Despite increasing media attention, adult Attention-deficit-hyperactivity disorder (ADHD) has not been systematically studied in large samples. As a result, there has been a debate in the field about the validity of ADHD in adults presenting at mental health clinics. To shed light on this debate, we propose to test hypothesis in one domain of adult ADHD that has received scant attention: its genetic epidemiology. As we review in the background section, there have been only two small pilot studies of the genetic epidemiology of ADHD. Such data are essential to validating the syndrome, creating developmentally appropriate diagnostic algorithms and laying the clinical foundation for genetic linkage studies. To fill this gap in the research literature, we will address the validity of adult ADHD from the genetic epidemiological perspective by testing the following hypothesis for the five main aims of our proposal: 1) Assessing the Familial Transmission of Adult ADHD; 2) Validating Adult ADHD with Molecular Genetic Data; 3) Assessing the Divergent Validity of Adult ADHD; 4) Using Family Study Data to Validate Diagnostic Models of Adult ADHD; AND 5) Creating a Resource for Future Follow-up and Molecular Genetic Studies of Adult ADHD. To acheive these aims, we will complete a double- blind family study of 140 ADHD families and 120 control families. We view our family study strategy as being a valuable investment for several reasons. A large double-blind study of adult ADHD has never been done before. Moreover, because consistent positive associations have been reported between childhood ADHD and two dopamine related genes, the collection of molecular genetic data will allow us to validate adult ADHD at the molecular level. Because we are collecting data about lifetime psychiatric diagnoses, we will be able to determine if other disorders can account for the familial transmission of ADHD or its molecular genetic associations. We will also be able to assess what age at onset criterion and what set of symptom thresholds should be used for the diagnosis of adult ADHD and will be able to define phenotypes and sample selection rules that will maximize the yield of future linkage studies. To maximize the scientific yield of this proposal, we will create a resource for future molecular genetic and follow-up studies of adult ADHD. We will set the stage for these studies by 1) providing a comprehensive baseline assessment for a follow-up study and 2) clarifying the nature of phenotypes and the sample sizes that will be needed for molecular genetic studies. Thus, if founded, we expect that the proposed work will lead to a program of research that can both clarify the nosological complexities of adult ADHD and clarify the nature of genes that are risk factors for the disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH057934-04
Application #
6392320
Study Section
Special Emphasis Panel (ZMH1-CRB-B (04))
Program Officer
Moldin, Steven Owen
Project Start
1998-07-01
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
4
Fiscal Year
2001
Total Cost
$460,807
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Makris, Nikos; Liang, Lichen; Biederman, Joseph et al. (2015) Toward Defining the Neural Substrates of ADHD: A Controlled Structural MRI Study in Medication-Naïve Adults. J Atten Disord 19:944-53
Surman, Craig B H; Biederman, Joseph; Spencer, Thomas et al. (2013) Understanding deficient emotional self-regulation in adults with attention deficit hyperactivity disorder: a controlled study. Atten Defic Hyperact Disord 5:273-81
Antshel, Kevin M; Kaul, Prashant; Biederman, Joseph et al. (2013) Posttraumatic stress disorder in adult attention-deficit/hyperactivity disorder: clinical features and familial transmission. J Clin Psychiatry 74:e197-204
Biederman, Joseph; Fried, Ronna; Petty, Carter R et al. (2012) Examining the association between stimulant treatment and cognitive outcomes across the life cycle of adults with attention-deficit/hyperactivity disorder: a controlled cross-sectional study. J Nerv Ment Dis 200:69-75
Brown, Ariel; Biederman, Joseph; Valera, Eve et al. (2012) Working memory network alterations and associated symptoms in adults with ADHD and Bipolar Disorder. J Psychiatr Res 46:476-83
Seidman, Larry J; Biederman, Joseph; Liang, Lichen et al. (2011) Gray matter alterations in adults with attention-deficit/hyperactivity disorder identified by voxel based morphometry. Biol Psychiatry 69:857-66
Brown, Ariel Beth; Biederman, Joseph; Valera, Eve et al. (2011) Relationship of DAT1 and adult ADHD to task-positive and task-negative working memory networks. Psychiatry Res 193:7-16
Surman, Craig B H; Biederman, Joseph; Spencer, Thomas et al. (2011) Deficient emotional self-regulation and adult attention deficit hyperactivity disorder: a family risk analysis. Am J Psychiatry 168:617-23
Valera, Eve M; Brown, Ariel; Biederman, Joseph et al. (2010) Sex differences in the functional neuroanatomy of working memory in adults with ADHD. Am J Psychiatry 167:86-94
Brown, Ariel B; Biederman, Joseph; Valera, Eve M et al. (2010) Effect of dopamine transporter gene (SLC6A3) variation on dorsal anterior cingulate function in attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 153B:365-375

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