Idiosyncratic pupil regulation in autistic children.

Recent neuroimaging and eye tracking studies have suggested that children with autism spectrum disorder (ASD) may exhibit more variable and idiosyncratic brain responses and eye movements than typically developing (TD) children. Here we extended this research for the first time to pupillometry recordings. We successfully completed pupillometry recordings with 103 children (66 with ASD), 4.5-years-old on average, who viewed three 90 second movies, twice. We extracted their pupillary time-course for each movie, capturing their stimulus evoked pupillary responses. We then computed the correlation between the time-course of each child and those of all others in their group. This yielded an average inter-subject correlation value per child, representing how similar their pupillary responses were to all others in their group. ASD participants exhibited significantly weaker inter-subject correlations than TD participants, reliably across all three movies. Differences across groups were largest in responses to a naturalistic movie containing footage of a social interaction between two TD children. This measure enabled classification of ASD and TD children with a sensitivity of 0.82 and specificity of 0.73 when trained and tested on independent datasets. Using the largest ASD pupillometry dataset to date, we demonstrate the utility of a new technique for measuring the idiosyncrasy of pupil regulation, which can be completed even by young children with co-occurring intellectual disability. These findings reveal that a considerable subgroup of ASD children have significantly more unstable, idiosyncratic pupil regulation than TD children, indicative of more variable, weakly regulated, underlying neural activity.

Oculomotor randomness is higher in autistic children and increases with the severity of symptoms.

A variety of studies have suggested that at least some children with autism spectrum disorder (ASD) view the world differently. Differences in gaze patterns as measured by eye tracking have been demonstrated during visual exploration of images and natural viewing of movies with social content. Here we analyzed the temporal randomness of saccades and blinks during natural viewing of movies, inspired by a recent measure of "randomness" applied to micro-movements of the hand and head in ASD (Torres et al., 2013; Torres & Denisova, 2016). We analyzed a large eye-tracking dataset of 189 ASD and 41 typically developing (TD) children (1-11 years old) who watched three movie clips with social content, each repeated twice. We found that oculomotor measures of randomness, obtained from gamma parameters of inter-saccade intervals (ISI) and blink duration distributions, were significantly higher in the ASD group compared with the TD group and were correlated with the ADOS comparison score, reflecting increased "randomness" in more severe cases. Moreover, these measures of randomness decreased with age, as well as with higher cognitive scores in both groups and were consistent across repeated viewing of each movie clip. Highly "random" eye movements in ASD children could be associated with high "neural variability" or noise, poor sensory-motor control, or weak engagement with the movies. These findings could contribute to the future development of oculomotor biomarkers as part of an integrative diagnostic tool for ASD.

Large increase in ASD prevalence in Israel between 2017 and 2021.

Accurate estimation of annual changes in autism spectrum disorders (ASD) prevalence is critical for planning the expansion of diagnostic, education, and intervention services at an adequate rate. Previous studies from Israel have reported that ASD prevalence among 8-year-old children has increased from estimates of 0.3% in 2008 to 0.65% in 2015 and 1.3% in 2018. Here, we analyzed data acquired from the National Insurance Institute of Israeli (NII), a governmental organization that approves and monitors all ASD children who receive welfare services in Israel, and Clalit Health Services (CHS), the largest Health Maintenance Organization in Israel that provides health services to ~52% of the population. Data from both sources included annual data files from 2017 to 2021 containing the number of ASD cases per year of birth for 1-17-year-old children. This allowed us to estimate annual ASD prevalence among 3.5 million children born between 2000 and 2020 in Israel. Both data sources revealed a nearly two-fold increase in ASD prevalence among 1-17-year-old children from 2017 to 2021. Estimated prevalence rates differed across age groups with 2-3-year-old (day-care) children increasing from 0.27% to 1.19% (>4 fold change), 4-6-year-old (pre-school) children increasing from 0.8% to 1.83%, and 8-year-old children increasing from 0.82% to 1.56% in NII data. These results demonstrate that autism prevalence continues to increase in Israel with a shift towards diagnosis at earlier ages. These findings highlight the challenge facing health and education service providers in meeting the needs of a rapidly growing autism population.

Functional connectivity of the human face network exhibits right hemispheric lateralization from infancy to adulthood.

