搜索结果：Research in autism spectrum disorders

Is preimplantation genetic testing (PGT) associated with adverse perinatal outcome and early childhood health? Children born after PGT had comparable perinatal outcomes to children born after IVF/ICSI and comparable findings regarding early childhood health. PGT is offered to couples affected by monogenic disorders (PGT-M) or inherited chromosomal aberrations (PGT-SR), limiting the risk of transferring the disorder to the offspring. PGT, an invasive technique, requires genetic analysis of one or up to ten cells from the embryo and is combined with IVF or ICSI. Several studies, most of them small, have shown comparable results after PGT and IVF/ICSI concerning perinatal outcome. Only a few studies with limited samples have been published on PGT and childhood health. We performed a register-based study including all singletons born after PGT (n = 390) in Sweden during 1 January 1996-30 September 2019. Singletons born after PGT were compared with all singletons born after IVF/ICSI (n = 61 060) born during the same period of time and with a matched sample of singletons (n = 42 034) born after spontaneous conception selected from the Medical Birth Register. Perinatal outcomes, early childhood health, and maternal outcomes were compared between pregnancies after PGT and IVF/ICSI as well as between pregnancies after PGT and spontaneous conception. Primary outcomes were preterm birth (PTB) and low birthweight (LBW) whereas childhood morbidity was the secondary outcome. Data on women who went through PGT and gave birth were obtained from the local databases at the two PGT centres in Sweden, whereas data on IVF treatment for the IVF/ICSI group were obtained from the national IVF registers. These data were then cross-linked to national health registers; the Medical Birth Register, the Patient Register, and the Cause of Death Register. Logistic multivariable regression analysis and Cox proportional hazards models were performed with adjustment for relevant confounders. The mean follow-up time was 4.6 years for children born after PGT and 5.1 years for children born after spontaneous conception, whereas the mean follow-up time was 9.0 years for children born after IVF/ICSI. For perinatal outcomes, PTB occurred in 7.7% of children after PGT and in 7.3% of children after IVF/ICSI, whereas the rates were 4.9% and 5.2% for LBW (adjusted odds ratio (AOR) 1.22, 95% CI 0.82-1.81 and AOR 1.17, 95% CI 0.71-1.91, respectively). No differences were observed for birth defects. In comparison to spontaneous conception, children born after PGT had a higher risk for PTB (AOR 1.73, 95% CI 1.17-2.58). Regarding early childhood health, the absolute risk of asthma was 38/390 (9.7%) in children born after PGT and 6980/61 060 (11.4%) in children born after in IVF/ICSI, whereas the corresponding numbers were 34/390 (8.7%) and 7505/61 060 (12.3%) for allergic disorders. Following Cox proportional hazards models, no significant differences were found for these outcomes. Sepsis, hypothyroidism, attention deficit hyperactivity disorder, autism spectrum disorders, mental retardation, cerebral palsy, and epilepsy were diagnosed in a maximum of three PGT children. No PGT children died during the follow-up period. Regarding maternal outcomes, the rates of placenta praevia and caesarean delivery were significantly higher after PGT in comparison to spontaneous conception (AOR 6.46, 95% CI 3.38-12.37 and AOR 1.52, 95% CI 1.20-1.92, respectively), whereas no differences were seen comparing pregnancies after PGT and IVF/ICSI. The rather small sample size of children born after PGT made it impossible to adjust for all relevant confounders including fertilization method and culture duration. Moreover, the follow-up time was short for most of the children especially in the PGT group, probably lowering the absolute number of diagnoses in early childhood. The results are reassuring and indicate that the embryo biopsy itself has no adverse effect on the perinatal, early childhood, or maternal outcomes. Although the results are comparable to IVF/ICSI also regarding early childhood outcome, they should be taken with caution due to the low number of children with diagnoses and short follow-up time. Long-term follow-up studies on children born after PGT are scarce and should be conducted considering the invasiveness of the technique. The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (LUA/ALF 70940), the Board of National Specialised Medical Care at Sahlgrenska University Hospital and Hjalmar Svensson Research Foundation. There are no conflicts of interest to declare. N/A.

