Neuroendocrine Substrates, Candidate Genes and Endophenotypes in ADHD
Status:
Unknown status
Trial end date:
2017-07-01
Target enrollment:
Participant gender:
Summary
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 crucial role in the phenotype and
endophenotypes of ADHD. The information may serve as an important reference for the direction
of future study and clinical treatment for patients with ADHD.