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Brain Derived Neurotrophic Factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia

Molecular Psychiatry volume 5, pages 558–562 (2000)Cite this article

Abstract

Schizophrenia is a heterogeneous disease involving genetic and environmental factors. The frequency of structural brain abnormalities1, 2 or physical anomalies3supports a neurodevelopmental etiology, especially in early onset schizophrenia.4Brain-Derived-Neurotrophic-Factor (BDNF) is involved in the neurodevelopment of dopaminergic (DA)-related systems5, 6 and interacts with the meso-limbic DA systems,7, 8, 9, 10 involved in the therapeutic response to antipsychotic drugs11 and substance abuse.12 In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression.13 In a French Caucasian population, we found no statistical difference in allele or genotype distribution of the BDNF gene dinucleotide repeat polymorphism (166–174 bp)14 between the whole group of schizophrenic patients and controls. By contrast, an excess of the 172–176 bp alleles was found in patients with late onset, in neuroleptic-responding patients and in non-substance-abusing patients. BDNF gene variants thus appear to be associated with developmental features of schizophrenia. In addition, this association with good treatment responding was independent from the association found with the DRD3 BalI gene polymorphism in the same population.15 These results suggest an independent contribution of each gene to a treatment-sensitive form of schizophrenia.

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Acknowledgements

This work was promoted by INSERM. OG was supported by a Lundbeck grant and by the Fondation pour la Recherche Medicale. We wish to thank Marylis Corbex for her advice on statistical analysis.

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Authors and Affiliations

  1. Department of Mental Health and Therapeutic, Biological Psychiatry Laboratory (UPRES EA 2501, University of Paris V), Sainte-Anne Hospital, Paris, France

    M O Krebs, O Guillin, M C Bourdel, J P Olie & M F Poirier

  2. Department of Neurobiology and Molecular Pharmacology (U109, INSERM), Paris, France

    O Guillin, J C Schwartz & P Sokoloff

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  1. M O Krebs
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  2. O Guillin
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  5. J P Olie
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  6. M F Poirier
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  7. P Sokoloff
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Correspondence to M O Krebs.

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Krebs, M., Guillin, O., Bourdel, M. et al. Brain Derived Neurotrophic Factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia. Mol Psychiatry 5, 558–562 (2000). https://doi.org/10.1038/sj.mp.4000749

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