nanovesicles that play a critical role in intercellular communication. Peripheral systems influence brain function under both physiological and pathological conditions. We investigated whether this influence was mediated by the direct sensing of peripheral blood exosomes by brain cells. Administration of serum exosomes from rats with valproic acid-induced ASD resulted in ASD-related phenotypes in mice, whereas exosomes from normal rats did not exhibit such effects. RNA sequencing and bioinformatics analysis suggested that negative regulation of medial prefrontal cortex (mPFC) insulin-like growth factor 1 (IGF-1) by exosome-derived miR-29b-3p may contribute to these ASD-associated effects. Further evidence showed that miR-29b-3p-enriched exosomes crossed the blood-brain barrier to reach the mPFC, subsequently inducing the suppression of IGF-1 expression in neurons. Optogenetic activation of excitatory neurons in the mPFC improved behavioral abnormalities in exosome-treated mice. The addition of exogenous IGF-1 or inhibition of miR-29b-3p expression in the mPFC also rescued the ASD-related phenotypes in mice. Importantly, administration of miR-29b-3p-enriched serum exosomes from human donors with ASD into the mouse medial prefrontal cortex was sufficient to induce hallmark ASD behaviors. Together, our findings indicate that blood-brain cross-talk is crucial for ASD pathophysiology and that the brain may sense peripheral system changes through exosomes, which could serve as the basis for future neurological therapies.

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6. Cummings KK, Jung J, Zbozinek TD, Wilhelm FH, Dapretto M, Craske MG, Bookheimer SY, Green SA. Shared and distinct biological mechanisms for anxiety and sensory over-responsivity in youth with autism versus anxiety disorders. Journal of neuroscience research. 2023.

Sensory over-responsivity (SOR) is a prevalent cross-diagnostic condition that is often associated with anxiety. The biological mechanisms underlying the co-occurrence of SOR and anxiety symptoms are not well understood, despite having important implications for targeted intervention. We therefore investigated the unique associations of SOR and anxiety symptoms with physiological and neural responses to sensory stimulation for youth with anxiety disorders (ANX), autism spectrum disorder (ASD), or typical development (TD). Age/IQ-matched youth aged 8-18 years (22 ANX; 30 ASD; 22 TD) experienced mildly aversive tactile and auditory stimuli during functional magnetic resonance imaging and then during skin conductance response (SCR) and heart rate (HR) measurements. Caregivers reported on participants’ SOR and anxiety symptoms. ASD/ANX youth had elevated SOR and anxiety symptoms compared to TD. ASD/ANX youth showed similar, heightened brain responses to sensory stimulation compared to TD youth, but brain responses were more highly related to SOR symptoms in ASD youth and to anxiety symptoms in ANX youth. Across ASD/ANX youth, anxiety symptoms uniquely related to greater SCR whereas SOR uniquely related to greater HR responses to sensory stimulation. Behavioral and neurobiological over-responsivity to sensory stimulation was shared across diagnostic groups. However, findings support SOR and anxiety as distinct symptoms with unique biological mechanisms, and with different relationships to neural over-reactivity dependent on diagnostic group. Results indicate a need for targeted treatment approaches.

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7. Douglas S, Sedgewick F. Experiences of interpersonal victimization and abuse among autistic people. Autism : the international journal of research and practice. 2023: 13623613231205630.

What do we already know?Autistic people are more likely to have negative life experiences than non-autistic people, from bullying and ostracization, to being victims of crime, to unemployment and homelessness. This includes being victims of intimate partner violence, sexual assault and domestic abuse. Quantitative work has suggested that as many as 90% of autistic people experience these forms of abuse in some form during their lives, but there is little work asking them to talk about harmful relationships in their own words.What does this article add?This article reports on interviews with 24 autistic adults about their experiences of being victims of intimate partner violence, sexual assault and/or domestic abuse. Some of the themes which came from these interviews are shared with non-autistic victims, but others appeared unique to autistic people. One of these was evidence for unique autism-related vulnerabilities, as well as the impact the abuse had on their relationships long term. Participants also talked about how the sex and relationship education they had received had inadequately prepared them for adult relationships, and how this had contributed to their struggle to recognize and react to abusive behaviour.Implications for practice, research and policyPolicies around intimate partner violence and sexual assault need to be updated to account for the different ways in which neurodivergent people (people whose brains process information differently from the majority) may discuss their experiences, rather than looking for ‘standard narratives’ as an indicator of a need for support. Relationship and sex education should be tailored for autistic young people to help them recognize abusive behaviours, and include how to respond to these safely. We recommend that future research tries to focus specifically on the abuse experiences of autistic men, non-binary and trans people, who have been under-represented in studies to date. In addition, much less is known about the abuse experiences of autistic people of colour or autistic people with intellectual disabilities, who also need to be actively included in these discussions.

