Are There any Relationships between Latent Toxoplasma gondii Infection, Testosterone Elevation, and Risk of Autism Spectrum Disorder?

AUTISM SPECTRUM DISORDER AND THE “EXTREME MALE BRAIN” THEORY Autism spectrum disorder (ASD) is a set of complex neurodevelopmental disorders. ASD is characterized by early-onset difficulties in social interaction, repetitive behavior, and verbal and non-verbal communication. Worldwide prevalence of ASD is about 1% (Lai et al., 2014). Several factors have been proposed in the etiology of ASD, including genetics background, obstetric complications, intrauterine infections, environmental conditions, immune imbalance, and fetal testosterone levels (Rutter, 2005; Currenti, 2010; Ratajczak, 2011; Gesundheit et al., 2013; Goines and Ashwood, 2013; Jyonouchi, 2013; Lai et al., 2014). Autism affects males more frequently than females (Baron-Cohen et al., 2011; Werling and Geschwind, 2013; Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators and Centers for Disease Control and Prevention, 2014), with ratios of 4:1 (male: female) for classic autism (Chakrabarti and Fombonne, 2001) and 11:1 in individuals with Asperger syndrome (AS) (Gillberg et al., 2006). This evidence raises an important question: what influencing factors are responsible for the higher male prevalence of autism? The exact answer to this question remains unclear; however, the “extreme male brain” theory of autism (Baron-Cohen, 2002) proposed that exposure to high levels of prenatal testosterone is one possible mechanisms (Baron-Cohen, 2002; Baron-Cohen et al., 2011). LATENT TOXOPLASMOSIS INFLUENCE TESTOSTERONE PRODUCTION Toxoplasmosis is one of the most common zoonotic diseases that has infected approximately one-third of the world’s human population (Montoya and Liesenfeld, 2004). Although it is estimated between 25 and 30% of the world’s human population is infected by T. gondii, and the most common form of infection is latent (asymptomatic) (Dalimi and Abdoli, 2012; Robert-Gangneux and Dardé, 2012). On the other hand, latent toxoplasmosis can induce different hormonal and behavioral alterations in humans and rodents (Flegr, 2013a,b) and involved in the etiology of various psychotic disorders (Dalimi and Abdoli, 2012; Flegr, 2013a; Abdoli et al., 2014). Different studies reported an increased concentration of testosterone in men with latent toxoplasmosis compared to the testosterone in Toxoplasmanegative individuals (Flegr et al., 2008a,b; Shirbazou et al., 2011; Zghair et al., 2014). Increased concentrations of testosterone were also confirmed in an animal model of latent toxoplasmosis (Lim et al., 2013). In addition, several indirect evidences exist for increased prenatal testosterone in latent toxoplasmosis (see the next sections). This condition raises an important question: does latent toxoplasmosis increase risk of ASD via mechanisms consistent with the “extreme male brain” theory of autism? If this hypothesis is correct, pregnant women with latent toxoplasmosis are more likely to give birth to a child with ASD. Hence, we summarize the evidences of increased prenatal testosterone in ASD and latent toxoplasmosis to offer a new insight into the role of T. gondii infection in the etiology of ASD.