The Brain Gene Registry: a data snapshot.

Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment Protocol (RNAP), which include cognitive, neurologic, and neuropsychiatric assessments, as well as assessments for attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Co-enrollment of BGR participants in the Clinical Genome Resource's (ClinGen's) GenomeConnect enables display of variant information in ClinVar. The BGR currently contains data on 479 participants who are 55% male, 6% Asian, 6% Black or African American, 76% white, and 12% Hispanic/Latine. Over 200 genes are represented in the BGR, with 12 or more participants harboring variants in each of these genes: CACNA1A, DNMT3A, SLC6A1, SETD5, and MYT1L. More than 30% of variants are de novo and 43% are classified as variants of uncertain significance (VUSs). Mean standard scores on cognitive or developmental screens are below average for the BGR cohort. EHR data reveal developmental delay as the earliest and most common diagnosis in this sample, followed by speech and language disorders, ASD, and ADHD. BGR data has already been used to accelerate gene-disease validity curation of 36 genes evaluated by ClinGen's BGR Intellectual Disability (ID)-Autism (ASD) Gene Curation Expert Panel. In summary, the BGR is a resource for use by stakeholders interested in advancing translational research for brain genes and continues to recruit participants with clinically reported variants to establish a rich and well-characterized national resource to promote research on neurodevelopmental disorders.

Sensory Phenotypes in Autism: Making a Case for the Inclusion of Sensory Integration Functions.

Sensory features are part of the diagnostic criteria for autism and include sensory hypo/hyper reactivity and unusual sensory interest; however, additional sensory differences, namely differences in sensory integration, have not been routinely explored. This study characterized sensory integration differences in a cohort of children (n = 93) with a confirmed diagnosis of autism (5-9 years) using a standardized, norm-referenced battery. Mean z scores, autism diagnostic scores, and IQ are reported. Participants showed substantial deficits in tactile perception, praxis, balance, visual perception, and visual-motor skills. Relationship with autism diagnostic test scores were weak or absent. Findings suggest additional sensory difficulties that are not typically assessed or considered when characterizing sensory features in autism. These data have implications for a greater understanding of the sensory features in the autism phenotype and the development of personalized treatments.

Notes from an epicenter: navigating behavioral clinical trials on autism spectrum disorder amid the COVID-19 pandemic in the Bronx.

BACKGROUND: The COVID-19 pandemic impacted nearly all facets of our daily lives, and clinical research was no exception. Here, we discuss the impact of the pandemic on our ongoing, three-arm randomized controlled trial (RCT) Sensory Integration Therapy (SIT) in Autism: Mechanisms and Effectiveness (NCT02536365), which investigates the immediate and sustained utility of SIT to strengthen functional daily-living skills and minimize the presence of maladaptive sensory behaviors in autistic children. MAIN TEXT: In this text, we detail how we navigated the unique challenges that the pandemic brought forth between the years 2020 and 2021, including the need to rapidly adjust our study protocol, recruitment strategy, and in-person assessment battery to allow for virtual recruitment and data collection. We further detail how we triaged participants and allocated limited resources to best preserve our primary outcome measures while prioritizing the safety of our participants and study team. We specifically note the importance of open and consistent communication with all participating families throughout the pandemic in ensuring all our protocol adjustments were successfully implemented. CONCLUSIONS: Though the COVID-19 pandemic resulted in an unprecedented interruption to in-person clinical research, clinical trials have always been and will continue to be at risk for unforeseen interruptions, whether from world events or participants' personal circumstances. By presenting our steps to preserving this RCT throughout the pandemic, we offer suggestions for successfully managing unexpected interruptions to research. Ideally, by taking these into account, future RCTs may be increasingly prepared to minimize the impact of these potential interruptions to research.

Neural differences in social and figurative language processing on the autism spectrum.

Individuals on the autism spectrum often have trouble with social and figurative language. As social language is often figurative, it can be challenging to disentangle the cognitive and neural sources of these difficulties. Neural systems for social cognition and language comprehension overlap in areas involved in retrieving linguistic meaning (semantics), such as the anterior temporal lobe (ATL), ventro-medial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), and posterior middle temporal gyrus (pMTG). Using adjective-noun phrases, we manipulated social/nonsocial and figurative/literal dimensions, which we expected to activate distinct but overlapping regions. We hypothesized that activation differences in the group with autism (AUT) would be greater for more social and figurative stimuli. During fMRI, participants in the AUT group (N = 19) and those in the non-autistic comparison (NAC) group (N = 22) made familiarity judgments to 192 phrases in a balanced 2 × 2 (social/nonsocial x figurative/literal) design. Social phrases activated the PCC in all participants, but only the NAC group activated the vmPFC. Figurative phrases were rated as more literal by the AUT group, with the figurative-literal phrase contrast showing no activation in the AUT group, but activating the PCC and right pMTG in the NAC group. The one significant group-level neural difference was for the social-figurative condition predicted to be most different between groups: greater activation for the AUT group in the right ATL. Differences in the right ATL and pMTG in the AUT group suggest altered engagement of right homologues of the canonical semantic network being recruited for processing combined social and figurative language.