title: 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: Department of Immunobiology, New Haven, CT 06520, USA.
authors: Zuzana
authors: Z
authors: Tobiasova
authors: Klaas H B
authors: KH
authors: van der Lingen
authors: Lawrence
authors: L
authors: Scahill
authors: James F
authors: JF
authors: Leckman
authors: Yan
authors: Y
authors: Zhang
authors: Wookjin
authors: W
authors: Chae
authors: James T
authors: JT
authors: McCracken
authors: Christopher J
authors: CJ
authors: McDougle
authors: Benedetto
authors: B
authors: Vitiello
authors: Elaine
authors: E
authors: Tierney
authors: Michael G
authors: MG
authors: Aman
authors: L Eugene
authors: LE
authors: Arnold
authors: Liliya
authors: L
authors: Katsovich
authors: Pieter J
authors: PJ
authors: Hoekstra
authors: Fred
authors: F
authors: Volkmar
authors: Alfred L M
authors: AL
authors: Bothwell
authors: Ivana
authors: I
authors: Kawikova
mesh_terms: D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001321:Autistic Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004815:Epidermal Growth Factor / Q000097:blood / Q000187:drug effects*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D007508:Irritable Mood / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018967:Risperidone / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D014150:Antipsychotic Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D018793:Interleukin-13; D004815:Epidermal Growth Factor; D018967:Risperidone