Epigenetics in Autism: An In Vivo PET Imaging Study
Abstract
Autism spectrum disorder (ASD) is common and affects about 1 in 54 children, with boys being diagnosed about 4.5 times more often than girls. It is still not known what leads to autism, but both genetics and environmental factors contribute to ASD, and so does the interaction between genes and environment. One key biological mechanism that lies at the intersection of genes and environment is epigenetics. Epigenetics refers to mechanisms through which the environment can influence whether our genes are turned on or off. In humans, brain studies conducted after death have shown that epigenetic enzymes (a special type of protein) known as histone deacetylases (HDACs) play a role in ASD. Through animal studies researchers have learned that HDACs are associated with social deficits, that changes in HDACs affect males more than females and that social deficits can be improved after administering a drug that inhibits HDACs. Despite the evidence implicating HDACs in ASD, they have not yet been investigated in vivo in individuals with ASD. In this study, we propose to investigate HDACs in adults with ASD using positron emission tomography (PET) imaging with a probe that allows seeing these enzymes in the living human brain. Using this technique in healthy adults, we saw that HDAC levels in several brain regions differ between women and men and that the level of HDACs in the brain is associated with socio-emotional skills. Here we will measure HDAC levels in adults with ASD and compare them to healthy controls who do not have ASD. We will also investigate whether HDACs differ between women and men with ASD and whether the levels of HDAC seen is associated with autism severity and autism symptoms such as social skills, communication, and language. This research proposal is aligned with two Fiscal Year 2021 Autism Research Program (ARP) Career Development Award Areas of Interest: Mechanisms underlying sex differences and Mechanisms of heterogeneous clinical expression of ASD. This research will increase our understanding of how these epigenetic enzymes may contribute to ASD. In the longer term, findings from the current work may lead to studies that will specifically investigate therapeutic interventions that are targeting these enzymes. Dr. Zürcher’s goal is to lead a neuroimaging program that will help better understand the biology underlying ASD, which will hopefully lead to treatments that improve quality of life for individuals living with ASD and their families. She uses simultaneous magnetic resonance imaging (MRI) and PET that allows investigating brain structure and biological markers (such as HDACs) at the same time. Dr. Zürcher was recently promoted to Assistant Professor of Radiology. At her career stage, an ARP Career Development Award is incredibly meaningful, allowing her to start pursuing her own research ideas more quickly.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210892
Entities
People
- Nicole Zurcher Wimmer
Organizations
- Massachusetts General Hospital
- United States Army