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23 septembre 2012 7 23 /09 /septembre /2012 16:44
The Pharmacogenomics Journal (2012) 12, 368–371; doi:10.1038/tpj.2011.23; published online 7 June 2011 Gene expression in blood is associated with risperidone response in children with autism spectrum disorders L Lit1, F R Sharp1, K Bertoglio2, B Stamova1, B P Ander1, A D Sossong3 and R L Hendren4 1Department of Neurology, University of California, Davis, MIND Institute, Davis, CA, USA 2University of California, Irvine, School of Medicine 3University of California, San Francisco, School of Medicine, San Francisco, CA, USA 4Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA Correspondence: Dr L Lit, Department of Neurology, University of California, Davis, MIND Institute, 2805 50th Street, Room 2415, Sacramento, Davis, CA 95817, USA. E-mail: llit@ucdavis.edu Received 16 November 2010; Revised 23 March 2011; Accepted 4 May 2011 Advance online publication 7 June 2011 Top of page Abstract Children with autism spectrum disorders (ASDs) often have severe behavioral problems. Not all children with these problems respond to atypical antipsychotic medications; therefore, we investigated whether peripheral blood gene expression before treatment with risperidone, an atypical antipsychotic, was associated with improvements in severe behavioral disturbances 8 weeks following risperidone treatment in 42 ASD subjects (age 112.7±51.2 months). Exon expression levels in blood before risperidone treatment were compared with pre–post risperidone change in Aberrant Behavior Checklist-Irritability (ABC-I) scores. Expression of exons within five genes was correlated with change in ABC-I scores across all risperidone-treated subjects: GBP6, RABL5, RNF213, NFKBID and RNF40 (α<0.001). RNF40 is located at 16p11.2, a region implicated in autism and schizophrenia. Thus, these genes expressed before treatment were associated with subsequent clinical response. Future studies will be needed to confirm these results and determine whether this expression profile is associated with risperidone response in other disorders, or alternative antipsychotic response within ASD.

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