Individuals diagnosed with autism spectrum disorder (ASD) commonly experience difficulties maintaining social gaze with others during interactions. Although behavioral interventions targeted to promote social gaze in ASD are evident in the literature, to our knowledge, no review of the literature has been conducted to summarize and evaluate the evidence for these interventions. We reviewed and summarized behavioral intervention studies designed to promote social gaze in individuals diagnosed with ASD and other developmental disabilities published in English between 1977 and January 2022 using PsychINFO and PubMed databases. 41 studies met the inclusion criteria describing interventions conducted on 608 individuals. A variety of intervention strategies were employed to promote social gaze in these individuals including discrete trial instruction, prompting, modeling, and imitation. Most studies employed single-case research designs and reported successful outcomes, but limited data were available concerning the generalization, maintenance and social validity of these interventions. An increasing number of studies utilized technology-based procedures including computer application gameplay, gaze-contingent eye tracking devices and humanoid robots. The present review indicates that behavioral interventions can be successfully employed to promote social gaze in individuals with ASD and other developmental disabilities. However, future research is needed to establish the generalization, maintenance and social validity of these interventions. There are also important ethical issues to be addressed given the increasing divide between treatment advocates and proponents of the neurodiversity movement.

Neurodevelopmental disorders including autism spectrum disorder (ASD) affect 5.9% of the global population. Research shows the potential therapeutic use of cannabidiol (CBD) to treat different neurodevelopmental disorders, including ASD. Intranasal drug delivery (i.n.) is a non-invasive and painless administration route that enhances drug bioavailability in the brain bypassing the blood-brain barrier. Various polymeric nanoparticles have been investigated for i.n. delivery with different success levels. In this study, we developed and characterized polymeric micelles of the poly(ethylene oxide)-b-poly(propylene oxide) block copolymer Pluronic® F127 loaded with 25% w/w CBD (based on solid weight) for nose-to-brain delivery in ASD. CBD-loaded polymeric micelles display a hydrodynamic diameter of 41 ± 1 nm by Intensity and 23 ± 1 nm by Number, as measured by dynamic light scattering, and very good compatibility and permeability in the human nasal septum cell line RPMI 2650, an in vitro model of the nasal epithelium. The accumulation of CBD-loaded polymeric micelles administered intranasally in the brain of ASD-like rats is confirmed by bioimaging. The CBD pharmacokinetics upon the i.n. (dose of 5 mg/kg) and oral (15 mg/kg) administration of the loaded polymeric micelles shows a 27.8% increase of the CBD concentration in the brain of ASD-like rats 20 min after i.n. administration, despite the 3-fold decrease in the dose. Finally, the efficacy of this nanoformulation to improve the core symptoms of ASD is demonstrated in behavioral studies in a behavioral model of the disorder in rats.

Children with ASD experience significant gross motor challenges that could be addressed using motor interventions. However, contemporary ASD interventions that are sedentary in nature often target communication and fine motor skills and not children's gross motor difficulties. In the current pilot RCT, we evaluated changes in various motor outcomes (i.e., gross/fine motor coordination, locomotor skills, functional endurance, and praxis/imitation performance) following two types of whole-body motor interventions (Creative Movement (CM) or General Movement (GM)) and compared them to a Sedentary Play (SP) intervention focused on improving fine motor skills in children with ASD. Forty-five children with ASD (Mean Age ±SE: 8.7 ± 0.3, 38 males) were randomly assigned to the CM, GM, or SP groups and received 8 weeks of group-specific training. Both CM and GM interventions led to medium-to-large improvements in gross motor performance, including improved body coordination, strength/agility, locomotor skills, and walking endurance. Children in the CM group additionally showed medium-to-large-sized improvements in praxis performance, while children in the SP group showed improvements in fine motor performance. These training-related improvements were supported by improvements reported via parental questionnaires. Researchers and clinicians should incorporate whole-body interventions targeting gross motor skills in the plan of care for children with ASD.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by deficiencies in communication, social interaction, and repetitive and restrictive behaviors. The discovery of genetic involvement in the etiology of ASD has made this condition a strong candidate for genome-based diagnostic tests. Next-generation sequencing (NGS) is useful for the detection of variants in the sequence of different genes in ASD patients. Herein, we present the implementation of a personalized NGS panel for autism (AutismSeq) for patients with essential ASD over a prospective period of four years in the clinical routine of a tertiary hospital. The cohort is composed of 48 individuals, older than 3 years, who met the DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) diagnostic criteria for ASD. The NGS customized panel (AutismSeq) turned out to be a tool with good diagnostic efficacy in routine clinical care, where we detected 12 "pathogenic" (including pathogenic, likely pathogenic, and VUS (variant of uncertain significance) possibly pathogenic variations) in 11 individuals, and 11 VUS in 10 individuals, which had previously been negative for chromosomal microarray analysis and other previous genetic studies, such as karyotype, fragile-X, or MLPA/FISH (Multiplex Ligation dependent Probe Amplification/Fluorescence in situ hybridization) analysis. Our results demonstrate the high genetic and clinical heterogeneity of individuals with ASD and the current difficulty of molecular diagnosis. Our study also shows that an NGS-customized panel might be useful for diagnosing patients with essential/primary autism and that it is cost-effective for most genetic laboratories.

