Male sex bias in early and late onset neurodevelopmental disorders: Shared aspects and differences in Autism Spectrum Disorder, Attention Deficit/hyperactivity Disorder, and Schizophrenia

Abstract

Neurodevelopmental disorders are characterized by relatively early onset, with temporal variations across conditions. These lifelong conditions lead to social and communication impairments, and cognitive deficits. In recent years, the importance of biological sex as a vital factor determining behavioural and cognitive vulnerability has been substantiated with a direct impact on both diagnosis and therapeutic response. Several theories have been raised as an attempt to explain psychiatric sex bias. These include the extreme male brain theory, female protective effect, maternal stress, and perinatal inflammation. Here, we address this issue in the context of three important neurodevelopmental disorders where male bias exists into variable extents: autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and schizophrenia (SCZ). Sex differences in behaviour and brain organization are reviewed both for patient and animal research, in the context of molecular theories that may explain differential disease vulnerability. Accumulating evidence suggests a complex mechanistic scenario, with genetic predisposition and endocrine and environmental factors as interacting components governing disease onset, progression, and severity.

Keywords: Attention deficit/hyperactivity disorder; Autism spectrum disorder; Male bias; Neurodevelopmental disorders; Schizophrenia; Sexual dimorphism.