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Altered peripheral BDNF mRNA expression and BDNF protein concentrations in blood of children and adolescents with autism spectrum disorder

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

Findings from molecular genetic studies and analyses of postmortem and peripheral tissue led to the hypothesis that neurotrophins—as crucial moderators of neuroplasticity—impact on the pathophysiology of autism spectrum disorder (ASD). The study projects aimed to complement former results on the role of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family with fundamental impact on brain development and function. The purpose of this work was to investigate peripheral BDNF mRNA expression and BDNF protein concentrations in ASD as potential surrogates for the effects observed in the central nervous system. In a BDNF protein quantification study, serum concentrations were analyzed using Enzyme-Linked Immunosorbent Assays in 24 male patients with ASD, all with an IQ > 70 (age 13.9 ± 3.0 years) and 20 age- and gender-matched healthy control subjects (age 14.4 ± 2.1 years; p = 0.522). In a further independent project, a BDNF mRNA expression analysis, mRNA levels from total blood were assessed by quantitative real-time polymerase chain reaction in a sample of 16 male ASD patients (age 10.8 ± 2.2), 15 age- and gender-matched healthy controls (age 12.1 ± 2.2) and 15 patients with attention deficit hyperactivity disorder as a clinical control group (age 11.8 ± 2.2; p = 0.207). In the protein quantification project, significantly decreased BDNF serum concentrations were found in ASD cases compared to healthy control children (t = −2.123, df = 42, p < 0.05). Analysis of covariance (ANCOVA) revealed this result in accordance with significant reductions in BDNF mRNA expression in ASD, observed in the mRNA expression study (F = 3.65; df = 2.43; p < 0.05); neither age nor IQ confounded the result, as indicated by ANCOVA (F = 3.961; df = 2.41; p < 0.05, η 2 = 0.162). Our study projects supported the notion that neurotrophins are involved in the pathophysiology of ASD. Further studies may eventually contribute to the identification of distinct peripheral mRNA expression and protein concentration patterns possibly supporting diagnostic and therapeutic processes.

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Acknowledgments

We wish to thank the patients and families who participated in this study, Miryame Hofmann and Thomas Elpel for their help with sample analyses as well as Dr. Alex C. Conner for his support with manuscript preparation.

Conflict of interest

J. T. has obtained financial support (e.g. lecture honoraria, grants for research projects and scientific meetings, advisory-board membership) from Actelion, AstraZeneca, Bristol-Meyers Squibb, Ever Neuro Pharma, Janssen-Cilag, Lilly, Lundbeck, Medice Arzneimittel Pütter, Merz Pharmaceuticals, Novartis Pharma, Pfizer Pharma, Roche, Servier, Shire. Some of these companies manufacture drugs used in the treatment of ADHD and ASD. S.W. has received lecture honoraria from Janssen Cilag, AstraZeneca and Eli Lilly in the last 5 years. Her work was partially supported in the last 5 years by the Swiss National Science Foundation (SNF), Deutsche Forschungsgemeinschaft, EU FP7, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland. All other authors have no competing interests.

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Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstraße 15, 97080, Wuerzburg, Germany

    Regina Taurines, Laura Albantakis, Thomas Jans, Benjamin Lyttwin, Berthold Martin, Marcel Romanos & Manfred Gerlach

  2. Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain

    Monica Segura

  3. Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany

    Martin Schecklmann

  4. Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland

    Edna Grünblatt & Susanne Walitza

  5. Department of Child and Adolescent Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany

    Michael Haberhausen

  6. Department of Child and Adolescent Psychiatry, Herz-Jesu-Krankenhaus, Fulda, Germany

    Frank M. Theisen

  7. Department of Child and Adolescent Psychiatry and Psychotherapy, Leopoldina Hospital, Schweinfurt, Germany

    Wolfgang Briegel

  8. Department of Psychiatry and Psychotherapy, University of Rostock, Rostock, Germany

    Johannes Thome

  9. College of Medicine, Swansea University, Swansea, UK

    Johannes Thome

  10. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-University, Frankfurt/M, Germany

    Christina Schwenck

Authors
  1. Regina Taurines
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  2. Monica Segura
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  3. Martin Schecklmann
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  4. Laura Albantakis
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  5. Edna Grünblatt
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  6. Susanne Walitza
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  7. Thomas Jans
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  8. Benjamin Lyttwin
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  9. Michael Haberhausen
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  10. Frank M. Theisen
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  11. Berthold Martin
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  12. Wolfgang Briegel
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  13. Johannes Thome
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  14. Christina Schwenck
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  15. Marcel Romanos
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  16. Manfred Gerlach
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Corresponding author

Correspondence to Regina Taurines.

Additional information

R. Taurines and M. Segura contributed equally to this work.

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Taurines, R., Segura, M., Schecklmann, M. et al. Altered peripheral BDNF mRNA expression and BDNF protein concentrations in blood of children and adolescents with autism spectrum disorder. J Neural Transm 121, 1117–1128 (2014). https://doi.org/10.1007/s00702-014-1162-x

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  • DOI: https://doi.org/10.1007/s00702-014-1162-x

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