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A working taxonomy for describing the sensory differences of autism. 描述自闭症感官差异的有效分类。
IF 6.2 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2023-04-11 DOI: 10.1186/s13229-022-00534-1
Jason L He, Zachary J Williams, Ashley Harris, Helen Powell, Roseann Schaaf, Teresa Tavassoli, Nicolaas A J Puts

Background: Individuals on the autism spectrum have been long described to process sensory information differently than neurotypical individuals. While much effort has been leveraged towards characterizing and investigating the neurobiology underlying the sensory differences of autism, there has been a notable lack of consistency in the terms being used to describe the nature of those differences.

Main body: We argue that inconsistent and interchangeable terminology-use when describing the sensory differences of autism has become problematic beyond mere pedantry and inconvenience. We begin by highlighting popular terms that are currently being used to describe the sensory differences of autism (e.g. "sensitivity", "reactivity" and "responsivity") and discuss why poor nomenclature may hamper efforts towards understanding the aetiology of sensory differences in autism. We then provide a solution to poor terminology-use by proposing a hierarchical taxonomy for describing and referring to various sensory features.

Conclusion: Inconsistent terminology-use when describing the sensory features of autism has stifled discussion and scientific understanding of the sensory differences of autism. The hierarchical taxonomy proposed was developed to help resolve lack of clarity when discussing the sensory differences of autism and to place future research targets at appropriate levels of analysis.

背景:长期以来,人们一直认为自闭症谱系的个体处理感觉信息的方式与神经正常个体不同。尽管人们在描述和调查自闭症感觉差异背后的神经生物学方面付出了很多努力,但在描述这些差异本质的术语上却明显缺乏一致性。正文:我们认为,在描述自闭症的感官差异时,不一致和可互换的术语使用已经成为一个问题,而不仅仅是迂腐和不便。我们首先强调目前用来描述自闭症的感官差异的流行术语(例如:“敏感性”,“反应性”和“反应性”),并讨论为什么糟糕的命名法可能会阻碍对自闭症感觉差异病因学的理解。然后,我们通过提出描述和参考各种感官特征的分层分类法,为不良术语使用提供了解决方案。结论:在描述自闭症的感觉特征时,不一致的术语使用阻碍了对自闭症感觉差异的讨论和科学理解。提出的分层分类法是为了帮助解决在讨论自闭症的感官差异时缺乏清晰度的问题,并将未来的研究目标置于适当的分析水平上。
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引用次数: 5
The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome. mGluR4的激活挽救了脆性X综合征小鼠模型中的平行纤维突触传递、LTP、运动学习和社会行为。
IF 6.2 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2023-04-07 DOI: 10.1186/s13229-023-00547-4
Ricardo Martín, Alberto Samuel Suárez-Pinilla, Nuria García-Font, M Luisa Laguna-Luque, Juan C López-Ramos, María Jesús Oset-Gasque, Agnes Gruart, José M Delgado-García, Magdalena Torres, José Sánchez-Prieto

Background: Fragile X syndrome (FXS), the most common inherited intellectual disability, is caused by the loss of expression of the Fragile X Messenger Ribonucleoprotein (FMRP). FMRP is an RNA-binding protein that negatively regulates the expression of many postsynaptic as well as presynaptic proteins involved in action potential properties, calcium homeostasis and neurotransmitter release. FXS patients and mice lacking FMRP suffer from multiple behavioral alterations, including deficits in motor learning for which there is currently no specific treatment.

Methods: We performed electron microscopy, whole-cell patch-clamp electrophysiology and behavioral experiments to characterise the synaptic mechanisms underlying the motor learning deficits observed in Fmr1KO mice and the therapeutic potential of positive allosteric modulator of mGluR4.

Results: We found that enhanced synaptic vesicle docking of cerebellar parallel fiber to Purkinje cell Fmr1KO synapses was associated with enhanced asynchronous release, which not only prevents further potentiation, but it also compromises presynaptic parallel fiber long-term potentiation (PF-LTP) mediated by β adrenergic receptors. A reduction in extracellular Ca2+ concentration restored the readily releasable pool (RRP) size, basal synaptic transmission, β adrenergic receptor-mediated potentiation, and PF-LTP. Interestingly, VU 0155041, a selective positive allosteric modulator of mGluR4, also restored both the RRP size and PF-LTP in mice of either sex. Moreover, when injected into Fmr1KO male mice, VU 0155041 improved motor learning in skilled reaching, classical eyeblink conditioning and vestibuloocular reflex (VOR) tests, as well as the social behavior alterations of these mice.

Limitations: We cannot rule out that the activation of mGluR4s via systemic administration of VU0155041 can also affect other brain regions. Further studies are needed to stablish the effect of a specific activation of mGluR4 in cerebellar granule cells.

Conclusions: Our study shows that an increase in synaptic vesicles, SV, docking may cause the loss of PF-LTP and motor learning and social deficits of Fmr1KO mice and that the reversal of these changes by pharmacological activation of mGluR4 may offer therapeutic relief for motor learning and social deficits in FXS.

背景:脆性X综合征(Fragile X syndrome, FXS)是最常见的遗传性智力残疾,由脆性X信使核糖核蛋白(Fragile X Messenger ribonnucleoprotein, FMRP)表达缺失引起。FMRP是一种rna结合蛋白,可负性调节许多突触后和突触前蛋白的表达,这些蛋白参与动作电位特性、钙稳态和神经递质释放。FXS患者和缺乏FMRP的小鼠会出现多种行为改变,包括运动学习缺陷,目前尚无具体治疗方法。方法:我们通过电镜、全细胞膜片钳电生理和行为实验来表征Fmr1KO小鼠运动学习缺陷的突触机制,以及mGluR4阳性变构调节剂的治疗潜力。结果:我们发现小脑平行纤维与浦肯野细胞Fmr1KO突触突触囊泡对接增强与异步释放增强相关,这不仅阻止了进一步的增强,而且还破坏了β肾上腺素能受体介导的突触前平行纤维长期增强(PF-LTP)。细胞外Ca2+浓度的降低恢复了易释放池(RRP)大小、基础突触传递、β肾上腺素能受体介导的增强和PF-LTP。有趣的是,mGluR4的选择性阳性变构调节剂VU 0155041也能恢复小鼠的RRP大小和PF-LTP。此外,当注射到Fmr1KO雄性小鼠时,VU 0155041改善了这些小鼠在熟练伸臂、经典眨眼条件反射和前庭反射(VOR)测试中的运动学习,以及社会行为的改变。局限性:我们不能排除通过系统给药VU0155041激活mGluR4s也可以影响其他大脑区域。需要进一步的研究来确定mGluR4在小脑颗粒细胞中的特异性激活作用。结论:我们的研究表明,突触囊泡、SV、对接的增加可能导致Fmr1KO小鼠PF-LTP的缺失以及运动学习和社交缺陷,通过药物激活mGluR4逆转这些变化可能对FXS的运动学习和社交缺陷提供治疗性缓解。
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引用次数: 0
Sex differences in the temporal dynamics of autistic children's natural conversations. 自闭症儿童自然对话时间动态的性别差异。
IF 6.2 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2023-04-06 DOI: 10.1186/s13229-023-00545-6
Sunghye Cho, Meredith Cola, Azia Knox, Maggie Rose Pelella, Alison Russell, Aili Hauptmann, Maxine Covello, Christopher Cieri, Mark Liberman, Robert T Schultz, Julia Parish-Morris

