研究背景:
第一型雙極症(Bipolar disorder type I, BP-I)和第二型雙極症(bipolar disorder type II, BP-II)的關係長久以來受到爭議。第二型雙極症過去被認為和第一型雙極症是同一疾病，僅症狀較輕；目前第二型雙極症被認為可能在基因和表現上都異於第一型雙極症。

研究目的:
了解第一型雙極症和第二型雙極症基因型分布、人格特質表現與其間的交互作用；測試雙極症光譜(bipolar spectrum)的假設。

研究方法:
經成大人體實驗委員會同意，追蹤評估第一型、第二型雙極症患者之漢氏憂鬱症狀量表(HDRS)、楊氏躁狂症狀量表(YMRS)嚴重度分數，以橫斷性研究方式對症狀緩解(HDRS≦10，YMRS≦10)的82位第一型雙極症患者、121位第二型雙極症患者和111位健康受試者施測Cloninger自填式三向度人格特質量表中文修訂版(TPQ)中逃避傷害和追求刺激兩個分量表，並檢測5-HTTLPR和DRD3 Bal1的基因多型性。所有受試者以修正版的中文化終生版精神疾病診斷之結構式晤談手冊(SADS-L)確立終身診斷，並排除第一型與第二型雙極症外之重大精神疾病與認知功能缺損之受試者。

研究結果:
使用多元邏輯式回歸分析方法(Multinomial logistic regression analysis)，以第一型、第二型雙極症和健康控制組為應變項，控制年齡和性別，發現5-HTTLPR基因型(p = 0.045)、追求刺激(NS) (p = 0.033)、逃避傷害(HA) (p = 0.012) 以及逃避傷害和5-HTTLPR基因型(p = 0.047)間的交互作用可顯著預測並區分第一型和第二型雙極症組。在5-HTTLPR基因型上具有long allele之患者中，第一型雙極症組之逃避傷害分數顯著較第二型雙極症組高(BP-I = 16.23, BP-II = 19.80; p = 0.023)。追求刺激(p = 0.001)和 (p = 0.001) 可顯著預測並區分第一型雙極症和健康控制組，而僅逃避傷害分數(p < 0.001) 可顯著預測並區分第二型雙極症和健康控制組。以上結果均顯示第一型雙極症和第二型雙極症之不同。

研究結論:
本研究發現5-HTTLPR基因型調控了第一型和第二型雙極症的逃避傷害特質之表現，對於第一型和第二型雙極症患者間，基因對行為之不同調控提供了初步證據，因此支持了第二型雙極症在基因和表現上都異於第一型雙極症之假設。

Background:
It has been debated whether bipolar II disorder (BP-II) a distinct disorder or simply a milder form of bipolar I disorder (BP-I).

Methods:
In this cross-sectional survey (2005-2009), we administered the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), and the Tridimensional Personality Questionnaire (TPQ) to 314 participants (82 BP-I patients, 121 BP-II patients, and 111 healthy controls). The Ser9Gly polymorphism of the dopamine D3 receptor gene (DRD3), and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) genotypes were examined. All the patients met the DSM-IV-TR diagnosis of bipolar disorder.

Results:
Multinomial logistic regression analysis showed a significant main effects for the 5-HTTLPR polymorphism (p = 0.045), novelty seeking (NS) (p = 0.033) and harm avoidance (HA) (p = 0.012) scores, and a significant interaction effect between HA and 5-HTTLPR genotypes (p = 0.047) in distinguishing between BP-I and BP-II patients. BP-I patients with the long allele at 5-HTTLPR had lower HA scores than did BP-II patients (BP-I = 16.23, BP-II = 19.80; p = 0.023). Multinomial analysis also showed that NS (p = 0.001) and HA (p = 0.001) scores significantly differed between BP-I patients and healthy controls (HC). However, only HA (p < 0.001) significantly differed between BP-II patients and healthy controls. All these data suggest a distinction between BP-I and BP-II.

Conclusions:
We provide initial evidence that 5-HTTLPR genotypes moderated the association between HA and BP-I and BP-II. We hypothesize that there are unique differences in the gene-temperament interactions of BP-I and BP-II patients.

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