Philadelphia, Feb. 7, 2018 - Exposure to androgens (male hormones) during brain development alters genes related to autism spectrum disorder (ASD), according to a new study published in Biological Psychiatry. Using male human cells, researchers at the University of Strasbourg, France, identified key genes that are regulated by testosterone and that contribute to the risk for autism, generating important insight into how male hormones might contribute to the increased male susceptibility to ASD.
The findings provide a clue as to why ASD affects boys about four times as much as girls. Male fetuses produce androgens during critical stages of brain development when cells divide and develop into neurons. The researchers showed that androgens increase the spread of cells and prevent them from death, which could predispose boys to ASD by contributing to the excessive brain growth that occurs in people with ASD during the first years of life.
"Understanding the mechanisms for the male preponderance for autism is like pulling on a lose thread. It could help to 'unravel' important mechanisms contributing to autism risk," said John Krystal, Editor of Biological Psychiatry. Identifying a role of androgens in this risk could be important for prevention or the development of potential treatments for ASD.
In the study, co-senior authors Jean-Louis Mandel, M.D., Ph.D., and Amélie Piton, Ph.D., and colleagues used human pluripotent neural stems cells to model the cells that generate neurons during brain development. Treatment with the testosterone metabolite DHT led to subtle changes in the expression of about 200 genes, several of which have previously been associated with ASD. Some of the genes that were most affected by DHT treatment included NRCAM, which has been linked to the brain abnormalities and symptoms in ASD, and FAM107A, which is increased in people with ASD. FAM107A also appeared to play a part in androgen's ability to increase cell numbers in the study.
"These effects of male hormones may therefore contribute to the increased sensitivity of the male brain to develop ASD when also exposed to other genetic or environmental factors," said Dr. Piton, suggesting that the biological explanation for the sex-specific inequality of ASD points to a predisposition in males, rather than a protective effect in females.
In addition to providing a clue into the male susceptibility to ASD, Dr. Piton says that the list of genes that were altered by androgens in the study might be useful to identify new genes that might be involved in ASD or in other diseases that occur more often in males.
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Notes for editors
The article is "Genes and pathways regulated by androgens in human neural cells, potential candidates for the male excess in autism spectrum disorders," by Angélique Quartier, Laure Chatrousse, Claire Redin, Céline Keime, Nicolas Haumesser, Anne Maglott-Roth, Laurent Brino, Stéphanie Le Gras, Alexandra Benchoua, Jean-Louis Mandel, and Amélie Piton. It appears in Biological Psychiatry, published by Elsevier.
Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at Biol.Psych@UTSouthwestern.edu or +1 214 648 0880. Journalists wishing to interview the authors may contact Amélie Piton, Ph.D., at piton@igbmc.fr.
The authors' affiliations and disclosures of financial and conflicts of interests are available in the article.
John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.
About Biological Psychiatry
Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.
The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.
Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 6th out of 142 Psychiatry titles and 10th out of 258 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2016 Impact Factor score for Biological Psychiatry is 11.412.
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