Adults typically exhibit right hemispheric dominance in the processing of faces. In this cross-sectional study, we investigated age-dependent changes in face processing lateralization from infancy to adulthood (1-48 years old; N = 194). We co-registered anatomical and resting state functional Magnetic Resonance Imaging (fMRI) scans of toddlers, children, adolescents, and adults into a common space and examined functional connectivity across the face, as well as place, and object-selective regions identified in adults. As expected, functional connectivity between core face-selective regions was stronger in the right compared to the left hemisphere in adults. Most importantly, the same lateralization was evident in all other age groups (infants, children, adolescents) and appeared only in face-selective regions, and not in place or object-selective regions. These findings suggest that the physiological development of face-selective brain areas may differ from that of object and place-selective areas. Specifically, the functional connectivity of the core-face selective regions exhibits rightward lateralization from infancy, years before these areas develop mature face-selective responses.

Comparison of three bioinformatics tools in the detection of ASD candidate variants from whole exome sequencing data.

Autism spectrum disorder (ASD) is a heterogenous multifactorial neurodevelopmental condition with a significant genetic susceptibility component. Thus, identifying genetic variations associated with ASD is a complex task. Whole-exome sequencing (WES) is an effective approach for detecting extremely rare protein-coding single-nucleotide variants (SNVs) and short insertions/deletions (INDELs). However, interpreting these variants' functional and clinical consequences requires integrating multifaceted genomic information. We compared the concordance and effectiveness of three bioinformatics tools in detecting ASD candidate variants (SNVs and short INDELs) from WES data of 220 ASD family trios registered in the National Autism Database of Israel. We studied only rare (< 1% population frequency) proband-specific variants. According to the American College of Medical Genetics (ACMG) guidelines, the pathogenicity of variants was evaluated by the InterVar and TAPES tools. In addition, likely gene-disrupting (LGD) variants were detected based on an in-house bioinformatics tool, Psi-Variant, that integrates results from seven in-silico prediction tools. Overall, 372 variants in 311 genes distributed in 168 probands were detected by these tools. The overlap between the tools was 64.1, 22.9, and 23.1% for InterVar-TAPES, InterVar-Psi-Variant, and TAPES-Psi-Variant, respectively. The intersection between InterVar and Psi-Variant (I âˆ© P) was the most effective approach in detecting variants in known ASD genes (PPV = 0.274; OR = 7.09, 95% CI = 3.92-12.22), while the union of InterVar and Psi Variant (I U P) achieved the highest diagnostic yield (20.5%).Our results suggest that integrating different variant interpretation approaches in detecting ASD candidate variants from WES data is superior to each approach alone. The inclusion of additional criteria could further improve the detection of ASD candidate variants.

Adherence to treatment and parents' perspective about effectiveness of melatonin in children with autism spectrum disorder and sleep disturbances.

OBJECTIVE: Melatonin is considered an effective pharmacological treatment for the sleep disturbances that are reported in > 50% of children with autism spectrum disorder (ASD). However, real-life data about the long-term course and effectiveness of melatonin treatment in children with ASD is lacking. METHODS: In this retrospective cohort study, we assessed the adherence to melatonin treatment and parents' perspective of its effect on sleep quality and daytime behavior in children with ASD via a parental phone survey of children in the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) database. Cox regression analysis was used to assess the effect of key demographic and clinical characteristics on treatment adherence. RESULTS: Melatonin was recommended for ~ 8% of children in the ANCAN database. These children were characterized by more severe symptoms of autism. The median adherence time for melatonin treatment exceeded 88 months, with the most common reason for discontinuation being a lack of effectiveness (14%). Mild side-effects were reported in 14% of children, and 86%, 54%, and 45% experienced improvements in sleep onset, sleep duration and night awakenings, respectively. Notably, melatonin also improved the daytime behaviors of > 28% of the children. Adherence to treatment was independently associated with improvements in night awakenings and educational functioning (aHR = 0.142, 95%CI = 0.036-0.565; and aHR = 0.195, 95%CI = 0.047-0.806, respectively). CONCLUSIONS: Based on parents' report, melatonin is a safe and effective treatment that improves both sleep difficulties and daily behavior of children with ASD.

Increased neural variability in adolescents with ADHD symptomatology: Evidence from a single-trial EEG study.

