The Neurobehavioral Clinical Research Section was formed in 2011, when Dr. Shaw joined the NHGRI as an Earl Stadtman Investigator. Dr. Shaw's research program examines the interplay of genomic, social and environmental factors in shaping the developmental trajectories of brain and behavior. The program focuses on one of the most common and heritable childhood mental illnesses, attention deficit hyperactivity disorder (ADHD). ADHD is a highly heritable disorder, with an estimated 70 percent of the affected phenotype explained by genetic factors. Genomics, therefore, is at the core of understanding the disorder. While some important advances have been made
In pervious studies, Dr. Shaw linked clinical symptoms of ADHD with atypical brain development using longitudinal anatomic neuroimaging. The section now aims to integrate these neural trajectories with genomics, behavioral and social scientific data, identifying the factors association with variations in brain development. The ultimate goal is to provide tools to aid diagnosis and prognosis, and to develop individualized treatments that reflect the diversity of the genetic, behavioral and neurocognitive problems found in ADHD.
The Neurobehavioral Clinical Research Section aims to conduct research into brain and behavior, which lies at the intersection between genomics, and the social and developmental psychological sciences. The position of the section within the Social and Behavioral research Branch of the NHGRI provides an ideal environment for such integrative clinical science.
The section has three main areas of research: 1) defining novel phenotypes pertinent to ADHD based in the neuroimaging, social and behavioral sciences, 2) identifying the genomic factors that contribute to the disorder, and 3) defining the neural mechanisms through which treatments work.
Refining the phenotype of ADHD: The diagnosis of ADHD is still based purely on symptoms with no consideration of underlying neurobehavioral deficits. The section aims to fully characterize the phenotypes of ADHD, using tools from the neurobiological, psychological and social sciences. This will allow advancement beyond a symptom-based approach to a mechanistic understanding of the disorder as a disruption to behavioral processes that can be mapped directly onto brain structure and function. The work linking brain development with the clinical course of ADHD symptoms exemplifies this approach. Thus, the section has demonstrated that among individuals who remitted from childhood ADHD by adulthood, the structure of cortical regions supporting attention and cognitive control veered towards typical dimensions or 'normalized' over the course of development. By contrast, those who had persistent symptoms into adulthood showed fixed, non-progressive cortical deficits. Currently, we are mapping the clinical course of ADHD directly onto brain function using the complementary technologies of functional magnetic resonance imaging and magnetoencephalography.
Given that children are embedded in multiple social contexts, whether families, schools, or local communities, our work aims to understand the social manifestation of ADHD thereby identifying new 'social' phenotypes. To that end, we are identifying systematicities in the social position of children affected by ADHD within these multiple, nested social contexts, with a focus on understanding how a child's social standing impacts their mental health. This work leverages advances in modeling and visualizing social networks to provide a nuanced understanding of how a child's social 'position' contributes to brain development and the clinical course of ADHD.
Integrating genomics: The next step is to use the novel phenotypes of brain development and social behavior in ADHD as the basis for genomic discovery and understanding. Many of the brain anomalies we have found to characterize childhood ADHD are dimensional and extend to typically developing children who have symptoms of the disorder, but not the full syndrome. This neurobiological evidence for continuity between ADHD and typical development thus provides a neuroanatomic quantitative phenotype for ongoing genomic studies.
Additionally, the section has recruited a number of extended families with multiple members affected by ADHD. In their family study, they are examining anomalies of brain, cognition and behavior with the goal of linking those phenotypes that cluster within families with genomic data.
Understanding how treatment works: Each year, about one in 20 children in the United States are prescribed psychostimulant medication as treatment for ADHD. However, researchers do not understand why 30 percent of those receiving this treatment show a marked loss of initial therapeutic benefit after several months. The section is thus examining the neural effects of pharmacological treatment for ADHD over both the short and longer term, focusing on effects on brain function and perfusion. Additionally, since many children with ADHD receive behavioral interventions, they are also examining the neural effects and genotypic moderators of behavioral management for ADHD. Such work may help improve current behavioral treatments for ADHD which are effective in only a minority of children. These studies benefit from alliances with local mental health practitioners, allowing the group to apply the technologies of the clinical center to the study of the effects of clinical care delivered in the community.
Neurobehavioral Clinical Research Section Members
Wendy Sharp, M.S.W., Study Coordinator
Eszter Szekeley, Ph.D., Postdoctoral Research Fellow
Gustavo Sudre, Ph.D., Postdoctoral Research Fellow
Daniel Weingart, B.S., Post-Baccalaureate IRTA
Teighlor Bonner, B.A., Post-Baccalaureate IRTA
Saadia Choudhuri, M.A., Recruitment Coordinator
Posted: January 7, 2014