Autistic traits, autism spectrum conditions, and foetal testosterone

Autism spectrum conditions (ASC) affect males far more often than females. This is likely to reflect the influence of hormones, genetics, diagnostic practice, or all three factors. This program grant tests the first of these by following up children whose mothers had amniocentesis, and where the amniotic fluid tesosterone levels are measured. It tests in both a small British Biobank (linked to 500 children) and in the much larger Danish Biobank (linked to 90,000 children) if foetal testosterone levels are elevated in children who later show more autistic traits, or who go on to receive a diagnosis of autism or Asperger Syndrome. In addition, since amniocentesis samples may not be representative of the general population, we test if foetal testosterone is correlated with newborn testosterone levels measured in blood spots collected at birth, and in saliva at 3 months, since ultimately such tests are less invasive, have less risk, and could be taken from every baby. We also measure neonatal testosterone levels in children later diagnosed with autism. Finally, we test a rare medical condition (AIS) in which males cannot bind foetal testosterone, to test the prediction that such males should have fewer autistic traits than typical males. The range of planned studies will help answer the question as to whether foetal testosterone increases the risk of autistic traits and ASC.

In our previous MRC program we tested if foetal testosterone (FT) has an effect on variation in behavioural development in children whose mothers had had amniocentesis. We found that FT was inversely correlated with frequency of eye contact at 12 months, vocabulary size at 18 and 24 months, peer relations, empathy, narrow interests, and number of autistic traits at 48 months. We also found that females with congenital adrenal hyperplasia (CAH) had more autistic traits than unaffected females. In this new proposal we wish to extend these studies in six ways: (1) We will repeat the earlier studies but expand the sample size from n = 70 to n = 500, in order to increase power; (2) We will add an independent measure of autistic traits (the AQ) to test if the relationship between FT and autistic traits is robust; (3) We will test FT levels in n = 467 cases of diagnosed autism vs. n = 934 controls, whose amniotic samples are in the Danish Biobank, to test categorical diagnosis of ASC in relation to FT; (4) We will test if FT levels in n = 500 children from amniotic fluid are correlated with neonatal tesosterone (NT) from Guthrie blood spots; (5) We will test NT in n = 100 cases of ASC from Guthrie blood spots, vs. 100 controls; and (6) We will test individuals with Androgen Insensitivity Syndrome (AIS), predicting they should have fewer autistic traits than chromosomally-matched controls. This design will test the validity of the foetal androgen theory of autistic traits and autism.