吳嵐村,伍緒忠
·論著·
抑郁癥未用藥患者唾液皮質(zhì)醇覺醒反應(yīng)與自殺意念的關(guān)系
吳嵐村,伍緒忠
目的:探討抑郁癥未用藥患者的自殺意念與唾液皮質(zhì)醇覺醒反應(yīng)(CAR)的關(guān)系。 方法:對(duì)30例未服藥的抑郁癥患者(抑郁癥組)及30名健康志愿者(健康對(duì)照組)進(jìn)行自殺意念自評(píng)量表(SIOSS)評(píng)估及早晨覺醒后0、30、45及60 min時(shí)的唾液皮質(zhì)醇水平檢測(cè);分析影響SIOSS評(píng)分的相關(guān)因素。 結(jié)果:抑郁癥組SIOSS總分及各因子評(píng)分(P均<0.01)、覺醒后0、30、45 min時(shí)唾液皮質(zhì)醇濃度及CAR曲線下面積(AUCg)顯著高于健康對(duì)照組(t=2.892,t=3.209,t=2.350,t=3.418;P<0.05或P<0.01);以年齡、性別、體質(zhì)量指數(shù)、睡眠時(shí)間以及覺醒時(shí)間作為協(xié)變量分析發(fā)現(xiàn),其對(duì)皮質(zhì)醇濃度既無(wú)主效應(yīng)也無(wú)交互作用。 結(jié)論:抑郁癥患者存在較強(qiáng)的自殺意念及CAR水平顯著升高;CAR可能是預(yù)測(cè)抑郁癥患者自殺意念強(qiáng)度的生物學(xué)指標(biāo)。
抑郁癥; 自殺意念; 皮質(zhì)醇覺醒反應(yīng)
抑郁癥患者存在下丘腦-垂體-腎上腺軸(HPA)系統(tǒng)的功能活性增高[1];其基礎(chǔ)皮質(zhì)醇水平上升[2]、促腎上腺皮質(zhì)激素釋放激素(CRH)和促腎上腺皮質(zhì)激素(ACTH)水平升高[3-4]以及對(duì)地塞米松抑制試驗(yàn)(DST)的脫抑制[5]在很多研究中都得以報(bào)道。自殺行為是抑郁癥常見癥狀,也是抑郁癥患者的主要死亡原因。國(guó)外研究[6]顯示25%的抑郁癥患者一生中有過(guò)自殺未遂,15%最終死于自殺,其比例遠(yuǎn)高于正常人群。預(yù)防抑郁癥患者自殺也成為臨床工作的重要任務(wù),而目前仍缺少對(duì)抑郁癥患者自殺行為的有效預(yù)測(cè)指標(biāo)。有研究[7]表明抑郁癥患者的自殺行為可能與HPA軸功能活性增高有關(guān);然而針對(duì)抑郁癥患者自殺行為與HPA軸功能亢進(jìn)相關(guān)的研究結(jié)果仍存在很多不一致性。皮質(zhì)醇覺醒反應(yīng)(CAR)是以皮質(zhì)醇水平在早晨覺醒后逐漸升高并于醒后20~30 min時(shí)達(dá)到頂峰隨后便逐漸下降為特征,是反映HPA軸動(dòng)態(tài)活性的可靠的生物學(xué)指標(biāo)[8]。經(jīng)襄陽(yáng)市安定醫(yī)院倫理委員會(huì)審批,本研究探討抑郁癥患者自殺意念與CAR的相關(guān)性,為抑郁癥患者的自殺行為提供可能的生物學(xué)預(yù)測(cè)指標(biāo)。
1.1 對(duì)象
抑郁癥組:為2014年10月至2015年3月本院門診患者。入組標(biāo)準(zhǔn):符合《美國(guó)精神障礙診斷與統(tǒng)計(jì)手冊(cè)》第4版(DSM-IV)中重性抑郁障礙的診斷標(biāo)準(zhǔn);>2周未接受任何治療;年齡18~45歲;性別不限;文化程度≥初中;漢密爾頓抑郁量表24項(xiàng)(HAMD-24)≥20分。排除標(biāo)準(zhǔn):患有常見的內(nèi)科疾病或者生化、血液、尿液檢查異常,DSM-IV其他軸I和軸II精神疾病、半年內(nèi)有物質(zhì)濫用史、神經(jīng)系統(tǒng)疾病或損傷史、電休克治療史、妊娠和哺乳期婦女、一級(jí)親屬有精神疾病史及自殺未遂史。共30例(最終完成26例),其中男女各13例;平均年齡(23.8±4.53)歲;平均受教育年限(14.3±2.8)年;平均體質(zhì)量指數(shù)(BMI)(21.4±1.72);平均病程(1.95±2.05)年;平均HAMD(30.1±5.43)分。
健康對(duì)照組:為同時(shí)期在社區(qū)招募的年齡、性別匹配的健康志愿者30名(最終完成29名),排除標(biāo)準(zhǔn)同上。其中男10名,女19名;平均年齡(23.0±6.0)歲;平均受教育年限(14.8±2.4)年;BMI(21.7±1.70)。兩組年齡、性別、受教育年限和BMI比較差異無(wú)統(tǒng)計(jì)學(xué)意義。入組者均簽署知情同意書。
1.2 方法
1.2.1 臨床診斷與評(píng)估 由2名精神科主治以上職稱的醫(yī)師采用DSM-IV結(jié)構(gòu)式臨床檢查手冊(cè)(SCID)對(duì)所有入組者進(jìn)行訪談及診斷;采用自制一般情況表采集入組者人口學(xué)及臨床資料;采用自殺意念自評(píng)量表(SIOSS)[9]評(píng)估受試者自殺意念程度,其中包括絕望因子、樂(lè)觀因子、睡眠因子和掩飾因子4個(gè)因子,總分由前3項(xiàng)組成,總分越高自殺意念越強(qiáng);采用HAMD-24評(píng)估抑郁癥組患者病情。
