Child Attention Deficit Hyperactivity Disorder (ADHD) represents a significant public health concern because it is common, costly, impairing, and chronic, placing children at substantial long-term risk. Since genetic and contextual factors are crucial to the development of ADHD, this proposal will elucidate molecular genetic mechanisms via multiple integrated strategies. Understanding of the specific molecular genetic correlates can influence definition of meaningful etiological subgroups, developmental course and pathophysiology, enabling early intervention and prevention. Using already obtained samples, haplotype discovery is proposed to establish the genomic structure in twelve theoretically relevant candidate genes involved in catecholamine synthesis and neuro-transmission. Then, with those samples and new samples to be obtained in this study, the haplotypes elucidated will be evaluated for association and linkage with ADHD, using family based TDT-type analyses. The first of these analyses will address links to symptom phenotypes, including ADHD DSM-IV subtypes and comorbid subtypes such as ADHD plus conduct disorder. We will examine categorical and continuous symptom measures. The second set of analyses will examine a battery of theoretically derived neuro-cognitive endophenotypes that either pilot data or theory suggest may relate to genetic transmission in ADHD. The neuro-cognitive model emphasizes a two-process conceptualization designed to capture both executive function components (e.g., behavioral inhibition) and delay-reward gradient and state regulation factors. We expect to be able to detect small effect sizes of the candidate genes using our approaches. The structure of the model and the analyses are designed to break new ground in identifying etiological heterogeneity in ADHD as well. Overall, the information to be gained has important ramifications for understanding etiology and thus contributing to eventual improved intervention and prevention for this costly group of disorders. Notably, understanding of the non-genetic, environmental contribution to disease is expected to increase when genetic factors are identified.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH070004-05
Application #
7608743
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Lehner, Thomas
Project Start
2005-03-05
Project End
2012-02-29
Budget Start
2009-03-01
Budget End
2012-02-29
Support Year
5
Fiscal Year
2009
Total Cost
$353,940
Indirect Cost
Name
Michigan State University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Momany, Allison M; Kamradt, Jaclyn M; Ullsperger, Josie M et al. (2017) Sex moderates the impact of birth weight on child externalizing psychopathology. J Abnorm Psychol 126:244-256
Kamradt, Jaclyn M; Nigg, Joel T; Friderici, Karen H et al. (2017) Neuropsychological performance measures as intermediate phenotypes for attention-deficit/hyperactivity disorder: A multiple mediation analysis. Dev Psychopathol 29:259-272
Martel, Michelle M; Nigg, Joel T; Schimmack, Ulrich (2017) Psychometrically Informed Approach to Integration of Multiple Informant Ratings in Adult ADHD in a Community-Recruited Sample. Assessment 24:279-289
Nigg, Joel T; Elmore, Alexis L; Natarajan, Neil et al. (2016) Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children. Psychol Sci 27:257-69
Ullsperger, Josie M; Nigg, Joel T; Nikolas, Molly A (2016) Does Child Temperament Play a Role in the Association Between Parenting Practices and Child Attention Deficit/Hyperactivity Disorder? J Abnorm Child Psychol 44:167-78
Wiggs, Kelsey; Elmore, Alexis L; Nigg, Joel T et al. (2016) Pre- and Perinatal Risk for Attention-Deficit Hyperactivity Disorder: Does Neuropsychological Weakness Explain the Link? J Abnorm Child Psychol 44:1473-1485
Elmore, Alexis L; Nigg, Joel T; Friderici, Karen H et al. (2016) Does 5HTTLPR Genotype Moderate the Association of Family Environment With Child Attention-Deficit Hyperactivity Disorder Symptomatology? J Clin Child Adolesc Psychol 45:348-60
Martel, Michelle M; Schimmack, Ulrich; Nikolas, Molly et al. (2015) Integration of symptom ratings from multiple informants in ADHD diagnosis: a psychometric model with clinical utility. Psychol Assess 27:1060-71
Nikolas, Molly A; Nigg, Joel T (2015) Moderators of neuropsychological mechanism in attention-deficit hyperactivity disorder. J Abnorm Child Psychol 43:271-81
Nikolas, Molly A; Nigg, Joel T (2013) Neuropsychological performance and attention-deficit hyperactivity disorder subtypes and symptom dimensions. Neuropsychology 27:107-20

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