High Psychopathology Subgroup in Young Children With Autism: Associations With Biological Sex and Amygdala Volume

Abstract

The aims of this study were to identify a subset of children with autism spectrum disorder (ASD) and co-occurring symptoms of psychopathology, and to evaluate associations between this subgroup and biological sex and amygdala volume. Method: Participants included 420 children (ASD: 91 girls, 209 boys; typically developing controls: 57 girls, 63 boys). Latent profile analysis was used to identify ASD subgroups based on symptoms of psychopathology, adaptive functioning, cognitive development, and autism severity. Differences in the proportions of girls and boys across subgroups were evaluated. Magnetic resonance imaging scans were acquired (346 children); amygdala volumes were evaluated in relation to subgroups and problem behavior scores. Results: Three ASD subgroups were identified. One group was characterized by high levels of psychopathology and moderate impairment on other measures (High Psychopathology Moderate Impairments [HPMI], comprising 27% of the sample). The other two subgroups had lower symptoms of psychopathology but were differentiated by high and low levels of impairment on other measures. A higher proportion of girls were classified into the HPMI subgroup (40% of girls versus 22% of boys). Relative to controls, amygdala volumes were enlarged only in the HPMI subgroup. There was a positive association between right amygdala volume and internalizing behaviors in girls but not in boys with ASD. Conclusion: A higher proportion of girls with ASD faced greater challenges with psychopathology, suggesting a need for closer evaluation and potentially earlier intervention to help improve outcomes. Amygdala enlargement was associated with co-occurring symptoms of psychopathology, and sex-specific correlations with symptoms were observed.

Sex differentiation of brain structures in autism: Findings from a gray matter asymmetry study

“…More interestingly, divergence in the brain‐behavior patterns was found in studies using other symptom measures. For example, Nordahl et al (2020) used behavioral performance in an internalizing task to measure autistic symptoms and reported an association between GM volume in the right amygdala and internalizing behaviors. Using the Social Responsiveness Scale (SRS) to measure autistic traits, Cauvet et al (2020) showed that GM volume and cortical thickness of the brain regions corresponding to the social brain network were related to autistic symptoms among both females and male with ASD.…”

Emotion Dysregulation is Substantially Elevated in Autism Compared to the General Population: Impact on Psychiatric Services

“…It should be noted that none of these studies, including ours, were specifically designed to test for sex differences. This may be important as studies aimed at understanding sex differences have reported relatively large differences between sexes, for example, a study of toddlers with ASD found that females were almost two times more likely to present with high psychopathology as compared to males [Nordahl et al, 2020]. Future studies with larger samples of females may be warranted to more conclusively determine the role of sex in emotion dysregulation and use of psychiatric services.…”

Maternal immune conditions are increased in males with autism spectrum disorders and are associated with behavioural and emotional but not cognitive co-morbidity

“…The GAIN study has an identical study design to the APP and enriches the predominantly male APP cohort with additional female participants. The study protocols, including recruitment and behavioural assessments for the APP and GAIN studies, have been previously described in detail 58 – 60 . All assessment measures described below were conducted as part of the APP and GAIN study protocols during enrolment in these studies.…”