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8. Ellul P, Maruani A, Vantalon V, Humeau E, Amestoy A, Anchordoqui A, Atzori P, Baleyte JM, Benmansour S, Bonnot O, Bouvard M, Cartigny A, Coulon N, Coutelle R, Da Fonseca D, Demily C, Givaudan M, Gollier-Briant F, Guénolé F, Koch A, Leboyer M, Lefebvre A, Lejuste F, Levy C, Mendes E, Robert N, Schroder CM, Speranza M, Zante E, Peyre H, Rosenzwajg M, Klatzmann D, Tchitchek N, Delorme R. Maternal immune activation during pregnancy is associated with more difficulties in socio-adaptive behaviors in autism spectrum disorder. Scientific reports. 2023; 13(1): 17687.

Autism spectrum disorder (ASD) are neurodevelopmental conditions characterised by deficits in social communication and interaction and repetitive behaviours. Maternal immune activation (MIA) during the mid-pregnancy is a known risk factor for ASD. Although reported in 15% of affected individuals, little is known about the specificity of their clinical profiles. Adaptive skills represent a holistic approach to a person’s competencies and reflect specifically in ASD, their strengths and difficulties. In this study, we hypothesised that ASD individual with a history of MIA (MIA(+)) could be more severely socio-adaptively impaired than those without MIA during pregnancy (MIA(-)). To answer this question, we considered two independent cohorts of individuals with ASD (PARIS study and FACE ASD) screened for pregnancy history, and used supervised and unsupervised machine learning algorithms. We included 295 mother-child dyads with 14% of them with MIA(+). We found that ASD-MIA(+) individuals displayed more severe maladaptive behaviors, specifically in their socialization abilities. MIA(+) directly influenced individual’s socio-adaptive skills, independent of other covariates, including ASD severity. Interestingly, MIA(+) affect persistently the socio-adaptive behavioral trajectories of individuals with ASD. The current study has a retrospective design with possible recall bias regarding the MIA event and, even if pooled from two cohorts, has a relatively small population. In addition, we were limited by the number of covariables available potentially impacted socio-adaptive behaviors. Larger prospective study with additional dimensions related to ASD is needed to confirm our results. Specific pathophysiological pathways may explain these clinical peculiarities of ASD- MIA(+) individuals, and may open the way to new perspectives in deciphering the phenotypic complexity of ASD and for the development of specific immunomodulatory strategies.

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9. Klitzman R, Bezborodko E, Chung WK, Appelbaum PS. Receiving de novo genetic diagnoses for autism with intellectual disability: parents’ views of impacts on families’ reproductive decisions. Journal of community genetics. 2023.

Parents of children with autism who receive genetic diagnoses of de novo variants face challenges in understanding the implications for reproductive decision-making. We interviewed 28 parents who received de novo genetic diagnoses for their child’s autism and intellectual disability (ID). These genetic variants proved to have reproductive implications for not only the child’s parents, but the child and his/her neurotypical siblings, aunts, uncles, and cousins. Parents had often already finished building their families but varied, overall, in whether the results had affected, or might have influenced, their reproductive decisions. Parents’ views were shaped by factors related to not only genetics, but also parental age, financial considerations, competing hopes and visions for their family’s future, perceived abilities to care for an additional child with similar symptoms, and the extent of the child’s symptoms. Members of a couple sometimes disagreed about whether to have more children. Parents pondered, too, the possibility of preimplantation genetic testing, though misunderstandings about it arose. Children with autism vary widely in their abilities to understand the reproductive implications of genetic diagnoses for themselves. Neurotypical offspring were much relieved to understand that their own children would not be affected. While some autism self-advocates have been concerned that genetic testing related to autism could lead to eugenics, the present data, concerning de novo genetic findings, raise other perspectives. These data, the first to explore several key aspects of the reproductive implications of genetic diagnoses for this group, have important implications for future practice, education, and research-e.g., concerning various family members.

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10. Lachiewicz AM, Stackhouse TM, Burgess K, Burgess D, Andrews HF, Choo TH, Kaufmann WE, Kidd SA. Sensory Symptoms and Signs of Hyperarousal in Individuals with Fragile X Syndrome: Findings from the FORWARD Registry and Database Multisite Study. Journal of autism and developmental disorders. 2023.

