Zheng Wang, Hang Qu, Danielle Christensen, Hanna M Gemmell, Ellen M Parks, Kyla E Wetherington, Ann-Marie Orlando, Regilda A Romero, Bikram Karmakar, David E Vaillancourt
Sensorimotor impairments are well documented in autism spectrum disorder (ASD). However, little is known about how these difficulties present in middle-aged and older autistic adults or how they relate to demographic factors and autistic traits. In this study, 52 autistic and 56 age- and sex-matched non-autistic adults (aged 30-73 years) completed a visually guided precision grip task designed to assess temporal (reaction time, duration), spatial (force accuracy, variability), and dynamic (rate of force change) features of grip control under two conditions: varying motor output demands (target force test) and visual feedback (visual gain test). Autistic adults showed prolonged duration, delayed reaction time, and greater target overshooting at lower force levels during the rise phase. During the sustained phase, they exhibited increased grip force variability across both tasks. In contrast, autistic adults demonstrated shorter reaction times during the relaxation phase. Subgroup analyses revealed that the middle-aged autistic subgroup displayed elevated grip force variability, whereas the older autistic subgroup showed broader impairments affecting both spatial and temporal aspects of precision gripping. Within the autistic group, temporal grip force variables under the low target force condition were significantly associated with age and repetitive behaviors. These findings demonstrate that manual motor impairments persist into adulthood in ASD, and suggest shared neurobiological networks that underlie both motor dysfunction and core autistic traits.
{"title":"Atypical Visually Guided Precision Grip Control in Middle-Aged and Older Autistic Adults.","authors":"Zheng Wang, Hang Qu, Danielle Christensen, Hanna M Gemmell, Ellen M Parks, Kyla E Wetherington, Ann-Marie Orlando, Regilda A Romero, Bikram Karmakar, David E Vaillancourt","doi":"10.1002/aur.70154","DOIUrl":"https://doi.org/10.1002/aur.70154","url":null,"abstract":"<p><p>Sensorimotor impairments are well documented in autism spectrum disorder (ASD). However, little is known about how these difficulties present in middle-aged and older autistic adults or how they relate to demographic factors and autistic traits. In this study, 52 autistic and 56 age- and sex-matched non-autistic adults (aged 30-73 years) completed a visually guided precision grip task designed to assess temporal (reaction time, duration), spatial (force accuracy, variability), and dynamic (rate of force change) features of grip control under two conditions: varying motor output demands (target force test) and visual feedback (visual gain test). Autistic adults showed prolonged duration, delayed reaction time, and greater target overshooting at lower force levels during the rise phase. During the sustained phase, they exhibited increased grip force variability across both tasks. In contrast, autistic adults demonstrated shorter reaction times during the relaxation phase. Subgroup analyses revealed that the middle-aged autistic subgroup displayed elevated grip force variability, whereas the older autistic subgroup showed broader impairments affecting both spatial and temporal aspects of precision gripping. Within the autistic group, temporal grip force variables under the low target force condition were significantly associated with age and repetitive behaviors. These findings demonstrate that manual motor impairments persist into adulthood in ASD, and suggest shared neurobiological networks that underlie both motor dysfunction and core autistic traits.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ru Ying Cai, David M Dueber, Michael D Toland, Vicki Gibbs, Chris Edwards, Abigail M A Love
Autistic adults face higher rates of loneliness and depression than non-autistic adults. Self-compassion may offer a protective buffer against mental health difficulties, but its measurement validity and interaction with loneliness have not been studied in autistic populations. This two-part study examined (1) the dimensional structure of the Self-Compassion Scale (SCS) in a global sample of autistic (n = 377) and non-autistic (n = 196) adults, and (2) whether self-compassion moderates the relationship between loneliness and depression in both groups. Confirmatory factor analyses tested multiple models of the SCS, and multigroup regression models tested moderation effects using loneliness and depression scores. The SCS was best represented by two factors-compassionate and uncompassionate self-responding-in both autistic and non-autistic groups. Measurement invariance was supported. In moderation analyses, uncompassionate self-responding significantly moderated the relationship between loneliness and depressive symptoms among non-autistic adults, but not autistic adults. Uncompassionate self-responding was significantly associated with greater depression symptoms in both groups. These findings support using a two-factor structure of the SCS in autistic samples and suggest that reducing uncompassionate self-responding may benefit mental health broadly. However, self-compassion did not buffer the loneliness-depression link for autistic adults, highlighting the need for alternative protective factors tailored to this population.
