Investigation of the underlying cognitive-neurophysiological and aetiological pathways in ADHD and cross-disorder comparison with bipolar disorder

Student thesis: Doctoral ThesisDoctor of Philosophy


Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelop-mental disorder that is associated with a wide range of cognitive and neurophysiolo-gical impairments. This thesis uses a multi-disciplinary approach to investigate the cognitive and neurophysiological impairments, as well as their aetiology, in ADHD. A further aim is to identify cognitive markers that differentiate between ADHD and bipolar disorder (BD).
The first study examines the cognitive and neurophysiological impairments associated with remission and persistence of ADHD from childhood to young adulthood using fine-grained ex-Gaussian reaction-time distribution and electroencephalographic (EEG) brain-oscillatory measures. Detailed ex-Gaussian measures of attention-vigilance and brain-oscillatory measures of phase variability and attention allocation emerged as novel markers of ADHD remission. The second study investigates, using a polygenic risk score approach, whether genetic variants that contribute to ADHD also influence two cognitive impairments widely associated with ADHD, attention regulation and inhibition. Findings from this study show that polygenic risk for ADHD is positively associated with a measure of attention allocation, but not with response inhibition. The third study examines, in a longitudinal design of ADHD and control sibling pairs, the direction of the association between ADHD and cognitive measures, and the stability of the familial and non-familial effects that underlie the association between ADHD and such measures across time. This study shows that ADHD diagnosis is a predictor of lower IQ and working memory at follow-up and that the familial and non-familial effects influencing the associations between ADHD and cognitive measures in childhood are stable across time. The last study examines whether the cognitive impairments observed in individuals with persistent ADHD are different or overlapping compared to those observed in individuals with BD. Findings from this study, which used detailed ex-Gaussian measures across different tasks and task conditions, indicate a shared impairment between the ADHD and BD groups in occasional lapses of attention, and a BD-disorder-specific impairment in the variability of typical reaction time responses when high cognitive control is needed. These findings, if replicated in future larger studies, may represent objective markers of these two disorders.
Overall, by using a combination of cognitive, neurophysiological, behavioural and molecular genetic approaches, this thesis furthers our understanding of the cognitive and neural profiles in children, adolescents and adults with ADHD, as well as their association with BD.
Date of Award1 Mar 2021
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorJonna Kuntsi (Supervisor), Fruhling Rijsdijk (Supervisor) & Giorgia Michelini (Supervisor)

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