Increased intrasubject variability of reaction time (RT) refers to inconsistency in an individual's speed of responding to a task. This increased variability has been suggested as a fundamental feature of attention deficit hyperactivity disorder (ADHD), however, its neural sources are still unclear. In this study, we aimed to examine whether such inconsistency at the behavioral level would be accompanied by inconsistency at the neural level; and whether different types of neural and behavioral variability would be related to ADHD symptomatology. We recorded electroencephalogram (EEG) data from 62 adolescents, who were part of a prospective longitudinal study on the development of ADHD. We examined trial-by-trial neural variability in response to visual stimuli in two cognitive tasks. Adolescents with high ADHD symptomatology exhibited an increased neural variability before the presentation of the stimulus, but when presented with a visual stimulus, this variability decreased to a level that was similar to that exhibited by participants with low ADHD symptomatology. In contrast with our prediction, neural variability was unrelated to the magnitude of behavioral variability. Our findings suggest that adolescents with higher symptoms are characterized by increased neural variability before the stimulation, which might reflect a difficulty in alertness to the forthcoming stimulus; but this increased neural variability does not seem to account for their RT variability.

Sleep disturbances are associated with irritability in ASD children with sensory sensitivities.

BACKGROUND: Parent reports suggest that 44-84% of children with ASD exhibit sleep disturbances that are of clinical concern. Previous studies have reported that, in children with ASD, the severity of sleep disturbances is associated with the severity of either sensory problems or aberrant behaviors, but none have performed combined analyses with measures of both sensory and aberrant behaviors symptom domains from the same children. METHODS: We examined parent reports of 237 children with ASD, 1.4-8.7 years old, using the child sleep habits questionnaire (CSHQ), sensory profile (SP), and aberrant behaviors checklist (ABC). RESULTS: The analyses revealed that sleep disturbances were most strongly associated with SP sensory sensitivity and ABC irritability scores. Together these scores explained 35% of the variance in total CSHQ scores. Moreover, sensory sensitivity scores moderated the association between irritability and sleep disturbances, indicating that sleep disturbances were significantly associated with irritability only in children with moderate to severe sensory sensitivities. CONCLUSION: We suggest that the three symptom domains may interact and exacerbate each other such that successful intervention in one symptom domain may have positive impact on the others. Further intervention studies testing this hypothesis are highly warranted.

Performance evaluation of Fitbit Charge 3 and actigraphy vs. polysomnography: Sensitivity, specificity, and reliability across participants and nights.

GOAL AND AIMS: Compare the accuracy and reliability of sleep/wake classification between the Fitbit Charge 3 and the Micro Motionlogger actigraph when applying either the Cole-Kripke or Sadeh scoring algorithms. Accuracy was established relative to simultaneous Polysomnography recording. Focus technology: Fitbit Charge 3 and actigraphy. Reference technology: Polysomnography. SAMPLE: Twenty-one university students (10 females). DESIGN: Simultaneous Fitbit Charge 3, actigraphy, and polysomnography were recorded over 3 nights at the participants' homes. CORE ANALYTICS: Total sleep time, wake after sleep onset, sensitivity, specificity, positive predictive value, and negative predictive value. ADDITIONAL ANALYTICS AND EXPLORATORY ANALYSES: Variability of specificity and negative predictive value across subjects and across nights. CORE OUTCOMES: Fitbit Charge 3 and actigraphy using the Cole-Kripke or Sadeh algorithms exhibited similar sensitivity in classifying sleep segments relative to polysomnography (sensitivity of 0.95, 0.96, and 0.95, respectively). Fitbit Charge 3 was significantly more accurate in classifying wake segments (specificity of 0.69, 0.33, and 0.29, respectively). Fitbit Charge 3 also exhibited significantly higher positive predictive value than actigraphy (0.99 vs. 0.97 and 0.97, respectively) and a negative predictive value that was significantly higher only relative to the Sadeh algorithm (0.41 vs. 0.25, respectively). IMPORTANT ADDITIONAL OUTCOMES: Fitbit Charge 3 exhibited significantly lower standard deviation in specificity values across subjects and negative predictive value across nights. CORE CONCLUSION: This study demonstrates that Fitbit Charge 3 is more accurate and reliable in identifying wake segments than the examined FDA-approved Micro Motionlogger actigraphy device. The results also highlight the need to create devices that record and save raw multi-sensor data, which are necessary for developing open-source sleep or wake classification algorithms.

Exogenous oxytocin administration during labor and autism spectrum disorder.