1.2.2 唾液皮質(zhì)醇濃度檢測(cè)采集 采集唾液樣本的前晚10點(diǎn)后不能進(jìn)食,采集樣本的1 h內(nèi)不能刷牙、進(jìn)食及劇烈運(yùn)動(dòng),不能飲用除水以外的任何飲品。同時(shí)需記錄前晚入睡時(shí)間、采集樣本當(dāng)天覺醒時(shí)間和采集每個(gè)樣本的時(shí)間。在任一周末早晨覺醒后0、30、45及60 min 4個(gè)時(shí)間點(diǎn)采集唾液樣本;將回收的唾液采集器在3 000 r/min離心機(jī)內(nèi)離心10 min,分離的唾液分裝于1.5 ml的EP管內(nèi),-70 ℃冰箱保存。采用酶聯(lián)免疫法檢測(cè)唾液皮質(zhì)醇水平,該試劑盒唾液皮質(zhì)醇濃度檢測(cè)范圍0.537~80 ng/ml;根據(jù)Pruessner等[10]提供的計(jì)算公式計(jì)算CAR曲線下面積(AUCg,即覺醒后1 h內(nèi)唾液分泌的皮質(zhì)醇總量)和增加面積(AUCi,即CAR的動(dòng)態(tài)變化)。
1.2.3 統(tǒng)計(jì)學(xué)方法 采用SPSS 16.0統(tǒng)計(jì)軟件包,兩組非參數(shù)資料采用卡方檢驗(yàn);計(jì)量資料比較采用兩獨(dú)立樣本的t檢驗(yàn)、重復(fù)測(cè)量的方差分析。相關(guān)分析采用Pearson線性相關(guān)和逐步回歸的多元線性回歸分析法。
2.1 兩組SIOSS評(píng)分比較
在收集唾液樣本時(shí)有4例抑郁癥患者以及1名健康對(duì)照者未按照要求執(zhí)行,因此最后納入分析的抑郁癥組為26例,健康對(duì)照組為29名。抑郁癥組SIOSS絕望因子、樂(lè)觀因子、睡眠因子及總分均顯著高于健康對(duì)照組(P均<0.01)。見表1。
表1 兩組SIOSS評(píng)分比較
2.2 兩組唾液皮質(zhì)醇水平比較
采集唾液前晚睡眠時(shí)間抑郁癥組為(6.63±0.94)h,健康對(duì)照組為(6.88±0.79)h,兩組差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);采集當(dāng)天的覺醒時(shí)間抑郁癥組為(6:32±39)分,健康對(duì)照組為(6:44±26)分,兩組差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。重復(fù)測(cè)量方差分析顯示唾液皮質(zhì)醇濃度存在顯著組別效應(yīng)及時(shí)間效應(yīng)(F=11.47,F(xiàn)=37.45,P均<0.01)。將年齡、性別、BMI、睡眠時(shí)間以及覺醒時(shí)間作為協(xié)變量引入分析發(fā)現(xiàn),其對(duì)皮質(zhì)醇濃度既無(wú)主效應(yīng)、也無(wú)交互作用。抑郁癥組在覺醒后0、30、45 min時(shí)唾液皮質(zhì)醇濃度健康對(duì)照組顯著升高(t=2.892,t=3.209,t=2.350;P<0.05或P<0.01),覺醒60 min時(shí)兩組差異無(wú)統(tǒng)計(jì)學(xué)意義。抑郁癥組CAR-AUCg顯著高于健康對(duì)照組(t=3.418,P<0.01);兩組CAR-AUCi比較差異無(wú)統(tǒng)計(jì)學(xué)意義。見表2。
表2 兩組CAR比較
本研究顯示,與健康對(duì)照者相比,抑郁癥患者有較強(qiáng)的自殺意念和CAR水平顯著升高;將年齡、性別、BMI、睡眠時(shí)間以及覺醒時(shí)間作為協(xié)變量引入分析發(fā)現(xiàn),其對(duì)皮質(zhì)醇濃度既無(wú)主效應(yīng)也無(wú)交互作用。提示抑郁癥患者的自殺意念可能與抑郁的嚴(yán)重程度以及HPA軸的活性增高有關(guān);這與國(guó)外許多的研究報(bào)道相一致[11-12]。
本研究中CAR顯示,無(wú)論是抑郁癥患者還是健康對(duì)照者,早晨唾液樣本中皮質(zhì)醇的濃度取決于覺醒后采集唾液的時(shí)間點(diǎn)。既往抑郁癥HPA軸功能的研究常通過(guò)在早晨固定的時(shí)間(例如8:00 am 或9:00 am)采集唾液或血液樣本檢測(cè)皮質(zhì)醇濃度,雖然本研究中兩組受試者在采集唾液當(dāng)天的覺醒時(shí)間無(wú)顯著性差異,但早醒卻是抑郁癥較為常見的臨床癥狀之一,因此相對(duì)于各自的覺醒時(shí)間,抑郁癥患者的這個(gè)固定時(shí)間會(huì)比健康人晚很多,這也可能是導(dǎo)致研究結(jié)果不一致的原因[13-14]。CAR檢測(cè)可以有效地克服這些缺陷。本研究還提示抑郁癥患者較健康對(duì)照唾液皮質(zhì)醇濃度升高僅在覺醒后持續(xù)很短的時(shí)間,因?yàn)樵谟X醒后60 min時(shí)兩組的唾液皮質(zhì)醇濃度已非常相似;這與國(guó)外的研究[15-16]結(jié)果相一致。此外,也有研究[17]表明,緩解期抑郁癥患者及有抑郁癥家族史的健康人[18]也存在CAR升高;提示CAR升高可能是抑郁癥的一個(gè)內(nèi)表型。
