Pub Date : 2024-01-31DOI: 10.1186/s13229-024-00588-3
Ozge Oztan, Laura A Del Rosso, Sierra M Simmons, Duyen K K Nguyen, Catherine F Talbot, John P Capitanio, Joseph P Garner, Karen J Parker
Background: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD.
Methods: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models.
Results: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found.
Limitations: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores.
Conclusions: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD.
{"title":"Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not?","authors":"Ozge Oztan, Laura A Del Rosso, Sierra M Simmons, Duyen K K Nguyen, Catherine F Talbot, John P Capitanio, Joseph P Garner, Karen J Parker","doi":"10.1186/s13229-024-00588-3","DOIUrl":"10.1186/s13229-024-00588-3","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD.</p><p><strong>Methods: </strong>Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models.</p><p><strong>Results: </strong>Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found.</p><p><strong>Limitations: </strong>This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores.</p><p><strong>Conclusions: </strong>Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"8"},"PeriodicalIF":6.3,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10829375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642504","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}
SHANK3 gene is a highly replicated causative gene for autism spectrum disorder and has been well characterized in multiple Shank3 mutant rodent models. When compared to rodents, domestic dogs are excellent animal models in which to study social cognition as they closely interact with humans and exhibit similar social behaviors. Using CRISPR/Cas9 editing, we recently generated a dog model carrying Shank3 mutations, which displayed a spectrum of autism-like behaviors, such as social impairment and heightened anxiety. However, the neural mechanism underlying these abnormal behaviors remains to be identified. We used Shank3 mutant dog models to examine possible relationships between Shank3 mutations and neuronal dysfunction. We studied electrophysiological properties and the synaptic transmission of pyramidal neurons from acute brain slices of the prefrontal cortex (PFC). We also examined dendrite elaboration and dendritic spine morphology in the PFC using biocytin staining and Golgi staining. We analyzed the postsynaptic density using electron microscopy. We established a protocol for the electrophysiological recording of canine brain slices and revealed that excitatory synaptic transmission onto PFC layer 2/3 pyramidal neurons in Shank3 heterozygote dogs was impaired, and this was accompanied by reduced dendrite complexity and spine density when compared to wild-type dogs. Postsynaptic density structures were also impaired in Shank3 mutants; however, pyramidal neurons exhibited hyperexcitability. Causal links between impaired PFC pyramidal neuron function and behavioral alterations remain unclear. Further experiments such as manipulating PFC neuronal activity or restoring synaptic transmission in Shank3 mutant dogs are required to assess PFC roles in altered social behaviors. Our study demonstrated the feasibility of using canine brain slices as a model system to study neuronal circuitry and disease. Shank3 haploinsufficiency causes morphological and functional abnormalities in PFC pyramidal neurons, supporting the notion that Shank3 mutant dogs are new and valid animal models for autism research.
{"title":"Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs","authors":"Feipeng Zhu, Qi Shi, Yong-hui Jiang, Yong Q. Zhang, Hui Zhao","doi":"10.1186/s13229-024-00587-4","DOIUrl":"https://doi.org/10.1186/s13229-024-00587-4","url":null,"abstract":"SHANK3 gene is a highly replicated causative gene for autism spectrum disorder and has been well characterized in multiple Shank3 mutant rodent models. When compared to rodents, domestic dogs are excellent animal models in which to study social cognition as they closely interact with humans and exhibit similar social behaviors. Using CRISPR/Cas9 editing, we recently generated a dog model carrying Shank3 mutations, which displayed a spectrum of autism-like behaviors, such as social impairment and heightened anxiety. However, the neural mechanism underlying these abnormal behaviors remains to be identified. We used Shank3 mutant dog models to examine possible relationships between Shank3 mutations and neuronal dysfunction. We studied electrophysiological properties and the synaptic transmission of pyramidal neurons from acute brain slices of the prefrontal cortex (PFC). We also examined dendrite elaboration and dendritic spine morphology in the PFC using biocytin staining and Golgi staining. We analyzed the postsynaptic density using electron microscopy. We established a protocol for the electrophysiological recording of canine brain slices and revealed that excitatory synaptic transmission onto PFC layer 2/3 pyramidal neurons in Shank3 heterozygote dogs was impaired, and this was accompanied by reduced dendrite complexity and spine density when compared to wild-type dogs. Postsynaptic density structures were also impaired in Shank3 mutants; however, pyramidal neurons exhibited hyperexcitability. Causal links between impaired PFC pyramidal neuron function and behavioral alterations remain unclear. Further experiments such as manipulating PFC neuronal activity or restoring synaptic transmission in Shank3 mutant dogs are required to assess PFC roles in altered social behaviors. Our study demonstrated the feasibility of using canine brain slices as a model system to study neuronal circuitry and disease. Shank3 haploinsufficiency causes morphological and functional abnormalities in PFC pyramidal neurons, supporting the notion that Shank3 mutant dogs are new and valid animal models for autism research.","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"11 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139645943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-23DOI: 10.1186/s13229-023-00581-2
Bradley J Wilkes, Derek B Archer, Anna L Farmer, Carly Bass, Hannah Korah, David E Vaillancourt, Mark H Lewis
Background: Restricted repetitive behavior (RRB) is one of two behavioral domains required for the diagnosis of autism spectrum disorder (ASD). Neuroimaging is widely used to study brain alterations associated with ASD and the domain of social and communication deficits, but there has been less work regarding brain alterations linked to RRB.
