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Association of Serum Cytokine Levels, Treatment Response, and Weight Gain in Children with Autism Spectrum Disorders Following 8 Weeks Treatment of Risperidone

Saturday, 4 May 2013: 09:00-13:00
Banquet Hall (Kursaal Centre)
J. E. Choi1, P. Ashwood2, F. Widjaja1, M. Careaga2 and R. L. Hendren3, (1)University of California, San Francisco, San Francisco, CA, (2)Medical Microbiology and Immunology, The M.I.N.D. Institute, University of California, Davis, Sacramento, CA, (3)Psychiatry, University of California, San Francisco, San Francisco, CA
Background: Children with Autism Spectrum Disorders (ASD) frequently exhibit irritability. Atypical antipsychotics are shown to decrease behavioral disturbances in this population. Recent studies sought to identify predictors of clinical improvement and side effects in children with ASD following treatment with risperidone. In this exploratory analysis, our aim is to determine predictors of response to treatment and of weight gain by comparing baseline and changes in cytokine levels in an 8 week risperidone study.

Objectives: Determine if response to treatment and weight gain following 8 weeks of risperidone treatment is associated with baseline serum levels and changes in cytokine levels.

Methods: We used data of the plasma levels of 27 different cytokines from 41 children who had an initial Aberrant Behavior Checklist Irritability (ABC-I) subscale rating of ≥18. Subjects were uptitrated to a daily total of 1.5 mg of risperidone over 8 weeks. Outcome measures were % decrease in ABC-I (%ABC-I) scores and Clinical Global Impression-Improvement (CGI-I) score. Subjects were overall responders to treatment if they had a decrease in %ABC-I>.25 and a CGI-I of “very much improved” or “much improved”. Cytokine analysis was performed using multiplex assays (Millipore) according to manufacturer's recommendation and read on Luminex 100TMplatform. Weight gain was represented through change in z-scores of anthropomorphically-adjusted BMI distributions. We assessed normality of the data and identified outliers and did not adjust p-values for multiple testing for this exploratory analysis. Correlations were determined using Spearman’s rank correlation coefficient, differences between baseline and post-treatment values were determined using Wilcoxin sign rank tests and changes between responder and nonresponder groups were determined using Mann-Whitney tests.

Results: D %ABC-I (p<.00001) was significantly decreased following 8 weeks of treatment. Plasma levels of Eotaxin (p=.0005) and MCP1 (p=.02) was significantly decreased. There are no significant correlations between D%ABC-I and change in cytokines levels. Baseline IL-15 is a significant predictor of ABC-I response only (p=.04) with an adjusted (sex, age) odds ratio of 3.5. The median values of DIL-5 (p=.006) are significantly higher in the overall responder group compared to nonresponders and DIL-15 (p=.07) is marginally higher. In comparing the highest responders (decrease %ABC-I>.60) to nonresponders, median values of DIL-15 (p=.04) are significantly higher and DIL-5 (p=.07) is marginally higher. There are no differences in baseline measure.There is no association between weight gain and response. Weight gain is negatively correlated with DIL-5 (p=.02) and DINFa2 (p=.01). We found no baseline predictors of weight gain.  

Conclusions: Responders had a greater increase in IL-5 compared to nonresponders. Greater overall improvement is associated with significant increases in IL-5 and IL-15. Those with higher levels of baseline IL-15 are more likely to have a reduction in irritability symptoms alone. There is a significant decrease in Eotaxin and MCP1 levels following 8 weeks of risperidone treatment. Previous studies report increased MCP-1 and Eotaxin levels in children with autism when compared to controls and are associated with higher ABC-I scores. The effects on cytokines due to weight gain and baseline cytokine levels are not predictive biomarkers of weight gain.

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