國(guó)外有研究[19]指出,地塞米松抑制試驗(yàn)脫抑制的抑郁癥患者在其后的隨訪研究中更容易出現(xiàn)自殺行為;提示抑郁癥患者的自殺行為可能與HPA軸的活性增高相關(guān)。皮質(zhì)醇水平升高與抑郁癥的癥狀和許多繼發(fā)的不良醫(yī)學(xué)狀況如:肥胖、糖尿病以及高血壓等有關(guān),這些都可以增加抑郁癥患者的自殺風(fēng)險(xiǎn)[20]。與此同時(shí),糖皮質(zhì)激素水平的大量升高在中樞神經(jīng)系統(tǒng)能產(chǎn)生神經(jīng)毒性,長(zhǎng)時(shí)間暴露可引起腦結(jié)構(gòu)與腦功能的異常,這些異常也可能與自殺行為有關(guān)[21]。盡管如此,目前對(duì)于皮質(zhì)醇水平升高引起抑郁癥患者自殺風(fēng)險(xiǎn)增高的確切機(jī)制仍不清楚。
綜上所述,未經(jīng)治療的抑郁癥患者存在較強(qiáng)的自殺意念以及CAR水平顯著升高,CAR水平可作為預(yù)測(cè)抑郁癥患者自殺意念強(qiáng)度的一個(gè)生物學(xué)指標(biāo)。
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Associations between cortisol awakening response and suicide idea in drug-naive patients with major depressive disorder
WULan-cun,WUXu-zhong.
XiangyangAndingHospital,Xiangyang441050,China
Objective: To investigate the suicide idea and cortisol awakening response (CAR)in patients with major depressive disorder (MDD) and to explore the relationship between those two aspects. Method:A total of 30 treatment free patients with MDD meeting DSM-IV diagnostic criteria were recruited,thirty age-and gender-matched healthy controls were involved in this study as well.All the subjects were evaluated with the self-rating idea of suicide scale (SIOSS) and were arranged to collect salivary cortisol samples at four time point throughout the morning:immediately upon awakening,30,45,and 60 min following awakening to assess the CAR.Salivary cortisol concentration was analyzed using a commercial available enzyme immunoassay. Results:As compared with healthy controls,MDD patients showed an increased SIOSS score,elevated cortisol levels at 0,30,45 min following awakening,and a greater CAR area under the curve relative to ground (t=2.892,t=3.209,t=2.350,t=3.418;P<0.05 orP<0.01).Scores of the Hamilton depression scale (HAMD),cortisol levels at 0,30,45 min following awakening,and the CAR AUC gwere associated with scores of SIOSS. Conclusion:MDD patients have increased suicide idea and enhanced CAR,the CAR level could be a biomarker to predict suicide idea in MDD patients.
major depressive disorder; suicide idea; cortisol awakening response
441050 湖北省襄陽(yáng)市安定醫(yī)院
吳嵐村,E-Mail:wlc929@sina.com
R749.4
A
1005-3220(2017)03-0175-03
2016-08-30
2016-12-22)