Methods: We utilized neuroimaging data from the National Institute of Mental Health Data Archive to assess basal ganglia and cerebellum structure in a cohort of children and adolescents with ASD compared to typically developing (TD) controls. We evaluated regional gray matter volumes from T1-weighted anatomical scans and assessed diffusion-weighted scans to quantify white matter microstructure with free-water imaging. We also investigated the interaction of biological sex and ASD diagnosis on these measures, and their correlation with clinical scales of RRB.
Results: Individuals with ASD had significantly lower free-water corrected fractional anisotropy (FAT) and higher free-water (FW) in cortico-basal ganglia white matter tracts. These microstructural differences did not interact with biological sex. Moreover, both FAT and FW in basal ganglia white matter tracts significantly correlated with measures of RRB. In contrast, we found no significant difference in basal ganglia or cerebellar gray matter volumes.
Limitations: The basal ganglia and cerebellar regions in this study were selected due to their hypothesized relevance to RRB. Differences between ASD and TD individuals that may occur outside the basal ganglia and cerebellum, and their potential relationship to RRB, were not evaluated.
Conclusions: These new findings demonstrate that cortico-basal ganglia white matter microstructure is altered in ASD and linked to RRB. FW in cortico-basal ganglia and intra-basal ganglia white matter was more sensitive to group differences in ASD, whereas cortico-basal ganglia FAT was more closely linked to RRB. In contrast, basal ganglia and cerebellar volumes did not differ in ASD. There was no interaction between ASD diagnosis and sex-related differences in brain structure. Future diffusion imaging investigations in ASD may benefit from free-water estimation and correction in order to better understand how white matter is affected in ASD, and how such measures are linked to RRB.
{"title":"Cortico-basal ganglia white matter microstructure is linked to restricted repetitive behavior in autism spectrum disorder.","authors":"Bradley J Wilkes, Derek B Archer, Anna L Farmer, Carly Bass, Hannah Korah, David E Vaillancourt, Mark H Lewis","doi":"10.1186/s13229-023-00581-2","DOIUrl":"10.1186/s13229-023-00581-2","url":null,"abstract":"<p><strong>Background: </strong>Restricted repetitive behavior (RRB) is one of two behavioral domains required for the diagnosis of autism spectrum disorder (ASD). Neuroimaging is widely used to study brain alterations associated with ASD and the domain of social and communication deficits, but there has been less work regarding brain alterations linked to RRB.</p><p><strong>Methods: </strong>We utilized neuroimaging data from the National Institute of Mental Health Data Archive to assess basal ganglia and cerebellum structure in a cohort of children and adolescents with ASD compared to typically developing (TD) controls. We evaluated regional gray matter volumes from T1-weighted anatomical scans and assessed diffusion-weighted scans to quantify white matter microstructure with free-water imaging. We also investigated the interaction of biological sex and ASD diagnosis on these measures, and their correlation with clinical scales of RRB.</p><p><strong>Results: </strong>Individuals with ASD had significantly lower free-water corrected fractional anisotropy (FA<sub>T</sub>) and higher free-water (FW) in cortico-basal ganglia white matter tracts. These microstructural differences did not interact with biological sex. Moreover, both FA<sub>T</sub> and FW in basal ganglia white matter tracts significantly correlated with measures of RRB. In contrast, we found no significant difference in basal ganglia or cerebellar gray matter volumes.</p><p><strong>Limitations: </strong>The basal ganglia and cerebellar regions in this study were selected due to their hypothesized relevance to RRB. Differences between ASD and TD individuals that may occur outside the basal ganglia and cerebellum, and their potential relationship to RRB, were not evaluated.</p><p><strong>Conclusions: </strong>These new findings demonstrate that cortico-basal ganglia white matter microstructure is altered in ASD and linked to RRB. FW in cortico-basal ganglia and intra-basal ganglia white matter was more sensitive to group differences in ASD, whereas cortico-basal ganglia FA<sub>T</sub> was more closely linked to RRB. In contrast, basal ganglia and cerebellar volumes did not differ in ASD. There was no interaction between ASD diagnosis and sex-related differences in brain structure. Future diffusion imaging investigations in ASD may benefit from free-water estimation and correction in order to better understand how white matter is affected in ASD, and how such measures are linked to RRB.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"6"},"PeriodicalIF":6.3,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10804694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521298","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}
Pub Date : 2024-01-23DOI: 10.1186/s13229-024-00585-6
Hangnyoung Choi, Jae Han Kim, Hee Sang Yang, Jong Yeob Kim, Samuele Cortese, Lee Smith, Ai Koyanagi, Elena Dragioti, Joaquim Radua, Paolo Fusar-Poli, Jae Il Shin, Keun-Ah Cheon, Marco Solmi
Background: Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions.
