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Task-based functional neural correlates of social cognition across autism and schizophrenia spectrum disorders 基于任务的自闭症和精神分裂症谱系障碍社交认知的功能神经相关性
IF 6.2 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-09-04 DOI: 10.1186/s13229-024-00615-3
Lindsay D. Oliver, Iska Moxon-Emre, Colin Hawco, Erin W. Dickie, Arla Dakli, Rachael E. Lyon, Peter Szatmari, John D. Haltigan, Anna Goldenberg, Ayesha G. Rashidi, Vinh Tan, Maria T. Secara, Pushpal Desarkar, George Foussias, Robert W. Buchanan, Anil K. Malhotra, Meng-Chuan Lai, Aristotle N. Voineskos, Stephanie H. Ameis
Autism and schizophrenia spectrum disorders (SSDs) both feature atypical social cognition. Despite evidence for comparable group-level performance in lower-level emotion processing and higher-level mentalizing, limited research has examined the neural basis of social cognition across these conditions. Our goal was to compare the neural correlates of social cognition in autism, SSDs, and typically developing controls (TDCs). Data came from two harmonized studies in individuals diagnosed with autism or SSDs and TDCs (aged 16–35 years), including behavioral social cognitive metrics and two functional magnetic resonance imaging (fMRI) tasks: a social mirroring Imitate/Observe (ImObs) task and the Empathic Accuracy (EA) task. Group-level comparisons, and transdiagnostic analyses incorporating social cognitive performance, were run using FSL’s PALM for each task, covarying for age and sex (1000 permutations, thresholded at p < 0.05 FWE-corrected). Exploratory region of interest (ROI)-based analyses were also conducted. ImObs and EA analyses included 164 and 174 participants, respectively (autism N = 56/59, SSD N = 50/56, TDC N = 58/59). EA and both lower- and higher-level social cognition scores differed across groups. While canonical social cognitive networks were activated, no significant whole-brain or ROI-based group-level differences in neural correlates for either task were detected. Transdiagnostically, neural activity during the EA task, but not the ImObs task, was associated with lower- and higher-level social cognitive performance. Despite attempting to match our groups on age, sex, and race, significant group differences remained. Power to detect regional brain differences is also influenced by sample size and multiple comparisons in whole-brain analyses. Our findings may not generalize to autism and SSD individuals with co-occurring intellectual disabilities. The lack of whole-brain and ROI-based group-level differences identified and the dimensional EA brain-behavior relationship observed across our sample suggest that the EA task may be well-suited to target engagement in novel intervention testing. Our results also emphasize the potential utility of cross-condition approaches to better understand social cognition across autism and SSDs.
自闭症和精神分裂症谱系障碍(SSD)都具有不典型的社会认知特征。尽管有证据表明这两种疾病在低级情绪处理和高级心智化方面的表现具有可比性,但对这两种疾病的社会认知神经基础的研究却十分有限。我们的目标是比较自闭症患者、社会功能障碍患者和发育正常对照组(TDCs)的社会认知神经相关性。数据来自两项统一的研究,研究对象是被诊断为自闭症或 SSD 的患者和 TDCs(年龄在 16-35 岁之间),包括行为社会认知指标和两项功能磁共振成像(fMRI)任务:社会镜像模仿/观察(ImObs)任务和移情准确性(EA)任务。使用 FSL 的 PALM 对每项任务进行了组级比较,并结合社会认知表现进行了跨诊断分析,同时对年龄和性别进行了协变量分析(1000 次排列,阈值为 P < 0.05 FWE 校正)。此外,还进行了基于兴趣区域(ROI)的探索性分析。ImObs 和 EA 分析分别包括 164 和 174 名参与者(自闭症 N = 56/59,SSD N = 50/56,TDC N = 58/59)。各组的 EA 以及低级和高级社会认知得分均有所不同。虽然典型的社会认知网络被激活,但在这两项任务的神经相关性方面,均未发现明显的全脑或基于 ROI 的组间差异。从横向诊断的角度看,EA 任务中的神经活动与低级和高级社会认知表现相关,而 ImObs 任务中的神经活动与低级和高级社会认知表现无关。尽管我们试图在年龄、性别和种族上对各组进行匹配,但仍存在显著的组间差异。在全脑分析中,检测大脑区域差异的能力还受到样本大小和多重比较的影响。我们的研究结果可能无法推广到自闭症和并发智力障碍的 SSD 患者。在我们的样本中,没有发现全脑和基于 ROI 的群体水平差异,也没有观察到 EA 大脑与行为之间的维度关系,这表明 EA 任务可能非常适合用于新型干预测试中的目标参与。我们的研究结果还强调了跨条件方法在更好地理解自闭症和特殊障碍儿童的社会认知方面的潜在作用。
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引用次数: 0
Enhanced motor noise in an autism subtype with poor motor skills. 自闭症亚型中运动技能较差者的运动噪音增强。
IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-09-03 DOI: 10.1186/s13229-024-00618-0
Veronica Mandelli, Isotta Landi, Silvia Busti Ceccarelli, Massimo Molteni, Maria Nobile, Alessandro D'Ausilio, Luciano Fadiga, Alessandro Crippa, Michael V Lombardo

