Tye, Charlotte

The highly complex and heterogeneous nature of overlapping neurodevelopmental disorders is likely to increase misspecification in group allocation and hinder the identification of the mechanisms involved. One strategy to facilitate gene identification and to improve understanding of the pathophysiological mechanisms underlying clinical co-occurrence is the investigation of intermediate phenotypes that lie between genes and behaviour. In particular, a neurophysiological perspective which utilises the exquisite time resolution of electroencephalography (EEC) allows objective quantification of the underlying mechanisms. Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are complex childhood-onset disorders that are traditionally treated as separate research fields, in part due to current diagnostic systems precluding a co-diagnosis. The past decade, however, has witnessed an increase in the awareness of significant behavioural, cognitive and genetic overlap between these disorders. The present thesis can be divided into two main objectives: (I) to examine the aetiological overlap between ADHD and quantitative EEG parameters, and (II) to identify shared and/or distinct cognitive-electrophysiological markers of ASD and ADHD and their common co-occurrence. This encompasses data collection in two samples: a community twin sample selected on the basis of consistently high or low ADHD symptoms, and a sample of clinically diagnosed children with ASD (n=19), ADHD (n=18), co-occurring ASD+ADHD (n=29) and typically developing controls (n=26). In Part I, structural equation modeling was used to demonstrate heritability of and substantial shared genetic influences between selected quantitative EEG measures and ADHD, supporting these measures as candidate intermediate phenotypes of the disorder.In Part II, ASD and ADHD were directly compared on these measures and ERP indices of attention and social cognition. Across these analyses, while it was possible to dissociate ASD-only and ADHD-only on their basis of cognitive-electrophysiological parameters, ASD+ADHD largely showed the unique deficits of both disorders, thus supporting an additive co-occurrence. Disentangling phenotypic variation in gene-brain-behaviour relationships is likely to aid the identification of susceptibility genes and other causal mechanisms underlying the complex aetiology of ADHD and ASD. In addition, elucidating the basis of comorbidity can help to refine classification systems and enhance the assessment of complex cases for more specific treatment strategies

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Identifying intermediate phenotypes of ADHD and ASD:a cognitive-electrophysiological approach

https://kclpure.kcl.ac.uk/portal/files/31810649/2013_Tye_Charlotte_0825020_ethesis.pdf

Identifying intermediate phenotypes of ADHD and ASD:a cognitive-electrophysiological approach

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