PMID- 17700574 OWN - NLM STAT- MEDLINE DCOM- 20080305 LR - 20220318 IS - 1359-4184 (Print) IS - 1359-4184 (Linking) VI - 12 IP - 12 DP - 2007 Dec TI - Is it time to reassess the BDNF hypothesis of depression? PG - 1079-88 AB - The brain-derived neurotrophic factor (BDNF) hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and that its restoration may underlie the therapeutic efficacy of antidepressant treatment. While this theory has received considerable experimental support, an increasing number of studies have generated evidence which is not only inconsistent, but also directly contradicts the hypothesis. This article provides a critical review of the clinical and preclinical studies which have been responsible for this controversy, outlining pharmacological, behavioural and genetic evidence which demonstrates the contrasting role of BDNF in regulating mood and antidepressant effects throughout the brain. I will also review key studies, both human and animal, which have investigated the association of a BDNF single-nucleotide polymorphism (Val66Met) with depression pathogenesis, and detail the number of inconsistencies which also afflict this novel area of BDNF research. The article will conclude by discussing why now is a critical time to reassess the original BDNF hypothesis of depression, and look towards the formation of new models that can provide a more valid account of the complex relationships between growth factors, mood disorders and their treatment. FAU - Groves, J O AU - Groves JO AD - The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. james.groves@well.ox.ac.uk LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20070814 PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 RN - 0 (Brain-Derived Neurotrophic Factor) RN - AE28F7PNPL (Methionine) RN - HG18B9YRS7 (Valine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Depression/genetics/*metabolism/physiopathology MH - Humans MH - Methionine/genetics MH - *Models, Biological MH - Polymorphism, Single Nucleotide/genetics MH - Valine/genetics RF - 106 EDAT- 2007/08/19 09:00 MHDA- 2008/03/06 09:00 CRDT- 2007/08/19 09:00 PHST- 2007/08/19 09:00 [pubmed] PHST- 2008/03/06 09:00 [medline] PHST- 2007/08/19 09:00 [entrez] AID - 4002075 [pii] AID - 10.1038/sj.mp.4002075 [doi] PST - ppublish SO - Mol Psychiatry. 2007 Dec;12(12):1079-88. doi: 10.1038/sj.mp.4002075. Epub 2007 Aug 14.