Background: Motor difficulties are common in many, but not all, autistic individuals. These difficulties can co-occur with other problems, such as delays in language, intellectual, and adaptive functioning. Biological mechanisms underpinning such difficulties are less well understood. Poor motor skills tend to be more common in individuals carrying highly penetrant rare genetic mutations. Such mechanisms may have downstream consequences of altering neurophysiological excitation-inhibition balance and lead to enhanced behavioral motor noise.

Methods: This study combined publicly available and in-house datasets of autistic (n = 156), typically-developing (TD, n = 149), and developmental coordination disorder (DCD, n = 23) children (age 3-16 years). Autism motor subtypes were identified based on patterns of motor abilities measured from the Movement Assessment Battery for Children 2nd edition. Stability-based relative clustering validation was used to identify autism motor subtypes and evaluate generalization accuracy in held-out data. Autism motor subtypes were tested for differences in motor noise, operationalized as the degree of dissimilarity between repeated motor kinematic trajectories recorded during a simple reach-to-drop task.

Results: Relatively 'high' (n = 87) versus 'low' (n = 69) autism motor subtypes could be detected and which generalize with 89% accuracy in held-out data. The relatively 'low' subtype was lower in general intellectual ability and older at age of independent walking, but did not differ in age at first words or autistic traits or symptomatology. Motor noise was considerably higher in the 'low' subtype compared to 'high' (Cohen's d = 0.77) or TD children (Cohen's d = 0.85), but similar between autism 'high' and TD children (Cohen's d = 0.08). Enhanced motor noise in the 'low' subtype was also most pronounced during the feedforward phase of reaching actions.

Limitations: The sample size of this work is limited. Future work in larger samples along with independent replication is important. Motor noise was measured only on one specific motor task. Thus, a more comprehensive assessment of motor noise on many other motor tasks is needed.

Conclusions: Autism can be split into at least two discrete motor subtypes that are characterized by differing levels of motor noise. This suggests that autism motor subtypes may be underpinned by different biological mechanisms.

背景:运动障碍常见于许多自闭症患者,但并非所有自闭症患者。这些困难可能与其他问题同时出现,如语言、智力和适应功能方面的迟缓。人们对造成这些障碍的生物学机制还不甚了解。运动能力差往往更常见于携带高渗透性罕见基因突变的个体。这些机制可能会产生改变神经生理兴奋-抑制平衡的下游后果,并导致行为运动噪声增强:本研究结合了自闭症儿童(156 人)、典型发育障碍儿童(149 人)和发育协调障碍儿童(23 人)(3-16 岁)的公开数据集和内部数据集。自闭症运动亚型是根据儿童运动评估电池第二版测量的运动能力模式确定的。采用基于稳定性的相对聚类验证来识别自闭症运动亚型,并评估保留数据的泛化准确性。测试了自闭症运动亚型在运动噪音方面的差异,运动噪音是指在简单的 "伸手投掷 "任务中记录的重复运动轨迹之间的差异程度:结果:可以检测出相对 "高"(87 人)和 "低"(69 人)的自闭症运动亚型,这些亚型在保留数据中的通用准确率为 89%。相对 "低 "亚型的一般智力水平较低,独立行走的年龄较大,但在首次开口说话的年龄、自闭症特征或症状方面没有差异。与 "高"(Cohen's d = 0.77)或 TD 儿童(Cohen's d = 0.85)相比,"低 "亚型儿童的运动噪音要高得多,但自闭症 "高 "儿童与 TD 儿童的运动噪音相似(Cohen's d = 0.08)。在伸手动作的前馈阶段,"低 "亚型儿童的运动噪声增强也最为明显:局限性:这项研究的样本量有限。局限性:这项研究的样本量有限,未来在更大样本中进行独立重复研究非常重要。仅在一项特定的运动任务中测量了运动噪音。因此,需要对许多其他运动任务的运动噪音进行更全面的评估:结论:自闭症至少可分为两种不同的运动亚型,它们的运动噪声水平各不相同。这表明自闭症运动亚型可能由不同的生物机制支撑。
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引用次数: 0
Mapping neural correlates of biological motion perception in autistic children using high-density diffuse optical tomography. 利用高密度弥散光学断层扫描绘制自闭症儿童生物运动感知的神经相关性图谱。
IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-08-22 DOI: 10.1186/s13229-024-00614-4
Dalin Yang, Alexandra M Svoboda, Tessa G George, Patricia K Mansfield, Muriah D Wheelock, Mariel L Schroeder, Sean M Rafferty, Arefeh Sherafati, Kalyan Tripathy, Tracy Burns-Yocum, Elizabeth Forsen, John R Pruett, Natasha M Marrus, Joseph P Culver, John N Constantino, Adam T Eggebrecht