{"title":"Understanding Self-Compassion in Autistic Adults: Validity Evidence and Its Links to Loneliness and Depression Across Autistic and Non-Autistic Individuals.","authors":"Ru Ying Cai, David M Dueber, Michael D Toland, Vicki Gibbs, Chris Edwards, Abigail M A Love","doi":"10.1002/aur.70150","DOIUrl":"https://doi.org/10.1002/aur.70150","url":null,"abstract":"<p><p>Autistic adults face higher rates of loneliness and depression than non-autistic adults. Self-compassion may offer a protective buffer against mental health difficulties, but its measurement validity and interaction with loneliness have not been studied in autistic populations. This two-part study examined (1) the dimensional structure of the Self-Compassion Scale (SCS) in a global sample of autistic (n = 377) and non-autistic (n = 196) adults, and (2) whether self-compassion moderates the relationship between loneliness and depression in both groups. Confirmatory factor analyses tested multiple models of the SCS, and multigroup regression models tested moderation effects using loneliness and depression scores. The SCS was best represented by two factors-compassionate and uncompassionate self-responding-in both autistic and non-autistic groups. Measurement invariance was supported. In moderation analyses, uncompassionate self-responding significantly moderated the relationship between loneliness and depressive symptoms among non-autistic adults, but not autistic adults. Uncompassionate self-responding was significantly associated with greater depression symptoms in both groups. These findings support using a two-factor structure of the SCS in autistic samples and suggest that reducing uncompassionate self-responding may benefit mental health broadly. However, self-compassion did not buffer the loneliness-depression link for autistic adults, highlighting the need for alternative protective factors tailored to this population.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonah McLaughlin, Deana Crocetti, Stewart H Mostofsky, Daniel E Lidstone
Prominent theories of autism suggest autism-associated differences in visual-motor integration (VMI) may disrupt learning of motor and social skills typically acquired by observation and imitation. Supporting these theories, children with autism spectrum disorder (ASD) show robust differences in motor tasks reliant on dynamic VMI (e.g., ball-catching and motor imitation) and anomalous visual-motor connectivity between higher-order visual (HOV) and sensory-motor cortices. Use of functional MRI (fMRI) to examine HOV functional connectivity (FC) has been particularly revealing with other conditions. For instance, research with congenitally blind adults reveals a particular pattern of altered HOV connectivity, showing reduced HOV connectivity with primary sensory-motor (SM1) and primary auditory (A1) cortices yet "compensatory" increased connectivity between HOV and prefrontal cortex (PFC). Informed by these findings, we used fMRI to examine HOV FC in children with ASD, hypothesizing they would show a distinct pattern of HOV connectivity relative to typically developing (TD) children, with decreased HOV-SM1 connectivity and increased "compensatory" HOV-PFC connectivity. We further hypothesized that this altered pattern of HOV connectivity would correlate with autism-associated difficulties with performing skilled actions ("praxis"), often learned through visual imitation. Our findings suggest ASD children show an altered pattern of HOV connectivity that is characterized by reduced HOV connectivity with SM1 yet increased connectivity with PFC. Further, this HOV connectivity correlated with impaired praxis in children with ASD, suggesting that altered patterns of HOV connectivity may contribute to difficulty acquiring a range of skilled behaviors observed in autism.