Methods: We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention.
Results: Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g - 0.857, 95% CI - 1.263 to - 0.451, certainty of evidence: high) and aripiprazole (Hedges' g - 0.559, 95% CI - 0.767 to - 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g - 0.893, 95% CI - 1.184 to - 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each.
Limitations: First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants.
Conclusions: Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.
背景:针对自闭症谱系障碍(ASD)易激惹性的许多干预措施已得到研究。我们的目的是评估针对自闭症谱系障碍易激惹性的药物和非药物干预措施的效果,对符合条件的干预措施不作任何限制:我们系统地检索了 PubMed/MEDLINE、Scopus 和 Web of Science,直至 2023 年 4 月 15 日。我们纳入了采用平行设计的随机对照试验(RCT),这些试验研究了治疗任何年龄段 ASD 患者易激惹性的干预措施的疗效,对符合条件的干预措施没有任何限制。我们将评估的干预措施分为以下几类:药物单一疗法、利培酮加辅助疗法与利培酮单一疗法、非药物干预和饮食干预。我们使用 Cochrane 工具评估了每项研究的偏倚风险,并使用 GRADE 方法评估了每项荟萃分析干预措施的证据确定性:在 5640 篇参考文献中,我们发现了 60 篇符合条件的文章,涉及 45 种不同的干预措施,包括 3531 名参与者,其中 80.9% 为男性(平均年龄 [SD] = 8.79 [3.85])。在单一药物疗法中,利培酮(Hedges' g - 0.857,95% CI - 1.263 to - 0.451,证据确定性:高)和阿立哌唑(Hedges' g - 0.559,95% CI - 0.767 to - 0.351,证据确定性:高)的疗效优于安慰剂。在非药物干预中,家长培训(Hedges' g - 0.893,95% CI - 1.184 to - 0.602,证据确定性:中)的效果显著。在利培酮+辅助疗法和膳食补充剂中,没有一项荟萃分析干预措施产生了显著效果。然而,在利培酮的辅助治疗中,几种新型分子药物的疗效优于利培酮单药治疗,但每种药物均来自一项研究:局限性:首先,测量ASD易激惹性的工具多种多样,这可能会导致结果的异质性。其次,每种干预措施的荟萃分析仅包括少量研究和参与者:结论:药物干预中只有利培酮、阿立哌唑和非药物干预中的家长培训可用于治疗ASD的易激惹性。作为利培酮的辅助治疗,几种新型疗法显示出了良好的效果,但还需要进一步的RCT研究来验证研究结果。试验注册PROSPERO,CRD42021243965。
{"title":"Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment.","authors":"Hangnyoung Choi, Jae Han Kim, Hee Sang Yang, Jong Yeob Kim, Samuele Cortese, Lee Smith, Ai Koyanagi, Elena Dragioti, Joaquim Radua, Paolo Fusar-Poli, Jae Il Shin, Keun-Ah Cheon, Marco Solmi","doi":"10.1186/s13229-024-00585-6","DOIUrl":"10.1186/s13229-024-00585-6","url":null,"abstract":"<p><strong>Background: </strong>Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions.</p><p><strong>Methods: </strong>We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention.</p><p><strong>Results: </strong>Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g - 0.857, 95% CI - 1.263 to - 0.451, certainty of evidence: high) and aripiprazole (Hedges' g - 0.559, 95% CI - 0.767 to - 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g - 0.893, 95% CI - 1.184 to - 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each.</p><p><strong>Limitations: </strong>First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants.</p><p><strong>Conclusions: </strong>Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"7"},"PeriodicalIF":6.3,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542774","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}
Background: Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability.
