Serotonin platelet-transporter measures in childhood attention-deficit/hyperactivity disorder (ADHD): clinical versus experimental measures of impulsivity.
Introduction: Impulsivity in terms of aggression, suicide or poor cognitive control has been associated with low synaptic availability of serotonin (5-HT) in adults and children. However characteristics of the 5-HT transporter have not been studied in children with attention-deficit/hyperactivity disorder (ADHD: combined type) where "impulsivity" is a core symptom. (But it may be noted that low measures of HVA/5-HIAA reported for ADHD children [Oades, 2002] could reflect increased 5-HT metabolism, the opposite to the widespread assumption just described.) Methods: Here, in 20 children with ADHD, we explored the relationship of the density (Bmax) and affinity (Kd) of the platelet 5-HT transporter measured with [3H]paroxetine to both clinical ratings of impulsivity (Conners' Parent Questionnaire), and an experimental measure of impulsivity (the ability to withhold a prepotent response in the "stop-signal" paradigm: See Slusarek et al. 2001, J.Am.Acad.Child Adolesc. Psychiat., 40, 355-363). Results: 1. Decreases of affinity (increased Kd) correlated with a low probability of response inhibition (a cognitive measure of "impulsivity" on the stop-signal task), but not with the clinical ratings of impulsivity (Fig. 1). 2. However, ratings of distractibility and impulsivity correlated with the experimental measure of response-inhibition. 3. In contrast, increased transporter affinity (low Kd) correlated modestly with higher ratings of aggressive and externalising behaviour (CBCL, Child Behavior Check List) - see Fig. 2.. 4. Bmax was not associated with any behavioural score. Conclusions: We conclude that the synaptic availability of 5-HT is under the control of the 5-HT transporter binding site affinity and that low affinity may be related to cognitive impulsivity (distractibility). Increased affinity of the transporter may also be related to conduct disturbance (and externalising behaviour).
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