June 3, 2014

expert reaction to autism and hormone levels

A study published in Molecular Psychiatry reported that elevated levels of steroid hormones in amniotic fluid may contribute to the development of autism, but the authors stressed their findings do not justify prenatal screening or for treatments that target steroid hormones.

Dr Rosa Hoekstra, Lecturer in Psychology, The Open University, said:

“This paper is the first to suggest that male fetuses who later develop autism may have been exposed to somewhat higher levels of prenatal steroid hormones, as measured in amniotic fluid, compared to male fetuses who develop typically after birth. However, the findings don’t suggest a prenatal test for autism is near. The variability in levels of prenatal steroid hormones was substantial, with some boys in the control group having been exposed to high steroid hormone levels before birth, and some boys in the autism group showing low levels of prenatal steroid hormones. It is therefore impossible to draw any inferences on an individual level, and screening for these hormone levels prenatally would be uninformative regarding the individual’s risk to develop autism later in life.

“Moreover, this study focused on comparisons between boys with autism and boys with no psychiatric diagnoses or learning difficulties. As the authors point out themselves, it is as yet unknown if similar differences apply to girls with autism, and to children with other conditions, such as ADHD or intellectual disability.”

Prof Richard Sharpe, MRC Centre for Reproductive Health at the University of Edinburgh, said:

“Finding the fetal causes of autism-spectrum disorders is a daunting task, so this carefully designed study needs to be viewed in this context. It is an important first step and provides good evidence that there is a relationship between the determinants of steroidogenic processes (which lead to steroid hormone production) and autistic disorders – the latter being associated with higher steroidogenic activity. At face value this appears to fit with the previously argued hypothesis that ‘over-exposure’ to fetal androgens may increase the risk of autistic disorders, and would also fit with the higher prevalence of these disorders in boys, who are naturally exposed to higher levels of fetal androgens than are girls (as part of the normal masculinisation process that occurs in early fetal life).

“However, as the authors are careful to point out, if you compare actual hormone levels (I.e. Testosterone) in the amniotic fluid samples in their study, there is no clear distinction  between hormone levels in controls and in those who went on to develop an autistic disorder. There could be many explanations for this, such as variation in individual sensitivity to hormones or that the time widow investigated is too early to detect a true elevation of hormone levels (the amniocentesis procedure from which these samples are collected is usually undertaken between 15-20 weeks). Alternatively, it may be that the overall elevation of steroidogenesis is an indicator of increased activity of an overall regulator (e.g. steroidgenic factor-1) or of metabolising enzymes (a point made by the authors), and it is this activity (rather than that of androgens per se) that somehow alters brain development/organisation so as to predispose to autistic disorders. If this was correct, it might still lead to generally higher testosterone (androgen) levels which would then be associated with the disorders.

“We now know that subtle variations in fetal development are an important determinant of later disease, which may be lifelong. Researching this in humans is incredibly difficult because of the obvious limitations in accessing what is happening in the fetus inside the womb, so investigations such as the present study have to be viewed as pioneering.”

‘Elevated fetal steroidogenic activity in autism’ by Baron-Cohen et al. will be published in Molecular Psychiatry on Tuesday 3^rd June.

Declared interests

Rosa Hoekstra: I am a long term collaborator with the research group that published this paper, but was not involved in the research reported here.