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  • Original Research Article
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Brain-derived neurotrophic factor Val66met polymorphism and volume of the hippocampal formation

Abstract

Magnetic resonance (MR) imaging studies have identified hippocampal structural alterations in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins that is widely expressed in the hippocampal formation and has been implicated in the neurobiology of schizophrenia. Polymorphisms in the BDNF gene may therefore confer risk for schizophrenia through hippocampal pathogenesis and/or making the hippocampus more susceptible to environmental insults. In this study, we investigated whether val66met, a functional and abundant missense polymorphism in the coding region of the BDNF gene, was associated with the volume of the hippocampal formation in 19 patients with first-episode schizophrenia and 25 healthy volunteers. A total of 124 contiguous T1-weighted coronal MR images (slice thickness=1.5 mm) were acquired through the whole head using a 3D Fast SPGR IR Prep sequence on a 1.5 T GE imaging system. Volumes of the right and left hippocampal formation were measured manually by an operator blind to group status and genotype. All participants were genotyped for the BDNF val66met locus. Mixed model analyses revealed a main effect of BDNF val66met genotype such that in the combined sample of patients and healthy volunteers, val/val homozygotes (N=27) had larger volumes of the hippocampal formation compared to val/met heterozygotes (N=17). In separate analyses by group, however, val66met genotype accounted for a greater proportion of the variance in the volume of the hippocampal formation in patients compared to healthy volunteers. These findings implicate genetic involvement of BDNF in variation of human hippocampal volume and suggest that this effect may be greater among patients compared to healthy volunteers.

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Acknowledgements

This work was supported in part by grants from NARSAD (PRS) and the National Institute of Mental Health to Dr Szeszko (MH01990), Dr Bilder (MH60374), Dr Kane (MH60575, MH60004) and Dr Malhotra (MH01760). This study was presented, in part, at the 2004 Meeting of the Society of Biological Psychiatry in New York, NY and the 2004 World Congress on Psychiatric Genetics in Dublin, Ireland.

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Correspondence to P R Szeszko.

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Szeszko, P., Lipsky, R., Mentschel, C. et al. Brain-derived neurotrophic factor Val66met polymorphism and volume of the hippocampal formation. Mol Psychiatry 10, 631–636 (2005). https://doi.org/10.1038/sj.mp.4001656

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