{"title":"Anomalous Pattern of Left Hemisphere Visual Connectivity in Children With Autism: Association With Impaired Praxis.","authors":"Jonah McLaughlin, Deana Crocetti, Stewart H Mostofsky, Daniel E Lidstone","doi":"10.1002/aur.70146","DOIUrl":"https://doi.org/10.1002/aur.70146","url":null,"abstract":"<p><p>Prominent theories of autism suggest autism-associated differences in visual-motor integration (VMI) may disrupt learning of motor and social skills typically acquired by observation and imitation. Supporting these theories, children with autism spectrum disorder (ASD) show robust differences in motor tasks reliant on dynamic VMI (e.g., ball-catching and motor imitation) and anomalous visual-motor connectivity between higher-order visual (HOV) and sensory-motor cortices. Use of functional MRI (fMRI) to examine HOV functional connectivity (FC) has been particularly revealing with other conditions. For instance, research with congenitally blind adults reveals a particular pattern of altered HOV connectivity, showing reduced HOV connectivity with primary sensory-motor (SM1) and primary auditory (A1) cortices yet \"compensatory\" increased connectivity between HOV and prefrontal cortex (PFC). Informed by these findings, we used fMRI to examine HOV FC in children with ASD, hypothesizing they would show a distinct pattern of HOV connectivity relative to typically developing (TD) children, with decreased HOV-SM1 connectivity and increased \"compensatory\" HOV-PFC connectivity. We further hypothesized that this altered pattern of HOV connectivity would correlate with autism-associated difficulties with performing skilled actions (\"praxis\"), often learned through visual imitation. Our findings suggest ASD children show an altered pattern of HOV connectivity that is characterized by reduced HOV connectivity with SM1 yet increased connectivity with PFC. Further, this HOV connectivity correlated with impaired praxis in children with ASD, suggesting that altered patterns of HOV connectivity may contribute to difficulty acquiring a range of skilled behaviors observed in autism.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heather L Moore, Samuel Brice, Natalya Spraggon, Barry Ingham, Mark Freeston, Jeremy R Parr, Jacqui Rodgers
Restricted and repetitive behaviors (RRB) are associated with sensory processing (SP) differences for autistic people, and are thought to be a coping strategy to help manage the sensory environment. Previous work shows that, for autistic people, alexithymia, intolerance of uncertainty (IU), and anxiety mediate the relationship between SP differences and RRB. However, these studies use anxiety measures developed for the general population, and more recent evidence suggests that autistic people may have a different anxiety experience. This study aims to extend previous findings by unpacking the anxiety experience for autistic adults in the relationship between SP differences and RRB, using an autism-specific anxiety measure. Data were available from 426 autistic adults. Serial mediation models tested the relationship between SP differences and RRB, with alexithymia, IU, anxious arousal, and social anxiety as mediators. We identified significant direct effects from SP differences to both repetitive motor behaviors (RMB) and insistence on sameness behaviors (ISB). For RMB, we found indirect effects through anxious arousal, alexithymia-anxious arousal, IU-anxious arousal, and alexithymia-IU-anxious arousal. For ISB, we found indirect effects through IU and alexithymia-IU. Thus, different mechanisms may underpin RMB and ISB. Understanding the anxiety experience of autistic people, alongside the role of SP and RRB, is key to providing tailored support, adjustments, and psychological interventions to autistic people. Future research could benefit from directly investigating the impact of strategies to support SP and anxiety.
