Brain derived neurotrophic factor and serotonin transporter binding as markers of clinical response to fluoxetine therapy in children with autism

Ismo Makkonen, Raili Riikonen, Jyrki T. Kuikka, Hannu Kokki, Joseph P. Bressler, Cathleen Marshall, Walter E. Kaufmann

Research output: Contribution to journalArticle

Abstract

Fluoxetine, a selective serotonin reuptake inhibitor, has shown favorable effects in some children with autism. There are no previous studies evaluating the connection between clinical outcome and markers of clinical response to fluoxetine treatment. In this prospective clinical trial we examined serum brain derived neurotrophic factor (BDNF) concentrations and serotonin transporter (SERT) binding in the medial frontal cortex and the midbrain, measured by single photon emission computed tomography scanning, in a group of 13 autistic children and adolescents (12 males; age 5-16 years), who were treated for 6 months with fluoxetine at a dose range of 10-40 mg/day. Clinical response was evaluated by the Autism Treatment Evaluation Checklist. Serum concentrations of BDNF and SERT binding were measured at baseline and 2 months after termination of fluoxetine treatment. At baseline, before starting fluoxetine treatment, the serum concentration of BDNF had a bimodal distribution in the autism group with either a low concentration (n=8, mean 1497 pg/mL) or a high concentration (n=5, mean 14062 pg/mL) with respect to controls (n=15, mean 9652 pg/mL), and SERT binding was uniformly low in the autistic subjects in the medial frontal cortex and the midbrain. Fluoxetine treatment led to positive effects in several aspects of communication, socialization and cognitive awareness, with six out 13 subjects being particularly good responders. These six also had a significant decrease in BDNF (P=0.03) and minimal change in SERT binding after therapy. The other seven subjects showed a trend towards an increase in BDNF and SERT binding. Our results indicate that fluoxetine may improve core autistic symptoms, and that this clinical response is linked to a decrease in serum BDNF.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalJournal of Pediatric Neurology
Volume9
Issue number1
DOIs
StatePublished - Mar 1 2011

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Keywords

  • Adolescent
  • BDNF
  • SPECT
  • autism
  • children
  • clinical outcome
  • fluoxetine
  • serotonin transporter

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

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