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Science:BDNF基因变异会导致焦虑

来源:腾讯科技 2010-01-21 09:35

专题:Science报道

美国研究人员发现人类和老鼠身上具有相同的“焦虑”相关基因,表明实验室动物研究可以用来研究相关人类行为。这项研究结果可帮助科学家开发出新的临床药物,治疗人类的恐惧症和创伤后应激障碍等焦虑症相关疾病。

据报道,研究者发现具有脑源性神经营养因子(BDNF)基因变异的人类和老鼠具有共同的行为反应,即当处于不良刺激环境中时,他们都很难去除掉和焦虑相关的反应。

科学家在试验中用的老鼠是转基因老鼠,在它们的基因组中插入了一个人类的基因变异。研究者还利用功能性磁共振成像技术(fMRI)对人类大脑进行扫描,以便区别具有正常或者异常神经营养因子的人群大脑功能的区别。

他们发现了具有异常脑源性神经营养因子的人群中大脑负责了解信号安危所涉及额叶皮层和杏仁核的回路,发生了改变,而具有正常脑源性神经营养因子的人群则没有这种变化。

精神病学和药理学副教授弗朗西斯·S·李(Francis S. Lee)博士说:“通过研究脑源性神经营养因子(BDNF)基因,在未来可帮助开发出新的治疗焦虑症的临床药物。”目前采用暴露疗法来进行焦虑、恐惧和创伤后应激障碍的治疗,研制者指出,暴露疗法也有可能对BDNF基因异常的病人有用,但是可能要花费更长的时间。(生物谷Bioon.com)

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Science DOI: 10.1126/science.1181886

A Genetic Variant BDNF Polymorphism Alters Extinction Learning in Both Mouse and Human

Fatima Soliman,1,2,* Charles E. Glatt,2 Kevin G. Bath,2 Liat Levita,1,2 Rebecca M. Jones,1,2 Siobhan S. Pattwell,2 Deqiang Jing,2 Nim Tottenham,1,2 Dima Amso,1,2 Leah Somerville,1,2 Henning U. Voss,3 Gary Glover,4 Douglas J. Ballon,3 Conor Liston,1,2 Theresa Teslovich,1,2 Tracey Van Kempen,1,2 Francis S. Lee,2 B. J. Casey1,2,*

Mouse models are useful for studying genes involved in behavior, but whether they are relevant for human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat and in the efficacy of treatments that rely on extinction mechanisms, such as exposure therapy.

1 The Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, NY 10065, USA.
2 Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA.
3 Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA.
4 Lucas Center for Imaging, Department of Radiology, Stanford University, Stanford, CA 94305, USA.

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