Autism, high-functioning autism, Asperger syndrome (AS) and pervasive developmental disorder not otherwise specified (PDD-NOS) are collectively referred to as autism spectrum conditions (ASC). Recent research has suggested that ASC represent the upper extreme of a collection of traits that are continuously distributed in the population [1
]. This continuum view provides a shift away from the categorical diagnostic approach and towards a quantitative approach for measuring autistic traits.
The strong bias of ASC towards males is well established [3
], with a clear male to female ratio, estimated at 4:1 for classic autism [4
] and as high as 10.8:1 in individuals with AS [5
]. The extreme male brain (EMB) theory of autism proposes that ASC are an exaggeration of certain male-typical traits [6
]. This theory has been extended to explain both cognition and neuroanatomy in individuals with autism [8
]. It has been suggested that prenatal exposure to testosterone may be a key biological mechanism for shaping sex differences in the brain, and may be involved in the biased sex ratio found in these conditions [8
Although genetic sex is determined at conception, it is the gonadal hormones (that is, androgens, estrogens and progestins) that are responsible for differentiation of the male and female phenotypes in the developing human foetus [10
]. Direct sampling of foetal serum or manipulation of foetal hormone levels would be very dangerous; hence, researchers have used indirect methods of measuring prenatal hormone exposure to study effects on later development.
One such indirect measure is the ratio between the length of the second and fourth digits (2D:4D) of the hand. This ratio has been found to be sexually dimorphic, being lower in males than in females. The 2D:4D ratio is thought to be fixed by week 14 of foetal life, and has been found to reflect foetal exposure to prenatal sex hormones in early gestation [11
]. Results from studies of 2D:4D ratios as a proxy for FT levels show that children with ASC have more masculinised digit ratios compared with typically developing boys. These patterns have also been observed in the siblings and parents of children with ASC, indicating the possibility of a link between genetically based elevated FT levels and the development of ASC [13
]. Other evidence of a genetic link to ASC was provided by a recent study, which showed that genes regulating sex steroids are associated with autistic traits, as measured by scores on the Autism Spectrum Quotient (AQ), in a typical adult sample [15
]. A parallel study also showed that genes regulating sex steroids are associated with a diagnosis of AS in a case-control sample [15
The medical condition of congenital adrenal hyperplasia (CAH) leads to abnormally high androgen levels, and has provided researchers with a 'natural experiment' in which to examine the effects of elevated androgen exposure. Girls with CAH have more autistic traits (measured using the adult AQ) than their unaffected sisters [16
]. Given that this condition is usually treated after birth, this suggests that the higher AQ scores in such children reflect elevated prenatal androgen levels. However, these findings should be interpreted with caution, because CAH carries a number of related problems (and requires extensive treatment) which may affect the atypical cognitive profiles found in this population [17
Some studies have also compared measurements of testosterone in umbilical cord (UC) blood with postnatal development. A recent study using UC blood testosterone measurements examined pragmatic language ability in girls followed up at 10 years of age. Results showed that the higher a girl's free testosterone level at birth, the higher the scores on a pragmatic language difficulties questionnaire [19
]. However, levels of FT are typically at very low levels from about week 24 of gestation, and UC samples can contain blood from the mother as well as the foetus (and hormone levels may vary due to labour itself) [20
], so UC blood testosterone does not allow testing of whether outcomes reflect FT per se
Currently, the best method to examine the effect of FT is to sample via amniocentesis the amniotic fluid surrounding the foetus. An advantage of amniotic fluid samples is that amniocentesis is often performed for routine clinical purposes within a relatively narrow time period that coincides with the hypothesised critical period for human sexual differentiation between weeks 8 and 24 of gestation [21
]. This is also more direct than the 2D: 4D method, as the hormones themselves can be assayed, rather than relying on a proxy for these.
Several studies have linked elevated levels of FT in the amniotic fluid with the masculinisation of certain behaviours, beginning shortly after birth. Elevated FT has been linked to reduced eye contact in infants, smaller vocabulary in toddlers, narrower interests at 4 years of age, less empathy at 4 and 8 years, and increased systemizing (the drive to analyse and construct systems) at 8 years [9
]. In addition, FT levels have been found to be positively correlated with the number of autistic traits in older children (6-10 years old), using two independent dimensional measures of autistic traits (the AQ-Child version and the Childhood Autism Spectrum Test) [27
The current study aimed to extend our understanding of the effect of prenatal hormones on the development of autistic traits, using a new measure for evaluating autistic traits in toddlers. The Quantitative Checklist for Autism in Toddlers (Q-CHAT) is a parent-report questionnaire that evaluates autistic traits in toddlers between 18 and 24 months old [28
]. Scores on this measure have shown a near-normal distribution in a large general population sample (n = 779), suggesting that it is a useful measure of individual differences in autistic traits in toddlers [28
]. In the present study, the relationship between measurements of FT and scores on the Q-CHAT were examined.