Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
Genes Brain Behav. 2013 Feb;12(1):98-107. doi: 10.1111/j.1601-183X.2012.00854.x. Epub 2012 Oct 11.
Neuroimaging studies have linked the methionine (Met) allele of the brain-derived neurotrophic factor (BDNF) gene to abnormal regional brain volumes in several psychiatric and neurodegenerative diseases. However, no neuroimaging studies assessed the effects of this allele on brain morphology in alcohol use disorders and its demonstrated change during abstinence from alcohol. Here we assessed the effects of the BDNF Val66Met (rs6265) polymorphism on regional brain tissue volumes and their recovery during short-term abstinence in treatment-seeking alcohol-dependent individuals. 3D T1 weighted magnetic resonance images from 62 individuals were acquired at 1.5 T at one week of abstinence from alcohol; 41 of the participants were rescanned at 5 weeks of abstinence. The images were segmented into gray matter (GM), white matter (WM) and cerebrospinal fluid and parcellated into regional volumes. The BDNF genotype was determined from blood samples using the TaqMan technique. Alcohol-dependent Val (Valine)/Met heterozygotes and Val homozygotes had similar regional brain volumes at either time point. However, Val homozygotes had significant GM volume increases, while Val/Met heterozygotes increased predominantly in WM volumes over the scan interval. Longitudinal increases in GM but not WM volumes were related to improvements in neurocognitive measures during abstinence. The findings suggest that functionally significant brain tissue volume recovery during abstinence from alcohol is influenced by BDNF genotype.
神经影像学研究将脑源性神经营养因子(BDNF)基因的蛋氨酸(Met)等位基因与几种精神和神经退行性疾病中的异常区域脑容量联系起来。然而,没有神经影像学研究评估该等位基因对酒精使用障碍中的脑形态的影响,以及在戒酒期间该等位基因的变化。在这里,我们评估了 BDNF Val66Met(rs6265)多态性对治疗性酒精依赖个体短期戒酒期间区域脑组织体积及其恢复的影响。62 名个体的 3D T1 加权磁共振图像在戒酒 1 周时在 1.5 T 处采集;41 名参与者在戒酒 5 周时重新扫描。图像被分割为灰质(GM)、白质(WM)和脑脊液,并分割为区域体积。使用 TaqMan 技术从血液样本中确定 BDNF 基因型。在任何时间点,酒精依赖的 Val(缬氨酸)/Met 杂合子和 Val 纯合子的区域脑容量相似。然而,Val 纯合子的 GM 体积增加显著,而 Val/Met 杂合子在扫描间隔期间主要增加 WM 体积。GM 而不是 WM 体积的纵向增加与戒酒期间神经认知测量的改善有关。这些发现表明,BDNF 基因型影响酒精戒断期间功能上显著的脑组织体积恢复。