Risperidone-related improvement of irritability in children with autism is not associated with changes in serum of epidermal growth factor and interleukin-13.

Abstract

Risperidone has been shown to improve serious behavioral problems in children with autism. Here we asked whether risperidone-associated improvement was related to changes in concentrations of inflammatory molecules in the serum of these subjects. Seven molecules were identified as worthy of further assessment by performing a pilot analysis of 31 inflammatory markers in 21 medication-free subjects with autism versus 15 healthy controls: epidermal growth factor (EGF), interferon-γ (IFN-γ), interleukin (IL)-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), IL-1 and IL-1-receptor antagonist. Serum concentrations of these markers were then established in a different set of subjects that participated in a double-blind, clinical trial and an expanded group of healthy subjects. In the first analysis, samples obtained from subjects with autism at baseline visits were compared to visits after 8-week treatment with placebo (n=37) or risperidone (n=40). The cytokine concentrations remained stable over the 8-week period for both risperidone and placebo groups. In the second analysis, we explored further the differences between medication-free subjects with autism (n=77) and healthy controls (recruited independently; n=19). Serum levels of EGF were elevated in subjects with autism (median=103 pg/mL, n=75) in comparison to healthy controls (75 pg/mL, n=19; p<0.05), and levels of IL-13 were decreased in autism (median=0.8 pg/mL, n=77) in comparison to controls (9.8 pg/mL, n=19; p=0.0003). These changes did not correlate with standardized measures used for a diagnosis of autism. In summary, risperidone-induced clinical improvement in subjects with autism was not associated with changes in the serum inflammatory markers measured. Whether altered levels of EGF and IL-13 play a role in the pathogenesis or phenotype of autism requires further investigation.

• Authors: Zuzana Tobiasova, Klaas H B van der Lingen, Lawrence Scahill, James F Leckman, Yan Zhang, Wookjin Chae, James T McCracken, Christopher J McDougle, Benedetto Vitiello, Elaine Tierney, Michael G Aman, L Eugene Arnold, Liliya Katsovich, Pieter J Hoekstra, Fred Volkmar, Alfred L M Bothwell, Ivana Kawikova
• Journal: Journal of child and adolescent psychopharmacology (J Child Adolesc Psychopharmacol) Vol. 21 Issue 6 Pg. 555-64 (Dec 2011) ISSN: 1557-8992 [Electronic] United States
• PMID: 22070180 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antipsychotic Agents
• Biomarkers
• Inflammation Mediators
• Interleukin-13
• Epidermal Growth Factor
• Risperidone

Topics

• Adolescent
• Anti-Inflammatory Agents (pharmacology)
• Antipsychotic Agents (pharmacology, therapeutic use)
• Autistic Disorder (blood, drug therapy, psychology)
• Biomarkers (blood)
• Child
• Child, Preschool
• Double-Blind Method
• Epidermal Growth Factor (blood, drug effects)
• Female
• Humans
• Inflammation Mediators (blood)
• Interleukin-13 (blood)
• Irritable Mood (drug effects, physiology)
• Male
• Risperidone (pharmacology, therapeutic use)