Background: Autism spectrum disorder (ASD), a neurodevelopmental disorder defined by social communication deficits plus repetitive behaviors and restricted interests, currently affects 1/36 children in the general population. Recent advances in functional brain imaging show promise to provide useful biomarkers of ASD diagnostic likelihood, behavioral trait severity, and even response to therapeutic intervention. However, current gold-standard neuroimaging methods (e.g., functional magnetic resonance imaging, fMRI) are limited in naturalistic studies of brain function underlying ASD-associated behaviors due to the constrained imaging environment. Compared to fMRI, high-density diffuse optical tomography (HD-DOT), a non-invasive and minimally constraining optical neuroimaging modality, can overcome these limitations. Herein, we aimed to establish HD-DOT to evaluate brain function in autistic and non-autistic school-age children as they performed a biological motion perception task previously shown to yield results related to both ASD diagnosis and behavioral traits.

Methods: We used HD-DOT to image brain function in 46 ASD school-age participants and 49 non-autistic individuals (NAI) as they viewed dynamic point-light displays of coherent biological and scrambled motion. We assessed group-level cortical brain function with statistical parametric mapping. Additionally, we tested for brain-behavior associations with dimensional metrics of autism traits, as measured with the Social Responsiveness Scale-2, with hierarchical regression models.

Results: We found that NAI participants presented stronger brain activity contrast (coherent > scrambled) than ASD children in cortical regions related to visual, motor, and social processing. Additionally, regression models revealed multiple cortical regions in autistic participants where brain function is significantly associated with dimensional measures of ASD traits.

Limitations: Optical imaging methods are limited in depth sensitivity and so cannot measure brain activity within deep subcortical regions. However, the field of view of this HD-DOT system includes multiple brain regions previously implicated in both task-based and task-free studies on autism.

Conclusions: This study demonstrates that HD-DOT is sensitive to brain function that both differentiates between NAI and ASD groups and correlates with dimensional measures of ASD traits. These findings establish HD-DOT as an effective tool for investigating brain function in autistic and non-autistic children. Moreover, this study established neural correlates related to biological motion perception and its association with dimensional measures of ASD traits.