BACKGROUND: Oxytocin is a neuropeptide hormone that plays a key role in social behavior, stress regulation, and mental health. Synthetic oxytocin administration is a common obstetrical practice, and importantly, previous research has suggested that intrapartum exposure may increase the risk of neurodevelopmental disorders, such as autism spectrum disorder. OBJECTIVE: This study aimed to examine the association between synthetic oxytocin exposure during labor and autism spectrum disorder diagnosis in the child. STUDY DESIGN: This population-based retrospective cohort study compared 2 cohorts of children: (1) all children born in British Columbia, Canada between April 1, 2000 and December 31, 2014 (n=414,336 births), and (2) all children delivered at Soroka University Medical Center in Be'er-Sheva, Israel between January 1, 2011 and December 31, 2019 (n=82,892 births). Nine different exposure groups were examined. Cox proportional hazards models were used to estimate crude and adjusted hazard ratios of autism spectrum disorder in both cohorts on the basis of induction and/or augmentation exposure status. To further control for confounding by indication, we conducted sensitivity analyses among a cohort of healthy, uncomplicated deliveries and among a group that was induced only for postdates. In addition, we stratified our analyses by infant sex to assess for potential sex differences. RESULTS: In the British Columbia cohort, 170,013 of 414,336 deliveries (41.0%) were not induced or augmented, 107,543 (26.0%) were exposed to oxytocin, and 136,780 (33.0%) were induced or augmented but not exposed to oxytocin. In the Israel cohort, 51,790 of 82,892 deliveries (62.5%) were not induced or augmented, 28,852 (34.8%) were exposed to oxytocin, and 2250 (2.7%) were induced or augmented but not exposed to oxytocin. On adjusting for covariates in the main analysis, significant associations were observed in the Israel cohort, including adjusted hazard ratios of 1.51 (95% confidence interval, 1.20-1.90) for oxytocin-augmented births and 2.18 (95% confidence interval, 1.32-3.57) for those induced by means other than oxytocin and not augmented. However, oxytocin induction was not significantly associated with autism spectrum disorder in the Israel cohort. In the Canadian cohort, there were no statistically significant adjusted hazard ratios. Further, no significant sex differences were observed in the fully adjusted models. CONCLUSION: This study supports that induction of labor through oxytocin administration does not increase the risk of autism spectrum disorder in the child. Our international comparison of 2 countries with differences in clinical practice regarding oxytocin administration for induction and/or augmentation suggests that previous studies reporting a significant association were likely confounded by the underlying indication for the induction.

Association Between Early Developmental Milestones and Autism Spectrum Disorder.

Early diagnosis and treatment of autism spectrum disorder (ASD) has been shown to lead to better prognosis. Here, we examined the association of commonly measured early developmental milestones (DMs) with later diagnosis of ASD. We conducted a case-control study of 280 children with ASD (cases) and 560 typically developed children (controls) matched to cases by date of birth, sex, and ethnicity in a control/case ratio of 2:1. Both cases and controls were ascertained from all children whose development was monitored at mother-child health clinics (MCHCs) in southern Israel. DM failure rates during the first 18 months of life in three developmental categories (motor, social, and verbal) were compared between cases and controls. Conditional logistic regression models were used to assess the independent association of specific DMs with the risk of ASD, while adjusting for demographic and birth characteristics.Significant case-control differences in DM failure rates were observed as early as 3 months of age (p < 0.001), and these differences increased with age. Specifically, cases were 2.4 times more likely to fail ≥ 1 DM at 3 months (aOR = 2.39; 95%CI = 1.41-4.06), and 15.3 times more likely to fail ≥ 3 DMs at 18 months (aOR = 15.32; 95%CI = 7.75-30.28). The most notable DM-ASD association was observed for social DM failure at 9-12 months (aOR = 4.59; 95%CI = 2.59-8.13). Importantly, the sex or ethnicity of the participants did not affect these DM-ASD associations. Our findings highlight the potential role of DMs as early signs of ASD that could facilitate earlier referral and diagnosis of ASD.

Children with autism exhibit similar longitudinal changes in core symptoms when placed in special or mainstream education settings.

LAY ABSTRACT: Today, children with autism spectrum disorder (ASD) are placed in mainstream or special education settings somewhat arbitrarily with no clear clinical recommendations. Here, we compared changes in core ASD symptoms, as measured by the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) clinical assessment, across ASD preschool children placed in special or mainstream education. Longitudinal changes in ADOS-2 scores did not differ significantly across settings over a 1- to 2-year period. While some children improved in core ASD symptoms, others deteriorated in both settings. This highlights the need to identify specific criteria for establishing meaningful placement recommendations.

The Importance of Language Delays as an Early Indicator of Subsequent ASD Diagnosis in Public Healthcare Settings.