D-aspartate is an endogenous agonist of NMDA and mGlu5 receptors, with a distinctive spatiotemporal expression profile that peaks in the prenatal and early postnatal brain. This suggests a critical role for D-aspartate metabolism in modulating neurodevelopmental processes linked to glutamatergic neurotransmission. However, the precise mechanisms through which D-aspartate exerts its effects remain unclear. To elucidate the molecular pathways orchestrated by early D-aspartate signalling, we employed a knock-in mouse model characterized by constitutive D-aspartate depletion due to the prenatal expression of its degradative enzyme, D-aspartate oxidase. Using an advanced quantitative proteomic approach based on Tandem Mass Tag isobaric labelling and nano-liquid chromatography coupled with high-resolution tandem mass spectrometry, we investigated the proteomic variations induced by D-aspartate depletion during postnatal brain development, comparing Ddo knock-in mice with their wild-type littermates. Our findings reveal that D-aspartate modulates the neonatal expression of proteins involved in glutamatergic neurotransmission, nervous system development, and cytoskeleton organization. Moreover, proteomic analysis identified a subset of D-aspartate-regulated proteins mapping molecular pathways associated with autism spectrum disorder and schizophrenia. These findings offer new perspectives on the complex protein networks influenced by D-aspartate metabolism in the developing brain and highlight its potential impact on cerebral function in health and psychiatric disorders.

Early intervention and treatment can help reduce disability in children diagnosed with autism spectrum disorder. Screening for autism spectrum disorder in young children identifies those at increased likelihood of diagnosis who may need further support. Previous research has reported that exposure to maternal obesity and diabetes during pregnancy is associated with higher likelihood of autism spectrum disorder diagnosis in children. However, little is known about whether these maternal conditions are associated with how very young children score on autism spectrum disorder screening tools. This study examined associations between exposure to maternal obesity and diabetes during pregnancy and offspring scores on the Quantitative Checklist for Autism in Toddlers, an autism spectrum disorder screening questionnaire administered between 18-24 months at well-child visits. A higher score on the Quantitative Checklist for Autism in Toddlers suggests a higher likelihood of autism spectrum disorder; children with scores 3 or greater are referred to developmental pediatricians for evaluation. Our study found that children of mothers with obesity or diabetes during pregnancy had higher scores than children whose mothers did not have these conditions. Associations with maternal obesity and gestational diabetes diagnosed at or before 26 weeks of pregnancy were also present in children who did not have later autism spectrum disorder diagnoses, suggesting that exposure to these conditions during early pregnancy may be associated with a broad range of social and behavioral abilities. Identifying associations between maternal health conditions and early Quantitative Checklist for Autism in Toddlers screening scores could influence future screening and provision of support for children of mothers with these conditions.

