Aspects of ADHD in Adults: neurocognitive functioning, actigraphy, effects of methylphenidate, and association with genetic polymorphisms.

Abstract

The current thesis encompasses a number of empirical, clinical studies into various aspects of ADHD in adults. The common theme of the studies and thereby the overall aim of the thesis is to further substantiate the external validity (especially the concurrent and predictive validity) of the diagnosis ADHD in adults. The first study describes a meta-analysis of executive and non-executive neurocognitive functioning in adults with ADHD, in which it is concluded that neurocognitive difficulties of this group may not be confined to executive functioning. In the second study we compared adults with ADHD and normal controls on a large battery of neurocognitive tests and we established that adult ADHD may be mainly about inhibition and set shifting difficulties. In the third study we found a positive effect of methylphenidate on inhibition and some other cognitive abilities in adults with ADHD. The fourth study discusses parameters of sleep, activity, and circadian rhythm as assessed by means of actigraphy. In comparison with normal controls, adults with ADHD proved to be more active during the day, showed less efficient sleep, took longer to fall asleep, and demonstrated shorter sleep-blocks. Treatment with methylphenidate ameliorated several aspects of this disturbed sleep. The final study of this thesis describes a first connection between key genetic polymorphisms and neurocognitive performance in an adult ADHD group. We demonstrated tentative relationships between the COMT Val158Met polymorphism and IQ and reaction time; between two DRD4 polymorphisms (48 bp repeat and 120 bp duplication) and verbal memory skills, and between the SLC6A3 40 bp VNTR polymorphism and inhibition. Taken together, these studies have contributed to the supporting of the external (concurrent and predictive) validity of the diagnosis ADHD in adults and they have helped build the phenotypic as well as the endophenotypic picture of the disorder.