OADES, R. D., (1999)
Impulsivity and serotonin (5-HT): is there relevance for ADHD ?
10th Eunethydis Meeting, Attention-deficit and Hyperactivity Disorder. (19-21 Nov. 1999) Paris, France.

Background:
a) "5-HT activity has little to do with ADHD psychopathology": this was the general opinion in the "80"s (Raskin et al., 1984; Zametkin & Rapoport, 1987; Oades, 1987). This was based on the failure to find group differences (in CSF or plasma measures) for 5-HIAA (metabolite), 5-HT metabolic changes (stimulant challenge), MAO-A relevant changes (enzyme-metabolism), and the failure of l-tryptophan or fenfluramine treatment. But it had been noted that treatment nonresponders with the residual syndrome had higher CSF levels of HVA and 5-HIAA (Reimherr et al., 1984).
b) Yet at the same time, low levels of CSF 5-HIAA were being asociated with impulsivity, sensation-seeking, increased extraversion, suicide attempts and bouts of aggression ..... i.e. impulsivity in adult personality variables, though with many confounds on age, type of aggression etc (Brown et al., 1982, Linnoila et al., 1983, Schalling et al., 1984).

More recently:
a) Adult Personality: 5HT uptake sites (platelets) were inversely related to impulsive behaviour in episodic aggression, but positively related to sensation-seeking in borderline personalities (Bryant et al., 1989; Verkes et al., 1998). Normal adults males tend to show a lower 5-HT utilization than females (Rubinow et al., 1998). [Recall the male prevalence for ADHD.]
b) Adolescents with impulsive disorders: Platelet 5-HT concentrations increased with measures of impulsivity (Askenazy et al., 2000):
c) ADHD: Impaired stop-task performance did not improve on methylphenidate, but did with desipramine treatment - that increased prolactin levels) (Verbaten et al., 1999). The prolactin response to fenfluramine challenge is higher in cases of aggressive ADHD youth with aggressive parents than those without aggressive parents (Halperin et al., 1997).

For CSF measures of 5-HIAA in ADHD a positive correlation was reported with hyperactivity and some other clinical features, with and without psychostimulant treatment (Castellanos et al., 1994, 1996). Is this an artefact of an inter-correlation with increases of HVA ? Could it reflect a homeostatic response to increased HVA ? What about the relative activities of the monoamines ? Could the result reflect impaired uptake control of 5-HT at the synapse ? - More or less 5-HT activity ?

Animal Models:
i ) Rats depleted of 5-HT (5,7-DHT lesion) could not withold the no-go component on a Go/no-go task (increased responses in first 1.2 sec, Harrison et al., 1999).
ii ) Yet the uptake-blocker imipramine, on a fixed number-of-responses schedule, decreased impulsivity (response rate decreased as the chain-length increased, Evenden 1998). Further, 5-HT utilization in the right frontal cortex correlated with premature nose-poke responses on a 5-choice serial response task (Puumala & Sirvio, 1998).

Our point of view:
..... the general metabolism of 5HT in 10y-old ADHD children is higher than normal, and leads to significantly lower relative metabolic rates with respect to dopamine (i.e. low HVA/5-HIAA ratios, 1997): this should be interpreted against a U-curve for the normal development of 5-HT utilization from the end of the first to the end of the second decades (1996 & 2001).
..... bearing in mind the claim that the N1-P2 augmenting response reflects serotonergic transmission (Hegerl et al., 1999), the finding of large auditory P2 amplitudes in many ADHD subjects obtains considerable significance (Satterfield, 1994, Oades et al., 1996; Johnstone 1999).
Perhaps some of the problems of ADHD children reflect an imbalance between dopamine and serotonin activity resulting from serotonin activity levels remaining inappropropriately high for the developmental age.