背景:自闭症谱系障碍(ASD)是一种神经发育障碍,表现为社交沟通障碍、重复行为和兴趣受限,目前有 1/36 的儿童受其影响。脑功能成像技术的最新进展表明,它有望为 ASD 诊断可能性、行为特征严重性、甚至对治疗干预的反应提供有用的生物标记。然而,由于成像环境的限制,目前的黄金标准神经成像方法(如功能磁共振成像,fMRI)在对 ASD 相关行为的大脑功能进行自然研究时受到了限制。与 fMRI 相比,高密度弥散光学断层扫描(HD-DOT)作为一种无创、限制性最小的光学神经成像模式,可以克服这些局限性。在此,我们旨在利用 HD-DOT 评估自闭症和非自闭症学龄儿童的大脑功能,当时他们正在执行一项生物运动感知任务,之前的研究表明该任务产生的结果与 ASD 诊断和行为特征有关:我们使用 HD-DOT 对 46 名 ASD 学龄参与者和 49 名非自闭症患者(NAI)的大脑功能进行成像,当时他们正在观看相干生物运动和干扰运动的动态点光显示。我们通过统计参数映射评估了群体水平的大脑皮层功能。此外,我们还利用分层回归模型测试了大脑行为与自闭症特征维度指标的关联,自闭症特征维度指标是用社会反应量表-2(Social Responsiveness Scale-2)测量的:我们发现,在与视觉、运动和社交处理相关的皮层区域,NAI 参与者的大脑活动对比度(连贯 > 杂乱)强于 ASD 儿童。此外,回归模型显示,在自闭症参与者的多个皮质区域,大脑功能与 ASD 特征的维度测量结果有显著关联:局限性:光学成像方法的深度灵敏度有限,因此无法测量深层皮层下区域的大脑活动。然而,HD-DOT 系统的视场包括多个先前在基于任务和无任务自闭症研究中涉及的脑区:本研究表明,HD-DOT 对大脑功能非常敏感,既能区分非自闭症和自闭症群体,又与自闭症特征的维度测量相关。这些研究结果表明,HD-DOT 是研究自闭症和非自闭症儿童大脑功能的有效工具。此外,本研究还确定了与生物运动感知相关的神经相关性及其与自闭症特征维度测量的关联。
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引用次数: 0
Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults. 自闭症多基因评分与成人小脑和脑干体积磁共振成像表型的关联。
IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-08-07 DOI: 10.1186/s13229-024-00611-7
Salahuddin Mohammad, Mélissa Gentreau, Manon Dubol, Gull Rukh, Jessica Mwinyi, Helgi B Schiöth

Previous research on autism spectrum disorders (ASD) have showed important volumetric alterations in the cerebellum and brainstem. Most of these studies are however limited to case-control studies with small clinical samples and including mainly children or adolescents. Herein, we aimed to explore the association between the cumulative genetic load (polygenic risk score, PRS) for ASD and volumetric alterations in the cerebellum and brainstem, as well as global brain tissue volumes of the brain among adults at the population level. We utilized the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and constructed the ASD PRS in an independent cohort, the UK Biobank. Regression analyses controlled for multiple comparisons with the false-discovery rate (FDR) at 5% were performed to investigate the association between ASD PRS and forty-four brain magnetic resonance imaging (MRI) phenotypes among ~ 31,000 participants. Primary analyses included sixteen MRI phenotypes: total volumes of the brain, cerebrospinal fluid (CSF), grey matter (GM), white matter (WM), GM of whole cerebellum, brainstem, and ten regions of the cerebellum (I_IV, V, VI, VIIb, VIIIa, VIIIb, IX, X, CrusI and CrusII). Secondary analyses included twenty-eight MRI phenotypes: the sub-regional volumes of cerebellum including the GM of the vermis and both left and right lobules of each cerebellar region. ASD PRS were significantly associated with the volumes of seven brain areas, whereby higher PRS were associated to reduced volumes of the whole brain, WM, brainstem, and cerebellar regions I-IV, IX, and X, and an increased volume of the CSF. Three sub-regional volumes including the left cerebellar lobule I-IV, cerebellar vermes VIIIb, and X were significantly and negatively associated with ASD PRS. The study highlights a substantial connection between susceptibility to ASD, its underlying genetic etiology, and neuroanatomical alterations of the adult brain.

以往关于自闭症谱系障碍(ASD)的研究显示,小脑和脑干的体积发生了重要变化。然而,这些研究大多局限于病例对照研究,临床样本较少,且主要包括儿童或青少年。在此,我们的目的是在人群水平上探讨 ASD 的累积遗传负荷(多基因风险评分,PRS)与小脑和脑干的体积变化以及成人大脑的整体脑组织体积之间的关联。我们利用了精神病遗传学联盟最新的 ASD 全基因组关联研究(18381 例病例,27969 例对照),并在英国生物库这一独立队列中构建了 ASD PRS。为了研究约 31,000 名参与者中 ASD PRS 与 44 种脑磁共振成像(MRI)表型之间的关联,我们进行了回归分析,控制多重比较,假发现率 (FDR) 为 5%。主要分析包括十六种 MRI 表型:大脑总体积、脑脊液 (CSF)、灰质 (GM)、白质 (WM)、整个小脑的 GM、脑干以及小脑的十个区域(I_IV、V、VI、VIIb、VIIIa、VIIIb、IX、X、CrusI 和 CrusII)。二次分析包括 28 种磁共振成像表型:小脑的亚区域体积,包括蚓部 GM 和每个小脑区域的左右小叶。ASD PRS与七个脑区的体积明显相关,PRS越高,全脑、WM、脑干、小脑I-IV、IX和X区的体积越小,脑脊液体积越大。包括左侧小脑小叶 I-IV、小脑蚓部 VIIIb 和 X 在内的三个子区域的体积与 ASD PRS 呈显著负相关。该研究强调了 ASD 易感性、其潜在的遗传病因和成人大脑神经解剖结构改变之间的重要联系。
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引用次数: 0
Spontaneous instrumental approach-avoidance learning in social contexts in autism. 自闭症患者在社交环境中的自发工具性接近-回避学习。
IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-07-31 DOI: 10.1186/s13229-024-00610-8
Morgan Beaurenaut, Klara Kovarski, Constance Destais, Rocco Mennella, Julie Grèzes

