Autism spectrum disorder beyond the extreme male brain

Sammanfattning: Autism spectrum disorder (ASD) is an umbrella-term for neurodevelopmental conditions characterized by both impairments in communication and social interaction and unusually restricted and repetitive or stereotyped interests and behaviors. Although proven to have a strong genetic etiology, the full biological background of ASD remains unclear. The higher frequency of ASD among males implies that a sex-related perspective may shed light on both the etiology and behavioral differences between males and females with ASD. The main aim of this thesis was to explore male and female ASD phenotypes and their possible relation to sex hormones, beyond the well-established high systemizing—low empathizing personality observed by the extreme male brain theory of autism. Studies I and II examined sex-dimorphic parameters such as sex hormone levels, anthropometry, self-rated gender identity, gender role and sexuality in 26 men and 24 women with high-functioning ASD and 53 age- and gender-matched neurotypical controls. Photographs of faces and bodies as well as voice recordings were blindly assessed with respect to gender coherence. Women with ASD had higher testosterone levels and less feminine facial features, while men in the ASD group were assessed as having less masculine body characteristics and voice quality than respective controls. A weak gender identity and low libido was more common in adults with ASD than in the control group. The hypothesis of prenatal testosterone as a risk factor for developing ASD and attention deficit/hyperactivity disorder (ADHD) was tested in study III in a cohort of dizygotic twins from the Child and Adolescent Twin Study in Sweden (CATSS). Parent-reported autistic and ADHD traits were compared between female index twins with either a co-twin brother or a co-twin sister. Contrary to what could be expected from a presumed testosterone transfer from a co-twin brother to his sister, girls with a co-twin brother had lower ASD and ADHD scores as compared to those who had a co-twin sister. Study IV examined psychometric properties as well as sex/gender differences in RAADS-14 Screen, a short version of the RAADS-R self-assessment questionnaire for ASD. Responses from 135 adults with ASD, 508 adults with other psychiatric disorders and 590 non- psychiatric controls were analyzed, showing satisfactory psychometric properties for men and women alike. Women scored higher than men in the sensory reactivity domain across all groups. In conclusion, aberrations in the expression of sex-dimorphic traits are present in ASD. Androgyny, weak gender identity and low libido seem overrepresented along with an extreme male cognitive style. These patterns are not easily explained solely by an effect of increased prenatal androgen blood levels. The observed sex-differences in ASD underscore the necessity of acknowledging possible diagnostic and biological sex-differences when conducting research on ASD.