Speech articulation difficulties have not traditionally been considered to be a feature of Autism Spectrum Disorder (ASD). In contrast, speech prosodic differences have been widely reported in ASD, and may even be expressed in subtle form among clinically unaffected first-degree relatives, representing the expression of underlying genetic liability. Some evidence has challenged this traditional dichotomy, suggesting that differences in speech articulatory mechanisms may be evident in ASD, and potentially related to perceived prosodic differences. Clinical measurement of articulatory skills has traditionally been phoneme-based, rather than by acoustic measurement of motor control. Subtle differences in articulatory/motor control, prosodic characteristics (acoustic), and pragmatic language ability (linguistic) may each be contributors to differences perceived by listeners, but the interrelationship is unclear. In this study, we examined the articulatory aspects of this relationship, in speech samples from individuals with ASD and their parents during narration. Using Speechmark® analysis, we examined articulatory landmarks, fine-grained representations of articulatory timing as series of laryngeal and vocal-tract gestures pertaining to prosodic elements crucial for conveying pragmatic information. Results revealed articulatory timing differences in individuals with ASD but not their parents, suggesting that although potentially not influenced by broader genetic liability to ASD, subtle articulatory differences may indeed be evident in ASD as the recent literature indicates. A follow-up path analysis detected associations between articulatory timing differences and prosody, and subsequently, pragmatic language ability. Together, results suggest a complex relationship where subtle differences in articulatory timing may result in atypical acoustic signals, and serve as a distal mechanistic contributor to pragmatic language ability ASD.

COVID-19 increased uncertainty for most and was especially disruptive to autistic people and their families, due in part to tendencies toward intolerance for uncertainty across this population. As such, COVID presented a natural experiment of uncertainty and its correlates in autism. Previous reports have shown associations between intolerance of uncertainty, sensory difficulty, and stress. We investigated changes in sensory difficulties and stress associated with COVID-related increases in uncertainty. Primary caregivers of 47 autistic children (ages 6-15) completed online surveys containing questions about demographics, experiences, and supports received during the pandemic. Additionally, caregivers filled out measures of intolerance of uncertainty and sensory processing for both pre- and during-COVID conditions. Eighty nine percent of children had significant sensory difficulties before the pandemic. This group showed significant increases in sensory difficulties and intolerance of uncertainty during the pandemic. These changes were significantly correlated with each other, suggesting that as uncertainty increased so did sensory difficulties. Disruption to routine was also significantly correlated with sensory differences and child, household, and parent stress. Our findings add to fundamental understanding of the relationship between uncertainty, sensory processing, and stress by leveraging a natural experiment in increased uncertainty. These results have the potential to contribute to improved supports for autistic individuals in clinical, educational, home, and other settings.

Cognitive and behavioral rigidity are observed in various psychiatric diseases, including in autism spectrum disorder (ASD). However, the underlying mechanism remains to be elucidated. In this study, we found that neuroligin-3 (NL3) R451C knockin mouse model of autism (KI mice) exhibited deficits in behavioral flexibility in choice selection tasks. Single-unit recording of medium spiny neuron (MSN) activity in the nucleus accumbens (NAc) revealed altered encoding of decision-related cue and impaired updating of choice anticipation in KI mice. Additionally, fiber photometry demonstrated significant disruption in dynamic mesolimbic dopamine (DA) signaling for reward prediction errors (RPEs), along with reduced activity in medial prefrontal cortex (mPFC) neurons projecting to the NAc in KI mice. Interestingly, NL3 re-expression in the mPFC, but not in the NAc, rescued the deficit of flexible behaviors and simultaneously restored NAc-MSN encoding, DA dynamics, and mPFC-NAc output in KI mice. Taken together, this study reveals the frontostriatal circuit dysfunction underlying cognitive inflexibility and establishes a critical role of the mPFC NL3 deficiency in this deficit in KI mice. Therefore, these findings provide new insights into the mechanisms of cognitive and behavioral inflexibility and potential intervention strategies.

