We are proposing to continue a multi-year conference grant that has provided a forum for researchers to pursue collaborative studies of the molecular genetics of attention deficit hyperactivity disorder (ADHD). The original application was conceived in response to a call from the NIMH for researchers to establish mechanisms for collaborating in a manner that would facilitate the detection of genes predisposing to psychiatric disorders. ADHD is a common disorder of childhood associated with school failure, psychiatric comorbidity and psychosocial disability. Because family and twin studies suggest that ADHD has a substantial genetic component, several research groups have been pursuing molecular genetic studies of the disorder. These studies have already produced several meta-analytic findings implicating the DRD4, DAT1, DRD5, SNAP-25, and 5HT1B genes in the etiology of ADHD. Although these findings are intriguing, they have not led to new pathways for treatment. Because genomewide linkage studies have been equivocal and a genomewide association scan of 938 ADHD trios found no genomewide significant associations, susceptibility genes for ADHD must, individually, have very small effects. Thus, discovering replicated associations for ADHD will require large samples and collaborative efforts. Collaborative strategies have been successful for diabetes, Crohn's disease and other complex disorders, but they required very large samples. Despite the need for collaboration, collaboration can be difficult. Many investigators are concerned that large collaborative studies will dilute the scientific impact of their work and will make it difficult for junior investigators to establish independent reputations. Moreover, when collaborations are considered, they frequently face hurdles that cannot be surmounted. For example, clinical traditions at each site often clash regarding what diagnostic instruments are appropriate for use. This leads to the creation of data sets that are not easily combined with one another. Although we have begun to work out many of these issues at prior conferences, we need to continue the series to build upon those achievements and to complete the collaborative plans laid out in prior conferences.

Public Health Relevance

Attention deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder of childhood, affecting 8 to 12 percent of youth. The disorder creates impairments in multiple life domains including school failure, substance abuse, antisocial behavior, traffic accidents, increased non-psychiatric health care utilization, relationship difficulties and occupational failure. Although several pharmacologic and psychosocial treatments are available, these are palliative, not curative and no available treatment leads to remission of symptoms and impairments for most patients. Genetic studies are one method of discovering new biological pathways for treatment. But, because ADHD is a complex genetic disorder caused by many genes, large collaborative studies are needed for gene discovery. Thus, the goal of the proposed conference series is to overcome hurdles to collaboration by bringing ADHD genetics researchers together in a manner that promotes collaborative work.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Conference (R13)
Project #
5R13MH059126-13
Application #
8265848
Study Section
Special Emphasis Panel (ZMH1-CNF-Z (01))
Program Officer
Addington, Anjene M
Project Start
1998-12-01
Project End
2015-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
13
Fiscal Year
2012
Total Cost
$50,000
Indirect Cost
Name
Upstate Medical University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
Richards, Jennifer S; Arias Vásquez, Alejandro; van Rooij, Daan et al. (2017) Testing differential susceptibility: Plasticity genes, the social environment, and their interplay in adolescent response inhibition. World J Biol Psychiatry 18:308-321
Aebi, Marcel; van Donkelaar, Marjolein M J; Poelmans, Geert et al. (2016) Gene-set and multivariate genome-wide association analysis of oppositional defiant behavior subtypes in attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 171:573-88
Mooney, Michael A; McWeeney, Shannon K; Faraone, Stephen V et al. (2016) Pathway analysis in attention deficit hyperactivity disorder: An ensemble approach. Am J Med Genet B Neuropsychiatr Genet 171:815-26
McGrath, Lauren M; Braaten, Ellen B; Doty, Nathan D et al. (2016) Extending the 'cross-disorder' relevance of executive functions to dimensional neuropsychiatric traits in youth. J Child Psychol Psychiatry 57:462-71
Veroude, Kim; Zhang-James, Yanli; Fernàndez-Castillo, Noèlia et al. (2016) Genetics of aggressive behavior: An overview. Am J Med Genet B Neuropsychiatr Genet 171B:3-43
Thapar, A; Martin, J; Mick, E et al. (2016) Psychiatric gene discoveries shape evidence on ADHD's biology. Mol Psychiatry 21:1202-7
Richards, Jennifer S; Arias Vásquez, Alejandro; Franke, Barbara et al. (2016) Developmentally Sensitive Interaction Effects of Genes and the Social Environment on Total and Subcortical Brain Volumes. PLoS One 11:e0155755
Joshi, Gagan; Wozniak, Janet; Faraone, Stephen V et al. (2016) A Prospective Open-Label Trial of Memantine Hydrochloride for the Treatment of Social Deficits in Intellectually Capable Adults With Autism Spectrum Disorder. J Clin Psychopharmacol 36:262-71
Richards, J S; Arias Vásquez, A; von Rhein, D et al. (2016) Adolescent behavioral and neural reward sensitivity: a test of the differential susceptibility theory. Transl Psychiatry 6:e771
Onnink, A Marten H; Franke, Barbara; van Hulzen, Kimm et al. (2016) Enlarged striatal volume in adults with ADHD carrying the 9-6 haplotype of the dopamine transporter gene DAT1. J Neural Transm (Vienna) 123:905-15

Showing the most recent 10 out of 45 publications