限制和重复行为(RRB)与自闭症患者的感觉处理(SP)差异有关,被认为是一种帮助管理感觉环境的应对策略。先前的研究表明,对于自闭症患者,述情障碍、不确定性不耐受(IU)和焦虑介导了SP差异和RRB之间的关系。然而,这些研究使用的是为普通人群开发的焦虑测量方法,最近的证据表明,自闭症患者可能有不同的焦虑体验。本研究旨在通过使用自闭症特异性焦虑测量,揭示自闭症成人焦虑经历中SP差异与RRB之间的关系,从而扩展先前的研究结果。数据来自426名自闭症成年人。以述情障碍、IU、焦虑唤醒和社交焦虑为中介,采用系列中介模型检验SP差异与RRB的关系。我们发现SP差异对重复运动行为(RMB)和坚持相同行为(ISB)有显著的直接影响。对于RMB,我们通过焦虑唤醒、述情-焦虑唤醒、iu -焦虑唤醒和述情- iu -焦虑唤醒发现了间接效应。对于ISB,我们通过IU和述情障碍-IU发现了间接影响。因此,不同的机制可以支撑人民币和ISB。了解自闭症患者的焦虑经历,以及SP和RRB的作用,是为自闭症患者提供量身定制的支持、调整和心理干预的关键。未来的研究可以从直接调查支持SP和焦虑的策略的影响中受益。
{"title":"Exploring Alexithymia, Uncertainty, Anxious Arousal, and Social Anxiety as Mediators of the Relationship Between Sensory Processing Differences and Restricted and Repetitive Behaviors in Autistic Adults.","authors":"Heather L Moore, Samuel Brice, Natalya Spraggon, Barry Ingham, Mark Freeston, Jeremy R Parr, Jacqui Rodgers","doi":"10.1002/aur.70145","DOIUrl":"https://doi.org/10.1002/aur.70145","url":null,"abstract":"<p><p>Restricted and repetitive behaviors (RRB) are associated with sensory processing (SP) differences for autistic people, and are thought to be a coping strategy to help manage the sensory environment. Previous work shows that, for autistic people, alexithymia, intolerance of uncertainty (IU), and anxiety mediate the relationship between SP differences and RRB. However, these studies use anxiety measures developed for the general population, and more recent evidence suggests that autistic people may have a different anxiety experience. This study aims to extend previous findings by unpacking the anxiety experience for autistic adults in the relationship between SP differences and RRB, using an autism-specific anxiety measure. Data were available from 426 autistic adults. Serial mediation models tested the relationship between SP differences and RRB, with alexithymia, IU, anxious arousal, and social anxiety as mediators. We identified significant direct effects from SP differences to both repetitive motor behaviors (RMB) and insistence on sameness behaviors (ISB). For RMB, we found indirect effects through anxious arousal, alexithymia-anxious arousal, IU-anxious arousal, and alexithymia-IU-anxious arousal. For ISB, we found indirect effects through IU and alexithymia-IU. Thus, different mechanisms may underpin RMB and ISB. Understanding the anxiety experience of autistic people, alongside the role of SP and RRB, is key to providing tailored support, adjustments, and psychological interventions to autistic people. Future research could benefit from directly investigating the impact of strategies to support SP and anxiety.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Alessandri-Bonetti, Federica Guglielmi, Andrea Faustini, Linda Sangalli, Edoardo Staderini, Patrizia Gallenzi
Children with autism spectrum disorder (ASD) often present with sleep disorders, including obstructive sleep apnea (OSA), a condition characterized by upper airway obstruction during sleep. Bruxism has been recently described as being associated with OSA. This study aimed to assess the prevalence of OSA risk and bruxism in pediatric ASD patients compared to age and sex-matched healthy controls using the validated screening tool Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (SRBD-PSQ). Fifty-eight consecutive pediatric ASD patients were screened for OSA and bruxism at the Dentistry Unit of A. Gemelli Policlinic and compared to 58 healthy patients using chi-square tests. Comparison between the two groups was repeated by controlling for body mass index (BMI) and behavioral symptoms with ANCOVA and logistic regression analyses. Of 58 ASD patients (10.3 ± 3.3 y/o, 74.5% males), 60.3% presented with an increased OSA risk, compared to 13.8% in the controls (p < 0.001, OR = 3.682, 95% CI: 1.933, 7.012). After controlling for BMI (which was significantly higher among ASD patients), those with ASD had significantly higher odds of OSA risk compared to controls (OR = 9.6, 95% CI: 3.56, 26.21). After controlling for the SRBD-PSQ behavioral component, the association between ASD and OSA risk lost its significant difference (p < 0.862). No significant difference was found between ASD patients and controls in awake (3.6% vs. 6.9%, p = 0.680) and sleep (25.5% vs. 32.8%, p = 0.393) bruxism. Pediatric patients with ASD present at higher risk of OSA, most likely explained by the behavioral symptoms; self-reported bruxism did not significantly differ compared to healthy controls.
