Neuroendocrine Substrates, Candidate Genes and Endophenotypes in ADHD

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common child and adolescent psychiatric disorders. In recent years, some researchers have become interested in analyzing neuroendocrine substrate levels in ADHD, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), cortisol and testosterone. Previous work in ADHD has established a strong heritable component to the phenotype. The STS gene, SULT2A1 gene and TH gene are associated with the function of DHEA/DHEA-S, and the NR3C1 gene is associated with the regulation of cortisol. Therefore, the relationship between these genes and the etiology of ADHD warrants investigation. Moreover, compared to the phenotype, the endophenotypes of ADHD may be more capable of detecting the underlying neurobiological and hereditary mechanisms. Therefore, this study aims to investigate the relationships between neuroendocrine substrates (DHEA, DHEA-S, cortisol and testosterone), candidate genes (STS gene, SULT2A1 gene, TH gene and NR3C1 gene) and the phenotype and endophenotypes (disease subtypes, neurocognitive function and response to treatment) of ADHD. To complete this work, we will recruit 300 patients with ADHD (probands) and 600 biological parents of the probands. DNA will be extracted from buccal cells by cheek swab. At baseline, saliva samples of ADHD patients will be collected between 7:00 and 8:00 am using the passive drool method, to analyze the levels of neuroendocrine substrates. The patients will undergo assessment for their clinical symptoms and neurocognitive function. Methylphenidate will then be administered to the patients and the usual practice followed. At week 4 and week 52, procedures similar to those performed at baseline will be repeated. The results of this study may further elucidate the complexity of the pathophysiology of ADHD. We may determine whether the neuroendocrine system, which contains levels of neuroendocrine substrates and associated genes, plays a cru