Adult Outcome of Children With Attention-deficit/Hyperactivity Disorder

Primary specific aim:

To describe the manifestation and persistence of ADHD symptoms and to investigate the psychiatric, social, and executive functioning outcomes at young adulthood among children with ADHD;

Secondary specific aims

1. To identify early individual (clinical, behavioral, and executive functioning and other neurocognitive variables), family, school, environmental factors to predict the symptom persistence and a wide-range of outcomes at young adulthood;
2. To validate structural and functional connectivity of frontostriatal circuitry as imaging endophenotypes of ADHD by demonstrating that structural connectivity and functional connectivity of frontostriatal circuitry are altered in patients with ADHD and their unaffected siblings, are associated with ADHD symptoms, and are associated with genes related to dopamine neurotransmitter system;
3. To identify brain area that is corresponding to the effect of methylphenidate; and
4. To confirm reported candidate genes related to dopamine and noradrenergic neurotransmitter systems in the association with ADHD severity and subtypes (persistence, comorbidity, functional impairment, and treatment effects) and endophenotypes (executive function and structural and functional brain connectivity) such as DAT1, DRD4, MAO-A, ADRA2A, ADRA2C, NET, and COMT.

The sample consists of a cohort of 217 young adults (180 males, 83%) who were diagnosed of ADHD at childhood and 173 healthy controls (123 males, 71%). At their ages of 17-24 (around 6 years after their assessments at adolescence), they will receive psychiatric interviews (ADHD+SADS, CAADID) to make the diagnosis of ADHD and other psychiatric disorders and blood sample collection. They will complete the following questionnaires: ASRS and CAARS-S:S for adult ADHD symptoms, TPQ for personality characteristics, ASRI-4 for DSM-IV psychopathology, AAQoL and WFIRS for social functions, and PBI for parenting styles; and perform the WAIS-III for current IQ and Cambridge Neuropsychological Test Automated Batteries for attention control and executive functioning. Among the cohort subjects, 30 subjects with persistent ADHD and their same-sex and -handedness unaffected siblings (n = 30), 30 ADHD subjects who have DAT1 and/or good response to methylphenidate (repeated MRI assessment one week later) based on clinical assessment, and 30 subjects without lifetime ADHD and any psychiatric disorder will receive diffusion spectrum imaging (DSI) and resting state functional MRI assessments (total number of MRI assessments, 150). We will genotype 3'VNTR of DAT1 gene and other candidate genes involving dopaminergic and adrenergic systems (DRD4, MAO-A, ADRA2A, ADRA2C, NET, and COMT) for case-control association studies by using SNP and haplotype analysis.

We anticipate that this study (1) will provide the first prospective, longitudinal data of children with ADHD at late adolescence and young adulthood in Asian populations; (2) will be one of the first to establish a comprehensive, multi-dimensional dataset combining clinical, family, psychosocial, academic/vocational, neuropsychological, neuroimaging, and genetic data of young adults with ADHD. With the inclusion of imaging genetics data, the behavioral and neurocognitive phenotypes of ADHD can be validated, the imaging endophenotype can be tested, and image genetics approach may help identify genetic variants for ADHD.