Advanced paternal age is one of the more replicated risk factors for autism – but maybe not autism as it as seen as a disorder. Recent studies by Mount Sinai School of Medicine and Kings College of London show in both animal models and in epidemiological studies that advanced age in fathers is associated with the “active but odd” phenotype and PDD NOS. In people, older (but not “old”) age in fathers led to increased IQ and social aloofness that led to higher academic achievement. Is this autism? Or just a subtype of autism where the outcomes are adaptive rather than maladaptive? There are lots of questions about the nature of autism in these findings.
With hundreds of genes, thousands of environmental factors, and now sex being variables in determining risk for autism, where should science start? Over the decades researchers have been able to start narrowing down the combinations based on specific behaviors of interest, genes, and mechanisms which may narrow down which gene, which environmental factor and which sex. Dr. Sara Schaafsma and Dr. Donald Pfaff from Rockefeller University combined the three, and found that epigenetic changes in an autism risk gene called contact in associated protein like 2 contributed to elevation of risk for autism behaviors following maternal infection. In other words, being male and having the mutation produced small changes, increased by the environmental factor. In another separate study, Dr. Keith Dunaway and Dr. Janine LaSalle at UC Davis used brain tissue to look at a rare variant for autism on chromosome 15. Typically, mutations of this area of the genome are thought to cause autism. However, the effects of these mutations are also increased when environmental factors are present, leading to more de novo mutations. These are all examples of scientific breakthroughs that are helping better understand what causes autism. Even when it looks like one thing, it’s multiple things.
This week’s podcast is inspired by a new study in PNAS thatlooked at the role of methylation of the oxytocin receptor in social behavior in people without autism. Together with studies of the brains of people with autism, it suggests that filling the brains with oxytocin may not be the best approach for treating social impairments. Instead, compounds that turn on or turn off the genes that control oxytocin may be more appropriate, and it also may help explain variability in why some people respond to oxytocin treatment, and why others do not. Also, scientific technology has a new way of studying the influence of the environment on brain development.
On Thursday October 1st, Autism Science Foundation, Autism Speaks and the Escher Fund for Autism co-organized an online symposium which examined the possibility that early mutations in cells that pass along genetic information from generation to generation (sperm and egg and cells that make the sperm an egg) has a role in the causes of autism. This symposium is on the ASF podcast feed, but a quick summary is presented on this week’s podcast. Jill Escher from the Escher Fund for Autism and Mat Pletcher from Autism Speaks provide their perspective. Also, a quick rundown on the study that caused so much monkeying around in the press.
On October 1st, Autism Science Foundation, Autism Speaks and the Escher Fund for Autism co-organized a webinar entitled “Early Germline Events in the Heritable Etiology of ASDs”. The goal was to bring together researchers who study the germline (the sperm and the egg and all cells which pass down genetic information) and those studying the genetics of autism to determine how “de novo” or “new” genetic mutations are happening and how environment plays a role in genetics of autism and vice versa, rather than separating the concepts out into “either/or” . This is part of an ongoing online symposium series on the epigenetics of autism. Dr. Amander Clark from UCLA and Dr. Ryan Yuen from SickKids Hospital presented and a panel of experts including Lisa Chadwick from NIEHS, Patrick Allard from UCLA, Stephan Sanders from UCSF and Janine LaSalle from UCDavis commented. We hope you enjoy the 2 hour webinar.