The recommended practice for individuals suspected of a genetic etiology for disorders including unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA) involves a genetic testing workflow including chromosomal microarray (CMA), Fragile-X testing, karyotype analysis, and/or sequencing-based gene panels. Since genomic imbalances are often found to be causative, CMA is recommended as first tier testing for many indications. Optical genome mapping (OGM) is an emerging next generation cytogenomic technique that can detect not only copy number variants (CNVs), triploidy and absence of heterozygosity (AOH) like CMA, but can also define the location of duplications, and detect other structural variants (SVs), including balanced rearrangements and repeat expansions/contractions. This study compares OGM to CMA for clinically reported genomic variants, some of these samples also have structural characterization by fluorescence in situ hybridization (FISH). OGM was performed on IRB approved, de-identified specimens from 55 individuals with genomic abnormalities previously identified by CMA (61 clinically reported abnormalities). SVs identified by OGM were filtered by a control database to remove polymorphic variants and against an established gene list to prioritize clinically relevant findings before comparing with CMA and FISH results. OGM results showed 100% concordance with CMA findings for pathogenic variants and 98% concordant for all pathogenic/likely pathogenic/variants of uncertain significance (VUS), while also providing additional insight into the genomic structure of abnormalities that CMA was unable to provide. OGM demonstrates equivalent performance to CMA for CNV and AOH detection, enhanced by its ability to determine the structure of the genome. This work adds to an increasing body of evidence on the analytical validity and ability to detect clinically relevant abnormalities identified by CMA. Moreover, OGM identifies translocations, structures of duplications and complex CNVs intractable by CMA, yielding additional clinical utility.

Many autistic individuals exhibit clinically-significant motor difficulties. Previous reviews focused on overall motor ability or coordination, but with little attention paid to quantifying differences in upper extremity skills, which are critical to many activities of daily living. Our objective was to identify and evaluate the published literature on upper extremity motor skills of autistic people. We conducted a literature search in PubMed, Scopus, and PsycInfo for empirical research articles reporting functional upper extremity movement performance in autism. We included articles reporting results of primary data collection from autistic people published before July 10, 2024. Articles were identified and data were extracted and evaluated using EndNote and Microsoft Excel by a team of three authors. Our search strategy yielded 1181 unique articles. After screening these articles, the final sample included 43 empirical research articles focused on functional upper extremity movements, including pointing (n = 13), reaching to grasp (n = 18), and handwriting (n = 12) in autism. Across these skills, autistic people exhibited slower, more variable movements than their non-autistic counterparts. Upper extremity movement differences in autism are likely the result of differences in motor planning and increased online monitoring of movement execution. Limitations and potential bias exist in the racial, ethnic, age, and gender diversity of available data, and in the variability of methods used to assess performance. However, the current body of literature suggests significant differences between autistic and non-autistic upper extremity movements. Slower, more variable upper extremity movements likely affect many functional difficulties experienced in autistic people's daily lives.

Variations in PAK3, a gene located on the X chromosome, are known to contribute to intellectual disability (ID) and are associated with a broad clinical spectrum. The correlation between genotype and phenotype in PAK3-related disorders remains incompletely understood. In this study, we focused on the PAK3-R67C variant, the most amino-terminal variation identified to date, which was initially associated with a non-syndromic form of X-linked ID. We describe the clinical picture of its second occurrence, and present additional clinical insights. Our findings indicate that the R67C mutation is associated with moderate to severe ID, along with speech and gait abnormalities, and features consistent with autism spectrum disorders. To explore these associations further, we conducted a comprehensive phenotypic analysis using a corresponding knock-in mouse model. The Pak3-R67C mice, which present significant microcephaly, displayed mild motor deficits, social avoidance behaviour, and impaired emotional learning and memory. At the physiological level, Pak3-R67C mice exhibited reduced hippocampal synaptic efficacy and defects in long-term potentiation, despite unaltered synapse structure. In vitro biochemical assays revealed that the PAK3-R67C variant enhances interactions with PAK-interacting exchange factors (PIX). Notably, the expression of this variant in COS7 cells, altered the distribution of focal adhesions, while cell migration capacity remained unaffected. Collectively, these data, which include the second reported occurrence of the R67C variant, a detailed characterization of the corresponding knock-in mouse line, and a multi-tiered analysis of its biological and biochemical properties, contribute to a better understanding of the genotype-phenotype relationship in PAK3-related disorders.

