Sex Differences in Autism Spectrum Disorder: Diagnostic, Neurobiological, and Behavioral Features

Abstract

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a worldwide prevalence of about 1%, characterized by impairments in social interaction, communication, repetitive patterns of behaviors, and can be associated with hyper- or hypo-reactivity of sensory stimulation and cognitive disability. ASD comorbid features include internalizing and externalizing symptoms such as anxiety, depression, hyperactivity, and attention problems. The precise etiology of ASD is still unknown and it is undoubted that the disorder is linked to some extent to both genetic and environmental factors. It is also well-documented and known that one of the most striking and consistent finding in ASD is the higher prevalence in males compared to females, with around 70% of ASD cases described being males. The present review looked into the most significant studies that attempted to investigate differences in ASD males and females thus trying to shade some light on the peculiar characteristics of this prevalence in terms of diagnosis, imaging, major autistic-like behavior and sex-dependent uniqueness. The study also discussed sex differences found in animal models of ASD, to provide a possible explanation of the neurological mechanisms underpinning the different presentation of autistic symptoms in males and females.

FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability

“…This study supports a preservation of striatal DAT availability following FMR1 deletion in rats and confirms that in vivo SPECT imaging paralleled by behavioral observation represents a useful tool to non-invasively investigate variations in neurotransmitter activity in neurodevelopmental disorders. Since sex-dependent differences in preclinical models of ASD have been documented 106 , the inclusion of both male and female animals should be considered in future studies.…”

Maternal Immune Activation Induced by Prenatal Lipopolysaccharide Exposure Leads to Long-Lasting Autistic-like Social, Cognitive and Immune Alterations in Male Wistar Rats

“…In our opinion, this remains a fascinating hypothesis to investigate in a follow-up of this study and underscores the importance of research focusing on the exact role of different cytokines in brain–periphery interactions during normal (fetal) development, and in NDDs such as ASD. Since sex-dependent differences in preclinical models of ASD have been documented [ 71 , 72 , 73 ], together with sexual dimorphism in a neuroinflammatory profile following perinatal inflammation [ 74 ], the inclusion of both male and female animals should be considered in future studies.…”

Recent Developments in Autism Genetic Research: A Scientometric Review from 2018 to 2022

“…In Cluster #8, Rylaarsdam and Guemez-Gamboa [ 14 ] authored the major citing document with a coverage of 11 references and a GCS of 118. The current label “Sex Difference” is derived from some studies in the cluster investigating the significant discrepancy in male-to-female individuals diagnosed with ASD and the effects of sex on ASD [ 125 , 165 , 166 , 167 , 168 ], with a small extension of research into ASD and gender dysphoria [ 169 ]. Notably, one of the most frequently cited references, with a citation frequency of 112, in the cluster is a systematic review and meta-analysis by [ 170 ] on the sex ratio in ASD.…”