Heritable factors that influence brain development result in multiple psychiatric conditions, including autism.
Researchers have determined that of the over 100 autism genes that exist, all act on early developmental functions and lead to diverse, overlapping outcomes, including psychiatric disorders, autism, and related conditions. Some genetic influences, while rare, can help define the mechanisms that lead to brain cells in autism developing over time. Although a link has been established connecting environmental influences to this same spectrum of conditions, few studies have successfully defined their interaction. These findings have implications for interventions and could lead to strategies for mitigating symptoms.
Given the comorbidity of mental health disorders with autism spectrum disorder, it should come as no surprise that new research reveals that ASD relevant genes act in fundamental ways that may influence multiple outcomes, ranging from ASD to schizophrenia, to ADHD27-30, neurodevelopmental disorders and intellectual disability31-33. Genes that act on such early and fundamental brain pathways have downstream effects on a number of brain functions, ASD being one of them. This might explain why there are so many ASD genes and why they are pleiotropic, meaning they have different functions. In fact, the list of genes associated with ASD keeps growing, as larger studies and better technology have revealed over 150 ASD associated genes34. Infant siblings of children with autism also show rare and common gene variants in ASD genes that can aid in a diagnosis9.
In addition, the presence of certain genetic mutations in ASD relevant genes can produce profound disabilities, which alone work to explain an ASD diagnosis. These mutations, referred to as rare genetic variants, are important to the community because their discovery has led to the creation of Patient Advocacy Groups that provide support and resources for focused research, as well as offer pathways to better understanding the basic circuitry of certain ASD behaviors35. Scientists are studying these rare genetic forms of ASD to understand all forms of ASD, particularly gene expression in the brain36,37. When compared to studies of the brains of people with bipolar disorder and schizophrenia, studies of brain tissue in people with ASD reveal overlapping genetic activity in genes that control synaptic signaling, neurotransmitter release, and immune response.36,37. The abnormal immune signaling in the brain might result in cell damage, as evidenced by accumulation of T-cells in brain tissue38. Studying the brains of people with ASD is the best way to understand the basic cellular and molecular basis of ASD, and is only possible through families who decide at the most difficult time to make the decision to donate. If you would like to learn more about the Autism BrainNet, which made these studies possible, visit www.takesbrains.org/signup.
While genetic factors are incredibly important in the diagnosis and presentation of symptoms of ASD, understanding the role of environmental factors in both the diagnosis and presentation of symptoms of ASD is crucial. One of the most studied environmental factors in ASD is exposure to air pollution during pregnancy. This year, ancillary evidence taken from additional locations via different methodologies shows a particular effect for a component in air pollution called PM (particulate matter) 2.5 (2.5 microns)39. Air pollution exposure may interact with maternal diabetes, which also increases the probability of ASD40. Air pollution also seems to influence an ASD diagnosis more strongly in boys41. It is important that public health policy address established, scientifically based environmental factors to address even smaller, but preventable, environmental factors.
There have been spurious reports of other environmental factors, but rather than look at factors in isolation, it is crucial to understand how these factors collectively influence brain development and interact with genetic susceptibility, either rare genetic or polygenic influences36. Another area of convergence of environmental and genetic factors is epigenetics, often called the “second genome”. The epigenome is a multitude of chemicals and tags on the DNA genome that is responsive to environmental factors that can turn on or turn off DNA expression, as early as when the embryo is formed. ASD risk genes identified in genetic studies can also work epigenetically42-46. The next generation of research will hopefully focus on understanding the multifactorial influences of an ASD diagnosis, how these factors affect symptoms and influence long term trajectories across neuropsychiatric diagnoses, including ASD.