{"title":"Prevalence of OSA Risk and Bruxism in Children With Autism Spectrum Disorders.","authors":"Anna Alessandri-Bonetti, Federica Guglielmi, Andrea Faustini, Linda Sangalli, Edoardo Staderini, Patrizia Gallenzi","doi":"10.1002/aur.70149","DOIUrl":"https://doi.org/10.1002/aur.70149","url":null,"abstract":"<p><p>Children with autism spectrum disorder (ASD) often present with sleep disorders, including obstructive sleep apnea (OSA), a condition characterized by upper airway obstruction during sleep. Bruxism has been recently described as being associated with OSA. This study aimed to assess the prevalence of OSA risk and bruxism in pediatric ASD patients compared to age and sex-matched healthy controls using the validated screening tool Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (SRBD-PSQ). Fifty-eight consecutive pediatric ASD patients were screened for OSA and bruxism at the Dentistry Unit of A. Gemelli Policlinic and compared to 58 healthy patients using chi-square tests. Comparison between the two groups was repeated by controlling for body mass index (BMI) and behavioral symptoms with ANCOVA and logistic regression analyses. Of 58 ASD patients (10.3 ± 3.3 y/o, 74.5% males), 60.3% presented with an increased OSA risk, compared to 13.8% in the controls (p < 0.001, OR = 3.682, 95% CI: 1.933, 7.012). After controlling for BMI (which was significantly higher among ASD patients), those with ASD had significantly higher odds of OSA risk compared to controls (OR = 9.6, 95% CI: 3.56, 26.21). After controlling for the SRBD-PSQ behavioral component, the association between ASD and OSA risk lost its significant difference (p < 0.862). No significant difference was found between ASD patients and controls in awake (3.6% vs. 6.9%, p = 0.680) and sleep (25.5% vs. 32.8%, p = 0.393) bruxism. Pediatric patients with ASD present at higher risk of OSA, most likely explained by the behavioral symptoms; self-reported bruxism did not significantly differ compared to healthy controls.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Issue Information","authors":"","doi":"10.1111/mpp.13295","DOIUrl":"https://doi.org/10.1111/mpp.13295","url":null,"abstract":"","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42341964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Issue Information","authors":"","doi":"10.1111/phpr.12792","DOIUrl":"https://doi.org/10.1111/phpr.12792","url":null,"abstract":"","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44225024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-19DOI: 10.1101/2021.10.19.465007
Stephania Assimopoulos, C. Hammill, D. Fernandes, T. L. Spencer Noakes, Yu-Qing Zhou, L. Nutter, J. Ellegood, E. Anagnostou, J. Sled, J. Lerch
Background Autism Spectrum Disorder (ASD) and Congenital Heart Disease (CHD) are strongly linked on a functional and genetic level. Most work has been focused on neurodevelopmental abnormalities in CHD. Conversely, cardiac abnormalities in ASD have been less studied. In this work we investigate the prevalence of cardiac comorbidities relative to genetic contributors of ASD. Methods Using high frequency ultrasound imaging, we screened 9 mouse models with ASD-related genetic alterations (Arid1b(+/-), Chd8(+/-), 16p11.2 (deletion), Sgsh(+/-), Sgsh(-/-), Shank3 Δexon 4-9(+/-), Shank3 Δexon 4-9(-/-), Fmr1(-/-), Vps13b(+/-)), and pooled wild-type littermates (WT). Using a standardised imaging protocol, we measured heart rate (HR), aorta diameter (AoD), thickness and thickening of the left-ventricular (LV) anterior and posterior walls, LV chamber diameter, fractional shortening, stroke volume and cardiac output, Peak E and A velocity ratio of mitral inflow, Velocity Time Integral (VTI) through the ascending aorta. Results Mutant groups presented small-scale alterations in cardiac structure and function compared to WTs. A greater number of significant differences was observed among mutant groups than between mutant groups and WTs. Mutant groups differed primarily in measures of structure (LV chamber diameter and anterior wall thickness, HR, AoD). When compared to WTs, they differed in both structure and function (LV anterior wall thickness and thickening, chamber diameter and fractional shortening, HR). The mutant groups with most differences to WTs were 16p11.2 (deletion), Fmrl(-/-), Arid1b(+/-). Among mutant groups, the groups differing most from others were 16p11.2 (deletion), Sgsh(+/-), Fmrl(-/-). Our results broadly recapitulate the associated clinical findings. Limitations Various genetically driven cardiac abnormalities occur early in life, so repeating this work in non-adult mice may be valuable. To identify possible sex differences, we must extend this work to female mice. The downsampling procedure used (total correlation calculation) must be verified. Only indirect comparison between our results and clinical literature is possible due to differing study designs. Conclusions The characteristic heterogeneity of ASD was recapitulated in the observed cardiac phenotype. The type of measures (morphological, functional) mutant groups differ in can highlight common underlying mechanisms. Clinically, knowledge of cardiac abnormalities in ASD can be essential as even non-lethal cardiac abnormalities can impact normal development.
