疾病狀態與嚴重程度對躁鬱症之可體松睡醒反應之影響

Abstract

引言: 躁鬱症病人之下視丘-腦下垂體-腎上腺軸呈現調控異常狀態已被大家所熟知。可體松睡醒反應是指人體在早上剛睡醒之後約30至40分鐘，可體松呈現大量上升的現象，而此現象被認為是了解下視丘-腦下垂體-腎上腺軸之功能的一種指標。躁鬱症病人在不同疾病狀態下(發作期及緩解期)與一般健康民眾之可體松濃度之比較的相關文獻較少且結果並不一致。另外，目前關於躁鬱症病人之可體松睡醒反應之研究只有一篇。本研究之目標在於檢測躁鬱症病人在不同疾病狀態(發作期與部分緩解)及疾病嚴重程度下，可體松睡醒反應之變化，並與健康民眾之可體松睡醒反應做比較。此外，我們也詳細測量一些過去文獻指出會影響可體松睡醒反應的變項。 方法: 本研究總共收入27位躁鬱症住院病人(15位在躁期、12位在鬱期)在不同疾病狀之下(發作期與部分緩解之狀態)與25位健康民眾。可體松睡醒反應之檢體收集為，於剛睡醒、睡醒30及45分鐘各收集一次唾液檢體，其指標之計算為可體松變化量(delta)與曲線下面積可體松預期增加量(AUCi)。疾病嚴重程度的測量是使用17題版本的漢氏憂鬱量表和楊氏躁症量表。測量之共變數包括人口學、睡眠以及臨床指標相關變項。病人組之間可體松睡醒反應之差異或與健康組之比較時，使用Student t-test，而病人自己在不同疾病狀態下，可體松睡醒反應之比較是使用Paired t-test。可體松睡醒反與疾病嚴重程度之間的相關性使用Pearson correlation作檢定，另外，自變項(可體松睡醒反應指標)、依變項(病人組與健康組)及共變量之間的相關性是使用tetrachroic correlation(類別變項之間)、biserial correlation(類別與連續變項之間)及Pearson correlation(連續變項之間)。 結果: 可體松睡醒反應於病人呈現較低的濃度，並可鑑別出雙極性憂鬱病人(無論發作或部分緩解時)與健康民眾。此外，急性雙極性憂鬱病人之可體松睡醒反應呈現變鈍的現象，而在部分緩解時變為趨向正常的狀態。可體松睡醒反應在雙極性躁期與雙極性鬱期病人於不同疾病狀態或不同疾病嚴重程度時並無顯著的變化(r= -0.32 to -0.36, p>0.05)。於所有變項中，只有夜眠是否少於6小時的變項對於可體松醒反應之指標呈顯著相關(r=0.31 to 0.39)。 結論: 可體松睡醒反應能區別出健康民眾與雙極性憂鬱病人。急性雙極性憂鬱病人之可體松睡醒反應呈現變鈍的現象，而在疾病趨於緩解變為趨向正常的狀態。這些結果有助未來對於躁鬱症病人在下視丘-腦下垂體-腎上腺軸之調控機制的研究。

Introduction: Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is known to occur in bipolar disorder patients. Cortisol awakening response (CAR), a pronounced increase in cortisol level that peaks at approximately 30 to 40 minutes after waking in the morning, is an indicator of the function of HPA axis. Literature on the cortisol level in patients with bipolar disorder at different disease status (e.g. acute episode vs. remission) and controls are few and did not report consistent findings. Moreover, there are only one prior study examined the CAR level in bipolar disorder patients. The goal of the present study is to examine the level of CAR in bipolar disorder patients at different disease status (acute episode vs. partial remission) and severity while compared with controls. Additionally, we measured detailed variables that previous studies suggest to have influence on the CAR level. Methods: Data were collected from 27 hospitalized bipolar disorder patients (15 in manic and 12 in depressive episode) at different disease status (acute episode and partial remission). In addition, 25 healthy controls were recruited. Saliva samples were collected at the time of awakening (T0), 30, and 45 minutes after awakening to determine the CAR; the CAR indicators including delta and AUCi (area under the curve respect to cortisol increase) were calculated. Episodic symptom severity was measured using 17-item Hamilton Depression Rating Scale (HAMD) and Young Mania Rating Scale (YMRS). Covariates including demographic, sleep variables and clinical variables were measured. Student t-test was used to examine the differences in comparing patients to controls or different patient groups. The CAR differences between episodes and partial remission within the same patient was examined by Paired t-test. We calculated Pearson correlation for the relationship between CAR levels and symptom severity. Moreover, the associations between independent variables (i.e. CAR indexes), dependent variables (e.g. patient/control) and covariates were examined by tetrachroic correlation between categorical variables, biserial correlation between categorical variables and continuous variables and Pearson correlation between continuous variables. Results: We found a lower level of CAR in patients and the CAR distinguishes healthy controls from bipolar depressive patients despite of the disease status (either in acute or partial remission). Additionally, patients in depressive episode seem to exhibit a blunted CAR, and this phenomenon changes to be normal at partial remission. The CAR levels were no different between episode and partial remission in both bipolar-mania and bipolar-depression patients and no association were found between symptom severity and the CAR levels (r= -0.32 to -0.36, p>0.05). The variable, whether sleep lower than 6 hours at night, exhibited significant correlations with the CAR indexes either in acute or partial remission data points (r=0.31 to 0.39). Conclusion: The CAR can distinguish healthy controls from bipolar depressive patients. Depressive patients with acute episode exhibit a blunted CAR and a normal CAR while in recovery. These findings could assist to design further studies to investigate the regulation mechanisms of the HPA axis in bipolar disorder.