This study was designed to increase our understanding about characteristics and the impact of sensory symptoms (SS) and signs of hyperarousal (HA) in individuals with fragile X syndrome (FXS) from childhood through early adulthood and by gender. Data derived from the Fragile X Online Registry With Accessible Research Database (FORWARD), a natural history study of FXS, were analyzed using descriptive statistics and multivariate linear and logistic regression models to examine SS and signs of HA, their impact on behavioral regulation and limitations on the subject/family. The sample (N = 933) consisted of 720 males and 213 females. More males were affected with SS (87% vs. 68%) and signs of HA (92% vs. 79%). Subjects who were endorsed as having a strong sensory response had more comorbidities, including behavioral problems. The predominant SS was difficulty with eye gaze that increased with age in both genders. As individuals age, there was less use of non-medication therapies, such as occupational therapy (OT)/physical therapy (PT), but there was more use of psychopharmacological medications and investigational drugs for behaviors. Multiple regression models suggested that endorsing SS and signs of HA was associated with statistically significantly increased ABC-C-I subscale scores and limited participation in everyday activities. This study improves our understanding of SS and signs of HA as well as their impact in FXS. It supports the need for more research regarding these clinical symptoms, especially to understand how they contribute to well-known behavioral concerns.

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11. Maltman N, Willer R, Sterling A. An Exploratory Study of Pragmatic Language Use Across Contexts With the Pragmatic Rating Scale-School Age Among Autistic Boys and Boys With Fragile X Syndrome Plus Autism. Journal of speech, language, and hearing research : JSLHR. 2023: 1-11.

PURPOSE: Autistic boys and boys with co-occurring fragile X syndrome and autism spectrum disorder (FXS + ASD) demonstrate similar pragmatic language difficulties. The Pragmatic Rating Scale-School Age (PRS-SA) captures ecologically valid metrics of pragmatic language impairments in these populations. It is traditionally scored based on the Autism Diagnostic Observation Schedule (ADOS), which may limit the use of the PRS-SA more broadly in research and clinical contexts. METHOD: This study evaluated the feasibility of the PRS-SA based on a shorter, semistructured conversational context compared to the ADOS in school-age autistic boys (n = 16) and boys with FXS + ASD (n = 16), matched on ASD traits. Differences across ADOS and conversational contexts and associations with ASD-related social difficulties were evaluated. RESULTS: Findings revealed differences in PRS-SA scores between ADOS and conversational contexts, but only for the FXS + ASD group. Limited associations were observed between PRS-SA scores and ASD traits. CONCLUSIONS: Results from this study indicate the feasibility of using the PRS-SA in a shorter conversational context than the ADOS to assess pragmatic language among autistic boys. For boys with FXS + ASD, contextual differences warrant careful consideration in future work.

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12. Mittmann G, Schrank B, Steiner-Hofbauer V. TV Series in Mainstream Media Depicting Autism and Self-Diagnosis of Autism in a General Population of Young Adults. Journal of autism and developmental disorders. 2023.

PURPOSE: The prevalence of autism diagnoses has increased in recent years. The portrayal of autistic characters in mainstream media, such as TV series, may be a contributing factor. This study investigated whether young adults who consume media featuring autistic characters are more likely to self-diagnose with autism. METHODS: 348 participants filled out an online questionnaire exploring their media consumption, subjective diagnosis of autism and objective indicators of autism using an Emotion Recognition Task. RESULTS: Results from linear regression analysis indicated a significant correlation between media consumption and self-diagnosis, while valence of the series and objective diagnosis did not have a significant influence. The study found no gender differences. CONCLUSION: The results suggest a need for further research on the relationship between media consumption and self-diagnosis, including for other forms of media beyond TV series.

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13. Muhammad T, Pastore SF, Good K, Ausió J, Vincent JB. Chromatin gatekeeper and modifier CHD proteins in development, and in autism and other neurological disorders. Psychiatric genetics. 2023.

Chromatin, a protein-DNA complex, is a dynamic structure that stores genetic information within the nucleus and adapts to molecular/cellular changes in its structure, providing conditional access to the genetic machinery. ATP-dependent chromatin modifiers regulate access of transcription factors and RNA polymerases to DNA by either « opening » or « closing » the structure of chromatin, and its aberrant regulation leads to a variety of neurodevelopmental disorders. The chromodomain helicase DNA-binding (CHD) proteins are ATP-dependent chromatin modifiers involved in the organization of chromatin structure, act as gatekeepers of genomic access, and deposit histone variants required for gene regulation. In this review, we first discuss the structural and functional domains of the CHD proteins, and their binding sites, and phosphorylation, acetylation, and methylation sites. The conservation of important amino acids in SWItch/sucrose non-fermenting (SWI/SNF) domains, and their protein and mRNA tissue expression profiles are discussed. Next, we convey the important binding partners of CHD proteins, their protein complexes and activities, and their involvements in epigenetic regulation. We also show the ChIP-seq binding dynamics for CHD1, CHD2, CHD4, and CHD7 proteins at promoter regions of histone genes, as well as several genes that are critical for neurodevelopment. The role of CHD proteins in development is also discussed. Finally, this review provides information about CHD protein mutations reported in autism and neurodevelopmental disorders, and their pathogenicity. Overall, this review provides information on the progress of research into CHD proteins, their structural and functional domains, epigenetics, and their role in stem cell, development, and neurological disorders.

