Research Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism - effects of medication

Background: Children with attention-deficit/hyperactivity disorder
(ADHD) show a marked temporal variability in their display of
symptoms and neuropsychological performance. This could be
explained in terms of an impaired glial supply of energy to support
neuronal activity. Method: We pursued one test of the idea with
measures of a neurotrophin reflecting glial integrity (S100B) and
the influences of 8 cytokines on the metabolism of amino-acids, and
of tryptophan/kynurenine to neuroprotective or potentially toxic
products that could modulate glial function. Serum samples from 21
medication-naive children with ADHD, 21 typically-developing
controls, 14 medicated children with ADHD and 7 healthy siblings
were analysed in this preliminary exploration of group differences
and associations. Results: There were no marked group differences
in levels of S100B, no major imbalance in the ratios of pro-to
anti-inflammatory interleukins nor in the metabolism of kynurenine
to toxic metabolites in ADHD. However, four trends are described
that may be worthy of closer examination in a more extensive study.
First, S100B levels tended to be lower in ADHD children that did
not show oppositional/conduct problems. Second, in medicated
children raised interleukin levels showed a trend to normalisation.
Third, while across all children the sensitivity to allergy
reflected increased levels of IL-16 and IL-10, the latter showed a
significant inverse relationship to measures of S100B in the ADHD
group. Fourthly, against expectations healthy controls tended to
show higher levels of toxic 3-hydroxykynurenine (3 HK) than those
with ADHD. Conclusions: Thus, there were no clear signs ( S100B)
that the glial functions were compromised in ADHD. However, other
markers of glial function require examination. Nonetheless there is
preliminary evidence that a minor imbalance of the immunological
system was improved on medication. Finally, if lower levels of the
potentially toxic 3 HK in ADHD children were confirmed this could
reflect a reduction of normal pruning processes in the brain that
would be consistent with delayed maturation ( supported here by
associations with amino-acid metabolism) and a reduced metabolic
source of energy.