ROLE OF THE SEROTONIN TRANSPORTER PROMOTER POLYMORPHISM IN PSYCHIATRIC DISORDERS

5-羟色胺能通路功能障碍可能是 几种精神障碍。5-羟色胺转运体(5-HTT) 在5-羟色胺能神经递质的终止中起关键作用 钠依赖摄取5-羟色胺的神经传递 突触前神经元。5-HTT也代表了最初的行动地点 某些抗抑郁药物和神经毒素。从功能上讲 发现了5-HTT启动子的显著多态 (5HTTLPR)这种多态影响5-HTT的转录， 最终实现5-HTT的功能。5-HTTLPR的频率为 在各种临床精神科人群中确定，包括 对酗酒者进行连锁和关联研究。正性 检测到5-HTTLPR和两者之间存在连锁 至少与焦虑相关的人格特征可在TPQ上使用 将报告的此变体的关联部分复制到 行为(见参考书目)。相反，没有发现任何关联 在意大利患有强迫症的患者中，恐慌 失调和饮食失调。然而，另外两个 具体疾病的发现有：1)与A. Malhotra和D.Pickar，5-HTTLPR被发现显著 精神分裂症患者与简明精神病评定量表相关2) 通过与N.Rosenthal的合作，HTTLPR显著地 与季节性情感障碍和季节性评分有关 悲伤的病人。

Dysfunctions in serotonergic pathways may underlie several psychiatric disorders. The serotonin transporter (5-HTT) plays a critical role in the termination of serotonergic neurotransmission by Na-dependent uptake of serotonin by the presynaptic neuron. 5-HTT also represents the initial site of action of certain antidepressant drugs and neurotoxins. A functionally significant polymorphism in the 5-HTT promoter was identified (5HTTLPR). The polymorphism affects 5-HTT transcription and, ultimately, 5-HTT function. Frequency of the 5-HTTLPR was determined in a variety of clinical psychiatric populations including alcoholics; linkage and association studies were performed. Positive linkage was detected between 5-HTTLPR and the two anxiety-related personality traits available on the TPQ, at least partially replicating the reported association of this variant to behavior (see bibliography). In contrast, no association was found in Italian patients with obsessive compulsive disorders, panic disorders and eating disorders. However, two additional disease-specific findings were made: 1) in a collaboration with A. Malhotra and D. Pickar, 5-HTTLPR was found to be significantly associated with BPRS-rated psychoticism in schizophrenia and 2) in a collaboration with N. Rosenthal, HTTLPR was significantly linked with seasonal affective disorder and seasonality rating in SAD patients.