Background: Autistic girls are underdiagnosed compared to autistic boys, even when they experience similar clinical impact. Research suggests that girls present with distinct symptom profiles across a variety of domains, such as language, which may contribute to their underdiagnosis. In this study, we examine sex differences in the temporal dynamics of natural conversations between naïve adult confederates and school-aged children with or without autism, with the goal of improving our understanding of conversational behavior in autistic girls and ultimately improving identification.

Methods: Forty-five school-aged children with autism (29 boys and 16 girls) and 47 non-autistic/neurotypical (NT) children (23 boys and 24 girls) engaged in a 5-min "get-to-know-you" conversation with a young adult confederate that was unaware of children's diagnostic status. Groups were matched on IQ estimates. Recordings were time-aligned and orthographically transcribed by trained annotators. Several speech and pause measures were calculated. Groups were compared using analysis of covariance models, controlling for age.

Results: Autistic girls used significantly more words than autistic boys, and produced longer speech segments than all other groups. Autistic boys spoke more slowly than NT children, whereas autistic girls did not differ from NT children in total word counts or speaking rate. Autistic boys interrupted confederates' speech less often and produced longer between-turn pauses (i.e., responded more slowly when it was their turn) compared to other children. Within-turn pause duration did not differ by group.

Limitations: Our sample included verbally fluent children and adolescents aged 6-15 years, so our study results may not replicate in samples of younger children, adults, and individuals who are not verbally fluent. The results of this relatively small study, while compelling, should be interpreted with caution and replicated in a larger sample.

Conclusion: This study investigated the temporal dynamics of everyday conversations and demonstrated that autistic girls and boys have distinct natural language profiles. Specifying differences in verbal communication lays the groundwork for the development of sensitive screening and diagnostic tools to more accurately identify autistic girls, and could inform future personalized interventions that improve short- and long-term social communication outcomes for all autistic children.

背景:与自闭症男孩相比,自闭症女孩的诊断率较低,即使她们受到的临床影响相似。研究表明,女孩在语言等多个领域表现出不同的症状特征,这可能是导致她们被低估的原因之一。在本研究中,我们研究了天真无邪的成人同伴与患有或未患有自闭症的学龄儿童之间自然对话的时间动态性别差异,目的是加深我们对自闭症女孩对话行为的理解,并最终提高识别能力:方法:45 名学龄自闭症儿童(29 名男孩和 16 名女孩)和 47 名非自闭症/神经症(NT)儿童(23 名男孩和 24 名女孩)与一名不了解儿童诊断状况的年轻成人同伴进行了 5 分钟的 "认识你 "对话。两组儿童的智商估计值相匹配。录音由训练有素的注释员进行时间对齐和正字法转录。计算了几种语音和停顿测量值。使用协方差分析模型对各组进行比较,同时控制年龄:结果:自闭症女孩的用词量明显多于自闭症男孩,所产生的语音片段也长于所有其他群体。自闭症男孩的语速比正常儿童慢,而自闭症女孩在总字数和语速上与正常儿童没有差异。与其他儿童相比,自闭症男孩打断同伴说话的次数较少,轮次间停顿的时间较长(即轮到自己时反应较慢)。不同组别在回合内的停顿时间没有差异:我们的样本包括语言流利的 6-15 岁儿童和青少年,因此我们的研究结果可能无法复制到年龄更小的儿童、成人和语言不流利的人的样本中。这项规模相对较小的研究结果虽然令人信服,但在解释时应谨慎,并应在更大的样本中重复:本研究调查了日常对话的时间动态,证明自闭症女孩和男孩具有不同的自然语言特征。明确语言交流的差异为开发敏感的筛查和诊断工具奠定了基础,从而更准确地识别自闭症女孩,并为未来的个性化干预措施提供依据,以改善所有自闭症儿童的短期和长期社会交流结果。
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引用次数: 0
A systematic review and meta-analysis of suicidality in autistic and possibly autistic people without co-occurring intellectual disability. 无智力障碍的孤独症及可能孤独症患者自杀行为的系统回顾和荟萃分析。
IF 6.2 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2023-03-15 DOI: 10.1186/s13229-023-00544-7
Victoria Newell, Lucy Phillips, Chris Jones, Ellen Townsend, Caroline Richards, Sarah Cassidy

Background: Suicidality is highly prevalent in autistic people without co-occurring intellectual disabilities, and high autistic traits are found in adults who have attempted suicide. However, prevalence rates for both autistic and possibly autistic people have not been synthesised meta-analytically.

Aims: To (1) calculate pooled prevalence estimates of suicidality in autistic people and possibly autistic people without co-occurring intellectual disability; (2) evaluate the influence of participant and study level characteristics on heterogeneity; and (3) determine the quality of evidence.

Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. PsycINFO, Embase, MEDLINE and Web of Science were systematically searched from 1992 to January 25, 2022. Empirical quantitative studies reporting prevalence of suicidal ideation, suicide plans, or suicide attempts and behaviours were considered for inclusion. Random effects models were used to estimate pooled prevalence of each suicidality outcome with 95% confidence intervals. Heterogeneity was explored using sensitivity and moderator analyses.

