ADHD is a significant mental health problem, with an estimated prevalence in children of 3-5%. The disorder frequently persists into adulthood and is associated with substantial acute and long-term impairment in academic, social, and occupational functioning, as well as increased risks for other psychopathology, including substance abuse disorders. A recent NIMH Consensus Development Conference (1998) highlighted the need for additional research to enhance knowledge and understanding of this disorder. This purpose of this application is to form an interdisciplinary research network to facilitate investigations into etiology, pathophysiology, and treatment response in ADHD focusing primarily on the role of dopamine (DA) and its relationship to other neurotransmitter systems. This network is comprised of clinical and basic scientists, with others working in related areas, including the neuroanatomy of attentional networks, normal development of attentional and inhibitory systems, neurobiology of DA systems and relationship of stimulant medications and substances of abuse, genetic models of neuropsychiatric disorders. The overarching goals of this work are to elucidate the role of DA systems in cognitive and behavioral deficits which are characteristic of ADHD and to facilitate the delineation of more precise subtypes of ADHD which have significance with respect to symptom profile, etiology, course, outcome, and response to treatment. Methods to be utilized include: behavioral assessment, neuropsychological testing, FMRI (adults and children) and PET (adults only), genotyping and sequencing of naturally occurring DAT and DRD4 variants, genetic manipulation in animals via """"""""knock-out' and """"""""knock-in"""""""" technology, and in vivo microdialysis. The proposed network will provide infrastructure support to strengthen existing but developing collaborators at both participating and new institutions, and provide training, for established researchers in the use of new methods, and for promising junior scientists. This consortium takes advantage of the wealth of scientific resources in the New York area to construct a network of interdisciplinary researchers that can meet regularly and share resources and research populations. We propose to conduct studies in which different phenotypic and biological/genotypic factors are systematically manipulated and evaluated using new research methodologies, in animals and humans, and informed by varied theoretical perspectives and technical expertise. The grant will facilitate this objective by funding 5 half-time postdoctoral students at various network sites, and they will implement add-on investigations directed by the network to research currently in progress. Cross-fertilization of ideas will occur through regular conference calls and working meetings. In addition, the post-doctoral students will be able to spend time in multiple laboratories, which will facilitate the transfer of key theoretical and technical expertise across sites.
