Integrated Neuroimaging Group, Department of Psychiatry and Institute of Neuroscience, School of Medicine, Trinity College Dublin, University of Dublin, College Green, Dublin, Ireland.
Biol Psychiatry. 2012 Oct 15;72(8):663-70. doi: 10.1016/j.biopsych.2012.04.015. Epub 2012 May 19.
Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene and its receptor neurotrophic tyrosine kinase receptor type 2 (NTRK2) have been implicated in mood disorders. The aim of this study was to examine whether the NTRK2 and BDNF polymorphisms impact brain white matter connections in major depressive disorder and whether they may also have an interactive effect with environmental stress in the form of early life adversity.
The study group comprised 45 depressed patients and 45 age- and gender-matched control subjects. High angular resolution diffusion images were obtained and analyzed using tract-based spatial statistics. Analysis of a single nucleotide polymorphism in the BDNF (rs6265/Valine66Methionine) and NTRK2 (rs11140714) genes was performed.
An interactive effect was found between NTRK2 and depression diagnosis maximally affecting the cingulum. Depressed patients homozygous for the A allele of NTRK2 showed significantly reduced fractional anisotropy compared with depressed patients with at least one copy of the G allele or control subjects with either the A/A or G carrier genotypes in the left and right corona radiata, left uncinate fasciculus, left inferior fronto-occipital fasciculus, left cerebral peduncle, posterior thalamic radiation, and middle cerebral peduncle. Significantly smaller gray matter volume was seen in frontal lobe regions in patients homozygous for the A allele.
Polymorphisms in NTRK2 gene increase risk of architectural changes in several brain regions involved in emotional regulation.
脑源性神经营养因子（BDNF）基因及其受体神经营养酪氨酸激酶受体 2（NTRK2）的多态性与心境障碍有关。本研究旨在探讨 NTRK2 和 BDNF 多态性是否影响重度抑郁症患者的脑白质连接，以及它们是否可能与早期生活逆境等环境应激产生交互作用。
研究组包括 45 名抑郁症患者和 45 名年龄和性别匹配的对照者。采用基于束流的空间统计学方法对高角分辨率弥散图像进行分析。分析 BDNF（rs6265/Valine66Methionine）和 NTRK2（rs11140714）基因的单核苷酸多态性。
发现 NTRK2 与抑郁诊断之间存在交互作用，最大程度地影响了扣带束。与至少携带一个 G 等位基因的抑郁症患者或 A/A 或 G 携带者基因型的对照组相比，NTRK2 纯合子 A 等位基因的抑郁症患者，左右放射冠、左侧钩束、左侧额枕下束、左侧大脑脚、后丘脑辐射和大脑中动脉的各向异性分数明显降低。在 A 等位基因纯合子患者的额叶区域观察到灰质体积明显减小。
NTRK2 基因的多态性增加了几个参与情感调节的脑区结构改变的风险。
