研究背景與目的
雙極症近來逐漸受到臨床與研究者的重視。患者受到其症狀影響，往往對其生活與社會功能產生重大的影響。而精神疾患往往合併其他疾病，這不僅延後患者症狀的緩解時間，還會影響其治療與癒後的情形。焦慮症是合併疾患中較為常見的，不僅影響病程的進展，患者的臨床症狀相較無合併症者較為嚴重，且具較高的自殺傾向，甚至對於患者的社交與職業狀態造成失功能的現象。
對於焦慮症如何影響雙極症，過去文獻多為描述性的調查，較缺乏對其合併症之心理病理方面的研究。且雙極症合併焦慮症的比例尚不一致。西元一九二一年，Kraepelin醫師首先提到anxious-mania (焦慮性躁狂)，往後的流行病學調查顯示雙極症合併焦慮症比例之高(約70-90%)，暗示焦慮症之合併症可能為雙極症之症狀。但隨著學者們對於雙極症有更多的研究與了解，提出雙極症光譜之概念，不同雙極症亞型也逐漸受到學者與臨床工作者之重視。而其中又以第一型與第二型，兩者其診斷準則之重複性，更廣為學者們探討。越來越多研究卻顯示此兩種亞型在基因型與認知功能表現上有許多的差異。但這兩種雙極症亞型合併焦慮症的盛行率的異同以及焦慮合併症在此兩種雙極症亞型之影響為何，尚未有相關的比較與探討。
研究方法
本論文主要有三個研究來探討合併焦慮症對雙極症的影響。第一個研究是探討台灣漢民族的雙極症合併焦慮症的比例。此一研究採橫斷研究，在國立成功大學附設醫院與台北三軍總醫院的精神科門診收集個案，並調查其焦慮合併症的比例。第二個研究採縱貫性研究法，了解是否合併焦慮症會影響雙極症之緩解期以及是否隨著雙極症症狀的緩解而有改變。共收集第一型與第二型雙極症患者進行追蹤，以了解當雙極症患者達病程緩解期時，其焦慮症是否消失，來探討焦慮症之合併在兩種雙極症亞型之影響。此外，因國人雙極症合併焦慮症之比例少，且追蹤困難，因此第三個研究試著藉由簡短作業(注意力網絡，ANT)，來探討焦慮症的合併是否為雙極症之一種特質亦或是一種狀態。
研究結果
第一個研究發現，我們的雙極症合併焦慮症(BP+AD)的比例為26.7%第一型雙極症合併焦慮症(BP-I+AD)，39.0%第二型雙極症合併焦慮症(BP-II+AD)，其中又以合併廣泛性焦慮症比例較多。且第一型雙極症中有5.8%以及第二型雙極症中有13.2%患者合併兩種以上焦慮症。第二個研究共收集了一百七十五位(BP-I+AD有8位；BP-I-AD有30位；BP-II+AD有51位；BP-II-AD有86位)，進行為期至少半年的追蹤。共有131位完成半年的追蹤，退出率為25.14%。其中有55位達部分緩解者 (BP-I+AD有3位； BP-I-AD有10； BP-II+AD有18位；BP-II+AD有24位)。症狀緩解達兩個月的共有24位，佔比例18.32% (BP-I-AD有7位；BP-II+AD有3位；BP-II+AD有14位)。結果顯示合併焦慮症的雙極症患者較無焦慮合併症之雙極症患者難以達到部分緩解。且在8位第二型雙極症患者達症狀部份緩解時有7位焦慮症狀消失(比例為87.5%)；3位第二型雙極症合併焦慮症患者達2個月緩解時，症狀消失者有2位(比例為66.67 %)。第三個研究共收集63位受試者 (3位第一型雙極症合併焦慮症；9位第一型雙極症不合併焦慮症；21位第二型雙極症合併焦慮症；11位第二型雙極症不合併焦慮症與19位健康受試者)。研究結果顯示患者群表現較健康受試者需較長的反應時間以及較低的正確率。在ANT指標中發現，在第二型雙極症合併焦慮症組中，警覺性(alerting network)與焦慮症初始年齡達顯著正相關，而執行控制(executive functioning)與其躁症嚴重度分數成正相關。當控制個案情緒症狀嚴重度時，第二型雙極症合併焦慮症者在執行功能(executive control network)指標上反應時間較不合併焦慮症者為長。而在第一型雙極症組的比較中發現，在導向(orienting network)指標上，第一型雙極症不合併焦慮症者受到空間位置導向的影響較合併焦慮症的第一型雙極症少，且受到其憂鬱嚴重度的影響。
結論與討論
臺灣漢民族雙極症合併焦慮症的比例較西方族群為少，顯示種族因素在此種疾患是否合併焦慮症可能扮演一定的角色。此外，透過縱貫式追蹤研究發現當雙極症者合併焦慮症時，其雙極症病程的緩解時間受到焦慮合併症之影響。且當患者達緩解期時，其合併之焦慮症消失了，但這些患者多為合併廣泛性焦慮症與恐慌症。而合併強迫症的雙極症患者，其強迫症並未隨著雙極症病程緩解而消失。另外，透過注意力網絡的測驗，更加提供了合併焦慮症在兩種常見的雙極症亞型中的不同影響。在第一型雙極症合併焦慮症則因人數過少，尚需進一步研究。而第二型雙極症合併焦慮症患者，其警醒性與罹患雙極症之時間長短以及焦慮合併症之初始年齡成正相關，顯示第二型雙極症合併焦慮症患者可能長期屬於高度警覺狀態。顯示焦慮症的合併在第二型雙極症中可能為一種特質而非其症狀。此結果也回應了前兩個研究，第二型雙極症合併焦慮症的比例較西方國家的研究為少，且透過追蹤調查，其焦慮合併症的變化隨著第二型雙極症達緩解而改變。換句話說，第二型雙極症合併焦慮症可能為雙極症光譜上的另一種亞型。透過了解焦慮症在兩種不同雙極症亞型間的比較，可提供未來在臨床治療上的建議。

Objective: Comorbidity is an issue impacts on mental disorders, and may worse prognosis and treatment. Anxiety disorders (AD) are the most commonly found comorbid illnesses of all in patients with bipolar disorder. More remarkable clinical characteristics, much severe symptoms, much severe mood instability, higher rates of suicide attempts, more substance use disorders, use of mental health resources, and lower social and occupational function have been reported in the BP patients with AD than do BP without AD comorbidity. Since more and more attention has been drawn in BP both in clinics and research, so far the mechanism of the impact of anxiety disorder with bipolar disorders is unclear.
