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Molecular Psychiatry (2015) 20, 916930 2015 Macmillan Publishers Limited All rights reserved 1359-4184/15
http://www.nature.com/mp
Web End =www.nature.com/mp
EXPERT REVIEW
The BDNF gene Val66Met polymorphism as a modier of psychiatric disorder susceptibility: progress and controversy
M Notaras1, R Hill1 and M van den Buuse1,2
Brain-derived neurotrophic factor (BDNF) has a primary role in neuronal development, differentiation and plasticity in both the developing and adult brain. A single-nucleotide polymorphism in the proregion of BDNF, termed the Val66Met polymorphism, results in decient subcellular translocation and activity-dependent secretion of BDNF, and has been associated with impaired neurocognitive function in healthy adults and in the incidence and clinical features of several psychiatric disorders. Research investigating the Val66Met polymorphism has increased markedly in the past decade, and a gap in integration exists between and within academic subelds interested in the effects of this variant. Here we comprehensively review the role and relevance of the Val66Met polymorphism in psychiatric disorders, with emphasis on suicidal behavior and anxiety, eating, mood and psychotic disorders. The cognitive and molecular neuroscience of the Val66Met polymorphism is also concisely reviewed to illustrate the effects of this genetic variant in healthy controls, and is complemented by a commentary on the behavioral neuroscience of BDNF and the Val66Met polymorphism where relevant to specic disorders. Lastly, a number of controversies and unresolved issues, including small effect sizes, sampling of allele inheritance but not genotype and putative ethnicity-specic effects of the Val66Met
polymorphism, are also discussed to direct future research.
Molecular Psychiatry (2015) 20, 916930; doi:http://dx.doi.org/10.1038/mp.2015.27
Web End =10.1038/mp.2015.27 ; published online 31 March 2015
INTRODUCTIONIt is now widely accepted that psychiatric disorders arise from complex genegene and geneenvironment interactions, and that their clinical heterogeneity may be the result of the differential involvement of discrete etiological and genetic factors. In recent years, a number of genetic variants have been identied as modulators of cognitive function.1 This includes genetic variants within the dopaminergic system, such as the DRD3 Ser9Gly and COMT Val158Met polymorphisms,1 as well as those within the serotonergic system, such as the 5HTTLPR (serotonin transporter gene-linked polymorphic region) variant.2 These variants have revealed how disruptions in optimal cellular or system function can modify cognition and risk of development of psychiatric disorders and their resulting clinical phenotype. Brain-derived neurotrophic factor (BDNF)...