This is the third of our Forum journal discussions, in which the editors of Schizophrenia Bulletin or Schizophrenia Research choose a thought-provoking recent article and provide access to the full text. A short introduction by a journal editor, below, will get us started, and then it's up to our readers to share their ideas and insights, questions and reactions to the selected paper. So read on"
Tochigi M, Otowa T, Suga M, Rogers M, Minato T, Yamasue H, Kasai K, Kato N, Sasaki T. No evidence for an association between the BDNF Val66Met polymorphism and schizophrenia or personality traits. Schizophr Res. 2006 Jul 17; [Epub ahead of print]
by Lynn DeLisi, New York University, and Editor, Schizophrenia Research
For more than a decade, spurred by the hypothesis of schizophrenia as a neurodevelopmental disorder, researchers have looked for associations between the brain-derived neurotrophic factor (BDNF) and schizophrenia. The Val66Met polymorphism has received the most attention recently, but results have been mixed, with some finding an association between the Val allele and schizophrenia or schizophrenia spectrum disorders (e.g., Neves-Pereira et al., 2005; Rosa et al., 2006) and others finding no association (e.g., Chen et al., 2006; Jonsson et al., 2006; Watanabe et al., 2006). The finding by Egan and colleagues of Val66Met-related differences in cognitive performance in normal subjects (Egan et al., 2003) has also led to a boom in studies of this polymorphism in normal cognition and behavior, with the implication of relevance to schizophrenia.
But is it now time to throw in the towel? In their paper in press at Schizophrenia Research, Tsukasa Sasaki and colleagues at the University of Tokyo describe a study of 401 patients with schizophrenia and 569 controls that failed to find an association of Val66Met with the disorder. Furthermore, there was no association of the polymorphism with personality traits in the control group.
Some questions for discussion: Are the study populations sufficient to draw firm conclusions in this or earlier studies? Can population differences be used to explain the discrepancies? Any other methodological concerns? Any other data that we should consider? And, as always, where should we go from here?
References: Chen QY, Chen Q, Feng GY, Wan CL, Lindpaintner K, Wang LJ, Chen ZX, Gao ZS, Tang JS, Li XW, He L. Association between the brain-derived neurotrophic factor (BDNF) gene and schizophrenia in the Chinese population.Neurosci Lett. 2006 Apr 24;397(3):285-90. Epub 2006 Jan 9. Abstract
Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function.Cell. 2003 Jan 24;112(2):257-69. Abstract
Jonsson EG, Edman-Ahlbom B, Sillen A, Gunnar A, Kulle B, Frigessi A, Vares M, Ekholm B, Wode-Helgodt B, Schumacher J, Cichon S, Agartz I, Sedvall GC, Hall H, Terenius L. Brain-derived neurotrophic factor gene (BDNF) variants and schizophrenia: an association study.Prog Neuropsychopharmacol Biol Psychiatry. 2006 Jul;30(5):924-33. Epub 2006 Apr 3. Abstract
Neves-Pereira M, Cheung JK, Pasdar A, Zhang F, Breen G, Yates P, Sinclair M, Crombie C, Walker N, St Clair DM. BDNF gene is a risk factor for schizophrenia in a Scottish population.Mol Psychiatry. 2005 Feb;10(2):208-12. Abstract
Rosa A, Cuesta MJ, Fatjo-Vilas M, Peralta V, Zarzuela A, Fananas L. The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with risk for psychosis: evidence from a family-based association study.Am J Med Genet B Neuropsychiatr Genet. 2006 Mar 5;141(2):135-8. Abstract
Watanabe Y, Muratake T, Kaneko N, Nunokawa A, Someya T. No association between the brain-derived neurotrophic factor gene and schizophrenia in a Japanese population.Schizophr Res. 2006 May;84(1):29-35. Epub 2006 Apr 21. Abstract