Sex differences in neuronal systems function and behaviour: beyond a single diagnosis in autism spectrum disorders

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is associated with functional brain alterations that underlie the expression of behaviour. Males are diagnosed up to four times more than females, and sex differences have been identified in memory, cognitive flexibility, verbal fluency, and social communication. Unfortunately, there exists a lack of information on the sex-dependent mechanisms of ASD, as well as biological markers to distinguish sex-specific symptoms in ASD. This can often result in a standardized diagnosis for individuals across the spectrum, despite significant differences in the various ASD subtypes. Alterations in neuronal connectivity and oscillatory activity, such as is observed in ASD, are highly coupled to behavioural states. Yet, despite the well-identified sexual dimorphisms that exist in ASD, these functional patterns have rarely been analyzed in the context of sex differences or symptomology. This review summarizes alterations in neuronal oscillatory function in ASD, discusses the age, region, symptom and sex-specific differences that are currently observed across the spectrum, and potential targets for regulating neuronal oscillatory activity in ASD. The need to identify sex-specific biomarkers, in order to facilitate specific diagnostic criteria and allow for more targeted therapeutic approaches for ASD will also be discussed.

Granulocyte colony‐stimulating factor has a sex‐dependent positive effect in the maternal immune activation‐induced autism model

“…The interest on possible environmental agents which would be associated with development of ASD increased for last decades (Lawler et al, 2004). Lipopolysaccharide (LPS) is obtained from the walls of gram‐negative bacteria and has been demonstrated to be a good candidate for producing infection in animal models (American Psychiatric Association, 2013; Williams et al, 2021). The data have shown that administration of LPS during the perinatal period alters long‐term behavioral patterns, including abnormal social communication and disturbed socialization skills (Arsenault et al, 2014; Lawler et al, 2004).…”

Sex differences in autism‐like behavior and dopaminergic neurons in substantia nigra of juvenile mice prenatally exposed to valproate

“…Intriguingly, sex dimorphism has been identified in the symptoms and diagnosis of ASD. Before adolescence, ASD is fourfold more frequent in male than female patients (de Giambattista et al., 2021), whereas during adolescence, the diagnosis is more frequent in female patients (Williams et al., 2021). These differences have been attributed to social and biological factors that may modify neural development between the sexes (Lai et al., 2015; Wood‐Downie et al., 2021).…”

EEG Signals Unveil Distinct Sex-Specific Patterns in Human Cohorts with Limited Implications for Pathological Diagnosis

“…A clear bias favouring males across various research stages contributes to this issue Lee [2018]. It is a crucial biological variable in dementia research Podcasy and Epperson [2016], the diagnosis of Autism Spectrum Disorder is up to four times more frequent in males than in females Williams et al [2021]. Therefore, recognizing sex as a crucial biological variable in primary and preclinical research is essential for ensuring accurate and reproducible results for diagnosis and treatment.…”