Results: Data from 48,186 autistic and possibly autistic participants in 36 primary studies were meta-analysed. Pooled prevalence of suicidal ideation was 34.2% (95% CI 27.9-40.5), suicide plans 21.9% (13.4-30.4), and suicidal attempts and behaviours 24.3% (18.9-29.6). High levels of heterogeneity (I2 > 75) were observed in all three analyses. Estimates did not differ between autistic or possibly autistic samples. Geographical location (p = 0.005), transgender or gender non-conforming samples (p < 0.001) and type of report (p < 0.001) significantly moderated suicidal ideation, whereas age group (p = 0.001) and measure of suicidality (p = 0.001) significantly moderated suicide plans. There was a significant association between the proportion of male participants and prevalence of suicide plans, with a decrease in the proportion of males for every unit change of suicide plan prevalence (p = 0.013). No variables were found to moderate estimates of suicide attempts and behaviours.

Conclusions: The results confirm suicidality is highly prevalent in both autistic and possibly autistic people without co-occurring intellectual disability and highlights potential moderators. Possibly autistic individuals require more attention in clinical and research considerations going forward to further understand and prevent suicide in both groups.

背景:自杀倾向在没有智力障碍的自闭症患者中非常普遍,在试图自杀的成年人中发现了高度的自闭症特征。然而,自闭症和可能患有自闭症的人的患病率还没有综合分析。目的:(1)计算自闭症患者和可能患有自闭症但没有并发智力障碍的患者自杀率的汇总估计;(2)评价参与者和研究水平特征对异质性的影响;(3)确定证据的质量。方法:遵循系统评价和元分析指南的首选报告项目。系统检索了1992年至2022年1月25日期间的PsycINFO、Embase、MEDLINE和Web of Science。报告自杀意念、自杀计划或自杀企图和行为的流行程度的实证定量研究被纳入考虑。随机效应模型用于估计每个自杀结局的总患病率,置信区间为95%。采用敏感性和调节因子分析探讨异质性。结果:对36项主要研究中48186名自闭症和可能自闭症的参与者的数据进行了荟萃分析。自杀意念的总患病率为34.2% (95% CI 27.9-40.5),自杀计划的总患病率为21.9%(13.4-30.4),自杀企图和行为的总患病率为24.3%(18.9-29.6)。在所有三个分析中均观察到高度异质性(I2 > 75)。自闭或可能自闭的样本之间的估计没有差异。结论:研究结果证实,在没有并发智力残疾的自闭症和可能自闭症患者中,自杀行为都非常普遍,并突出了潜在的调节因素。可能自闭症患者需要在临床和研究方面给予更多的关注,以进一步了解和预防这两组人的自杀。
{"title":"A systematic review and meta-analysis of suicidality in autistic and possibly autistic people without co-occurring intellectual disability.","authors":"Victoria Newell,&nbsp;Lucy Phillips,&nbsp;Chris Jones,&nbsp;Ellen Townsend,&nbsp;Caroline Richards,&nbsp;Sarah Cassidy","doi":"10.1186/s13229-023-00544-7","DOIUrl":"https://doi.org/10.1186/s13229-023-00544-7","url":null,"abstract":"<p><strong>Background: </strong>Suicidality is highly prevalent in autistic people without co-occurring intellectual disabilities, and high autistic traits are found in adults who have attempted suicide. However, prevalence rates for both autistic and possibly autistic people have not been synthesised meta-analytically.</p><p><strong>Aims: </strong>To (1) calculate pooled prevalence estimates of suicidality in autistic people and possibly autistic people without co-occurring intellectual disability; (2) evaluate the influence of participant and study level characteristics on heterogeneity; and (3) determine the quality of evidence.</p><p><strong>Methods: </strong>Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. PsycINFO, Embase, MEDLINE and Web of Science were systematically searched from 1992 to January 25, 2022. Empirical quantitative studies reporting prevalence of suicidal ideation, suicide plans, or suicide attempts and behaviours were considered for inclusion. Random effects models were used to estimate pooled prevalence of each suicidality outcome with 95% confidence intervals. Heterogeneity was explored using sensitivity and moderator analyses.</p><p><strong>Results: </strong>Data from 48,186 autistic and possibly autistic participants in 36 primary studies were meta-analysed. Pooled prevalence of suicidal ideation was 34.2% (95% CI 27.9-40.5), suicide plans 21.9% (13.4-30.4), and suicidal attempts and behaviours 24.3% (18.9-29.6). High levels of heterogeneity (I<sup>2</sup> > 75) were observed in all three analyses. Estimates did not differ between autistic or possibly autistic samples. Geographical location (p = 0.005), transgender or gender non-conforming samples (p < 0.001) and type of report (p < 0.001) significantly moderated suicidal ideation, whereas age group (p = 0.001) and measure of suicidality (p = 0.001) significantly moderated suicide plans. There was a significant association between the proportion of male participants and prevalence of suicide plans, with a decrease in the proportion of males for every unit change of suicide plan prevalence (p = 0.013). No variables were found to moderate estimates of suicide attempts and behaviours.</p><p><strong>Conclusions: </strong>The results confirm suicidality is highly prevalent in both autistic and possibly autistic people without co-occurring intellectual disability and highlights potential moderators. Possibly autistic individuals require more attention in clinical and research considerations going forward to further understand and prevent suicide in both groups.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"14 1","pages":"12"},"PeriodicalIF":6.2,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9145273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
Atypical functional connectivity of temporal cortex with precuneus and visual regions may be an early-age signature of ASD. 颞叶皮层与楔前和视觉区域的非典型功能连接可能是 ASD 的早期特征。
IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2023-03-10 DOI: 10.1186/s13229-023-00543-8
Yaqiong Xiao, Teresa H Wen, Lauren Kupis, Lisa T Eyler, Vani Taluja, Jaden Troxel, Disha Goel, Michael V Lombardo, Karen Pierce, Eric Courchesne

Background: Social and language abilities are closely intertwined during early typical development. In autism spectrum disorder (ASD), however, deficits in social and language development are early-age core symptoms. We previously reported that superior temporal cortex, a well-established social and language region, shows reduced activation to social affective speech in ASD toddlers; however, the atypical cortical connectivity that accompanies this deviance remains unknown.