Maternal diabetes during pregnancy has been associated with long-term health outcomes in offspring, but studies on specific neuropsychiatric outcomes remain limited. We aimed to evaluate the association between maternal diabetes and neuropsychiatric disorders. This binational cohort study included 2 722 687 mother-child pairs from South Korea and 181 134 mother-child pairs from Japan, from 2010 to 2017, followed until December 31, 2023. Maternal diabetes was categorized as pregestational or gestational using ICD-10 codes. Offspring outcomes included severe neuropsychiatric disorder, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models in a stabilized inverse probability of treatment weighted cohort and sibling-comparison cohort. Sibling-comparison analyses were conducted and validated in an independent Japanese cohort. Among 2 722 687 mother-child pairs (mean follow-up, 10.3 years) in the full cohort, 783 265 offspring (26.7%) were exposed to maternal diabetes (756 193 gestational; 20 815 pregestational). Pregestational diabetes was associated with increased risks of any neuropsychiatric disorder (aHR, 1.29 [95% CI, 1.22-1.36]), severe neuropsychiatric disorder (1.33 [1.16-1.53]), ADHD (1.24 [1.16-1.31]), ASD (1.39 [1.25-1.55]), and intellectual disability (1.57 [1.40-1.77]). Associations remained consistent across maternal and perinatal subgroups. Gestational diabetes showed only modest associations (aHR, 1.05 [95% CI, 1.00-1.08]) and was nonsignificant in sibling analyses in both Korea (1.01 [0.98-1.05]) and Japan (0.90 [0.76-1.06]). Pregestational diabetes was associated with increased neuropsychiatric risk in offspring, whereas gestational diabetes showed no meaningful association in sibling analyses, and adequate management before and during pregnancy remains important.

To evaluate long-term adverse neurodevelopmental outcomes of discordant twins delivered at term. Retrospective cohort study. Nationwide (Republic of Korea). All twin children delivered at term between 2007 and 2010. The study population was divided into two groups according to inter-twin birthweight discordancy: the 'concordant twin group', twin pairs with inter-twin birthweight discordancy less than 20%; and the 'discordant twin group', twin pairs with inter-twin birthweight discordancy of 20% or more. The risk of long-term adverse neurodevelopmental outcomes was compared between the concordant twin group and the discordant twin group. Long-term adverse neurodevelopmental outcomes between smaller and larger twin children within twin pairs were further analysed. The composite adverse neurodevelopmental outcome was defined as the presence of at least one of the following: motor developmental delay, cognitive developmental delay, autism spectrum disorders/attention deficit hyperactivity disorders, tics/stereotypical behaviour or epileptic/febrile seizure. Long-term adverse neurodevelopmental outcome. Of 22 468 twin children (11 234 pairs) included, 3412 (15.19%) twin children were discordant. The risk of composite adverse neurodevelopmental outcome was higher in the discordant twin group than in the concordant twin group (adjusted hazard ratio [HR] 1.13, 95% CI 1.03-1.24). The long-term adverse neurodevelopmental outcomes were not significantly different between smaller and larger twin children in discordant twin pairs (adjusted HR 1.01, 95% CI 0.81-1.28). In twin pairs delivered at term, an inter-twin birthweight discordancy of 20% or greater was associated with long-term adverse neurodevelopmental outcomes; and long-term adverse neurodevelopmental outcomes were not significantly different in smaller or larger twin children in discordant twin pairs.

Pragmatic language weaknesses, a core feature of autism spectrum disorder (ASD), are implicated in externalizing behavior disorders (Gremillion & Martel, 2014). Particularly in a clinical setting, these co-occurring externalizing disorders are very common in autism; rates of Attentional Deficit-Hyperactive Disorder (ADHD) and Oppositional Defiant Disorder (ODD) are as high as 83% (ADHD) and 73% (ODD; Joshi et al., 2010). It is possible that pragmatic language weaknesses impact the ability to effectively communicate one's needs, which may lead autistic children to utilize externalizing behaviors in order to achieve a desired outcome (Ketelaars et al., 2010; Rodas et al., 2017). The aim of the current study is to investigate the relationship between pragmatic language, assessed via multiple modalities, and externalizing behaviors, assessed by parent interview, in youth with autistic (n=33) or neurotypical (NT; n=34) developmental histories, along with youth diagnosed with autism, who lost the diagnosis (LAD) by adolescence (n=31). The autism group had significantly more pragmatic language difficulties, and more externalizing behaviors and disorders; ADHD symptoms were particularly more prevalent, while LAD and NT groups did not differ. Challenges in pragmatic language abilities were associated with more externalizing symptoms when controlling for other facts that typically influence such symptoms, including nonverbal cognition, structural language, executive functioning, and autistic characteristics, but did not remain when age was included in the model. We discuss the mechanisms underlying difficult-to-manage externalizing behaviors and implications for interventions and long-term outcomes for youth with and without a history of autism.

