During the last 10-15 years, it has been gradually recognized that Attention Deficit Hyperactivity Disorder (ADHD) persists into late adolescence and adult life in a substantial number of cases. While there are pockets of information which provide clues to neurobiologic abnormalities in ADHD at different age periods (structural brain abnormalities in boys, small samples demonstrating functional brain abnormalities in adults), there is very little systematic neurobiological information on ADHD throughout life. In particular, there is a paucity of neurobiological research in adults with the syndrome. The identification and integration of neuropsychological, neuroanatomical, and functional brain abnormalities in ADHD is crucial for identifying neurobiological mechanisms and improving treatment. Such information is necessary to help clarify the neurodevelopmental evolution of the disorder, treatment response, and the meaning of the disorder to patients, families and clinicians. In light of evidence of clinical continuity between pediatric and adult ADHD, we expect similarities in brain dysfunction across the life cycle. We hypothesize that a key brain abnormality in ADHD involves frontal-striatal circuitry reflected in neurocognitive deficits in attention and executive functions (especially working memory and inhibition). A primary goal of this study is to identify brain and neuropsychological abnormalities in ADHD across life, focusing on inhibition, working memory and vigilance, and the brain structures responsible for these functions. We propose to use state-of-the- art morphometric and functional measures (Counting Stroop, """"""""Two- back"""""""" and CPT) of magnetic resonance images (MRI) to evaluate adults with ADHD and their ADHD children. These tools will allow a comprehensive and highly detailed analysis of the brain circuitry putatively abnormal in ADHD: dorsolateral and orbital prefrontal cortex, caudate and pallidum, nucleus accumbens, thalamus, anterior cingulate, cerebellum, and corpus callosum. Because ADHD is very heterogeneous, with substantial psychiatric and cognitive comorbidity (i.e., learning disabilities), it is crucial to study a large enough sample to gain a comprehensive understanding of the disorder (n=140 ADHD adults, n=120 adult controls; 75 ADHD offspring, 75 control offspring). The proposed study will enable us to evaluate the effects of comorbidity, family history, gender, and genetic factors on brain abnormalities in ADHD. Finally, the feasibility and cost effectiveness of the proposed study is quite high because it builds on a large, systematic, ongoing study (MH 57934) which will provide all clinical data on ADHD, and on ongoing relationships between investigators.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH062152-04
Application #
6866681
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Rumsey, Judith M
Project Start
2002-03-01
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
4
Fiscal Year
2005
Total Cost
$434,836
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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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
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Makris, Nikos; Seidman, Larry J; Brown, Ariel et al. (2012) Further understanding of the comorbidity between Attention-Deficit/Hyperactivity Disorder and bipolar disorder in adults: an MRI study of cortical thickness. Psychiatry Res 202:1-11
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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
Makris, Nikos; Seidman, Larry J; Valera, Eve M et al. (2010) Anterior cingulate volumetric alterations in treatment-naïve adults with ADHD: a pilot study. J Atten Disord 13:407-13
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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