Methods: We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells.
Results: Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells.
Limitations: Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants.
Conclusions: Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS.
背景:Helsmoortel-Van der Aa 综合征(HVDAS)是一种罕见的遗传性疾病,由活动依赖性神经保护基因(ADNP)变异引起,因此也被称为 ADNP 综合征。ADNP 是一种多任务蛋白,具有转录因子的功能,在大脑发育过程中起着至关重要的作用。此外,ADNP变异已被确定为自闭症谱系障碍(ASD)和智力障碍最常见的单基因病因之一:方法:我们收集了15名中国儿童患者,鉴定了ADNP基因编码区的13个变体,并评估了他们的临床表型。此外,我们还构建了相应的ADNP变体,并对其在人HEK293T和SH-SY5Y细胞中的蛋白表达和亚细胞定位进行了Western印迹和免疫荧光分析:我们的研究对15名ADNP变异型患儿的临床表现进行了全面分析,发现了包括全面发育迟缓、智力障碍、ASD、面部畸形和其他特征在内的广泛症状。研究人员还进行了体外研究,以检测ADNP变异体的表达情况。两个病例出现了错义变异,其余病例则出现了无义或框移位变异,导致体外过表达系统中出现截短突变体。在 HEK293T 细胞中,过表达的野生型 ADNP 和所有不同的突变体都被限制在细胞核中;然而,野生型 ADNP 形成的独特核体模式被突变体蛋白部分或完全破坏。此外,ADNP核定位信号(NLS)上p.Y719*的两个变体破坏了核表达模式,在SH-SY5Y细胞中主要表现为胞质表达:我们的研究受到样本量相对较小以及缺乏纵向框架来监测患者病情随时间推移的进展等因素的限制。此外,我们缺乏体内证据来进一步说明已确定的 ADNP 变异的因果影响:我们的研究报告了中国人群中首个 HVDAS 患者队列,并提供了系统的临床表现和实验室检查。此外,我们还发现了多种基因变异,并在体外进行了验证。我们的研究结果为了解与 HVDAS 相关的多种基因变异提供了宝贵的见解。
{"title":"Clinical impact and in vitro characterization of ADNP variants in pediatric patients.","authors":"Chuanhui Ge, Yuxin Tian, Chunchun Hu, Lianni Mei, Dongyun Li, Ping Dong, Ying Zhang, Huiping Li, Daijing Sun, Wenzhu Peng, Xiu Xu, Yan Jiang, Qiong Xu","doi":"10.1186/s13229-024-00584-7","DOIUrl":"10.1186/s13229-024-00584-7","url":null,"abstract":"<p><strong>Background: </strong>Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability.</p><p><strong>Methods: </strong>We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells.</p><p><strong>Results: </strong>Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells.</p><p><strong>Limitations: </strong>Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants.</p><p><strong>Conclusions: </strong>Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"5"},"PeriodicalIF":6.3,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10804707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521370","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}
Pub Date : 2024-01-17DOI: 10.1186/s13229-023-00575-0
Nisha E. Mathew, Delyse McCaffrey, Adam K. Walker, Kylie-Ann Mallitt, Anne Masi, Margaret J. Morris, Chee Y. Ooi
Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract. We extracted data from case–control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279). There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]). All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults. There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.
{"title":"The search for gastrointestinal inflammation in autism: a systematic review and meta-analysis of non-invasive gastrointestinal markers","authors":"Nisha E. Mathew, Delyse McCaffrey, Adam K. Walker, Kylie-Ann Mallitt, Anne Masi, Margaret J. Morris, Chee Y. Ooi","doi":"10.1186/s13229-023-00575-0","DOIUrl":"https://doi.org/10.1186/s13229-023-00575-0","url":null,"abstract":"Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract. We extracted data from case–control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279). There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]). All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults. There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"73 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139481396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-17DOI: 10.1186/s13229-024-00583-8
Ting Mei, Alberto Llera, Natalie J Forde, Daan van Rooij, Dorothea L Floris, Christian F Beckmann, Jan K Buitelaar
Background: Autism spectrum disorder (henceforth autism) is a complex neurodevelopmental condition associated with differences in gray matter (GM) volume covariations, as reported in our previous study of the Longitudinal European Autism Project (LEAP) data. To make progress on the identification of potential neural markers and to validate the robustness of our previous findings, we aimed to replicate our results using data from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) autism working group.
