創傷後壓力症候群的遺傳與環境危險因子: 1999年台灣大地震後的一個原住民社區研究

Abstract

背景：創傷後障礙症是相當常見的精神疾病，其發病的必要條件是重大的創傷事件，例如人為的暴力攻擊或性虐待等，還有天災地變，像是地震或海嘯等。主要症狀分三群，包括回溯創傷經歷的症狀，迴避創傷相關事物且對一般生活事物感到麻木的症狀，還有警覺程度較高的症狀。並非每一位經歷創傷者都會罹患創傷後障礙症，所以，創傷以外之危險因子在此病形成上扮演重要角色，也是預防醫學上的重要課題。台灣在1999年9月21日發生了百年來最大的地震，達芮氏7.3級，而自1987年開始的一個台灣原住民研究計劃的研究對象中，布農族樣本剛好居住於震央附近，提供了探討創傷後障礙症的絕佳機會。 方法：研究對象包括196名布農族的受訪者，訪談自大地震發生後5個月開始，採用的主要評估工具包括：（1）診斷精神疾病的神經精神臨床評估表(中文版WHO SCAN)；（2）測量個人涵化程度的台灣原住民涵化量表(TAAS)；（3）詢問地震前6月內重大生活事件的生活事件評估表(LTE)；（4）評估地震後受創程度的量表。其中SCAN的訪談評估由5位資深的精神科專科醫師執行。在告知研究內容與目的，徵得其同意後，受訪者接受上述量表的訪談，並接受抽取靜脈血液，以萃取DNA進行基因研究，所探討的基因為主要的神經介質，包括多巴胺、血清素、GABA、和嗎啡系統等。統計分析採用單變項與多變項的logistic regression analysis。 結果：包含環境及精神疾病的四種因素與地震造成的創傷後障礙症顯著相關，呈現獨立效應:（1）地震的強度:芮氏六級以上的震度會增加罹病的危險性；（2）地震後的創傷程度:受創程度越高，則罹病危險性也越高；（3）涵化程度:涵化程度越低者，產生創傷後障礙症的可能性越高；（4）震前存在重鬱症者，罹患創傷後障礙症的危險性較高。在基因的危險因子方面，發現五種SNPs具有獨立的作用，一個是Kappa嗎啡受體基因，一個是多巴胺第二型受體，一個為GABA受體基因，有二個為血清素酵素基因。進一步分析環境因素、精神疾病和基因因子對創傷後障礙症的風險作用時，發現六個因素呈現顯著的獨立效應：（1）地震強度；（2）震後創傷程度；（3）震前重鬱症；（4）一個多巴胺第二型受體基因型；（5）一個GABA受體基因型；（6）一個血清素酵素基因型。此外，有兩個基因因子則與震度呈現顯著的交互作用，其中一個為血清素酵素基因，另一個為Kappa嗎啡受體基因。 結論：研究結果顯示地震造成的創傷後障礙症的二級預防，應注意個案在創傷前是否有精神疾病(尤其是重鬱症)，對於來自不同社會文化背景的族群，必須考量社會文化方面的因素對創傷後障礙症發病的影響，而遺傳和環境因素的交互作用，對創傷後的心理健康亦有重大影響。

Background: Posttraumatic stress disorder (PTSD) is a common mental disorder in response to an identifiable traumatic event. This diagnostic category contains a constellation of symptoms, including re-experiencing, avoidance and numbed responsiveness, and symptoms of increased arousal. Traumas are often classified as natural and man-made. Although the characteristics of a trauma have been shown to influence the risk of PTSD, only 27.8% of such risk was significantly attributable to the trauma exposure itself. Individual vulnerability and pre- and post-trauma situations are also important pathogenic factors in the development of PTSD. It is therefore important to examine the relative weight of environmental factors versus genetic vulnerability. This study investigates PTSD in one Taiwanese aboriginal group (the Bunun) exposed to a severe earthquake disaster. The earthquake shook central Taiwan at 01:47:15 am on September 21, 1999 local time, measuring 7.3 on the Richter scale, the strongest one among several earthquakes over the past one hundred years in Taiwan. Study subjects came from a cohort of the Bunun established in 1987-88 in a longitudinal study of mental disorders among four major aboriginal groups in Taiwan. They were randomly selected from four villages in Hsingyi County located in the central mountain region of Taiwan; happen to be close to the epicenter of the 9-21 earthquakes (about 18 kilometers away), and has thus provided an excellent opportunity for studying PTSD. Methodology: Respondents (n=196) were assessed 5 months after the earthquake. Information regarding the magnitude of the 9-21 earthquakes was obtained from the website of the Seismological Center, Central Weather Bureau in Taiwan. The local area where our study subjects resided was under 7.3 in Richter scale. Different Richter scales encountered by study subjects who stayed in other areas during the earthquakes were checked individually. A five-item questionnaire was designed to measure the extent of traumas from the earthquakes, using the Likert-type scoring system. Psychiatric diagnoses were performed by five senior psychiatrists, using a Chinese version of the WHO Schedules for Clinical Assessment in Neuropsychiatry. The degree of acculturation was measured using the Taiwan Aboriginal Acculturation Scale. A Chinese version of the List of Threatening Experiences (LTE) was used to assess stressful life events within 6 months prior to the 9-21 earthquakes. For genotypic study, we also prepared DNA using venous blood drawn from study subjects using standard methods. Polymorphisms were examined in the genes which are involved in the serotonin, dopamine, opioid, and GABA pathways. Results: A majority of respondents (n=163, 83.2%) encountered with higher degrees of shaking (159 with 7.3 and 4 with 6 in Richter scale). According to DSM-IV criteria, a total of 76 subjects (38.8%) were diagnosed as having suffered from PTSD related to the 921 earthquakes. There were much higher rates of antecedent psychiatric disorders, including alcohol use disorders (59.7%), generalized anxiety disorder (34.7%), major depressive disorder (26.0%), and panic disorder (6.1%). Four environmental and psychiatric risk factors exerted independent effect on the risk of PTSD, including magnitude of the earthquake, subsequent traumas, antecedent major depressive disorder and acculturation status. Five single nucleotide polymorphisms (SNPs) played significant effects on the risk of PTSD, including DRD2-rs11214607 in the dopamine system, KOR-rs16918928 in the opiod system, GABRB2-rs6881515 in the GABA system and TPH-rs1843811 and TPH-rs172423 in the serotonin system. Joint effects of genetic and environmental factors were further examined. Risk factors still with independent main effects were degree of the earthquake exposure, its subsequent trauma, major depressive disorder, GABRB2- rs6881515, TPH-rs1843811, and DRD2-rs11214607. Significant two-way interactions include KOR-rs16918928 and magnitude of quake (Ritcher scale), as well as TPH-rs172423 and magnitude of quake. Conclusions: Public mental health programs need to consider the liability to PTSD in populations with different ethnicity and socio-cultural environments. Findings in this study suggest that for early detection of PTSD and prompt management, attention should be paid among survivors of natural disasters who exposed to higher extents of the disaster; had higher subsequent traumas; had genetic vulnerability; and had antecedent mental disorders, notably major depressive disorder. For aboriginal populations, further attention should be given to those with a lower extent of acculturation.