A multidisciplinary investigation of underlying pathways in ADHD: A study of ADHD genes, endophenotypes and phenotypes

This thesis adopts a multidisciplinary approach, combining cognitive-experimental and physiological data, with quantitative and molecular genetic analyses, to investigate pathways from genes to ADHD behaviours.<br/><br/>In chapter 2 we investigated socio-demographic factors as contributors of contrast effects (exaggeration of behavioural differences) in parental ADHD ratings. Gender moderated contrast effects, but only in opposite-sex pairs. Family size also contributed to contrast effects, which was further modified by gender. The reliance on rating scales and contrast effects may undermine gene-finding efforts. Accordingly, interest has been directed at objective ADHD- related measures. Promising candidates include heightened reaction time variability (RTV) and inhibitory deficits, indexed by commission errors (CE). Using a population-based twin sample we identified RTV and CE as separate cognitive pathways underlying inattention and hyperactivity-impulsivity (chapter 3). Molecular genetic investigations in the same sample (chapter 4) identified overlapping associations in line with these findings. However, no associations survived correction for multiple testing or were replicated in analysis of a clinical sample; we therefore cannot discount the possibility that they reflect chance findings.<br/><br/>Behaviours that frequently co-occur with ADHD were investigated to elucidate shared versus unique pathways, and moderators. We found that social autistic-like traits (ALTs) largely underlie the covariation of ADHD behaviours and ALTs (chapter 5), and observed significant phenotypic and genetic covariation between RTV and social ALTs. In chapter 6, we investigated the aetiological covariation of ADHD and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, indexed by salivary cortisol. Using growth curve modelling, we identified an association between ADHD affection status and rate of change (declined faster). Further analysis suggested that this association was primarily driven by oppositional behaviours, and that there was a familial component underlying this covariation.<br/><br/>Overall, the research summarised in this thesis will facilitate the further development of causal models linking genetic variation via mediating processes to ADHD behaviours.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2013

Author dc:creator

• Pinto, Rebecca

Advisors dc:contributor.advisor

• Kuntsi, Jonna Pauliina
• Rijsdijk, Fruhling Vesta

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/7c37717a-78bc-463b-ae26-0f8ee69bd394

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/7c37717a-78bc-463b-ae26-0f8ee69bd394