{"title":"Genetic mouse models of autism spectrum disorder present subtle heterogenous cardiac abnormalities","authors":"Stephania Assimopoulos, C. Hammill, D. Fernandes, T. L. Spencer Noakes, Yu-Qing Zhou, L. Nutter, J. Ellegood, E. Anagnostou, J. Sled, J. Lerch","doi":"10.1101/2021.10.19.465007","DOIUrl":"https://doi.org/10.1101/2021.10.19.465007","url":null,"abstract":"Background Autism Spectrum Disorder (ASD) and Congenital Heart Disease (CHD) are strongly linked on a functional and genetic level. Most work has been focused on neurodevelopmental abnormalities in CHD. Conversely, cardiac abnormalities in ASD have been less studied. In this work we investigate the prevalence of cardiac comorbidities relative to genetic contributors of ASD. Methods Using high frequency ultrasound imaging, we screened 9 mouse models with ASD-related genetic alterations (Arid1b(+/-), Chd8(+/-), 16p11.2 (deletion), Sgsh(+/-), Sgsh(-/-), Shank3 Δexon 4-9(+/-), Shank3 Δexon 4-9(-/-), Fmr1(-/-), Vps13b(+/-)), and pooled wild-type littermates (WT). Using a standardised imaging protocol, we measured heart rate (HR), aorta diameter (AoD), thickness and thickening of the left-ventricular (LV) anterior and posterior walls, LV chamber diameter, fractional shortening, stroke volume and cardiac output, Peak E and A velocity ratio of mitral inflow, Velocity Time Integral (VTI) through the ascending aorta. Results Mutant groups presented small-scale alterations in cardiac structure and function compared to WTs. A greater number of significant differences was observed among mutant groups than between mutant groups and WTs. Mutant groups differed primarily in measures of structure (LV chamber diameter and anterior wall thickness, HR, AoD). When compared to WTs, they differed in both structure and function (LV anterior wall thickness and thickening, chamber diameter and fractional shortening, HR). The mutant groups with most differences to WTs were 16p11.2 (deletion), Fmrl(-/-), Arid1b(+/-). Among mutant groups, the groups differing most from others were 16p11.2 (deletion), Sgsh(+/-), Fmrl(-/-). Our results broadly recapitulate the associated clinical findings. Limitations Various genetically driven cardiac abnormalities occur early in life, so repeating this work in non-adult mice may be valuable. To identify possible sex differences, we must extend this work to female mice. The downsampling procedure used (total correlation calculation) must be verified. Only indirect comparison between our results and clinical literature is possible due to differing study designs. Conclusions The characteristic heterogeneity of ASD was recapitulated in the observed cardiac phenotype. The type of measures (morphological, functional) mutant groups differ in can highlight common underlying mechanisms. Clinically, knowledge of cardiac abnormalities in ASD can be essential as even non-lethal cardiac abnormalities can impact normal development.","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":"15 1","pages":"1189 - 1208"},"PeriodicalIF":0.0,"publicationDate":"2021-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44093703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The problem of heterogeneity in autism: Response to Mottron (2021) \"Aradical change in our autism research strategy is needed: Back to prototypes\".","authors":"Lynn Waterhouse","doi":"10.1002/aur.2584","DOIUrl":"10.1002/aur.2584","url":null,"abstract":"","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39260288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel E Lidstone, Rebecca Rochowiak, Stewart H Mostofsky, Mary Beth Nebel
