title: A role for the BDNF gene Val66Met polymorphism in schizophrenia? A comprehensive review.
abstract: Schizophrenia is believed to arise from complex gene-environment interactions. Brain-derived neurotrophic factor (BDNF) is involved in neuronal development, differentiation and plasticity. A functional single nucleotide polymorphism that results in a valine (Val) to methionine (Met) substitution at codon 66 (Val66Met) results in the aberrant sorting and release of mature BDNF through the activity-dependent secretion pathway. The Val66Met polymorphism has been linked to impaired neurocognitive function in healthy adults, and identified as a locus of risk for a range of neuropsychiatric disorders including schizophrenia. Here we provide a comprehensive review of the relationship between the BDNF Val66Met polymorphism and schizophrenia, integrating evidence from the fields of genetic epidemiology, clinical psychiatry, behavioral neuroscience and neuroimaging. We argue that while the Val66Met polymorphism may not be a major risk-conferring agent for the development of schizophrenia per se, there is mounting evidence that the polymorphism modulates a range of clinical features of the illness, including age of onset, symptoms, therapeutic responsiveness, neurocognitive function and brain morphology.
authors.affiliation: Behavioural Neuroscience Laboratory, Florey Institute of Neuroscience & Mental Health, VIC, Australia; Psychoneuroendocrinology Laboratory, Florey Institute of Neuroscience & Mental Health, VIC, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Notaras
authors.affiliation: Behavioural Neuroscience Laboratory, Florey Institute of Neuroscience & Mental Health, VIC, Australia; Psychoneuroendocrinology Laboratory, Florey Institute of Neuroscience & Mental Health, VIC, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hill
authors.affiliation: Behavioural Neuroscience Laboratory, Florey Institute of Neuroscience & Mental Health, VIC, Australia; Department of Pharmacology & Therapeutics, University of Melbourne, VIC, Australia; School of Psychological Science, La Trobe University, VIC, Australia. Electronic address: m.vandenbuuse@latrobe.edu.au.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: Age of onset; Animal models of schizophrenia; BDNF; Brain morphology; Brain-derived neurotrophic factor; Clinical pleiotropy; Cognition; Comorbid symptoms; G196A; Psychosis; Schizophrenia; Therapeutic responsiveness; Val66Met; Val66Met mice; rs6265