Sex-related brain connectivity correlates of compensation in adults with autism: insights into female protection

Abstract

The male preponderance in autism spectrum disorder (ASD) led to the hypothesis that aspects of female biology are protective against ASD. Females with ASD (ASD-F) report more compensatory behaviors (i.e. “camouflaging”) to overcome ASD-related social differences, which may be a mechanism of protection. No studies have examined sex-related brain pathways supporting camouflaging in ASD-F, despite its potential to inform mechanisms underlying the ASD sex bias. We used functional connectivity (FC) to investigate “sex-atypical” and “sex-typical” FC patterns linked to camouflaging in adults with ASD and examined multimodal coherence of findings via structural connectometry. Exploratory associations with cognitive/emotional functioning examined the adaptive nature of FC patterns. We found (i) “sex-atypical” FC patterns linked to camouflaging in the hypothalamus and precuneus and (ii) “sex-typical” patterns in the right anterior cingulate and anterior parahippocampus. Higher hypothalamic FC with a limbic reward cluster also correlated with better cognitive control/emotion recognition. Structural connectometry validated FC results with consistent brain pathways/effect patterns implicated in ASD-F. In summary, “male-typical” and “female-typical” brain connectivity patterns support camouflaging in ASD-F in circuits implicated in reward, emotion, and memory retrieval. “Sex-atypical” results are consistent with fetal steroidogenic/neuroinflammatory hypotheses. However, female genetics/biology may contribute to “female-typical” patterns implicated in camouflaging.

Sex-Based Asymmetry in the Association between Challenging Behaviours and Five Anxiety Disorders in Autistic Youth

“…It has been suggested that "sexrelated biology may interact with peripheral processes, in particular the stress axis and brain arousal system, to produce distinct neurodevelopmental patterns in males and females with ASD" ([55], p. 1]), and this hypothesis may be of use in explaining the sex-based asymmetry found here for the ways that CBs and anxiety disorders were associated. For example, Calderoni [56] has argued that neurological differences may occur in autistic males and females from in utero stages of development and continue during life, and Walsh, Pagni et al [57] found different neural connectivity patterns between autistic male and female adults, arguing that these may account for differences in the male/female presentation of ASD features. However, while these are potentially invaluable in accounting for the sex-based differences in ASD feature presentation per se, they do not directly consider the underlying associations between specific aspects of CBs and particular anxiety disorders, leaving this field open to further investigation.…”

The default mode network is associated with changes in internalizing and externalizing problems differently in adolescent boys and girls

“…The voxel clusters were then used as the seed for a secondary seed-to-voxel analysis to confirm the direction in which they are associated with changes in YSR scores. This method has been used with both clinical and nonclinical samples of children and adolescents (Cahart et al, 2022;Mateu-Estivill et al, 2021;Walsh et al, 2022); more technical details can be found in Nieto-Castanon (2022). In regression analyses using MVPAderived FC values to predict change in internalizing and externalizing problems in boys and girls, power was >.99 for all analyses.…”

Schema therapy in adults with autism spectrum disorder: A scoping review

“…About one third of the ASD population present with concurrent diagnosis of intellectual disability (Baio et al, 2018; Lord et al, 2020; Rydzewska et al, 2018; Shenouda et al, 2023; Zeidan et al, 2022). Male‐to‐female ratios for ASD and sex‐related differences in ASD presentation have been a subject of debate (McCrossin, 2022; Napolitano et al, 2022; Rujeedawa & Zaman, 2022; Walsh et al, 2023). Though a systematic review, meta‐analysis and pooled data analysis suggest no differences in social communication and interaction or ASD severity between males and females (Tillmann et al, 2018; Van Wijngaarden‐Cremers et al, 2014), underrepresentations of average to high intellectual ability females limit the generalizability of these outcomes (Van Wijngaarden‐Cremers et al, 2014).…”