Methods: We collected clinical, eye tracking, and resting-state fMRI data from 86 ASD and non-ASD subjects (mean age 2.3 ± 0.7 years). Functional connectivity of left and right superior temporal regions with other cortical regions and correlations between this connectivity and each child's social and language abilities were examined.

Results: While there was no group difference in functional connectivity, the connectivity between superior temporal cortex and frontal and parietal regions was significantly correlated with language, communication, and social abilities in non-ASD subjects, but these effects were absent in ASD subjects. Instead, ASD subjects, regardless of different social or nonsocial visual preferences, showed atypical correlations between temporal-visual region connectivity and communication ability (r(49) = 0.55, p < 0.001) and between temporal-precuneus connectivity and expressive language ability (r(49) = 0.58, p < 0.001).

Limitations: The distinct connectivity-behavior correlation patterns may be related to different developmental stages in ASD and non-ASD subjects. The use of a prior 2-year-old template for spatial normalization may not be optimal for a few subjects beyond this age range.

Conclusions: Superior temporal cortex is known to have reduced activation to social affective speech in ASD at early ages, and here we find in ASD toddlers that it also has atypical connectivity with visual and precuneus cortices that is correlated with communication and language ability, a pattern not seen in non-ASD toddlers. This atypicality may be an early-age signature of ASD that also explains why the disorder has deviant early language and social development. Given that these atypical connectivity patterns are also present in older individuals with ASD, we conclude these atypical connectivity patterns persist across age and may explain why successful interventions targeting language and social skills at all ages in ASD are so difficult to achieve.

背景介绍在早期典型发育过程中,社交能力和语言能力密切相关。然而,在自闭症谱系障碍(ASD)中,社交和语言发展的缺陷是早期的核心症状。我们以前曾报道过,颞上皮层是一个成熟的社交和语言区域,在自闭症谱系障碍学步儿童中,该区域对社交情感言语的激活减少;然而,伴随这种偏差的非典型皮层连通性仍然未知:我们收集了 86 名 ASD 和非 ASD 受试者(平均年龄为 2.3 ± 0.7 岁)的临床、眼动追踪和静息态 fMRI 数据。我们研究了左右颞上区与其他皮层区域的功能连接,以及这种连接与每个儿童的社交和语言能力之间的相关性:结果:虽然在功能连接性方面不存在组间差异,但在非 ASD 受试者中,颞上皮层与额叶和顶叶区域之间的连接性与语言、沟通和社交能力显著相关,但在 ASD 受试者中却不存在这些影响。相反,无论ASD受试者的社交或非社交视觉偏好如何,他们的颞叶-视觉区域连通性与沟通能力之间都表现出非典型的相关性(r(49) = 0.55, p 局限性:连接性与行为之间不同的相关模式可能与ASD和非ASD受试者不同的发育阶段有关。使用 2 岁前的模板进行空间归一化可能对超过这一年龄范围的少数受试者不是最佳选择:颞上皮层在ASD幼儿早期对社会情感言语的激活减少是众所周知的,在此我们发现,ASD幼儿的颞上皮层与视觉和楔前皮层的非典型连接也与沟通和语言能力相关,这种模式在非ASD幼儿中未见。这种非典型性可能是自闭症幼儿的早期特征,也可以解释为什么自闭症幼儿的早期语言和社交发展会出现偏差。鉴于这些非典型连接模式也出现在年龄较大的 ASD 患者身上,我们得出结论:这些非典型连接模式在不同年龄段都会持续存在,这或许可以解释为什么针对 ASD 各年龄段的语言和社交能力的成功干预如此难以实现。
{"title":"Atypical functional connectivity of temporal cortex with precuneus and visual regions may be an early-age signature of ASD.","authors":"Yaqiong Xiao, Teresa H Wen, Lauren Kupis, Lisa T Eyler, Vani Taluja, Jaden Troxel, Disha Goel, Michael V Lombardo, Karen Pierce, Eric Courchesne","doi":"10.1186/s13229-023-00543-8","DOIUrl":"10.1186/s13229-023-00543-8","url":null,"abstract":"<p><strong>Background: </strong>Social and language abilities are closely intertwined during early typical development. In autism spectrum disorder (ASD), however, deficits in social and language development are early-age core symptoms. We previously reported that superior temporal cortex, a well-established social and language region, shows reduced activation to social affective speech in ASD toddlers; however, the atypical cortical connectivity that accompanies this deviance remains unknown.</p><p><strong>Methods: </strong>We collected clinical, eye tracking, and resting-state fMRI data from 86 ASD and non-ASD subjects (mean age 2.3 ± 0.7 years). Functional connectivity of left and right superior temporal regions with other cortical regions and correlations between this connectivity and each child's social and language abilities were examined.</p><p><strong>Results: </strong>While there was no group difference in functional connectivity, the connectivity between superior temporal cortex and frontal and parietal regions was significantly correlated with language, communication, and social abilities in non-ASD subjects, but these effects were absent in ASD subjects. Instead, ASD subjects, regardless of different social or nonsocial visual preferences, showed atypical correlations between temporal-visual region connectivity and communication ability (r(49) = 0.55, p < 0.001) and between temporal-precuneus connectivity and expressive language ability (r(49) = 0.58, p < 0.001).</p><p><strong>Limitations: </strong>The distinct connectivity-behavior correlation patterns may be related to different developmental stages in ASD and non-ASD subjects. The use of a prior 2-year-old template for spatial normalization may not be optimal for a few subjects beyond this age range.</p><p><strong>Conclusions: </strong>Superior temporal cortex is known to have reduced activation to social affective speech in ASD at early ages, and here we find in ASD toddlers that it also has atypical connectivity with visual and precuneus cortices that is correlated with communication and language ability, a pattern not seen in non-ASD toddlers. This atypicality may be an early-age signature of ASD that also explains why the disorder has deviant early language and social development. Given that these atypical connectivity patterns are also present in older individuals with ASD, we conclude these atypical connectivity patterns persist across age and may explain why successful interventions targeting language and social skills at all ages in ASD are so difficult to achieve.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"14 1","pages":"11"},"PeriodicalIF":6.3,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10007788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9491397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex differences in social and emotional insight in youth with and without autism. 自闭症青少年和非自闭症青少年在社会和情感洞察力方面的性别差异。
IF 6.2 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2023-03-04 DOI: 10.1186/s13229-023-00541-w
Hunter Mattern, Meredith Cola, Kimberly G Tena, Azia Knox, Alison Russell, Maggie Rose Pelella, Aili Hauptmann, Maxine Covello, Julia Parish-Morris, Joseph P McCleery