Methods: This study consists of three sub-studies. All participants were recruited from two general medical outpatient services, and the healthy controls were recruited from the community. The participants were evaluated and their diagnoses confirmed by a psychiatrist using the Chinese version of the Modified Schedule of Affective Disorder and Schizophrenia-Lifetime. The exclusion criteria were: any DSM-IV-TR Axis I diagnosis, other than bipolar disorder, being outside the 18-65-year-old age range, any other major and minor mental illnesses except anxiety disorder, any neurological disorders or organic mental disorders. In the first sub-study, three hundred twenty-five patients with bipolar disorder (bipolar I: 120; bipolar II: 205) were studied to explore the prevalence rate of anxiety comorbidity rate between two subtypes of BP. In the second sub-study, 175 patients with bipolar disorder (bipolar I: 38; bipolar II: 137) were recruited and followed-up to evaluate their symptom changed during episode and remission stage. In the last study, attention network test (ANT) was used to examine the hypothesis that the comorbidity of AD with BP could be a subtype of BP, especially in BP-II.
Results: Thirty-two (26.7%) of patients were comorbid with lifetime anxiety disorder and bipolar I, 80 (39.0%) with lifetime anxiety disorder, the generalized anxiety disorder (GAD) was the most common comorbid AD. And in bipolar II, 7 (5.8%) were comorbid with two or more anxiety disorders and bipolar I, and 27 (13.2%) with two or more anxiety disorders and bipolar II. In the second-sub study, 175 participants were recruited. Total 131 participants (BP-I+AD: 8; BP-I-AD: 21; BP-II+AD:45; BP-II-AD:57) were followed up, and 44 participants drop-out from this study (drop-out rate 25.14%). Within the follow-up, 24 participants met the criteria for full remission (7 BP-I-AD；3 BP-II+AD；14 BP-II-AD), showing that the BP with AD comorbidity would have difficulty to reach full remission compared to those without AD (χ2=10.53, p=0.02). For the BP-I groups, none of the BP-I+AD participants met the criteria of full remission while 7 BP-I-AD (33.33%) met the criteria of full remission. Three BP-II+AD (6.67%) and 14 BP-II-AD (24.56%) met the full remission criteria. At the full remission, 87.5% BP-II+AD and 66.67% of BP-I+AD patients reported no AD remained. The patients comorbid with GAD and panic disorder disappear when they were at partial full remission, but those with obsessive-compulsion disorder remained their AD symptoms. In the last sub-study, the results showed that both BP+AD groups had relative higher error rate compared to those without AD and healthy controls. Moreover, in the BP-II+AD, their alerting score was associated with their duration of illness and age onset of AD, and executive control score was correlated to the YMRS score. In addition, while controlling the mood state, BP-II+AD had greater impairment of executive control network compared to the BP-II-AD.
Conclusion: The relatively lower AD comorbidity rate with BP, both BP-I and BP-II, could help us to recruit pure BP without comorbidity. In addition, the relatively lower AD comorbidity rate compared to previous studies in the Western population indicated a non-symptom of AD in the BP among Han Chinese in Taiwan. Moreover, more than twice as many bipolar II than bipolar I patients reported two or more anxiety disorders implies that the complication is more prevalent in bipolar II patients. When the BP patients comorbid with AD, their prognosis would be prolonged even when they received medical treatment, and when they had full remission, the AD eliminated, indicating a possibility that the AD might derived from BP symptoms, especially GAD. In the last sub-studies using ANT as an assessment to investigate whether BP patients with AD have such impairment. The patient groups had higher error rate and longer reaction time while doing the task compared to the healthy controls. Taking AD comorbidity as a factor, The BP-II+AD could be counted as another subtype in the bipolar spectrum, but the subtypes of AD might have different influences and should be taken into account in the future studies. The more understanding of AD comorbidity in BP, the better treatment we could provide.

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