研究背景：
社會認知功能的缺損，尤其是情緒調節（emotional management），乃精神分裂症的一個重要特色，但其潛在機制仍尚不清楚。神經傳導物質—血清素（Serotonin; 5-HT）已被推論和社會認知之調節有關。乙型色胺酸水解酶（tryptophan hydroxylase-2; TPH2）為限制血清素組成速率的酶，與血清素轉運子（serotonin transporter; 5-HTT）共同調控血清素的神經傳導運輸。

研究目的：
本研究欲探討精神分裂症患者的TPH2基因與5-HTT基因之基因多型性（rs4570625 G-703T和SLC6A4-linked polymorphic region; 5-HTTLPR）與社會認知之關連。

研究方法：
共收集116位穩定接受抗精神病藥物治療的慢性精神分裂症患者。所有患者皆進行抽血與DNA萃取，經過實驗室方法獲得上述兩基因的基因多型性資料，且採用Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT) Version 2.0 的第四向度分測驗（National Institute of Mental Health建議用來評估精神分裂症患者的社會認知功能之使用工具）評估其社會認知功能；採用Positive and Negative Syndrome Scale (PANSS)評估其症狀嚴重度。

研究結果：
TPH2基因的T/T和G/T基因型（T組）比G/G基因型（G組）患者有更佳的情緒調節表現（p = 0.013）。5-HTT基因的l/l和s/l基因型（l組）亦傾向比s/s基因型（s組）患者有較佳的情緒調節表現（p = 0.07）。除此之外，兩基因型對其情緒調節表現有加成效果：同時在TPH2基因的T組及5-HTT基因的l組的患者展現最佳的情緒調節表現(p = 0.033)。

研究結論：
本研究發現調節血清素的兩個重要基因會分別影響精神分裂症患者的社會認知功能且有其加成效果。

Background:
Impaired social cognition, particularly emotion management, is an essential feature of schizophrenia, but its underlying mechanism remains unclear. Serotonin (5-HT) transmission has been implicated in modulation of social cognition. Tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of 5-HT synthesis, and serotonin transporter (5-HTT) both regulate 5-HT neurotransmission. The current study aimed to investigate the genetic effects of TPH2 and 5-HTT on social cognition in patients with schizophrenia.

Methods:
One hundred and sixteen chronic schizophrenia patients were stabilized with antipsychotic treatment. They were genotyped for the rs4570625 (G-703T) SNP of TPH2 and SLC6A4 of 5-HTT and assessed by the managing emotion branch of Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), which is recommended by the National Institute of Mental Health as the sole measure of social cognition for schizophrenia. All were also measured by the Positive and Negative Syndrome Scale.

Results:
T allele carriers of the TPH2 had better emotion management than the G/G homozygotes (p = 0.013). Long variant carriers of the 5-HTT also tended to do so than individuals with the s/s genotype (p = 0.07). Moreover, the two gene variances had additive effects on emotion management; patients carrying both T variant of TPH2 and long variant of 5-HTT showed the best emotion performance (p = 0.033).

Conclusions:
The findings suggest an additive effect of two critical genes in the 5-HT regulation on social cognitive functioning in patients with schizophrenia.

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