Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of expression of the maternal copy of the UBE3A gene. Individuals with AS have a multifaceted behavioral phenotype consisting of deficits in motor function, epilepsy, cognitive impairment, sleep abnormalities, as well as other comorbidities. Effectively modeling this behavioral profile and measuring behavioral improvement will be crucial for the success of ongoing and future clinical trials. Foundational studies have defined an array of behavioral phenotypes in the AS mouse model. However, no single behavioral test is able to fully capture the complex nature of AS-in mice, or in children. We performed multidimensional analysis (principal component analysis + k-means clustering) to quantify the performance of AS model mice (n = 148) and wild-type littermates (n = 138) across eight behavioral domains. This approach correctly predicted the genotype of mice based on their behavioral profile with ~95% accuracy, and remained effective with reasonable sample sizes (n = ~12-15). Multidimensional analysis was effective using different combinations of behavioral inputs and was able to detect behavioral improvement as a function of treatment in AS model mice. Overall, multidimensional behavioral analysis provides a tool for evaluating the effectiveness of preclinical treatments for AS. Multidimensional analysis of behavior may also be applied to rodent models of related neurodevelopmental disorders, and may be particularly valuable for disorders where individual behavioral tests are less reliable than in AS.

A Qualitative Study of Self and Caregiver Perspectives on How Autistic Individuals Cope With Trauma.

Background: Coping can moderate the relationship between trauma exposure and trauma symptoms. There are many conceptualisations of coping in the general population, but limited research has considered how autistic individuals cope, despite their above-average rates of traumatic exposure. Objectives: To describe the range of coping strategies autistic individuals use following traumatic events. Methods: Fourteen autistic adults and 15 caregivers of autistic individuals, recruited via stratified purposive sampling, completed semi-structured interviews. Participants were asked to describe how they/their child attempted to cope with events they perceived as traumatic. Using an existing theoretical framework and reflexive thematic analysis, coping strategies were identified, described, and organized into themes. Results: Coping strategies used by autistic individuals could be organized into 3 main themes: (1) Engaging with Trauma, (2) Disengaging from Trauma, and (3) Self-Regulatory Coping. After the three main themes were developed, a fourth integrative theme, Diagnostic Overshadowing, was created to capture participants' reports of the overlap or confusion between coping and autism-related behaviors. Conclusions: Autistic individuals use many strategies to cope with trauma, many of which are traditionally recognized as coping, but some of which may be less easily recognized given their overlap with autism-related behaviors. Findings highlight considerations for conceptualizing coping in autism, including factors influencing how individuals cope with trauma, and how aspects of autism may shape or overlap with coping behavior. Research building on these findings may inform a more nuanced understanding of how autistic people respond to adversity, and how to support coping strategies that promote recovery from trauma.