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14. Shaw SC, Carravallah L, Johnson M, O’Sullivan J, Chown N, Neilson S, Doherty M. Barriers to healthcare and a ‘triple empathy problem’ may lead to adverse outcomes for autistic adults: A qualitative study. Autism : the international journal of research and practice. 2023: 13623613231205629.

Autistic people live with more mental and physical health conditions and, on average, die younger than non-autistic people. Despite widespread commitments to tackling these issues, autistic people still report various barriers to accessing healthcare. This article aims to explore the area in depth, from the perspective of autistic people. This research benefits from being led by autistic people, for autistic people – all of the researchers are autistic, and most of us are also medical doctors. Data, in the form of written comments and stories, were collected as part of a large survey. Here, we explored these for common themes and possible deeper meaning within the experiences. People who took part reported a variety of barriers. Here, our article gives voice to their stories, in their own words. Themes included: early barriers; communication mismatch; doubt – in oneself and from doctors; helplessness and fear; and healthcare avoidance and adverse health outcomes. Our findings allowed us to create a model that aimed to understand and explain the reported barriers in the context of the previously known consequences. We also built on wider autism theories to explain our findings in more depth.

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15. Tian R, Li Y, Zhao H, Lyu W, Zhao J, Wang X, Lu H, Xu H, Ren W, Tan QQ, Shi Q, Wang GD, Zhang YP, Lai L, Mi J, Jiang YH, Zhang YQ. Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing. Molecular psychiatry. 2023.

Despite intensive studies in modeling neuropsychiatric disorders especially autism spectrum disorder (ASD) in animals, many challenges remain. Genetic mutant mice have contributed substantially to the current understanding of the molecular and neural circuit mechanisms underlying ASD. However, the translational value of ASD mouse models in preclinical studies is limited to certain aspects of the disease due to the apparent differences in brain and behavior between rodents and humans. Non-human primates have been used to model ASD in recent years. However, a low reproduction rate due to a long reproductive cycle and a single birth per pregnancy, and an extremely high cost prohibit a wide use of them in preclinical studies. Canine model is an appealing alternative because of its complex and effective dog-human social interactions. In contrast to non-human primates, dog has comparable drug metabolism as humans and a high reproduction rate. In this study, we aimed to model ASD in experimental dogs by manipulating the Shank3 gene as SHANK3 mutations are one of most replicated genetic defects identified from ASD patients. Using CRISPR/Cas9 gene editing, we successfully generated and characterized multiple lines of Beagle Shank3 (bShank3) mutants that have been propagated for a few generations. We developed and validated a battery of behavioral assays that can be used in controlled experimental setting for mutant dogs. bShank3 mutants exhibited distinct and robust social behavior deficits including social withdrawal and reduced social interactions with humans, and heightened anxiety in different experimental settings (n = 27 for wild-type controls and n = 44 for mutants). We demonstrate the feasibility of producing a large number of mutant animals in a reasonable time frame. The robust and unique behavioral findings support the validity and value of a canine model to investigate the pathophysiology and develop treatments for ASD and potentially other psychiatric disorders.

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16. Wang Z, Qiao D, Chen H, Zhang S, Zhang B, Zhang J, Hu X, Wang C, Cui H, Wang X, Li S. Effects of Fmr1 gene mutations on sex differences in autism-like behavior and dendritic spine development in mice and transcriptomic studies. Neuroscience. 2023.

Fragile X syndrome (FXS) is the most common single gene disorder contributing to autism spectrum disorder (ASD). Although significant sex differences are observed in FXS, few studies have focused on the phenotypic characteristics as well as the differences in brain pathological changes and gene expression in FXS by sex. Therefore, we analyzed sex differences in autism-like behavior and dendritic spine development in two-month-old male and female Fmr1 KO and C57 mice and evaluated the mechanisms at transcriptome level. Results suggest that Fmr1 KO mice display sex differences in autism-like behavior and dendritic spine density. Compared to females, male had more severe effects on anxiety, repetitive stereotype-like behaviors, and socializing, with higher dendritic spine density. Furthermore, two male-biased and five female-biased expressed genes were screened based on KEGG pathway enrichment and protein-protein interaction (PPI) analyses. In conclusion, our findings show mutations in the Fmr1 gene lead to aberrant expression of related genes and affect the sex-differentiated behavioral phenotypes of Fmr1 KO mice by affecting brain development and functional architecture, and suggest future studies should focus on including female subjects to comprehensively reflect the differentiation of FXS in both sexes and develop more precise and effective therapeutic strategies.

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