Background: Individuals with Autism Spectrum Condition (ASC) are characterized by atypicalities in social interactions, compared to Typically Developing individuals (TD). The social motivation theory posits that these difficulties stem from diminished anticipation, reception, and/or learning from social rewards. Although learning from socioemotional outcomes is core to the theory, studies to date have been sparse and inconsistent. This possibly arises from a combination of theoretical, methodological and sample-related issues. Here, we assessed participants' ability to develop a spontaneous preference for actions that lead to desirable socioemotional outcomes (approaching/avoiding of happy/angry individuals, respectively), in an ecologically valid social scenario. We expected that learning abilities would be impaired in ASC individuals, particularly in response to affiliative social feedback.

Method: We ran an online social reinforcement learning task, on two large online cohorts with (n = 274) and without (n = 290) ASC, matched for gender, age and education. Participants had to indicate where they would sit in a waiting room. Each seat was associated with different probabilities of approaching/avoiding emotional individuals. Importantly, the task was implicit, as participants were not instructed to learn, and emotional expressions were never mentioned. We applied both categorical analyses contrasting the ASC and TD groups and dimensional factor analysis on affective questionnaires.

Results: Contrary to our hypothesis, participants showed spontaneous learning from socioemotional outcomes, regardless of their diagnostic group. Yet, when accounting for dimensional variations in autistic traits, as well as depression and anxiety, two main findings emerged among females who failed to develop explicit learning strategies: (1) autism severity in ASC correlated with reduced learning to approach happy individuals; (2) anxiety-depression severity across both ASC and TD participants correlated with reduced learning to approach/avoid happy/angry individuals, respectively.

Conclusions: Implicit spontaneous learning from socioemotional outcomes is not generally impaired in autism but may be specifically associated with autism severity in females with ASC, when they do not have an explicit strategy for adapting to their social environment. Clinical diagnosis and intervention ought to take into account individual differences in their full complexity, including the presence of co-morbid anxiety and depression, when dealing with social atypicalities in autism.

背景:与发育正常的个体(TD)相比,自闭症谱系障碍(ASC)患者在社会交往方面具有非典型特征。社会动机理论认为,这些困难源于对社会奖励的预期、接受和/或学习能力的减弱。虽然从社会情感结果中学习是该理论的核心,但迄今为止的研究却很少,而且不一致。这可能是理论、方法和样本相关问题的综合结果。在这里,我们评估了参与者在生态学上有效的社会情景中自发偏好能带来理想社会情感结果(分别接近/避开高兴/愤怒的个体)的行动的能力。我们预计ASC患者的学习能力会受损,尤其是在对附属性社会反馈做出反应时:我们在性别、年龄和教育程度相匹配的两个大型在线群体中,分别测试了患有(n = 274)和不患有(n = 290)ASC 的人的在线社交强化学习任务。参与者必须指出他们在候车室的座位。每个座位都与接近/回避情绪化个体的不同概率相关联。重要的是,这项任务是隐性的,因为参与者没有被要求学习,也从未提及情绪表达。我们对ASC组和TD组进行了分类分析,并对情感问卷进行了维度因素分析:结果:与我们的假设相反,无论受试者属于哪个诊断组,他们都能自发地从社会情感结果中学习。然而,当考虑到自闭症特征以及抑郁和焦虑的维度差异时,在未能发展出明确学习策略的女性中出现了两个主要发现:(1)自闭症患者的自闭症严重程度与接近快乐个体的学习能力降低相关;(2)自闭症患者和TD参与者的焦虑抑郁严重程度分别与接近/回避快乐/愤怒个体的学习能力降低相关:结论:自闭症患者对社会情感结果的内隐自发学习一般不会受损,但对于患有自闭症的女性患者来说,当她们没有明确的适应社会环境的策略时,内隐自发学习可能与自闭症的严重程度特别相关。在处理自闭症社交异常时,临床诊断和干预应充分考虑个体差异的复杂性,包括是否合并焦虑和抑郁。
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引用次数: 0
Correction: Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice. 更正:Shank2和Shank3突变小鼠的社会支配和合作行为发生了不同程度的改变。
IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-07-30 DOI: 10.1186/s13229-024-00612-6
Kyung Ah Han, Taek Han Yoon, Jungsu Shin, Ji Won Um, Jaewon Ko
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引用次数: 0
1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome. 基于 1H-NMR 的代谢组学揭示了安杰曼综合征小鼠模型早期发育过程中的代谢改变。
IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-07-24 DOI: 10.1186/s13229-024-00608-2
Pooja Kri Gupta, Sharon Barak, Yonatan Feuermann, Gil Goobes, Hanoch Kaphzan