Autism was formally recognized by the medical community in the first half of the twentieth century. Almost 100 years later, a small but growing literature has reported sex differences in the behavioral expression of autism. Recent research has also begun to explore the internal experiences of individuals with autism, including social and emotional insight. The current study examines sex differences in language-based markers of social and emotional insight in girls and boys with autism and non-autistic peers during semi-structured clinical interviews. Sixty-four participants aged 5 to 17 years were individually matched on chronological age and full-scale IQ to form four groups: autistic girls, autistic boys, non-autistic girls, and non-autistic boys. Transcribed interviews were scored using four scales that index aspects of social and emotional insight. Results revealed the main effects of diagnosis, such that youth with autism exhibited lower insight than non-autistic youth on scales indexing social cognition and object relations, emotional investment, and social causality. With regards to sex differences, across diagnoses, girls were rated higher than boys on the social cognition and object relations, emotional investment, and social causality scales. Examined within each diagnosis separately, clear sex differences emerged: both autistic and non-autistic girls demonstrated better social cognition and understanding of social causality than boys in their respective diagnostic groups. No within-diagnosis sex differences were found on the emotional insight scales, however. These results suggest that relatively enhanced social cognition and understanding of social causality in girls may be a population-level sex difference that is preserved in autism, despite the core social challenges that characterize this condition. The current findings reveal critical new information about insight into social and emotional thinking and relationships in autistic girls versus boys that have important implications for improving identification and designing effective interventions.

自闭症在20世纪上半叶被医学界正式承认。近100年后,一份规模虽小但不断增长的文献报道了自闭症行为表现的性别差异。最近的研究也开始探索自闭症患者的内在体验,包括社会和情感洞察力。目前的研究在半结构化的临床访谈中,对患有自闭症和非自闭症的女孩和男孩的社会和情感洞察力的语言标记进行了性别差异研究。64名年龄在5岁到17岁之间的参与者分别按照实际年龄和全面智商进行匹配,分为四组:自闭症女孩、自闭症男孩、非自闭症女孩和非自闭症男孩。采访记录使用四种量表进行评分,这些量表对社会和情感洞察力的各个方面进行了索引。结果揭示了诊断的主要影响,如自闭症青少年在社会认知和客体关系、情感投入和社会因果关系指标上表现出低于非自闭症青少年的洞察力。关于性别差异,在诊断中,女孩在社会认知和客体关系、情感投入和社会因果关系量表上的评分高于男孩。在每个诊断中分别检查,明显的性别差异出现了:在各自的诊断组中,自闭症和非自闭症女孩都比男孩表现出更好的社会认知和对社会因果关系的理解。然而,在情绪洞察力量表上没有发现诊断内的性别差异。这些结果表明,女孩对社会因果关系的相对增强的社会认知和理解可能是一种人口水平的性别差异,这种差异在自闭症中被保留下来,尽管这种疾病的核心社会挑战是自闭症的特征。目前的研究结果揭示了关于自闭症女孩和男孩的社会和情感思维以及关系的重要新信息,这对提高识别和设计有效的干预措施具有重要意义。
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引用次数: 1
Sex differences in friendships and loneliness in autistic and non-autistic children across development. 自闭症儿童和非自闭症儿童在友谊和孤独方面的性别差异。
IF 6.2 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2023-02-24 DOI: 10.1186/s13229-023-00542-9
Natalie Libster, Azia Knox, Selin Engin, Daniel Geschwind, Julia Parish-Morris, Connie Kasari

Background: Autistic children have been shown to have less complete definitions of friendships and higher levels of loneliness than their non-autistic peers. However, no known studies have explored sex differences in autistic children's understanding of friendships and reported loneliness across development. Autistic girls demonstrate higher levels of social motivation than autistic boys and appear to "fit in" with their peers, but they often have difficulty recognizing reciprocal friendships during middle childhood. As autistic girls develop a more complex understanding of friendship during adolescence, they may begin to redefine their friendships and experience heightened loneliness. Here, we explored how autistic and non-autistic boys and girls define the meaning of friendship and report feelings of loneliness across development. We also examined their perceptions of friendships and loneliness.

Methods: This mixed-methods study analyzed the transcribed clinical evaluations of 58 autistic children (29 girls) matched to 42 non-autistic children (21 girls) on age and IQ. Transcripts were coded for four categories that children used to define friendships-personality, companionship, dependability, and intimacy-and for reported loneliness. We then compared these codes across diagnosis, sex, and age. Content analyses were further implemented to gain a more holistic understanding of children's perceptions of friendships and loneliness.

Results: Girls, regardless of diagnosis, were more likely than boys to refer to personality when defining the meaning of friendship, and the likelihood of referring to dependability and intimacy increased with age. Most children reported having at least one friend, though some autistic adolescents reported not having friends or were uncertain whether they had friends. While autistic and non-autistic boys and girls were equally likely to report feeling lonely at times, several autistic girls and boys reported being frequently lonely.

Limitations: This study was a secondary data analysis. The standardized set of questions on the ADOS limited the amount of information that children provided about their friendships and perceptions of loneliness.

Conclusion: As with non-autistic children, autistic children acquire a more complex understanding of friendship throughout development. However, as children begin to prioritize dependability and intimacy in friendships, autistic adolescents may have difficulty developing friendships characterized by these constructs. Furthermore, the quantity and/or quality of autistic children's friendships may not be sufficient to alleviate loneliness.

