Relationship between the Neuroendocrine Substrates and Candidate Genes in Patients with Attention-Deficit/Hyperactivity Disorder

• Main Authors: Liang-Jen Wang, 王亮人
• Other Authors: Cheng-Fang Yen
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/6p43pt

博士 === 高雄醫學大學 === 醫學研究所博士班 === 106 === Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common child and adolescent psychiatric disorders. Some researchers have become interested in analyzing neuroendocrine substrate levels in ADHD, including dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S). The STS gene and SULT2A1 gene are associated with the function of DHEA/DHEA-S. Therefore, this study aimed to investigate the relationships between neuroendocrine substrates (DHEA and DHEA-S), candidate genes (STS gene and SULT2A1 gene) and the clinical presentations of ADHD. Methods: We recruited a total of 255 ADHD patients in this study. Genomic DNA samples of ADHD patients and their biological parents were extracted from buccal cells by cheek swab. Three single nucleotide polymorphisms (SNPs) in the STS gene (rs6639786, rs2270112, and rs17268988) and one SNP in the SULT2A1 gene (rs182420) were genotyped. Saliva samples of ADHD patients were collected between 7:00 and 8:00 am using the passive drool method, to analyze the levels of DHEA and DHEA-S using an enzyme immunoassay (ELISA) methods. Comorbidities and behavioral symptoms were evaluated using the Schedule for Affective Disorder and Schizophrenia for School-Age Children, Epidemiologic Version (K-SADS-E) and the Swanson, Nolan, and Pelham Version IV Scale for ADHD (SNAP-IV), respectively. Neurocognitive function was assessed using the Wechsler Intelligence Scale for Children–Fourth Edition (WISC-IV) and Conners’ Continuous Performance Test (CPT). Results: We found rs2270112 within the STS gene to be over-transmitted in males with ADHD, but not in the female patients. Polymorphisms of rs182420 within the SULT2A1 gene were not associated with ADHD. In the male patients, the C allele carriers of rs2270112 demonstrated significantly higher DHEA-S levels than non-C carriers. In contrast, the C allele carriers of rs17268988 had significantly lower DHEA levels than non-C carriers in the female patients. Levels of DHEA and DHEA-S were positively correlated with attention as measured by the CPT in boys and girls, respectively. Conclusions: These findings support potential sex differences in the underlying biological pathogenesis of ADHD with regard to STS polymorphisms and neurosteroid levels. The information may serve as an important reference for elucidating the endocrine-related pathophysiology of ADHD.