Background: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development.

Methods: We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis.

Results: Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways.

Limitations: Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain.

Conclusions: Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development.

背景:安杰尔曼综合征(AS)是一种罕见的神经发育遗传性疾病,由泛素连接酶 E3A(UBE3A)基因功能缺失引起,约有 1:15,000 的活产儿患病。我们最近发现,在胚胎中后期的大脑发育过程中,AS 的线粒体功能会发生改变,导致氧化应激增加和神经前体细胞凋亡增强。然而,新陈代谢过程的整体改变仍是未知数。因此,作为后续研究,我们旨在调查野生型(WT)和AS同窝鼠的代谢概况,并确定AS模型小鼠在胚胎发育期间大脑中哪些代谢过程出现异常:我们收集了小鼠胚胎发育至16.5岁时的脑组织样本,并使用质子核磁共振(1H-NMR)光谱进行了代谢组学分析。通过多变量和单变量分析,确定强直性脊柱炎小鼠体内发生显著改变的代谢物。利用代谢物集富集分析确定了与代谢物改变相关的通路:结果:我们的分析表明,AS胚胎大脑的代谢组指纹总体上与WT同窝鼠不同。此外,与 WT 样本相比,我们发现 AS 样本中乙酸盐、乳酸盐和琥珀酸盐等代谢物明显升高。代谢物的升高与丙酮酸代谢和糖酵解途径密切相关:局限性:本研究仅成功鉴定并调查了 14 种代谢物。局限性:本研究只成功鉴定和调查了 14 种代谢物,未确定未鉴定代谢物及其未解析峰的影响。此外,我们对整个脑组织样本进行了代谢组学研究。对不同脑区进行高分辨率核磁共振研究可进一步扩展我们对 AS 脑代谢改变的认识。此外,增加样本量可以揭示更多明显改变的代谢物参与了强直性脊柱炎大脑的病理生理学:结论:Ube3a功能缺失会改变AS大脑胚胎发育过程中与生物能相关的代谢。此外,这些神经化学变化可能与强直性脊柱炎胚胎发育过程中出现的线粒体活性氧和氧化应激有关。
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引用次数: 0
Publisher Correction: Measuring self and informant perspectives of restricted and repetitive behaviours (RRBs): psychometric evaluation of the repetitive Behaviours Questionnaire-3 (RBQ-3) in adult clinical practice and research settings. 出版商更正:测量受限和重复行为(RRBs)的自我视角和信息提供者视角:在成人临床实践和研究环境中对重复行为问卷-3(RBQ-3)的心理测量学评估。
IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-07-18 DOI: 10.1186/s13229-024-00609-1
Catherine R G Jones, Lucy A Livingston, Christine Fretwell, Mirko Uljarević, Sarah J Carrington, Punit Shah, Susan R Leekam
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引用次数: 0
Mate selection and current trends in the prevalence of autism. 配偶选择与自闭症发病率的当前趋势。
IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-07-16 DOI: 10.1186/s13229-024-00607-3
Elizabeth Forsen, Natasha Marrus, Jacqueline Joyce, Yi Zhang, John N Constantino

Background: According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children.

