Wednesday, April 16, 2008
AD/HD and Research Priorities
Thank you for the opportunity to address the members of CHADD and the readers of CHADD’s Leadership Blog. As director of the National Institute of Mental Health (NIMH), I am excited by CHADD’s enthusiasm and support for progress in clinical and basic research that will lead to improved outcomes of individuals with mental disorders, including attention deficit/hyperactivity disorder. AD/HD is a neurobiological mental disorder that affects approximately five percent of school-aged children (G. Polanczyk and L. A. Rohde, 2007), and is recognized by the NIMH, the Centers for Disease Control, and the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Recent studies have demonstrated alterations in neurotransmitter systems and cortical development that may be fundamental to AD/HD. Even though we do not yet understand the exact causes of AD/HD, we know that approximately 75 percent of the likelihood of developing AD/HD is due to genetic influences (S. V. Faraone et al., 2005), and the remaining risk is composed of environmental factors.
The National Institutes of Health (NIH) has a vision for clinical care built around four Ps: medical care that is predictive, pre-emptive, personalized, and participatory. NIMH has been pursuing this vision for mental disorders. Toward this aim, in 2007 we funded 219 awards related to AD/HD research, totaling over $80 million.* These investigations range from the identification of genetic and behavioral features to predict who is at risk, to early intervention studies to pre-empt the disability of AD/HD, to treatment studies aimed at identifying personalized, individual patterns of response to behavioral or medical interventions. As we continue to acquire information that will lead to improved therapies, we encourage the recognition of, diagnosis of, and treatment of AD/HD by clinicians. NIMH is also committed to participatory research, which means that we work closely with groups like CHADD to ensure that our science is relevant to the needs of patients and their families. For us, research is a partnership between our scientists who want to make a difference and our families who volunteer to ensure that research will make a difference.
Biomedical research rarely follows a linear path of progress. There are many years of incremental findings before major jumps forward. The renowned physicist Freeman Dyson famously noted more than ten years ago that “new directions in science are launched by new tools more often than new concepts"(1997). New tools for genetics and imaging are changing the landscape of biomedical research from mental disorders to cancer, leading to advancements in the understanding of many common disorders. The past year has been a time of extraordinary progress, arguably the beginning of a jump forward, in research on AD/HD. The first whole genome association study was completed, with data available in dbGAP so that researchers anywhere can join the search for genes associated with AD/HD (GAIN: International Multi-Center ADHD Genetics Project Database). Imaging studies demonstrated that children with AD/HD have delayed cortical maturation (P. Shaw et al., 2007). After years of debate about the validity of AD/HD as a behavioral or cognitive disorder, this finding reminds us that AD/HD is a developmental brain disorder, specifically a disorder of cortical development. Finally, studies in the past year support the value of treating preschool children with AD/HD with behavioral interventions (L. Kern et al., 2007), providing additional options to earlier data about the effectiveness of psychostimulant medication in this age group (B. Vitiello et al., 2007).
If we now view AD/HD as a disorder of cortical maturation, what does this mean about diagnosis and treatment? Should children receive repeated MRI scans to make a diagnosis or to follow treatment response? Can we find genes that regulate cortical maturation or develop novel treatments that accelerate it? Do early individual differences in cortical maturation have any predictive significance? These are all questions that will need to be addressed in future research. But clearly, in this case, a new tool has yielded a new concept. AD/HD is not just a behavioral disorder; it is a developmental brain disorder. This conceptual shift suggests not only an entirely new generation of research but new prospects for prediction, pre-emption, personalization, and, yes, participation of families as we generate research to pave the way for improved treatments, prevention, and ultimately cures for AD/HD.
Thomas R. Insel, MD
Director, National Institute of Mental Health
* NIH is currently improving the system for coding disease-related projects. This change may alter the number of projects that are coded as “AD/HD-related” in 2008 and future years; however this will not alter our strong commitment to funding the best basic and clinical research, working to improve the lives of AD/HD-affected individuals and their families.
Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P (2005) Molecular genetics of attention-deficit/hyperactivity disorder. Biological Psychiatry 57:1313-1323.
Kern L, DuPaul GJ, Volpe RJ, Sokol NG, Lutz JG, Arbolino LA, Pipan M, VanBrakle JD (2007) Multisetting assessment-based intervention for young children at risk for attention deficit hyperactivity disorder: Initial effects on academic and behavioral functioning. School Psychology Review 36:237-255.
Polanczyk G, Rohde LA (2007) Epidemiology of attention-deficit/hyperactivity disorder across the lifespan. Current Opinion in Psychiatry 20:386-392.
Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP, Greenstein D, Clasen L, Evans A, Giedd J, Rapoport JL (2007) Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proceedings of the National Academy of the Sciences USA 104:19649-19654.
Vitiello B, Abikoff HB, Chuang SZ, Kollins SH, McCracken JT, Riddle MA, Swanson JM, Wigal T, McGough JJ, Ghuman JK, Wigal SB, Skrobala AM, Davies M, Posner K, Cunningham C, Greenhill LL (2007) Effectiveness of methylphenidate in the 10-month continuation phase of the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS). Journal of Child and Adolescent Psychopharmacology 17:593-604.