期刊
PSYCHONEUROENDOCRINOLOGY
卷 36, 期 3, 页码 393-405出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2010.12.012
关键词
Serotonin; Tryptophan hydroxylase; TPH1; TPH2; Knockout; Development; Anxiety aggression; Depression; Suicide; OCD; ADHD
资金
- DFG [KFO 125, SFB 581/B9, SFB TRR 58/A1, A5]
- BMBF [01KS9603]
- EC [NEWMOOD LSHM-CT-2003-503474]
Based on genetic variation, there is accumulating evidence that altered function of tryptophan hydroxylase-2 (TPH2), the enzyme critical for synthesis of serotonin (5-HT) in the brain, plays a role in anxiety-, aggression- and depression-related personality traits and in the pathogenesis of disorders featuring deficits in cognitive control and emotion regulation. Here, we appraise the genetic and neurobiological evidence to illustrate the critical role of TPH2 in central 5-HT system function and in the pathophysiology of a wide spectrum of disorders of cognitive control and emotion regulation, ranging from depression to attention-deficit/hyperactivity disorder (ADHD), a phenotype commonly associated with difficulties in the control of emotion and with a high co-morbidity of depression. Findings from psychophysiological and functional imaging studies are indicative of various TPH2 polymorphisms directly influencing serotonergic function and thus impacting on mood disorders and on the response to antidepressant treatment. Especially a combination with uncontrollable stress seems to potentiate these effects linking gene-environment interaction directly with behavioral dysfunction in human and animal models. TPH2-deficient mice display alterations in anxiety-like behavior which is accompanied by adaptational changes of 5-HT1A receptors and its associated signaling pathway. Mouse models in conjunction with cognitive neuroscience approaches in humans are providing unexpected results and it may well be that future research on TPH2 will provide an entirely new view of 5-HT in brain development and function related to neuropsychiatric disorders. (C) 2011 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据