Methods: Birth records were used to identify all twin pairs born between 2011 and 2013 in California and Missouri. Families were selected at random from pools of English-speaking Hispanic families in California and Non-Hispanic White families in Missouri. Autistic trait data of parents was obtained using the Adult Report Form of the Social Responsiveness Scale (SRS-2).

Results: We did not identify a statistically significant difference in the degree of mate selection for autism related traits between Hispanic and non-Hispanic white spousal pairs. However, the degree of spousal correlation observed in this recent cohort was pronounced (on the order of ICC 0.45) and exceeded that typically reported in prior research (on the order of 0.30), surpassing also widely reported estimates for sibling correlation (also on the order of 0.30).

Limitations: The sample did not allow for a direct appraisal of change in the magnitude of spousal correlation over time and the ascertainments of trait burden were derived from spouse report.

Conclusion: Across two epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white families across two U.S. states (respectively, California and Missouri), the extent of autism-related trait co-variation for parents of the current generation of young children is substantial and exceeds correlations typically observed for siblings. Given the heritability of these traits and their relation to autism risk, societal trends in the degree of mate selection for these traits should be considered as possible contributors to subtle increases in the incidence of autism over time and across generations.

背景:根据美国疾病预防控制中心的最新监测数据,少数族裔儿童自闭症谱系障碍患病率的上升速度已开始超过非西班牙裔白人儿童。由于之前的研究发现不同种族的家庭对自闭症特征的择偶程度可能存在差异,因此本研究考察了代表西班牙裔和非西班牙裔白人的同期流行病学确定的配偶样本中自闭症相关特征的变化。目的是确定不同种族之间的差异是否会导致当代幼儿患病率的不同增长:使用出生记录识别 2011 年至 2013 年间在加利福尼亚州和密苏里州出生的所有双胞胎。研究人员从加利福尼亚州讲英语的西语裔家庭和密苏里州非西语裔白人家庭中随机抽取家庭。父母的自闭症特征数据是通过社会反应性量表(SRS-2)的成人报告表获得的:结果:我们没有发现西班牙裔和非西班牙裔白人配偶双方在自闭症相关特质的择偶程度上存在统计学意义上的显著差异。然而,在这一最新队列中观察到的配偶相关程度非常明显(ICC 为 0.45),超过了以往研究中通常报告的相关程度(约为 0.30),也超过了广泛报告的兄弟姐妹相关估计值(也约为 0.30):局限性:样本无法直接评估配偶相关性随时间推移而发生的变化,特质负担的确定来自配偶的报告:在美国两个州(分别是加利福尼亚州和密苏里州)的西班牙裔和非西班牙裔白人家庭的两个经流行病学确定的配偶样本中,这一代幼儿的父母与自闭症相关的性状共变程度很大,超过了通常在兄弟姐妹中观察到的相关性。鉴于这些性状的遗传性及其与自闭症风险的关系,这些性状的配偶选择程度的社会趋势应被视为自闭症发病率随时间和跨代微妙增加的可能因素。
{"title":"Mate selection and current trends in the prevalence of autism.","authors":"Elizabeth Forsen, Natasha Marrus, Jacqueline Joyce, Yi Zhang, John N Constantino","doi":"10.1186/s13229-024-00607-3","DOIUrl":"10.1186/s13229-024-00607-3","url":null,"abstract":"<p><strong>Background: </strong>According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children.</p><p><strong>Methods: </strong>Birth records were used to identify all twin pairs born between 2011 and 2013 in California and Missouri. Families were selected at random from pools of English-speaking Hispanic families in California and Non-Hispanic White families in Missouri. Autistic trait data of parents was obtained using the Adult Report Form of the Social Responsiveness Scale (SRS-2).</p><p><strong>Results: </strong>We did not identify a statistically significant difference in the degree of mate selection for autism related traits between Hispanic and non-Hispanic white spousal pairs. However, the degree of spousal correlation observed in this recent cohort was pronounced (on the order of ICC 0.45) and exceeded that typically reported in prior research (on the order of 0.30), surpassing also widely reported estimates for sibling correlation (also on the order of 0.30).</p><p><strong>Limitations: </strong>The sample did not allow for a direct appraisal of change in the magnitude of spousal correlation over time and the ascertainments of trait burden were derived from spouse report.</p><p><strong>Conclusion: </strong>Across two epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white families across two U.S. states (respectively, California and Missouri), the extent of autism-related trait co-variation for parents of the current generation of young children is substantial and exceeds correlations typically observed for siblings. Given the heritability of these traits and their relation to autism risk, societal trends in the degree of mate selection for these traits should be considered as possible contributors to subtle increases in the incidence of autism over time and across generations.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627181","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
Phenotypic and ancestry-related assortative mating in autism. 自闭症患者的表型与祖先相关的同类交配。
IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Pub Date : 2024-06-14 DOI: 10.1186/s13229-024-00605-5
Jing Zhang, J Dylan Weissenkampen, Rachel L Kember, Jakob Grove, Anders D Børglum, Elise B Robinson, Edward S Brodkin, Laura Almasy, Maja Bucan, Ronnie Sebro

