The environmental and genetic aetiology of the severity and presence of attention and hyperactivity related disorders in a population from South Africa

[摘要] English: Attention-Deficit Hyperactivity Disorder is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, and impulsivity. This disorder has been increasingly diagnosed in children and adults since the early 1990s. Genetics has been largely implicated in the aetiology of ADHD, with environment influencing the severity of the condition.The purpose of this research was to study the influence of polymorphisms in the serotonin system on ADHD, and to investigate the extent to which certain environmental factors affect the severity of the condition. In total, 74 individuals took part in this study by completing an online self-report survey, a semi-structured interview, and/or providing genetic material in the form of saliva (52 individuals in total). Of these, a sub-set of comparative participants comprised of 45 individuals, and a sub-set of participants previously diagnosed with ADHD comprised of 29 individuals.Environmental analysis involved the assessment of medical, psychological, and developmental problems, learning disorders, sleep problems, nicotine dependence, and exposure to oxygen deprived conditions. Impairments in various other aspects were also assessed, including life skills, social concept, work or education, family life, and risky activities. Molecular analysis focussed on three genes in the serotonin system. These genes are responsible for various aspects of the functioning of the system. These genes encode for two serotonin receptors (HTR1B and HTR2A) and the serotonin transporter (SLC6A4). Three single nucleotide polymorphisms (SNPs) were genotyped using restriction enzyme digestion and confirmatory sequencing. A single variable number of tandem repeats (VNTR) in the SLC6A4 gene was also assessed.Results of environmental analysis alone revealed that exposure to hypoxic conditions and/or second-hand nicotine inhalation worsen inattentive and hyperactive symptoms of ADHD. Aspects found to be present alongside ADHD were increased psychological, medical and learning problems, and high nicotine dependence. The most significant impairments in life functioning in ADHD individuals arose in familial, social, and school or work environments, as well as significant impairments in self-concept and an increased affinity for risky behaviours. Exercise was found to have a positive self-reported effect on ADHD symptoms.Molecular analysis showed that the serotonin system plays a significant role in modulating ADHD. The HTR2A (rs6311) SNP in heterozygous form is linked to high levels of hyperactivity. The heterozygous form of the 5-HTT SNP (located in the SLC6A4 gene) was indicative of the presence of ADHD. The GG genotype of the SNP HTR1B (rs6296) showed significant associations with inattention score. The S allele of VNTR in the SLC6A4 gene showed the strongest association to ADHD in terms of type of ADHD (mainly inattentive), presence of ADHD, and severity of inattention and hyperactivity symptoms.Molecular and environmental components taken together reveal an indirect association between the HTR1B (rs6296) GG genotype and increased psychological problems. The HTR2A polymorphism (AG genotype), on the other hand, is associated with poor self-perception. This polymorphism, coupled with the 5-HTTLPR S allele, and medical problems shows significant associations with inattentive type ADHD. The 5-HTTLPR VNTR showed the strongest association to ADHD, even when coupled with environmental influences. The S allele of this VNTR, along with increased medical and psychological problems show significant correlations to ADHD.This study also shows that methods of measurement, while different, produce similar quantifiable information, however, may produce differing resulting diagnoses and should thus be viewed in context for study purposes.In concluding, this study provides a potential profile for the diagnosis of ADHD, in terms of both environmental and genetic components. The research also implicates the importance of the serotonin system as an integral modulator of the presence and severity of ADHD and its symptoms.

[发布机构] University of the Free State