Dopamine may be ‘hyper’ with respect to noradrenaline metabolism, but ‘hypo’ with respect to serotonin metabolism in children with attention-deficit hyperactivity disorder

Abstract

Noradrenaline: Hechtman (J Psychiat Neurosci 1994;19:193) argued for a role for frontal dopamine (DA) and noradrenaline (NA) in ADHD, where Oades (Prog Neurobiol 1987;29:365) has described lateralised functional impairments. Mechanisms (e.g. via alpha-2 sites) for stimulating low NA activity in ADHD children (J Am Acad Child Adolesc Psychiatry 1997;36:1688) in order to promote interactions with mesocortical DA have been discussed (J Psychopharmacology 1997;11:151; Psychiatr Res 1994;52:305). We described with indicators of overall transmitter metabolism (monoamines, metabolites in 24 h urine samples (Behav Brain Res 1997;88:95)) significantly lower utilisation ratios (MHPG/NA) in ADHD children with respect to healthy controls. 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. These results are consistent with reports of lower DOPEG and increased DOPAC in ADHD urine (J Child Adolesc Psychopharmacol 1996;6:63) and indicate that the relatively hyperactive DA versus NA systems may have functional consequences. Serotonin: the relevance for ADHD of an association of impulsivity with low serotonin (5-HT) metabolism (Behav Brain Sci 1986;9:319) 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 (Psychiatr Res 1994;52:305). We find that while urinary measures of 5-HIAA are somewhat higher, the ratio HVA/5-HIAA is markedly lower in ADHD children versus controls. In these ADHD children 5-HIAA levels were negatively related to d-prime measures in a continuous performance task (CPTax), and the HVA/5-HIAA was negatively associated with conditioned blocking. These results suggest a relatively low DA versus 5-HT activity may have functional consequences, albeit in a subgroup of ADHD. This is consistent with drug-induced prolactin changes reported by Verbaten et al. (Eur Child Adolesc Psychiatry 1999;8:30).