Previous studies have reported that ASD children with more severe symptoms are diagnosed earlier. However, previous studies in community settings have mostly relied on retrospective parental reports without the use of quantitative standardized test scores. Here, we evaluated the association of language, cognitive, and ASD severity standardized scores with the age of diagnosis in 1-6-year-old children diagnosed in a public healthcare setting. The results revealed that language scores were the strongest variable associated with the age of diagnosis, explaining ~ 30% of the variability across children. Indeed, all children diagnosed before 30-months of age exhibited moderate-to-severe language delays. These results further substantiate the prominence of language delay as a highly visible symptom associated with earlier ASD diagnosis in community clinical settings.

Children and adolescents with ASD treated with CBD-rich cannabis exhibit significant improvements particularly in social symptoms: an open label study.

In recent years there has been growing interest in the potential benefits of CBD-rich cannabis treatment for children with ASD. Several open label studies and one double-blind placebo-controlled study have reported that CBD-rich cannabis is safe and potentially effective in reducing disruptive behaviors and improving social communication. However, previous studies have mostly based their conclusions on parental reports without the use of standardized clinical assessments. Here, we conducted an open label study to examine the efficacy of 6 months of CBD-rich cannabis treatment in children and adolescents with ASD. Longitudinal changes in social communication abilities and restricted and repetitive behaviors (RRB) were quantified using parent report with the Social Responsiveness Scale and clinical assessment with the Autism Diagnostic Observation Schedule (ADOS). We also quantified changes in adaptive behaviors using the Vineland, and cognitive abilities using an age-appropriate Wechsler test. Eighty-two of the 110 recruited participants completed the 6-month treatment protocol. While some participants did not exhibit any improvement in symptoms, there were overall significant improvements in social communication abilities as quantified by the ADOS, SRS, and Vineland with larger improvements in participants who had more severe initial symptoms. Significant improvements in RRB were noted only with parent-reported SRS scores and there were no significant changes in cognitive scores. These findings suggest that treatment with CBD-rich cannabis can yield improvements, particularly in social communication abilities, which were visible even when using standardized clinical assessments. Additional double-blind placebo-controlled studies utilizing standardized assessments are highly warranted for substantiating these findings.

The Impact of Speaker Diarization on DNN-based Autism Severity Estimation.

This paper presents a speech-based system for autism severity estimation combined with automatic speaker diarization. Speaker diarization was performed by two different methods. The first used acoustic features, which included Mel-Frequency Cepstral Coefficients (MFCC) and pitch, and the second used x-vectors - embeddings extracted from Deep Neural Networks (DNN). The speaker diarization was trained using a Fully Connected Deep Neural Network (FCDNN) in both methods. We then trained a Convolutional Neural Network (CNN) to estimate the severity of autism based on 48 acoustic and prosodic features of speech. One hundred thirty-two young children were recorded in the Autism Diagnostic Observation Schedule (ADOS) examination room, using a distant microphone. Between the two diarization methods, the MFCC and Pitch achieved a better Diarization Error Rate (DER) of 26.91%. Using this diarization method, the severity estimation system achieved a correlation of 0.606 (Pearson) between the predicted and the actual autism severity scores (i.e., ADOS scores). Clinical Relevance- The presented system identifies children's speech segments and estimates their autism severity sc30:310ore.

A distinct route for efficient learning and generalization in autism.

Visual skill learning is the process of improving responses to surrounding visual stimuli.1 For individuals with autism spectrum disorders (ASDs), efficient skill learning may be especially valuable due to potential difficulties with sensory processing2 and challenges in adjusting flexibly to changing environments.3,4 Standard skill learning protocols require extensive practice with multiple stimulus repetitions,5-7 which may be difficult for individuals with ASD and create abnormally specific learning with poor ability to generalize.4 Motivated by findings indicating that brief memory reactivations can facilitate skill learning,8,9 we hypothesized that reactivation learning with few stimulus repetitions will enable efficient learning in individuals with ASD, similar to their learning with standard extensive practice protocols used in previous studies.4,10,11 We further hypothesized that in contrast to experience-dependent plasticity often resulting in specificity, reactivation-induced learning would enable generalization patterns in ASD. To test our hypotheses, high-functioning adults with ASD underwent brief reactivations of an encoded visual learning task, consisting of only 5 trials each instead of hundreds. Remarkably, individuals with ASD improved their visual discrimination ability in the task substantially, demonstrating successful learning. Furthermore, individuals with ASD generalized learning to an untrained visual location, indicating a unique benefit of reactivation learning mechanisms for ASD individuals. Finally, an additional experiment showed that without memory reactivations ASD subjects did not demonstrate efficient learning and generalization patterns. Taken together, the results provide proof-of-concept evidence supporting a distinct route for efficient visual learning and generalization in ASD, which may be beneficial for skill learning in other sensory and motor domains.

