Dopamine may be ‘hyper’ with respect to noradrenaline (NA) metabolism, but ‘hypo’ with respect to serotonin (5-HT) metabolism in ADHD children.
1. Noradrenaline: Hechtman (1994) argued for a role for frontal dopamine (DA) and noradrenaline (NA) in ADHD, where Oades (1998) has described lateralised functional impairments of right frontal cortical development and function. Mechanisms (e.g. via alpha-2 sites) for stimulating low NA activity in ADHD children (Halperin et al., 1997) in order to promote interactions with mesocortical DA have been discussed (Arnsten, 1997; Castellanos et al., 1994). Oades and Müller (1997) described, with indicators of overall transmitter metabolism (monoamines, metabolites in 24h urine samples) significantly lower utilisation ratios (MHPG/NA) in ADHD children with respect to healthy controls (fig. 1). Interestingly, a comparison of between catecholamine levels (DA/NA) showed a correlation with the conditioned blocking measure of selective attention recorded at the time of collection. This measure was negatively associated with blocking in controls (fig. 2) These results are consistent with reports of lower DOPEG and increased DOPAC in ADHD urine (Hanna et al., 1996) and indicate that the relatively hyperactive DA vs. NA systems may have functional consequences. 2. Serotonin: The relevance for ADHD of an association of impulsivity with low serotonin (5-HT) metabolism (Soubrie, 1986) has long been played down. Yet, some symptoms have been related to CSF measures of the metabolite 5-HIAA, and in particular the HVA/5-HIAA ratio has been reported to correlate with ratings of activity (Castellanos et al., 1994). We found that while urinary measures of 5-HIAA were somewhat higher, the ratio HVA/5-HIAA was markedly lower in ADHD children versus controls (fig. 1). In these ADHD children 5-HIAA levels were negatively related to d-prime measures in a continuous performance task requiring response to 'x' only after 'a' (Oades, 2000), and the HVA/5-HIAA was negatively associated with conditioned blocking (Oades & Müller, 1997, fig. 2). Conclusions: These results suggest a relatively low DA vs. 5-HT activity may have functional consequences, albeit in a subgroup of ADHD. This is consistent with drug-induced prolactin changes reported by Verbaten and colleagues (1999). For therapeutic purposes these results mean a more serious and widespread consideration of co-treatment or adjunctive forms of therapy. Representative of this point of view Kewley (1999) recently reported a positive experience with adjunctive clonidine or risperidone.