Methods: We studied 781 autistic and 927 non-autistic individuals (6-30 years, IQ ≥ 50), across 37 sites. Voxel-based morphometry was used to quantify GM volume as before. Subsequently, we used spatial maps of the two autism-related independent components (ICs) previously identified in the LEAP sample as templates for regression analyses to separately estimate the ENIGMA-participant loadings to each of these two ICs. Between-group differences in participants' loadings on each component were examined, and we additionally investigated the relation between participant loadings and autistic behaviors within the autism group.
Results: The two components of interest, previously identified in the LEAP dataset, showed significant between-group differences upon regressions into the ENIGMA cohort. The associated brain patterns were consistent with those found in the initial identification study. The first IC was primarily associated with increased volumes of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and caudate in the autism group relative to the control group (β = 0.129, p = 0.013). The second IC was related to increased volumes of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to non-autistic individuals (β = 0.116, p = 0.024). However, when accounting for the site-by-group interaction effect, no significant main effect of the group can be identified (p > 0.590). We did not find significant univariate association between the brain measures and behavior in autism (p > 0.085).
Limitations: The distributions of age, IQ, and sex between LEAP and ENIGMA are statistically different from each other. Owing to limited access to the behavioral data of the autism group, we were unable to further our understanding of the neural basis of behavioral dimensions of the sample.
Conclusions: The current study is unable to fully replicate the autism-related brain patterns from LEAP in the ENIGMA cohort. The diverse group effects across ENIGMA sites demonstrate the challenges of generalizing the average findings of the GM covariation patterns to a large-scale cohort integrated retrospectively from multiple studies. Further analyses need to be conducted to gain additional insights into the generalizability of these two GM covariation patterns.
{"title":"Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort.","authors":"Ting Mei, Alberto Llera, Natalie J Forde, Daan van Rooij, Dorothea L Floris, Christian F Beckmann, Jan K Buitelaar","doi":"10.1186/s13229-024-00583-8","DOIUrl":"10.1186/s13229-024-00583-8","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (henceforth autism) is a complex neurodevelopmental condition associated with differences in gray matter (GM) volume covariations, as reported in our previous study of the Longitudinal European Autism Project (LEAP) data. To make progress on the identification of potential neural markers and to validate the robustness of our previous findings, we aimed to replicate our results using data from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) autism working group.</p><p><strong>Methods: </strong>We studied 781 autistic and 927 non-autistic individuals (6-30 years, IQ ≥ 50), across 37 sites. Voxel-based morphometry was used to quantify GM volume as before. Subsequently, we used spatial maps of the two autism-related independent components (ICs) previously identified in the LEAP sample as templates for regression analyses to separately estimate the ENIGMA-participant loadings to each of these two ICs. Between-group differences in participants' loadings on each component were examined, and we additionally investigated the relation between participant loadings and autistic behaviors within the autism group.</p><p><strong>Results: </strong>The two components of interest, previously identified in the LEAP dataset, showed significant between-group differences upon regressions into the ENIGMA cohort. The associated brain patterns were consistent with those found in the initial identification study. The first IC was primarily associated with increased volumes of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and caudate in the autism group relative to the control group (β = 0.129, p = 0.013). The second IC was related to increased volumes of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to non-autistic individuals (β = 0.116, p = 0.024). However, when accounting for the site-by-group interaction effect, no significant main effect of the group can be identified (p > 0.590). We did not find significant univariate association between the brain measures and behavior in autism (p > 0.085).</p><p><strong>Limitations: </strong>The distributions of age, IQ, and sex between LEAP and ENIGMA are statistically different from each other. Owing to limited access to the behavioral data of the autism group, we were unable to further our understanding of the neural basis of behavioral dimensions of the sample.</p><p><strong>Conclusions: </strong>The current study is unable to fully replicate the autism-related brain patterns from LEAP in the ENIGMA cohort. The diverse group effects across ENIGMA sites demonstrate the challenges of generalizing the average findings of the GM covariation patterns to a large-scale cohort integrated retrospectively from multiple studies. Further analyses need to be conducted to gain additional insights into the generalizability of these two GM covariation patterns.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"3"},"PeriodicalIF":6.2,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477366","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}
Pub Date : 2024-01-10DOI: 10.1186/s13229-024-00582-9
Benedikt P Langenbach, Dominik Grotegerd, Peter C R Mulders, Indira Tendolkar, Jasper van Oort, Fleur Duyser, Philip van Eijndhoven, Janna N Vrijsen, Udo Dannlowski, Zarah Kampmann, Katja Koelkebeck
Background: Autistic and non-autistic individuals often differ in how they perceive and show emotions, especially in their ability and inclination to infer other people's feelings from subtle cues like facial expressions. Prominent theories of autism have suggested that these differences stem from alterations in amygdala functioning and that amygdala hypoactivation causes problems with emotion recognition. Thus far, however, empirical investigations of this hypothesis have yielded mixed results and largely relied on relatively small samples.