背景:与非自闭症儿童相比,自闭症儿童对友谊的定义更不完整,孤独感也更高。然而,没有已知的研究探索自闭症儿童对友谊的理解和发展过程中报告的孤独感的性别差异。自闭症女孩比自闭症男孩表现出更高的社交动机,似乎与同龄人“合群”,但在童年中期,她们往往很难认识到互惠的友谊。随着自闭症女孩在青春期对友谊有了更复杂的理解,她们可能会开始重新定义自己的友谊,并经历更强烈的孤独感。在这里,我们探讨了自闭症和非自闭症男孩和女孩如何定义友谊的意义,并在整个发展过程中报告孤独感。我们还调查了他们对友谊和孤独的看法。方法:采用混合方法对58名自闭症儿童(29名女孩)和42名非自闭症儿童(21名女孩)的年龄和智商进行转录临床评价。孩子们用来定义友谊的记录被分为四类——个性、陪伴、可靠性和亲密度——以及报告的孤独感。然后,我们将这些代码在诊断、性别和年龄之间进行比较。进一步实施内容分析,以更全面地了解儿童对友谊和孤独的看法。结果:在定义友谊的意义时,女孩比男孩更倾向于用性格来定义,而随着年龄的增长,女孩更倾向于用可靠性和亲密性来定义。大多数儿童报告至少有一个朋友,尽管一些自闭症青少年报告没有朋友或不确定他们是否有朋友。虽然自闭症和非自闭症的男孩和女孩偶尔感到孤独的可能性是一样的,但一些自闭症女孩和男孩报告说经常感到孤独。局限性:本研究为二次数据分析。ADOS的标准化问题集限制了孩子们提供的关于他们的友谊和对孤独的看法的信息量。结论:与非自闭症儿童一样,自闭症儿童在整个发展过程中对友谊的理解更为复杂。然而,当孩子们开始在友谊中优先考虑可靠性和亲密性时,自闭症青少年可能难以发展以这些结构为特征的友谊。此外,自闭症儿童友谊的数量和/或质量可能不足以减轻孤独。
{"title":"Sex differences in friendships and loneliness in autistic and non-autistic children across development.","authors":"Natalie Libster,&nbsp;Azia Knox,&nbsp;Selin Engin,&nbsp;Daniel Geschwind,&nbsp;Julia Parish-Morris,&nbsp;Connie Kasari","doi":"10.1186/s13229-023-00542-9","DOIUrl":"https://doi.org/10.1186/s13229-023-00542-9","url":null,"abstract":"<p><strong>Background: </strong>Autistic children have been shown to have less complete definitions of friendships and higher levels of loneliness than their non-autistic peers. However, no known studies have explored sex differences in autistic children's understanding of friendships and reported loneliness across development. Autistic girls demonstrate higher levels of social motivation than autistic boys and appear to \"fit in\" with their peers, but they often have difficulty recognizing reciprocal friendships during middle childhood. As autistic girls develop a more complex understanding of friendship during adolescence, they may begin to redefine their friendships and experience heightened loneliness. Here, we explored how autistic and non-autistic boys and girls define the meaning of friendship and report feelings of loneliness across development. We also examined their perceptions of friendships and loneliness.</p><p><strong>Methods: </strong>This mixed-methods study analyzed the transcribed clinical evaluations of 58 autistic children (29 girls) matched to 42 non-autistic children (21 girls) on age and IQ. Transcripts were coded for four categories that children used to define friendships-personality, companionship, dependability, and intimacy-and for reported loneliness. We then compared these codes across diagnosis, sex, and age. Content analyses were further implemented to gain a more holistic understanding of children's perceptions of friendships and loneliness.</p><p><strong>Results: </strong>Girls, regardless of diagnosis, were more likely than boys to refer to personality when defining the meaning of friendship, and the likelihood of referring to dependability and intimacy increased with age. Most children reported having at least one friend, though some autistic adolescents reported not having friends or were uncertain whether they had friends. While autistic and non-autistic boys and girls were equally likely to report feeling lonely at times, several autistic girls and boys reported being frequently lonely.</p><p><strong>Limitations: </strong>This study was a secondary data analysis. The standardized set of questions on the ADOS limited the amount of information that children provided about their friendships and perceptions of loneliness.</p><p><strong>Conclusion: </strong>As with non-autistic children, autistic children acquire a more complex understanding of friendship throughout development. However, as children begin to prioritize dependability and intimacy in friendships, autistic adolescents may have difficulty developing friendships characterized by these constructs. Furthermore, the quantity and/or quality of autistic children's friendships may not be sufficient to alleviate loneliness.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"14 1","pages":"9"},"PeriodicalIF":6.2,"publicationDate":"2023-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder. SETBP1 紊乱的人类干细胞模型中受损的神经发生和神经祖细胞命运选择。
IF 6.2 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2023-02-20 DOI: 10.1186/s13229-023-00540-x
Lucia F Cardo, Daniel C de la Fuente, Meng Li

Background: Disruptions of SETBP1 (SET binding protein 1) on 18q12.3 by heterozygous gene deletion or loss-of-function variants cause SETBP1 disorder. Clinical features are frequently associated with moderate to severe intellectual disability, autistic traits and speech and motor delays. Despite the association of SETBP1 with neurodevelopmental disorders, little is known about its role in brain development.

Methods: Using CRISPR/Cas9 genome editing technology, we generated a SETBP1 deletion model in human embryonic stem cells (hESCs) and examined the effects of SETBP1-deficiency in neural progenitors (NPCs) and neurons derived from these stem cells using a battery of cellular assays, genome-wide transcriptomic profiling and drug-based phenotypic rescue.

Results: Neural induction occurred efficiently in all SETBP1 deletion models as indicated by uniform transition into neural rosettes. However, SETBP1-deficient NPCs exhibited an extended proliferative window and a decrease in neurogenesis coupled with a deficiency in their ability to acquire ventral forebrain fate. Genome-wide transcriptome profiling and protein biochemical analysis revealed enhanced activation of Wnt/β-catenin signaling in SETBP1 deleted cells. Crucially, treatment of the SETBP1-deficient NPCs with a small molecule Wnt inhibitor XAV939 restored hyper canonical β-catenin activity and restored both cortical and MGE neuronal differentiation.

Limitations: The current study is based on analysis of isogenic hESC lines with genome-edited SETBP1 deletion and further studies would benefit from the use of patient-derived iPSC lines that may harbor additional genetic risk that aggravate brain pathology of SETBP1 disorder.

Conclusions: We identified an important role for SETBP1 in controlling forebrain progenitor expansion and neurogenic differentiation. Our study establishes a novel regulatory link between SETBP1 and Wnt/β-catenin signaling during human cortical neurogenesis and provides mechanistic insights into structural abnormalities and potential therapeutic avenues for SETBP1 disorder.

