研究背景：
酒癮是一種具有多重因素(multiple- factorial)又極為複雜(complicate)的疾病表現型(phenotype)，擁有高度的異質性(heterogeneity)。因此在酒癮成因的探討上，區分適當的酒癮亞型有其必要性。其中，焦慮憂鬱型酒癮不僅在各種臨床酒癮亞型中超過50%，且已被黃等人(2004)驗證該亞型具有一定的基因效度，因此本研究專注於焦慮憂鬱型酒癮成因的探討上。目前，學者多認同以性格特質和遺傳基因兩變項，分別作為個體發展出酒癮的心理病理和神經生物之致病基礎。Cloninger 等人(1987)更進一步依據生理-心理-社會取向，提出酒癮的神經生物學習模式，認為特定的性格型態為發展出特定酒癮亞型的危險因子，且該性格有其遺傳基礎。例如在過去研究發現，第11 對染色體上長臂q22 至q23 的多巴胺乙型接受器( DRD2 )基因和第17 號染色體上長臂q.12 的血清素運轉子( 5-HTTLPR )均為與酒癮相關之候選基因（candidate
genes），並分別和尋求新奇及逃避傷害這兩種性格特質有關。故本研究希望透過Cloninger 的理論架構，驗證其性格向度具有遺傳性的說法，進而釐清性格與遺傳在參與焦慮憂鬱型酒癮的發展上所扮演的角色。
研究目的：
本研究擬探討(1) 藉由臨床診斷的分類及Cloninger 的理論，瞭解性格向度與特定亞型--焦慮憂鬱型酒癮者的關係; (2) 探討酒癮候選基因多巴胺乙型接受器基因(DRD2)、血清素運轉子基因(5-HTTLPR)，是否與焦慮憂鬱型酒癮的性格向度有關，以驗證Cloninger 性格具備遺傳性的觀點，並進一步釐清基因-性格-酒癮間的關聯。
研究方法：
本研究使用個案對照研究設計，分別自精神科門診及社區收集87 名焦慮憂鬱型酒癮個案與46 名單純酒癮組個案；使用t-test 檢定比較焦慮憂鬱型酒癮組與單純酒癮組在尋求刺激(novelty seeking)與逃避傷害(harm avoidance)性格向度上的差異。使用t-test 檢定比較兩組在多巴胺乙型接受器(DRD )基因型TagI A、血清素運轉子(5-HTTLPR )不同基因型分組下，二診斷組間尋求新奇(novelty seeking) 與逃避傷害(harm avoidance )兩性格向度上的表現差異。
研究結果：
(一)在性格方面，焦慮憂鬱型酒癮在尋求刺激和逃避傷害向度上均高於單純型酒癮組。(二)在基因與性格方面，以不同基因型分組後比較二組在人格向度的差異，結果發現焦慮憂鬱型酒癮的高尋求新奇特質僅出現在DRD2 基因型為A1+(A1/A1 or A1/A2)對偶基因，5-HTTLPR基因型為S/S，以及同時具有DRD2 的A1+和5-HTTLPR的S/S 基因型的受試者中。至於焦慮憂鬱型酒癮組的高逃避傷害特質，則僅出現在5-HTTLPR 基因型為L 對偶基因的受試者中。
研究討論：
本研究發現，在進一步控制可能的干擾因素後，以單純酒癮為控制組，焦慮憂鬱型酒癮在尋求新奇和逃避傷害的特質上，均比單純型酒癮高，這除了更進一步驗證焦慮憂鬱型酒癮為一特殊亞型，我們也發現焦慮憂鬱型酒癮診斷組中，多巴胺乙型接受器基因DRD2 和血清素運轉子基因5-HTTLPR 確實參與性格向度的遺傳性組成，並有可能為焦慮憂鬱型酒癮的特定致病因子。因此本研究提供了Cloninger 理論中認為性格向度具遺傳基礎的實徵數據，也提出Cloninger 理論需修正的觀點。

Background: Cloninger (1987) had proposed a psychobiological model suggesting that three main personality dimensions distinguish the alcoholism into two subtypes (type I and type II). However, the classification was equivocal for clinical diagnosis. Recently, Anxiety-depressive alcohol dependence (ANX/DEP ALC) has been posited as a
genetically specific subtype of alcoholism. Its clinical characteristics were similar to individuals with type I alcoholism (Cloninger, 1987) such as having a high comorbidity with mood disorder, late-onset and more anxious/depressed traits. We attempted to investigate whether the dopamine D2 receptor (DRD2) and the serotonin transporter promoter region (5-HTTLPR) genes were involved in Novelty Seeking (NS) and Harm Avoidance (HA) of ANX/DEP ALC.
Methods: We recruited 46 pure alcohol dependents (Pure ALC) and 87 anxiety-depression alcohol dependents (ANX/DEP ALC). All participants were diagnosed by DSM-IV criteria, genotyped by the PCR method and assessed with Tridimensional Personality Questionnaire (TPQ).
Results: Both NS and HA were high in ANX/DEP ALC (p=0.021; p=0.001, respectively). The association between NS and ANX/DEP ALC only existed in subjects with DRD2 TaqI A1+ allele (A1/A1 or A1/A2 genotypes) (p=0.004) and in those with S/S genotype of 5-HTTLPR (p=0.005). With the stratification of DRD2 TaqI A1+ allele, high NS of ANX/DEP ALC existed only in carriers of 5-HTTLPR S/S genotype (p=0.001). Moreover, ANX/DEP ALC was related to high HA only in samples carrying 5-HTTLPR S/L or L/L genotype (p=0.02).
Conclusions: These findings provided the empirical genetic characterization of the specific personality traits in ANX/DEP ALC among Han Chinese population in Taiwan.

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