Autism spectrum disorder (ASD) is a heterogeneous developmental neuropsychiatric condition characterized by two core symptom criteria: (1) deficits in social communication and social interaction; and (2) restricted patterns of repetitive behaviors and interests or activities.1 Previously, ASD was not a formal diagnostic term. Autistic disorder was included under the broader category of pervasive developmental disorders (PDDs) with other neurodevelopmental conditions characterized by impaired social behavior and communication along with restricted interests and repetitive behavior. Those additional conditions included Asperger’s disorder, Rett’s disorder, child disintegrative disorder and PDD, not otherwise specified (NOS). In DSM-5, autistic disorder, Asperger’s disorder, and PDD NOS have been subsumed under the category of ASD while Rett’s disorder and childhood disintegrative disorder have been removed and are not considered to fall within the rubric of ASD. In DSM-5, if ASD symptoms are clinically present in the setting of a genetic condition such as Rett’s disorder, the individual is diagnosed with ASD with the specifier, “associated with a known medical or genetic condition or environmental factor.”
A vast range of comorbid neuropsychiatric and medical conditions are associated with ASD. Common comorbid psychiatric conditions include anxiety, attention-deficit hyperactivity disorder (ADHD), depression, tic disorders, oppositional defiant disorder, and intellectual disability (ID).2,3 Common medical comorbidities include gastrointestinal (GI) disturbances, sleep disorders, epilepsy, mitochondrial dysfunction, and immune system abnormalities.4
Prevalence estimates for ASD have increased steadily over recent decades. For example, a 78% estimated increase in the prevalence of ASD was documented between 2002 and 2008 by the Autism and Developmental Disabilities Monitoring Network of the U.S. Centers for Disease Control and Prevention, with a rate of 1 in 88.5 A rate of 1 in 50 was reported a few years later based on results from a 2011–2012 telephone survey study.6 Reasons for this increase in prevalence have not been fully explained. Many factors, including changing diagnostic criteria, better identification of cases of ASD, and possibly an increase in environmental contributions may be involved. In part, increased rates in recent studies are thought to be related to improvements in identifying ASD in underserved and nonwhite populations.7
The gender ratio in ASD is generally reported as a 4 to 1, male to female ratio.8 Theories to explain the reasons for the reported sex difference differ. One theory is that of “the extreme male brain.” This theory posits that ASD may be mediated by abnormal prenatal sex steroids resulting in characteristics at the very far end of the normal curve of what is considered a more typical male pattern of cognitive functioning, which includes features such as higher scores in systemization tasks and a relative lack of empathic expression.9,10 An alternative theory is “the female protective effect” model which suggests resilience to genetic insults, such as copy number variants (CNVs) and single-nucleotide variants, whereby females are protected from more severe ...