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OADES, R. D.,
Dauvermann, M.R.,
Schwarz, M. J., & Myint, A.
M., Does glial function underlie ADHD variability? Evidence from measures
of S100B, interleukins, tryptophan metabolism and the kynurenine metabolic
pathway. 10th Psychoimmunology Expert Meeting, Ulm/Günzburg,
Nov. 12-14):
Neurology, Psychiatry and Brain Research, suppl.
1, 44.
Objectives: Response variability
is a core feature of ADHD. A deficient supply of energy
from astrocytes to support sustained neural activity may underlie this
characteristic (1). We report a measure of the integrity of glial function
(the neurotrophin S100B) and on measures
of tryptophan metabolism (kynurenine
pathway) where toxic metabolites could induce dysfunction (2). We
also considered 8 interleukins/cytokines
where the balance of pro/anti-inflammatory elements bias metabolism
to neuroprotective or potentially toxic products. We predicted low S100B
activity in ADHD where increased levels characterise psychosis and dementia
(3).
Methods:
We compared 21 young medication-naïve ADHD-ct
children with 21 healthy controls, 14 patients on medication and 7 siblings.
All patients demonstrated variability on a Qb test. Serum was analysed
for S100B, IL-1ß,
IL-2, IL-6, IL-10, IL-13, IL-16, TNFa and IFNy;
for 17 amino acids, kynurenine, kynurenate and 3-hydroxykynurenine (3HK).
Results:
1 - There were no
group differences for levels of S100B. However decreasing
levels related to increasing internalizing symptoms (e.g. anxiety)
in the patients.
2
- There were no clear group differences for the interleukins.
But, medication tended to normalise the alterations
recorded.
3 - The positive/negative relationships
of IL-16/IL-10 to allergy sensitivity were modulated by oppositional/hyperactive
symptoms.
4 - Lastly, levels
of the potentially toxic 3HK were higher in controls than patients.
The implied increase of catabolism was supported by associations with
amino acid levels not seen in the patients.
Discussion: 1/
Our hypothesis of decreased S100B levels in ADHD children
was not supported. But other markers of glial function should be examined
(e.g. myo-inositol, LIF). 2/ The
modest immunological imbalance (interleukins) was positively influenced
by stimulant medication. This indicates a neglected glial source (and
target) for therapeutic effects. 3/ Increased
toxic metabolite activity in typically developing children rather than
the patients was not anticipated. This may reflect normal pruning activity
in the CNS in late childhood (4) which appears to be reduced or delayed
in the ADHD children.
1) Russell, Oades, Tannock et
al (2006) Behav Brain Funct 2: 30:
2) Myint, Kim, Verkerk et al (2007) J Affect Disord, 98, 143-151:
3) Schwarz, Riedel, Holdenrieder et al 2008 In Vivo, 21, 951:
4) Huttenlocher (1984) Am J Ment Defic Res, 88, 488-496:
The study was supported by the UCB GmbH. We thank Victoria Kirchhoff
and Ellen Uslar for assistance.
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