A Deletion in Tropomyosin-Related Kinase B and the Development of Human Anxiety
A Deletion in Tropomyosin-Related Kinase B and the Development of Human Anxiety
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DOI：
10.1016/j.biopsych.2010.10.008
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发表时间：
2011-03-15
影响因子：
10.6
通讯作者：
Turecki, Gustavo
中科院分区：
文献类型：
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作者：
Ernst, Carl;Wanner, Brigitte;Turecki, Gustavo
背景：原肌球蛋白相关激酶B(TrkB)/脑源性神经营养因子系统与精神障碍有关，该系统缺陷的动物模型表明其在焦虑中可能具有特殊的作用。方法：采用DNA测序和克隆方法鉴定TrkB的突变，并使用四种不同的细胞株来评估功能。临床样本来自代表魁北克普通人群的22年纵向队列(n=640名受试者)，他们在幼儿园时随机选择。采用社会行为问卷、人格病理诊断简明问卷和DSM-IIIR诊断访谈程序对焦虑相关特质进行测量。结果：TrkB基因11个碱基对缺失与儿童焦虑特质的增加和成年后焦虑障碍的发展显著相关。我们发现该缺失会损害某些人类细胞系的转录。结论：该缺失的鉴定为TrkB在调节人类焦虑相关特征中的作用提供了额外的支持。
Background: The tropomyosin-related kinase B (TrkB)/brain-derived neurotrophic factor system has been associated with psychiatric disorders, and animal models of defects in this system suggest that it might have a particular role in anxiety.Methods: DNA sequencing and cloning were used to identify a mutation in TrkB, and four different cell lines were used to assess functionality. Clinical samples were from a 22-year longitudinal cohort representative of the Quebec general population (n = 640 subjects), randomly selected when they were in kindergarten. Anxiety-related traits were measured with the Social Behaviour Questionnaire, the Diagnostic Assessment of Personality Pathology-Brief Questionnaire, and the Diagnostic Interview Schedule for DSM-IIIR.Results: An 11 base pair deletion in TrkB is significantly associated with increases in anxiety traits during childhood and the development of anxiety disorders in adulthood. We found that this deletion impaired transcription in some human cell lines.Conclusions: The identification of this deletion provides additional support for the role of TrkB in modulating anxiety-related traits in human.