背景:18q12.3上的SETBP1(SET结合蛋白1)因杂合子基因缺失或功能缺失变异而导致紊乱。临床特征通常与中度至重度智力障碍、自闭症特征以及语言和运动迟缓有关。尽管 SETBP1 与神经发育障碍有关,但人们对其在大脑发育中的作用知之甚少:方法:我们利用CRISPR/Cas9基因组编辑技术,在人类胚胎干细胞(hESCs)中生成了SETBP1缺失模型,并通过一系列细胞检测、全基因组转录组分析和基于药物的表型拯救,研究了SETBP1缺失对神经祖细胞(NPCs)和神经元的影响:结果:在所有SETBP1缺失模型中,神经诱导都能有效地发生,这表现为神经细胞均匀地过渡到神经莲座。然而,SETBP1缺失的NPCs表现出增殖窗口期延长、神经发生减少以及获得腹侧前脑命运的能力不足。全基因组转录组分析和蛋白质生化分析表明,在 SETBP1 缺失的细胞中,Wnt/β-catenin 信号激活增强。最重要的是,用小分子Wnt抑制剂XAV939处理SETBP1缺失的NPC,可恢复超典型β-catenin活性,并恢复皮质和MGE神经元分化:目前的研究基于对基因组编辑SETBP1缺失的同源hESC系的分析,进一步的研究将受益于使用患者衍生的iPSC系,这些iPSC系可能携带额外的遗传风险,从而加重SETBP1紊乱的脑病理学:我们发现了 SETBP1 在控制前脑祖细胞扩增和神经原分化中的重要作用。我们的研究在人类大脑皮层神经发生过程中建立了 SETBP1 与 Wnt/β-catenin 信号之间的新型调控联系,并为 SETBP1 障碍的结构异常和潜在治疗途径提供了机制性见解。
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引用次数: 0
CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions. CRISIS AFAR:一项关于COVID-19大流行对自闭症和神经发育障碍青年心理健康和服务获取影响的国际合作研究。
IF 6.2 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2023-02-14 DOI: 10.1186/s13229-022-00536-z
Bethany Vibert, Patricia Segura, Louise Gallagher, Stelios Georgiades, Panagiota Pervanidou, Audrey Thurm, Lindsay Alexander, Evdokia Anagnostou, Yuta Aoki, Catherine S Birken, Somer L Bishop, Jessica Boi, Carmela Bravaccio, Helena Brentani, Paola Canevini, Alessandra Carta, Alice Charach, Antonella Costantino, Katherine T Cost, Elaine A Cravo, Jennifer Crosbie, Chiara Davico, Federica Donno, Junya Fujino, Alessandra Gabellone, Cristiane T Geyer, Tomoya Hirota, Stephen Kanne, Makiko Kawashima, Elizabeth Kelley, Hosanna Kim, Young Shin Kim, So Hyun Kim, Daphne J Korczak, Meng-Chuan Lai, Lucia Margari, Lucia Marzulli, Gabriele Masi, Luigi Mazzone, Jane McGrath, Suneeta Monga, Paola Morosini, Shinichiro Nakajima, Antonio Narzisi, Rob Nicolson, Aki Nikolaidis, Yoshihiro Noda, Kerri Nowell, Miriam Polizzi, Joana Portolese, Maria Pia Riccio, Manabu Saito, Ida Schwartz, Anish K Simhal, Martina Siracusano, Stefano Sotgiu, Jacob Stroud, Fernando Sumiya, Yoshiyuki Tachibana, Nicole Takahashi, Riina Takahashi, Hiroki Tamon, Raffaella Tancredi, Benedetto Vitiello, Alessandro Zuddas, Bennett Leventhal, Kathleen Merikangas, Michael P Milham, Adriana Di Martino

Background: Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services.

Methods: Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups.

Results: Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup.

Limitations: Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic.

Conclusions: Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.

