OADES, R. D., (2011). An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD).

2011, ADHD attention deficit hyperactivity disorders, 3, 301-318 - [request a pdf] -- View Article

Introduction :
Intra-individual variability of the characteristics of children with attention-deficit hyperactivity (ADHD) may reflect compromised glial energy supply in the synapse (Russell et al. 2006). -- We reported recently that while serum levels of a glial marker, the cytokine S100B, were not seriously altered, levels of other cytokines and tryptophan metabolites were related to symptoms, attention (vs. IL-13) (fig.1, below ), impulsivity and variability (vs. TNF-alpha) - fig. 2 - (Oades et al. 2009, - 2010a, - 2010b: )
Aims :
Here, we-explore with a regression analysis whether levels of these substances (cytokines/interleukins and tryptophan metabolites relevant to glial function) were associated with features of the index pregnancy and thus offer indications of potential aetiological significance.

Methods :
Serum was taken from 35 children with DSM-IV ADHD (14 on medication) & 21 typically developing control children to measure 8 cytokines (S100B, IL-2, IL-6, IL-10, IL-13, IL-16, TNF-alpha and IFN-gamma) & 5 metabolites (Tryptophan, Kynurenine, Kynurenate [KA], 3-hydroxy-kynurenine [3HK] and 5-HIAA). All children with ADHD showed >50% higher coefficient of reaction time variance on a continuous performance task than the controls The mothers received a 124-item questionnaire on features surrounding the pregnancy.

Results :
1/ For children with ADHD, a shorter pregnancy & smaller birth weight were associated statistically with increased 3HK and IFN-gamma and along with obstetric problems with decreased TNF-alpha levels (fig.3).
2/ a) Regular maternal smoking in the pregnancy related to decreasing kynurenine & increasing 3HK & S100B levels in children with ADHD: b) Paternal smoking was associated with increased tryptophan in the controls and increased IL-6 levels in ADHD children.
3/ a) The taking of supplements during the pregnancy often related to decreasing TNF-alpha, increasing IL-10 (fig. 4) and lower 5-HIAA levels in the ADHD children. b) Less 5-HIAA but more tryptophan was associated with earlier and later life events, respectively.
4/ a) Increased IL-16 and 5-HIAA levels in the ADHD group related to reports of poorer infant health. b) Unexpectedly, more child care (regular seafood and time together) in ADHD than healthy families was observed to be implicated by lower tryptophan levels & an altered balance of pro-inflammatory cytokines.
5/ Across measures, control families generally showed either non-significant associations or the opposite to those of the ADHD group.

Conclusions :
In children with ADHD more than control children, the balance of potentially toxic or protective kynurenine metabolites, and of pro- over anti-inflammatory cytokines may reflect the perinatal experience associated with stress (but not with any actual maternal illness).

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