Using a Systems Biology Approach to Inform an Understanding of Gene-Chemical Relationships Associated with Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder (ADHD) is a complex neuropsychiatric disorder currently impacting the lives of more than 5 million children in the U. S. The pathophysiological mechanisms of ADHD and its links to environmental chemicals are largely unknown. In contrary to traditional reductionist theory, where genes and environmental factors are teased apart, we employed multiple systems level approach to understand gene-gene interactions and gene-environmental interactions, and their contribution to ADHD outcome. Systems analyses of chemical-gene interactions identified dopamine but also non-dopamine related pathways including corticotrophin hormone releasing signaling pathways, cAMP mediated signaling, glucocorticoid signaling, and apoptosis pathways to be associated with ADHD. The present study provided insights into understanding of the combined contribution of genes and chemicals, and facilitated generation of testable hypothesis, which have great potential to help develop more effective treatments and prevention methods for reducing the growing public health burden of ADHD.Master of Public Healt