背景:在普通人群中记录了2019冠状病毒病大流行期间的异质性心理健康结果。这种异质性尚未在患有自闭症谱系障碍(ASD)和相关神经发育障碍(NDD)的青少年中进行系统评估。为了确定大流行影响的不同模式及其在ASD/NDD青少年中的预测因素,我们重点研究了与大流行相关的症状变化和获得服务的机会。方法:采用自然观察设计,评估家长对适用于自闭症及相关神经发育状况的冠状病毒健康和影响调查倡议(CRISIS)的反应。横断面AFAR数据汇集了14个欧洲和北美地区的数据,得到了临床特征良好的样本N = 1275名ASD/NDD患者(年龄= 11.0±3.6岁;N名女性= 277)。为了确定具有不同结果的亚组,我们应用了跨11个变量的分层聚类,测量症状和获得服务的变化。然后,随机森林分类评估社会人口统计学、大流行前服务率、asd相关症状的临床严重程度以及COVID-19大流行经历/环境在预测结果亚组中的重要性。结果:聚类可分为4个亚组。一个亚组——症状仅广泛恶化(20%)——包括一系列症状恶化但服务中断与总样本的平均水平相似的年轻人。其他三个亚组在临床上相对稳定,但在服务获取方面存在差异:主要是修改服务(23%),主要是失去服务(6%),以及平均服务/症状变化(53%)。一组大流行前服务、大流行环境(如COVID-19新病例、限制)、经历(如COVID-19担忧)和年龄的不同组合预测了每个结果亚组。局限性:该研究的显著局限性是其横断面性质和重点关注大流行的前六个月。结论:同时评估大流行第一阶段症状变化和服务获取的差异,揭示了ASD/NDD青年的不同结局概况。亚组的特点是在一组与大流行有关的前期和相关经历/背景中具有不同的预测模式。研究结果可为今后危机的恢复工作和准备工作提供信息;它们还强调了国际数据共享和合作在危机时期解决最弱势群体需求方面的关键价值。
{"title":"CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions.","authors":"Bethany Vibert,&nbsp;Patricia Segura,&nbsp;Louise Gallagher,&nbsp;Stelios Georgiades,&nbsp;Panagiota Pervanidou,&nbsp;Audrey Thurm,&nbsp;Lindsay Alexander,&nbsp;Evdokia Anagnostou,&nbsp;Yuta Aoki,&nbsp;Catherine S Birken,&nbsp;Somer L Bishop,&nbsp;Jessica Boi,&nbsp;Carmela Bravaccio,&nbsp;Helena Brentani,&nbsp;Paola Canevini,&nbsp;Alessandra Carta,&nbsp;Alice Charach,&nbsp;Antonella Costantino,&nbsp;Katherine T Cost,&nbsp;Elaine A Cravo,&nbsp;Jennifer Crosbie,&nbsp;Chiara Davico,&nbsp;Federica Donno,&nbsp;Junya Fujino,&nbsp;Alessandra Gabellone,&nbsp;Cristiane T Geyer,&nbsp;Tomoya Hirota,&nbsp;Stephen Kanne,&nbsp;Makiko Kawashima,&nbsp;Elizabeth Kelley,&nbsp;Hosanna Kim,&nbsp;Young Shin Kim,&nbsp;So Hyun Kim,&nbsp;Daphne J Korczak,&nbsp;Meng-Chuan Lai,&nbsp;Lucia Margari,&nbsp;Lucia Marzulli,&nbsp;Gabriele Masi,&nbsp;Luigi Mazzone,&nbsp;Jane McGrath,&nbsp;Suneeta Monga,&nbsp;Paola Morosini,&nbsp;Shinichiro Nakajima,&nbsp;Antonio Narzisi,&nbsp;Rob Nicolson,&nbsp;Aki Nikolaidis,&nbsp;Yoshihiro Noda,&nbsp;Kerri Nowell,&nbsp;Miriam Polizzi,&nbsp;Joana Portolese,&nbsp;Maria Pia Riccio,&nbsp;Manabu Saito,&nbsp;Ida Schwartz,&nbsp;Anish K Simhal,&nbsp;Martina Siracusano,&nbsp;Stefano Sotgiu,&nbsp;Jacob Stroud,&nbsp;Fernando Sumiya,&nbsp;Yoshiyuki Tachibana,&nbsp;Nicole Takahashi,&nbsp;Riina Takahashi,&nbsp;Hiroki Tamon,&nbsp;Raffaella Tancredi,&nbsp;Benedetto Vitiello,&nbsp;Alessandro Zuddas,&nbsp;Bennett Leventhal,&nbsp;Kathleen Merikangas,&nbsp;Michael P Milham,&nbsp;Adriana Di Martino","doi":"10.1186/s13229-022-00536-z","DOIUrl":"https://doi.org/10.1186/s13229-022-00536-z","url":null,"abstract":"<p><strong>Background: </strong>Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services.</p><p><strong>Methods: </strong>Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups.</p><p><strong>Results: </strong>Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup.</p><p><strong>Limitations: </strong>Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic.</p><p><strong>Conclusions: </strong>Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"14 1","pages":"7"},"PeriodicalIF":6.2,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9634310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
The subcortical correlates of autistic traits in school-age children: a population-based neuroimaging study. 学龄儿童自闭症特征的皮层下相关性:一项基于人群的神经影像学研究。
IF 6.2 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2023-02-11 DOI: 10.1186/s13229-023-00538-5
T H Sharp, M Elsabbagh, A Pickles, R Bedford

Background: There is emerging evidence that the neuroanatomy of autism forms a spectrum which extends into the general population. However, whilst several studies have identified cortical morphology correlates of autistic traits, it is not established whether morphological differences are present in the subcortical structures of the brain. Additionally, it is not clear to what extent previously reported structural associations may be confounded by co-occurring psychopathology. To address these questions, we utilised neuroimaging data from the Adolescent Brain Cognitive Development Study to assess whether a measure of autistic traits was associated with differences in child subcortical morphology, and if any observed differences persisted after adjustment for child internalising and externalising symptoms.

Methods: Our analyses included data from 7005 children aged 9-10 years (female: 47.19%) participating in the Adolescent Brain Cognitive Development Study. Autistic traits were assessed using scores from the Social Responsiveness Scale (SRS). Volumes of subcortical regions of interest were derived from structural magnetic resonance imaging data.

Results: Overall, we did not find strong evidence for an association of autistic traits with differences in subcortical morphology in this sample of school-aged children. Whilst lower absolute volumes of the nucleus accumbens and putamen were associated with higher scores of autistic traits, these differences did not persist once a global measure of brain size was accounted for.

Limitations: It is important to note that autistic traits were assessed using the SRS, of which higher scores are associated with general behavioural problems, and therefore may not be wholly indicative of autism-specific symptoms. In addition, individuals with a moderate or severe autism diagnosis were excluded from the ABCD study, and thus, the average level of autistic traits will be lower than in the general population which may bias findings towards the null.

Conclusions: These findings from our well-powered study suggest that other metrics of brain morphology, such as cortical morphology or shape-based phenotypes, may be stronger candidates to prioritise when attempting to identify robust neuromarkers of autistic traits.

背景:越来越多的证据表明,自闭症的神经解剖学形成了一个延伸到普通人群的谱系。然而,虽然一些研究已经确定了皮层形态与自闭症特征的相关性,但尚不确定大脑皮层下结构是否存在形态差异。此外,尚不清楚先前报道的结构关联在多大程度上可能被共同发生的精神病理所混淆。为了解决这些问题,我们利用青少年大脑认知发展研究的神经影像学数据来评估自闭症特征的测量是否与儿童皮层下形态学的差异有关,以及在调整儿童内化和外化症状后是否存在观察到的差异。方法:我们的分析包括参加青少年大脑认知发展研究的7005名9-10岁儿童(女性:47.19%)的数据。自闭症特征是用社会反应量表(SRS)的分数来评估的。皮层下感兴趣区域的体积来源于结构磁共振成像数据。结果:总的来说,我们没有发现强有力的证据表明自闭症特征与学龄儿童皮层下形态的差异有关。虽然伏隔核和壳核的绝对体积较低与自闭症特征得分较高有关,但一旦考虑到大脑大小的整体测量,这些差异就不复存在了。局限性:值得注意的是,自闭症特征是使用SRS评估的,其中较高的分数与一般行为问题有关,因此可能不能完全表明自闭症的特定症状。此外,被诊断为中度或重度自闭症的个体被排除在ABCD研究之外,因此,自闭症特征的平均水平将低于一般人群,这可能使研究结果偏向零值。结论:我们强有力的研究结果表明,当试图识别自闭症特征的强大神经标志物时,大脑形态学的其他指标,如皮层形态学或基于形状的表型,可能是优先考虑的更强的候选者。
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引用次数: 5
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Molecular Autism
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