This study examined whether disruptions in connectivity involving regions critical for learning, planning, and executing movements are relevant to core autism symptoms. Spatially constrained ICA was performed using resting-state fMRI from 419 children (autism spectrum disorder (ASD) = 105; typically developing (TD) = 314) to identify functional motor subdivisions. Comparing the spatial organization of each subdivision between groups, we found voxels that contributed significantly less to the right posterior cerebellar component in children with ASD versus TD (P <0.001). Next, we examined the effect of diagnosis on right posterior cerebellar connectivity with all other motor subdivisions. The model was significant (P = 0.014) revealing that right posterior cerebellar connectivity with bilateral dorsomedial primary motor cortex was, on average, stronger in children with ASD, while right posterior cerebellar connectivity with left-inferior parietal lobule (IPL), bilateral dorsolateral premotor cortex, and supplementary motor area was stronger in TD children (all P ≤0.02). We observed a diagnosis-by-connectivity interaction such that for children with ASD, elevated social-communicative and excessive repetitive-behavior symptom severity were both associated with right posterior cerebellar-left-IPL hypoconnectivity (P ≤0.001). Right posterior cerebellar and left-IPL are strongly implicated in visuomotor processing with dysfunction in this circuit possibly leading to anomalous development of skills, such as motor imitation, that are crucial for effective social-communication. LAY SUMMARY: This study examines whether communication between various brain regions involved in the control of movement are disrupted in children with autism spectrum disorder (ASD). We show communication between the right posterior cerebellum and left IPL, a circuit important for efficient visual-motor integration, is disrupted in children with ASD and associated with the severity of ASD symptoms. These results may explain observations of visual-motor integration impairments in children with ASD that are associated with ASD symptom severity.
{"title":"A Data Driven Approach Reveals That Anomalous Motor System Connectivity is Associated With the Severity of Core Autism Symptoms.","authors":"Daniel E Lidstone, Rebecca Rochowiak, Stewart H Mostofsky, Mary Beth Nebel","doi":"10.1002/aur.2476","DOIUrl":"10.1002/aur.2476","url":null,"abstract":"<p><p>This study examined whether disruptions in connectivity involving regions critical for learning, planning, and executing movements are relevant to core autism symptoms. Spatially constrained ICA was performed using resting-state fMRI from 419 children (autism spectrum disorder (ASD) = 105; typically developing (TD) = 314) to identify functional motor subdivisions. Comparing the spatial organization of each subdivision between groups, we found voxels that contributed significantly less to the right posterior cerebellar component in children with ASD versus TD (P <0.001). Next, we examined the effect of diagnosis on right posterior cerebellar connectivity with all other motor subdivisions. The model was significant (P = 0.014) revealing that right posterior cerebellar connectivity with bilateral dorsomedial primary motor cortex was, on average, stronger in children with ASD, while right posterior cerebellar connectivity with left-inferior parietal lobule (IPL), bilateral dorsolateral premotor cortex, and supplementary motor area was stronger in TD children (all P ≤0.02). We observed a diagnosis-by-connectivity interaction such that for children with ASD, elevated social-communicative and excessive repetitive-behavior symptom severity were both associated with right posterior cerebellar-left-IPL hypoconnectivity (P ≤0.001). Right posterior cerebellar and left-IPL are strongly implicated in visuomotor processing with dysfunction in this circuit possibly leading to anomalous development of skills, such as motor imitation, that are crucial for effective social-communication. LAY SUMMARY: This study examines whether communication between various brain regions involved in the control of movement are disrupted in children with autism spectrum disorder (ASD). We show communication between the right posterior cerebellum and left IPL, a circuit important for efficient visual-motor integration, is disrupted in children with ASD and associated with the severity of ASD symptoms. These results may explain observations of visual-motor integration impairments in children with ASD that are associated with ASD symptom severity.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931705/pdf/nihms-1690119.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38784882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}