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.


METHODS
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-naïve 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.
Oades
Robert D
RD
Clinic for Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany. robert.oades@uni-due.de
Dauvermann
Maria R
MR
Schimmelmann
Benno G
BG
Schwarz
Markus J
MJ
Myint
Aye-Mu
AM
D000293:Adolescent; D000596:Amino Acids / Q000097:blood; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D016207:Cytokines / Q000097:blood*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000031:analogs & derivatives / Q000097:blood*; D008297:Male; D009414:Nerve Growth Factors / Q000097:blood*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D010865:Pilot Projects; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*; D014364:Tryptophan / Q000097:blood
D000596:Amino Acids; D000697:Central Nervous System Stimulants; D016207:Cytokines; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C005045:3-hydroxykynurenine; D007737:Kynurenine; D014364:Tryptophan