Home-quarantine during the initial Covid-19 outbreak in Israel: parent perceived impact on children with ASD.

Background: Studies have reported that Covid-19 home-quarantine periods have had mostly negative psychological impact on children with ASD and their families. Here we examined parent perceived impact of a 6-week quarantine period imposed in Israel at the beginning of the Covid-19 outbreak, in mid-March 2020. Methods: An anonymous online questionnaire was completed by parents of 268 children with ASD. Parents rated deterioration/improvement in their child's behaviors, abilities, mood, sleep, and anxiety along with changes in their own mood, sleep, parenting skills, and family relationships. We performed t-tests and ANOVA analyses to assess the significance of perceived impact on each domain and potential differences in the impact across families with children of different ages, genders, and levels of required support as well as families that experienced different magnitudes of economic hardships. Results: Parents reported significant deterioration in their mood and sleep along with significant improvements in relationships with their spouse and child with ASD, and in their parenting skills. Parents also reported significant increases in the severity of tantrums, anxiety, and restricted and repetitive behavior symptoms along with significant improvements in social and communication abilities of their child with ASD. Ratings were significantly lower in families of ASD children who regularly require more support and in families that experienced economic hardships. Conclusions: While periods of home-quarantine create numerous hardships for families of children with ASD, they may also offer an opportunity for improving parenting skills, family relationships, and children's social communication abilities with potential relevance for improving remote services.

Association between ultrasonography foetal anomalies and autism spectrum disorder.

Multiple pieces of evidence support the prenatal predisposition of autism spectrum disorder (ASD). Nevertheless, robust data about abnormalities in foetuses later developing into children diagnosed with ASD are lacking. Prenatal ultrasound is an excellent tool to study abnormal foetal development as it is frequently used to monitor foetal growth and identify foetal anomalies throughout pregnancy. We conducted a retrospective case-sibling-control study of children diagnosed with ASD (cases); their own typically developing, closest-in-age siblings (TDS); and typically developing children from the general population (TDP), matched by year of birth, sex and ethnicity to investigate the association between ultrasonography foetal anomalies and ASD. The case group was drawn from all children diagnosed with ASD enrolled at the National Autism Research Center of Israel. Foetal ultrasound data from the foetal anatomy survey were obtained from prenatal ultrasound clinics of Clalit Health Services in southern Israel. The study comprised 659 children: 229 ASD, 201 TDS and 229 TDP. Ultrasonography foetal anomalies were found in 29.3% of ASD cases versus only 15.9% and 9.6% in the TDS and TDP groups [adjusted odds ratio (aOR) = 2.23, 95% confidence interval (CI) = 1.32-3.78, and aOR = 3.50, 95%CI = 2.07-5.91, respectively]. Multiple co-occurring ultrasonography foetal anomalies were significantly more prevalent among ASD cases. Ultrasonography foetal anomalies in the urinary system, heart, and head and brain were the most significantly associated with ASD diagnosis (aORUrinary = 2.08, 95%CI = 0.96-4.50 and aORUrinary = 2.90, 95%CI = 1.41-5.95; aORHeart = 3.72, 95%CI = 1.50-9.24 and aORHeart = 8.67, 95%CI = 2.62-28.63; and aORHead&Brain = 1.96, 95%CI = 0.72-5.30 and aORHead&Brain = 4.67, 95%CI = 1.34-16.24; versus TDS and TDP, respectively). ASD females had significantly more ultrasonography foetal anomalies than ASD males (43.1% versus 25.3%, P = 0.013) and a higher prevalence of multiple co-occurring ultrasonography foetal anomalies (15.7% versus 4.5%, P = 0.011). No sex differences were seen among TDS and TDP controls. ASD foetuses were characterized by a narrower head and a relatively wider ocular-distance versus TDP foetuses (ORBPD = 0.81, 95%CI = 0.70-0.94, and aOROcular distance = 1.29, 95%CI = 1.06-1.57). Ultrasonography foetal anomalies were associated with more severe ASD symptoms. Our findings shed important light on the multiorgan foetal anomalies associated with ASD.

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure.

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.