Forde Natalie J, Ronan Lisa, Suckling John, Scanlon Cathy, Neary Simon, Holleran Laurena, Leemans Alexander, Tait Roger, Rua Catarina, Fletcher Paul C, Jeurissen Ben, Dodds Chris M, Miller Sam R, Bullmore Edward T, McDonald Colm, Nathan Pradeep J, Cannon Dara M
Clinical Neuroimaging Laboratory, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK.
Neuroimage. 2014 Apr 15;90:280-9. doi: 10.1016/j.neuroimage.2013.12.050. Epub 2013 Dec 31.
The brain-derived neurotrophic factor (BDNF) val66met polymorphism is associated with altered activity dependent secretion of BDNF and a variable influence on brain morphology and cognition. Although a met-dose effect is generally assumed, to date the paucity of met-homozygotes have limited our understanding of the role of the met-allele on brain structure.
To investigate this phenomenon, we recruited sixty normal healthy subjects, twenty in each genotypic group (val/val, val/met and met/met). Global and local morphology were assessed using voxel based morphometry and surface reconstruction methods. White matter organisation was also investigated using tract-based spatial statistics and constrained spherical deconvolution tractography.
Morphological analysis revealed an "inverted-U" shaped profile of cortical changes, with val/met heterozygotes most different relative to the two homozygous groups. These results were evident at a global and local level as well as in tractography analysis of white matter fibre bundles.
In contrast to our expectations, we found no evidence of a linear met-dose effect on brain structure, rather our results support the view that the heterozygotic BDNF val66met genotype is associated with cortical morphology that is more distinct from the BDNF val66met homozygotes. These results may prove significant in furthering our understanding of the role of the BDNF met-allele in disorders such as Alzheimer's disease and depression.
脑源性神经营养因子（BDNF）Val66Met多态性与BDNF活性依赖性分泌改变以及对脑形态和认知的可变影响相关。尽管通常假定存在Met剂量效应，但迄今为止，Met纯合子数量稀少限制了我们对Met等位基因在脑结构中作用的理解。
为了研究这一现象，我们招募了60名正常健康受试者，每个基因型组（Val/Val、Val/Met和Met/Met）各20名。使用基于体素的形态测量法和表面重建方法评估整体和局部形态。还使用基于束的空间统计学和约束球面反卷积纤维束成像技术研究白质组织。
形态学分析揭示了皮质变化呈“倒U”形分布，Val/Met杂合子相对于两个纯合子组差异最大。这些结果在整体和局部水平以及白质纤维束的纤维束成像分析中都很明显。
与我们的预期相反，我们没有发现对脑结构存在线性Met剂量效应的证据，相反，我们的结果支持这样的观点，即杂合性BDNF Val66Met基因型与皮质形态有关，这种形态与BDNF Val66Met纯合子更不同。这些结果可能对进一步理解BDNF Met等位基因在阿尔茨海默病和抑郁症等疾病中的作用具有重要意义。
