生物谷报道：抑郁症是困绕当代社会的重大的疾病，虽然神经科学工作者研究了很多年，但是其机理一直不明朗。既往的研究认为5-HT系统失调可能是其关键因素，但为什么会失调，其分子背景并不清楚。
将于2005年1月出版的Neuron上将刊登华人学者张晓东的一篇最新研究成果，hTPH2基因可能是关键基因。这个基因直接影响了5-HT的合成，从而与抑郁相关。他们采用了分析该基因的SNP，以及通过loss of function的方法证实了这一基因的关键性作用。下面的摘要，全文（PDF）提供下载。
Dysregulation of central serotonin neurotransmission has been widely suspected as an important contributor to major depression. Here, we identify a (G1463A) single nucleotide polymorphism (SNP) in the rate-limiting enzyme of neuronal serotonin synthesis, human tryptophan hydroxylase-2 (hTPH2). The functional SNP in hTPH2 replaces the highly conserved Arg441 with His, which results in ∼80% loss of function in serotonin production when hTPH2 is expressed in PC12 cells. Strikingly, SNP analysis in a cohort of 87 patients with unipolar major depression revealed that nine patients carried the mutant (1463A) allele, while among 219 controls, three subjects carried this mutation. In addition, this functional SNP was not found in a cohort of 60 bipolar disorder patients. Identification of a loss-of-function mutation in hTPH2 suggests that defect in brain serotonin synthesis may represent an important risk factor for unipolar major depression
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