Attitudes of the autism community to early autism research

Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as: use of ‘at-risk’ language; communicating study findings to parents; and the future perspective of enrolled infants when they reach adulthood. The current study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism, and practitioners in health and education settings across eleven European countries. Survey respondents (n=2317) were positively disposed towards early autism research and there was significant overlap in their priorities for the field, and preferred language to describe infant research participants. However there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase ‘at-risk’ to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account

Autonomic disequilibrium at rest in autistic children and adults

Autism Spectrum Disorders (ASD) symptoms have been proposed to be linked to Autonomic Nervous System (ANS) dysfunctions, in particular sympathetic hyper-arousal and parasympathetic under-activation. The objective of this study was to characterize these possible ANS dysfunctions at rest in children and adults. To characterize several aspects of autonomic functioning, we recorded simultaneously pupil diameter, heart rate and electrodermal activity during 5 minutes of rest in 44 children (6-12 years old, 22 autistic) and 42 adults (19-52 years old, 21 autistic). Several parameters allowed to characterize tonic and phasic indices of sympathetic and parasympathetic systems at rest. Autistic children exhibited the expected pattern of parasympathetic under-activation at rest compared to their typically developing (TD) peers, and with a tendency for a higher phasic sympathetic activity. Adults exhibited a reverse autonomic pattern, with ASD individuals showing higher sympathetic tonus and lower sympathetic phasic activity than their TD peers. In conclusion, we observed dysautonomia at rest both in autistic children and adults, but with opposite patterns that could reflect adaptive compensation mechanisms during maturation. The autonomic disequilibrium observed in autistic children would switch from excessive phasic components to excessive tonic components in adults, possibly subtended by an atypical locus coeruleus functioning

The power of combining oculometric and pupillometric parameters for autism screening in children

Autism Spectrum Disorder is a neurodevelopmental trouble for which no objective biomarker has yet been discovered. The search for an accessible biomarker aims, in particular, for early autism screening, in order to optimize tailored intervention when necessary. In this context, eye-tracking has been now used for numerous years in the field of research on autism as it allows for non-intrusive, no-contact recordings even in very young children. However, individual oculometric parameters, while showing significant differences between groups of autistic and non-autistic individuals, are not discriminative enough for individual screening. In this study, we combined oculometric measures with pupillary parameters obtained simultaneously by the eye-tracker, and used a machine-learning approach to estimate the discriminative performance of such combinations of parameters. Data were obtained in 72 autistic and 93 neurotypical 2-13 years old children observing objects and faces during less than a minute. We used the Weka datamining software, testing 36 machine-learning algorithms without any a priori, in order to describe robust and convergent performance. Moreover, we chose to report only performance associated with high sensitivity, specificity and accuracy. We showed that oculo-pupillometric combinations of parameters allowed to reach outstanding discriminative performance in young children, paving the way for a clinical use

The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction

Purpose Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding A alpha subunit. Methods Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. Results We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55 alpha subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55 alpha but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. Conclusion We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported