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Journal of Pediatric Neurology 2011; 09(01): 001-008
DOI: 10.3233/JPN-2010-0446
Georg Thieme Verlag KG Stuttgart – New York

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

Authors

  • Ismo Makkonen

    a   Department of Pediatrics, Unit of Child Neurology, Kuopio University Hospital, Kuopio, Finland

  • Raili Riikonen

    a   Department of Pediatrics, Unit of Child Neurology, Kuopio University Hospital, Kuopio, Finland

  • Jyrki T. Kuikka

    b   Imaging Center, Kuopio University Hospital, and Niuvanniemi Hospital, Kuopio, Finland

  • Hannu Kokki

    c   Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland

  • Joseph P. Bressler

    d   Center for Genetic Disorders of Cognition & Behavior, Kennedy Krieger Institute and the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

  • Cathleen Marshall

    e   Center for Genetic Disorders of Cognition & Behavior, Kennedy Krieger Institute and the Johns Hopkins University School of Medicine, Baltimore, MD, USA

  • Walter E. Kaufmann

    e   Center for Genetic Disorders of Cognition & Behavior, Kennedy Krieger Institute and the Johns Hopkins University School of Medicine, Baltimore, MD, USA

Subject Editor:
Further Information

Publication History

23 February 2010

19 May 2010

Publication Date:
30 July 2015 (online)

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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.

Keywords

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