Difficulties with praxis, the ability to perform learned skilled movements, have been robustly demonstrated in autism spectrum disorder (autism). However, praxis assessment is not routinely included in autism characterization batteries, in part because it is traditionally time consuming to administer and score. We test whether dyspraxia in autism can be captured with a brief measure. Youth with autism (n = 41) and matched typically developing controls (n = 32), aged 8 to 16 years, completed a 5-minute praxis battery. The 19-item battery included four subtests: gesture to command, tool use, familiar imitation, and meaningless imitation. Video recordings were coded for error types and compared to participant characterization variables. Consistent with research using a lengthy battery, autistic youth made more errors overall, with a large effect size. Groups demonstrated similar distributions of error types, suggesting that dyspraxia in autism is not limited to a particular error form. In the autism group, praxis was associated with adaptive functioning, but not autism traits. A shortened battery is sufficiently sensitive to praxis differences between autistic and typically developing youth, increasing the feasibility of including praxis within clinical assessments or larger research batteries aimed at testing relationships with downstream skills.

Comorbidity of eczema with autism spectrum disorder (ASD) is increasing. We investigated the associations of eczema and its possible interaction with polymorphisms in glutathione S-transferase (GST) genes in relation to ASD and ASD severity. Using data from 344 1:1 age- and sex-matched ASD cases and typically developing controls, we assessed additive and interactive associations of eczema with GST genes in relation to ASD by applying conditional logistic regression models, and in relation to ASD severity in ASD cases as measured by the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) total and domain-specific comparison scores (CSs) by fitting general linear models. After adjusting for child's age and history of breastfeeding, eczema had no additive association with ASD [Matched Odds ratio (MOR) and 95% Confidence Intervals (CI): 1.04 (0.76, 1.41), P = 0.82] or ASD severity (all P > 0.20). Using a recessive genetic model, eczema was significantly associated with ASD only among children with the Val/Val genotype for the GSTP1 Ile105Val polymorphism [MOR (95% CI) = 2.04 (1.02, 4.08), P = 0.04, P for interaction = 0.03]. In addition, among ASD cases with the GSTM1 DD genotype, those with eczema had a marginally significant higher mean ADOS-2 Social Affect CS than those without eczema (7.3 vs. 6.8, P = 0.08, P for interaction = 0.09). Our findings suggest children with certain genotypes for GST genes may be more susceptible for comorbidity of eczema and ASD, which is consistent with the role of GST genes in both conditions.

Maternal hormonal risk factors for autism spectrum disorder (ASD) in offspring could intersect genetic and environmental risk factors. This analysis explored ASD risk in association with maternal testosterone, androstenedione, and dehydroepiandrosterone (DHEA) measured in first, second, and third trimesters of pregnancy. MARBLES is a prospective pregnancy cohort study based at the MIND Institute in Northern California that enrolls mothers who have at least one child previously diagnosed with ASD and are expecting, or planning to have another child. At 36 months the younger sibling is clinically classified as having ASD, or as non-typically developing (Non-TD), or typically developing (TD). Maternal androgens during pregnancy were measured in serum samples from 196 mothers. Multivariable logistic regression models estimated risk of ASD and Non-TD in offspring compared to TD, in relation to the log-transformed maternal androgen concentrations, at each trimester. Non-significant associations were observed, and borderline significant associations were only observed in some stratified unadjusted models. Second trimester maternal testosterone was non-significantly associated with ASD in female offspring, although not after adjustment, aRR 1.54 (95% CI 0.71, 3.33), and second trimester maternal DHEA was non-significantly associated with non-TD in male offspring, again not after adjustment, aRR 0.50 (95% CI 0.21, 1.21). Secondary analysis suggested that third trimester androgen concentrations in mothers with male offspring had significant or near significant associations with their child's Social Responsiveness Scale score. No significant associations were found between maternal androgen concentrations and risk of ASD or Non-TD in the child.