Methods: In a sample of 72 autistic and 79 non-autistic participants, we conducted a study in which we used the Hariri paradigm to test whether amygdala activation during emotional face processing is altered in autism spectrum disorder, and whether common mental disorders like depression, ADHD or anxiety disorders influence any potential alterations in activation patterns.
Results: We found no evidence for differences in amygdala activation, neither when comparing autistic and non-autistic participants, nor when taking into account mental disorders or the overall level of functional impairment.
Limitations: Because we used one basic emotion processing task in a Dutch sample, results might not generalise to other tasks and other populations.
Conclusions: Our results challenge the view that autistic and non-autistic processing of emotional faces in the amygdala is vastly different and call for a more nuanced view of differences between non-autistic and autistic emotion processing.
{"title":"Autistic and non-autistic individuals show the same amygdala activity during emotional face processing.","authors":"Benedikt P Langenbach, Dominik Grotegerd, Peter C R Mulders, Indira Tendolkar, Jasper van Oort, Fleur Duyser, Philip van Eijndhoven, Janna N Vrijsen, Udo Dannlowski, Zarah Kampmann, Katja Koelkebeck","doi":"10.1186/s13229-024-00582-9","DOIUrl":"10.1186/s13229-024-00582-9","url":null,"abstract":"<p><strong>Background: </strong>Autistic and non-autistic individuals often differ in how they perceive and show emotions, especially in their ability and inclination to infer other people's feelings from subtle cues like facial expressions. Prominent theories of autism have suggested that these differences stem from alterations in amygdala functioning and that amygdala hypoactivation causes problems with emotion recognition. Thus far, however, empirical investigations of this hypothesis have yielded mixed results and largely relied on relatively small samples.</p><p><strong>Methods: </strong>In a sample of 72 autistic and 79 non-autistic participants, we conducted a study in which we used the Hariri paradigm to test whether amygdala activation during emotional face processing is altered in autism spectrum disorder, and whether common mental disorders like depression, ADHD or anxiety disorders influence any potential alterations in activation patterns.</p><p><strong>Results: </strong>We found no evidence for differences in amygdala activation, neither when comparing autistic and non-autistic participants, nor when taking into account mental disorders or the overall level of functional impairment.</p><p><strong>Limitations: </strong>Because we used one basic emotion processing task in a Dutch sample, results might not generalise to other tasks and other populations.</p><p><strong>Conclusions: </strong>Our results challenge the view that autistic and non-autistic processing of emotional faces in the amygdala is vastly different and call for a more nuanced view of differences between non-autistic and autistic emotion processing.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"2"},"PeriodicalIF":6.2,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10782610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417488","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}
Pub Date : 2024-01-04DOI: 10.1186/s13229-023-00579-w
Fumiyo Oshima, Toru Takahashi, Masaki Tamura, Siqing Guan, Mikuko Seto, Laura Hull, William Mandy, Kenji Tsuchiya, Eiji Shimizu
To examine the relationship between social camouflage and mental health in Japanese autistic adults and make an international comparison with a sample from the UK. This study analysed secondary data of participants with a self-reported diagnosis of autism from Japan (N = 210; 123 men and 87 women) and the UK (N = 305; 181 women, 104, men, and 18 nonbinary). The relationships between the quadratic term of the Camouflaging Autistic Traits Questionnaire and mental health scales, including depression and anxiety, were assessed. The UK sample showed linear relationships, whereas the Japanese sample showed significant nonlinear relationships. The quadratic terms of the Camouflaging Autistic Traits Questionnaire slightly explained generalised anxiety (β = .168, p = .007), depression (β = .121, p = .045), and well-being (β = − .127, p = .028). However, they did not explain the association between social anxiety and the Camouflaging Autistic Traits Questionnaire. Participants had self-reported diagnoses, and while the autism-spectrum quotient provides a cut-off value for screening, it does not enable confirming diagnoses. Mean scores of the Japanese version of the Camouflaging Autistic Traits Questionnaire were lower as compared to the original CAT-Q, which implies that the social camouflage strategy types used by autistic people in Japan and the UK could differ. The cross-sectional design limits causal inferences. In the UK, more social camouflage was associated with poorer mental health scores, whereas too little or too much social camouflage was associated with a low mental health score in Japan. The Japanese population is seemingly less aware of and educated on autistic characteristics and considers ‘average’ behaviour a good thing. This could influence Japanese autistic people’s social camouflage use, differing from that of autistic people in the UK. The differences in the relationship between social camouflage and mental health between Japan and the UK could be associated with national-level divergence regarding the culture of autism.
