The environmental and genetic aetiology of the severity and presence of attention and hyperactivity related disorders in a population from South Africa
| dc.contributor.advisor | Odendaal, Z. | |
| dc.contributor.advisor | Schneider, S-R. | |
| dc.contributor.author | Mansfield, Jade | |
| dc.date.accessioned | 2016-08-30T07:53:48Z | |
| dc.date.available | 2016-08-30T07:53:48Z | |
| dc.date.issued | 2015-07 | |
| dc.description.abstract | 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. | en_ZA |
| dc.description.abstract | Afrikaans: Aandag-afleibaarheid en hiperaktiwiteit sindroom, bekend as “ADHD”, is ‘n neuro-ontwikkelende afwyking gekaraktiriseer deur ‘n gebrek aan aandag, gepaardgaande met hiperaktiwiteit en impulsiwitieit. Hierdie afwyking word al hoe meer in kinders en volwassenes gediagnoseer van die vroeë 1990s. Genetika is meestal betrokke by die ontwikkeling van ADHD, met omgewingsfaktore wat die toestand vererger. Die doel van hierdie navorsing is om die uitwerking wat polimorfismes in die serotonienstelsel op ADHD het, te ondersoek, asook om te bepaal in hoe ‘n mate omgewingsfaktore die intensiteit van die afwyking bepaal. In total het 74 individue deelgeneem aan hierdie studie deur ‘n aanlyn self-verslag opname te voltooi , aan ‘n semi-gestruktureerde onderhoud deel te neem en/of genetiese material in die vorm van sputum te verskaf (52 individue in totaal). Van hierdie 74 individue, het 45 ‘n sub-groep van vergelykende deelnemers gevorm, en die orige 29 was ‘n sub-groep van deelnemers wat voorheen met ADHD gediagnoseer was. Daar was onder andere vir mediese, psigologiese- en ontwikkelingsprobleme, leer en slaap versteurings, nikotien afhanklikheid, en suurstof-gebreks toestande, as omgewingsinvloede getoets. Agterstande in verskeie ander aspekte, onder andere lewensvaardighede, sosiale konsepte, werk of geleerdheid, familie lewe, en deelname aan gevaarlike aktiwiteite, was ook geassesseer. Die molekulêre analises het op drie gene gefokus wat deel vorm van die serotonienstelsel. Die gene is verantwoordelik vir verskeie funksionele aspekte van die serotonienstelsel. Hierdie gene kodeer twee serotonien reseptore (HTR1B en HTR2A) en die serotonien transporter (SLC6A4). Drie enkelnukleotied polimorfismes (“SNP”) was gegenotipeer met behulp van beperkingsensieme en bevestigende nukleotiedvolgorde bepaling. ‘n Enkele veranderlike aantal tandem herhalings (“VNTR”) in die SLC6A4 geen was ook geassesseer. Resultate van die analisering, van slegs die omgewingsinvloede, het aangedui dat blootstelling tot hipoksiese omstandighede en/of tweedehandse nikotien inaseming vererger aandagsgebrek en hiperaktiwiteit simptome van ADHD kan vererger. Ander aspekte wat saam met ADHD voorgekom het sluit verhoogte psigologiese-, mediese- en leerprobleme, asook nikotien afhanklikheid in. Die mees beduidende leefbeperkings van individue met ADHD, is familie, sosiale, en skool- of werksomgewings, asook beduidende beperkings in self-konsep en ‘n verhoogde geneigdheid vir waaghalsige gedrag. Daar is bevind dat fisieke aktiwiteit ‘n positiewe uitwerking op ADHD simptome het. Die molekulêre analise het getoon dat die serotonienstelsel ‘n groot rol in die modulering van ADHD speel. Die HTR2A (rs6311) SNP se heterosigotiese vorm is geassosieer met hoë vlakke van hiperaktiwiteit. Die heterosigotiese vorm van die 5-HTT SNP (gevind in die SLC6A4 geen) dui op die voorkoms van ADHD. Die GG-genotipe van die HTR1B (rs6296) SNP het sterk geassosieer met aandagsgebrekkigheid. Die S-alleel van die VNTR in die SLC6A4 geen het die strekste assosiasie met ADHD getoon in terme van die tipe ADHD (hoofsaaklik aandagsgebrekkigheid), ADHD teenwoordigheid, en die graad van aandagsgebrekkigheid en hiperaktiwiteit. Molekulêre- en omgewingskomponente toon oor die algemeen ‘n indirekte assosiasie met die HTR1B (rs6296) GG-genotipe en meer psigologiese probleme. Aan die ander kant word die HTR2A polimorfisme (AG-genotipe) geassossieer met swak self-persepsie. Hierdie polimorfisme, tesame met die 5-HTTLPR S-alleel, asook die mediese probleme, het beduidende assosiasies met ADHD-impulsiwiteit gehad. Die 5-HTTLPR VNTR toon die sterkste assosiasie met ADHD, selfs wanneer dit met omgewingsfaktore gekoppel word. Die S-alleel van die VNTR, saam met verhoogte mediese- en psigologiese probleme, korreleer betekenisvol met ADHD. Hierdie studie toon ook dat verskillende maatstawwe soortgelyke kwantifiseerbare inligting genereer, alhoewel dit tot verskillende diagnoses mag lei. Dit moet binne die studie konteks geïnterpreteer word. Ter afsluiting: die studie verskaf ‘n moontlike profiel vir die diagnose van ADHD, beide in terme van omgewings- en genetiese komponente. Die navorsing beklemtoon die belang van die serotonienstelsel as ‘n integrale modulator van die teenwoordigheid en die graad van ADHD simptome. | af |
| dc.description.sponsorship | National Research Foundation (NRF) | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11660/4022 | |
| dc.language.iso | en | en_ZA |
| dc.publisher | University of the Free State | en_ZA |
| dc.rights.holder | University of the Free State | en_ZA |
| dc.subject | Adult ADHD self-report scale | en_ZA |
| dc.subject | Attention-deficit hyperactivity disorder | en_ZA |
| dc.subject | Environment | en_ZA |
| dc.subject | HTR2A | en_ZA |
| dc.subject | HT1B | en_ZA |
| dc.subject | Impulsivity | en_ZA |
| dc.subject | Inattention | en_ZA |
| dc.subject | Serotonin | en_ZA |
| dc.subject | SLC6A4 | en_ZA |
| dc.subject | Weiss functional impairment rating scale | en_ZA |
| dc.subject | Dissertation (M.Sc. (Behavioural Genetics))--University of the Free State, 2015 | en_ZA |
| dc.title | The environmental and genetic aetiology of the severity and presence of attention and hyperactivity related disorders in a population from South Africa | en_ZA |
| dc.type | Dissertation | en_ZA |