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

Behav Brain Funct. 2010 May 28:6:29. doi: 10.1186/1744-9081-6-29.

Abstract

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acids / blood
  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Attention Deficit Disorder with Hyperactivity* / metabolism
  • Attention Deficit Disorder with Hyperactivity* / pathology
  • Brain / cytology
  • Brain / metabolism
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Cytokines / blood*
  • Energy Metabolism / physiology
  • Female
  • Humans
  • Kynurenine / analogs & derivatives
  • Kynurenine / blood*
  • Male
  • Nerve Growth Factors / blood*
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Pilot Projects
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / blood*
  • Tryptophan / blood

Substances

  • Amino Acids
  • Central Nervous System Stimulants
  • Cytokines
  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins
  • S100B protein, human
  • 3-hydroxykynurenine
  • Kynurenine
  • Tryptophan