Background: Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in phenotypically defined autism subgroups [e.g., autism with and without intellectually disability (ID)]. It is also unclear what proportion of the phenotypic AM can be explained by the genetic similarity between parents of children with an autism diagnosis, and the consequences of AM on the genetic structure of the population.

Methods: To address these questions, we analyzed two family-based autism collections: the Simons Foundation Powering Autism Research for Knowledge (SPARK) (1575 families) and the Simons Simplex Collection (SSC) (2283 families).

Results: We found a similar degree of phenotypic and ancestry-related AM in parents of children with an autism diagnosis regardless of the presence of ID. We did not find evidence of AM for autism based on autism polygenic scores (PGS) (at a threshold of |r|> 0.1). The adjustment of ancestry-related AM or autism PGS accounted for only 0.3-4% of the fractional change in the estimate of the phenotypic AM. The ancestry-related AM introduced higher long-range linkage disequilibrium (LD) between single nucleotide polymorphisms (SNPs) on different chromosomes that are highly ancestry-informative compared to SNPs that are less ancestry-informative (D2 on the order of 1 × 10-5).

Limitations: We only analyzed participants of European ancestry, limiting the generalizability of our results to individuals of non-European ancestry. SPARK and SSC were both multicenter studies. Therefore, there could be ancestry-related AM in SPARK and SSC due to geographic stratification. The study participants from each site were unknown, so we were unable to evaluate for geographic stratification.

Conclusions: This study showed similar patterns of AM in autism with and without ID, and demonstrated that the common genetic influences of autism are likely relevant to both autism groups. The adjustment of ancestry-related AM and autism PGS accounted for < 5% of the fractional change in the estimate of the phenotypic AM. Future studies are needed to evaluate if the small increase of long-range LD induced by ancestry-related AM has impact on the downstream analysis.

背景:在包括自闭症在内的几种神经精神特征中,都发现了正向同配(AM)现象。然而,在表型定义的自闭症亚群(如有智力障碍(ID)和无智力障碍(ID)的自闭症)中,AM 的模式是否有所不同,目前尚不清楚。此外,还不清楚自闭症诊断儿童父母之间的遗传相似性可以解释表型AM的比例,以及AM对人群遗传结构的影响:为了解决这些问题,我们分析了两个以家庭为基础的自闭症资料库:西蒙斯基金会自闭症研究知识库(SPARK)(1575个家庭)和西蒙斯简单性资料库(SSC)(2283个家庭):结果:我们发现,无论是否存在 ID,自闭症患儿父母的表型和祖先相关 AM 的程度相似。根据自闭症多基因评分(PGS)(阈值|r|>0.1),我们没有发现自闭症AM的证据。与祖先相关的 AM 或自闭症 PGS 的调整仅占表型 AM 估计值分数变化的 0.3-4%。与祖先相关AM相比,祖先相关性较高的不同染色体上的单核苷酸多态性(SNPs)与祖先相关性较低的SNPs之间的长程连锁不平衡(LD)较高(D2约为1×10-5):我们只分析了欧洲血统的参与者,这限制了我们的结果对非欧洲血统个体的普适性。SPARK 和 SSC 都是多中心研究。因此,在SPARK和SSC中,由于地域分层,可能存在与祖先相关的AM。每个研究地点的研究参与者情况不明,因此我们无法对地域分层进行评估:本研究显示,有 ID 和无 ID 的自闭症患者的 AM 模式相似,并证明自闭症的共同遗传影响因素可能与这两个自闭症群体相关。通过调整与祖先相关的 AM 和自闭症 PGS,我们得出了以下结论
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引用次数: 0
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Molecular Autism
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