{"title":"The association between social camouflage and mental health among autistic people in Japan and the UK: a cross-cultural study","authors":"Fumiyo Oshima, Toru Takahashi, Masaki Tamura, Siqing Guan, Mikuko Seto, Laura Hull, William Mandy, Kenji Tsuchiya, Eiji Shimizu","doi":"10.1186/s13229-023-00579-w","DOIUrl":"https://doi.org/10.1186/s13229-023-00579-w","url":null,"abstract":"To examine the relationship between social camouflage and mental health in Japanese autistic adults and make an international comparison with a sample from the UK. This study analysed secondary data of participants with a self-reported diagnosis of autism from Japan (N = 210; 123 men and 87 women) and the UK (N = 305; 181 women, 104, men, and 18 nonbinary). The relationships between the quadratic term of the Camouflaging Autistic Traits Questionnaire and mental health scales, including depression and anxiety, were assessed. The UK sample showed linear relationships, whereas the Japanese sample showed significant nonlinear relationships. The quadratic terms of the Camouflaging Autistic Traits Questionnaire slightly explained generalised anxiety (β = .168, p = .007), depression (β = .121, p = .045), and well-being (β = − .127, p = .028). However, they did not explain the association between social anxiety and the Camouflaging Autistic Traits Questionnaire. Participants had self-reported diagnoses, and while the autism-spectrum quotient provides a cut-off value for screening, it does not enable confirming diagnoses. Mean scores of the Japanese version of the Camouflaging Autistic Traits Questionnaire were lower as compared to the original CAT-Q, which implies that the social camouflage strategy types used by autistic people in Japan and the UK could differ. The cross-sectional design limits causal inferences. In the UK, more social camouflage was associated with poorer mental health scores, whereas too little or too much social camouflage was associated with a low mental health score in Japan. The Japanese population is seemingly less aware of and educated on autistic characteristics and considers ‘average’ behaviour a good thing. This could influence Japanese autistic people’s social camouflage use, differing from that of autistic people in the UK. The differences in the relationship between social camouflage and mental health between Japan and the UK could be associated with national-level divergence regarding the culture of autism.","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139094571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-18DOI: 10.1186/s13229-023-00580-3
Doha Bemmouna, Amine Lagzouli, Luisa Weiner
Emotion dysregulation (ED) is a core symptom of borderline personality disorder (BPD), whose aetiology has been attributed to biosocial factors. In autism spectrum condition (ASC), although ED is prevalent and is associated with decreased well-being (e.g. self-harm, suicidality), it has been understudied, especially in adults. It is therefore crucial to further understand ED in autistic adults to improve its treatment. Our study investigates ED, its behavioural correlates (e.g. self-harm, suicidality) and biosocial predictors in autistic adults relative to BPD and nonclinical controls (NC). A total of 724 participants (ASC = 154; BPD = 111; NC = 459) completed 11 self-reported questionnaires assessing ED, ASC and BPD traits, co-occurring disorders, alexithymia, emotional vulnerability and invalidating experiences (e.g. bullying, autistic camouflaging). The occurrence of ED behavioural correlates (i.e. self-harm, history of suicide attempts, and psychiatric hospitalizations) was collected. In addition, between-groups analyses, linear regressions and machine learning (ML) models were used to identify ED predictors in each group. ED and its behavioural correlates were higher in ASC compared to NC, but milder than in BPD. While gender did not predict ED scores, autistic women had increased risk factors to ED, including sexual abuse and camouflaging. Interestingly, BPD traits, emotional vulnerability and alexithymia strongly predicted ED scores across the groups. Using ML models, sensory sensitivity and autistic camouflaging were associated with ED in ASC, and ADHD symptoms with ED in BPD. ASC and BPD diagnoses were self-reported, which did not allow us to check their accuracy. Additionally, we did not explore the transactional and the moderating/mediating relationships between the different variables. Moreover, our research is cross-sectional and cannot draw conclusions regarding the direction and causality of relationships between ED and other clinical dimensions. ED and its behavioural correlates are heightened in BPD compared to ASC and nonclinical controls. In the ASC group, there were no gender differences in ED, despite the heightened exposure of autistic women to ED risk factors. BPD traits, emotional vulnerability, and alexithymia are core to ED regardless of diagnosis. Although less central, sensory sensitivity and autistic camouflaging seem to be specific predictors of ED in autistic adults.
