It is increasingly recognised that the broadly defined behavioural phenotype of attention deficit – hyperactivity disorder (ADHD) is a heterogeneous condition and that this heterogeneity is seen across all levels of analysis from the genetic and environmental causes to the associated neuropsychological deficits, the clinical presentation and response to treatment. This work investigated whether the more restrictive and clinically homogeneous hyperkinetic disorder (HKD) phenotype is associated with reduced neuropsychological heterogeneity compared with the broader ADHD phenotype. Using a well known, broad based battery of neuropsychological tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and a computerised Go/NoGo task in a large well described group of boys with rigorously diagnosed HKD who were stimulant medication naïve at baseline, it was demonstrated that the neuropsychological heterogeneity in the HKD boys was very similar to that seen previously in children with ADHD. Interestingly, and contrary to popular opinion, the strongest associations were with more simple recognition memory tasks with a low executive demand. Although there were significant associations between HKD and deficits on a range of tasks with high executive demands these were less strong. Could this neuropsychological heterogeneity be a function of different developmental issues or comorbidity? With respect to development there was evidence that boys with HKD lagged behind the healthy boys with respect to the development of their neuropsychological performance. However the pattern of development was similar with the performance of the HKD boys paralleling that of the healthy boys, suggesting that the neuropsychological heterogeneity seen in HKD is not accounted for by developmental issues. With respect to the relationship between neuropsychological functioning and comorbidity, the impact of comorbid oppositional defiant disorder (ODD) and conductdisorder (CD), it was found that all three clinical groups (pure HKD, HKD + ODD and HKD + CD) demonstrated deficits on several tasks compared with the healthy boys. Compared with healthy boys each of the three clinical groups was associated with at least one unique neuropsychological deficit. This suggests that comorbidity between HKD and both ODD and CD may contribute to the neuropsychological heterogeneity in the HKD boys. Is there an association between clinical and neuropsychological responses to the treatment of HKD with the stimulant drug methylphenidate (MPH)? Detailed analyses were conducted to investigate heterogeneity of clinical and neuropsychological response in these boys to MPH. As predicted in previous studies there is evidence for clinical heterogeneity in response with between 68 and 78% of boys with HKD responding to MPH treatment at either one or both of the doses. The precise proportion responding was dependent on the scale and definition of response used. Clinical response was not predicted by age but was predicted to a degree by severity of symptoms at baseline and it was generally true that better response was predicted by lower (better) scores at baseline. Baseline performance on a component reflecting recognition memory performance at baseline predicted clinical response to the lower (0.3 mg/kg/dose), but not the higher (0.6, mg/kg/dose) dose of MPH with poorer baseline neuropsychological performance predicting a better clinical response. Whilst there was improvement on some neuropsychological measures following administration of MPH there was little association between clinical and neuropsychological responses to medication. Clinical response was only associated with neuropsychological response on a single measure from a single task (Go/NoGo Block 2 Errors to Distractors), a task that did not itself discriminate between the HKD boys and healthy Controls at baseline.
|Date of Award||2010|
|Supervisor||Keith Matthews (Supervisor)|
- Attention deficit hyperactivity disorder (ADHD)