情绪失调(ED)是边缘型人格障碍(BPD)的核心症状,其病因归结于生物社会因素。在自闭症谱系障碍(ASC)中,虽然情绪失调很普遍,而且与幸福感下降(如自残、自杀)有关,但对它的研究一直不足,尤其是在成年人中。因此,进一步了解自闭症成人的 ED 情况以改进治疗至关重要。我们的研究调查了自闭症成年人的 ED、其行为相关性(如自残、自杀)和生物社会预测因素(相对于 BPD 和非临床对照组 (NC))。共有724名参与者(ASC=154人;BPD=111人;NC=459人)完成了11份自我报告问卷,评估了ED、ASC和BPD特质、共患疾病、自闭症、情感脆弱性和无效经历(如欺凌、自闭症伪装)。此外,还收集了发生自闭症行为的相关因素(即自残、自杀未遂和精神病住院史)。此外,还采用了组间分析、线性回归和机器学习(ML)模型来确定各组的 ED 预测因素。与NC相比,ASC的ED及其行为相关性更高,但比BPD更轻。虽然性别并不能预测 ED 的得分,但自闭症女性的 ED 风险因素有所增加,包括性虐待和伪装。有趣的是,BPD特质、情感脆弱性和自闭症对各组的ED得分都有很强的预测作用。使用ML模型,感觉敏感性和自闭伪装与ASC的ED有关,而ADHD症状与BPD的ED有关。ASC和BPD的诊断都是自我报告的,因此我们无法检查其准确性。此外,我们没有探讨不同变量之间的交易关系和调节/中介关系。此外,我们的研究是横断面的,无法就 ED 与其他临床维度之间的关系的方向和因果关系得出结论。与 ASC 和非临床对照组相比,BPD 患者的 ED 及其行为相关性更强。在 ASC 组中,尽管自闭症女性更容易受到 ED 风险因素的影响,但她们的 ED 没有性别差异。无论诊断结果如何,BPD 特征、情绪脆弱性和自闭症都是 ED 的核心因素。感官敏感性和自闭症伪装似乎是自闭症成人发生 ED 的特异性预测因素,但这两点并不那么重要。
{"title":"The biosocial correlates and predictors of emotion dysregulation in autistic adults compared to borderline personality disorder and nonclinical controls","authors":"Doha Bemmouna, Amine Lagzouli, Luisa Weiner","doi":"10.1186/s13229-023-00580-3","DOIUrl":"https://doi.org/10.1186/s13229-023-00580-3","url":null,"abstract":"Emotion dysregulation (ED) is a core symptom of borderline personality disorder (BPD), whose aetiology has been attributed to biosocial factors. In autism spectrum condition (ASC), although ED is prevalent and is associated with decreased well-being (e.g. self-harm, suicidality), it has been understudied, especially in adults. It is therefore crucial to further understand ED in autistic adults to improve its treatment. Our study investigates ED, its behavioural correlates (e.g. self-harm, suicidality) and biosocial predictors in autistic adults relative to BPD and nonclinical controls (NC). A total of 724 participants (ASC = 154; BPD = 111; NC = 459) completed 11 self-reported questionnaires assessing ED, ASC and BPD traits, co-occurring disorders, alexithymia, emotional vulnerability and invalidating experiences (e.g. bullying, autistic camouflaging). The occurrence of ED behavioural correlates (i.e. self-harm, history of suicide attempts, and psychiatric hospitalizations) was collected. In addition, between-groups analyses, linear regressions and machine learning (ML) models were used to identify ED predictors in each group. ED and its behavioural correlates were higher in ASC compared to NC, but milder than in BPD. While gender did not predict ED scores, autistic women had increased risk factors to ED, including sexual abuse and camouflaging. Interestingly, BPD traits, emotional vulnerability and alexithymia strongly predicted ED scores across the groups. Using ML models, sensory sensitivity and autistic camouflaging were associated with ED in ASC, and ADHD symptoms with ED in BPD. ASC and BPD diagnoses were self-reported, which did not allow us to check their accuracy. Additionally, we did not explore the transactional and the moderating/mediating relationships between the different variables. Moreover, our research is cross-sectional and cannot draw conclusions regarding the direction and causality of relationships between ED and other clinical dimensions. ED and its behavioural correlates are heightened in BPD compared to ASC and nonclinical controls. In the ASC group, there were no gender differences in ED, despite the heightened exposure of autistic women to ED risk factors. BPD traits, emotional vulnerability, and alexithymia are core to ED regardless of diagnosis. Although less central, sensory sensitivity and autistic camouflaging seem to be specific predictors of ED in autistic adults.","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"194 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138715656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}