何振宏 張丹丹 羅躍嘉

(深圳大學(xué)情緒與社會(huì)認(rèn)知科學(xué)研究所,深圳 518060)

抑郁癥是一種常見的復(fù)發(fā)性心境障礙(mood disorder),在臨床上又稱重度抑郁障礙(major depressive disorder,MDD)。在抑郁癥的諸多致病因素中,認(rèn)知因素特別是認(rèn)知偏向(對負(fù)性信息的過度關(guān)注)是抑郁癥狀產(chǎn)生、持續(xù)和發(fā)展的重要原因之一(Taylor & John,2004)。這種由于抑郁等心境障礙引起的對負(fù)性信息的過度關(guān)注被稱為心境一致性偏向(mood-congruent bias) (Delle-Vigne,Wang,Kornreich,Verbanck,& Campanella,2014)。Beck曾在其抑郁認(rèn)知模型中提出,認(rèn)知加工對心境一致性信息的偏好維持了抑郁的心境狀態(tài)(Beck,1967)。新近的抑郁認(rèn)知理論認(rèn)為抑郁癥狀是由心境一致性情緒加工偏向(Mood-congruent emotion processing bias)所引起(Beck,2008; Scher,Ingram,& Segal,2005)。這兩種理論提到的認(rèn)知加工偏向和情緒加工偏向其實(shí)是從認(rèn)知或情緒角度對抑郁癥人群心境一致性偏向的表述,為簡化表述,統(tǒng)稱其為認(rèn)知偏向。Joormann等人認(rèn)為,認(rèn)知偏向可能會(huì)增加抑郁發(fā)作的易感性(vulnerability)(Joormann,Gilbert,& Gotlib,2010)。MDD病人由于注意和記憶的嚴(yán)重?fù)p害,其認(rèn)知偏向可能會(huì)妨礙言語信息傳遞的有效性(Everaert,Koster,&Derakshan,2012),甚至抵消治療干預(yù)的效果(Baert,Koster,& de Raedt,2011)。因此無論從理論還是臨床角度看來,對抑郁癥認(rèn)知偏向進(jìn)行一個(gè)整體和深入的了解十分必要。

目前國外已有一些探討抑郁癥認(rèn)知偏向的綜述文獻(xiàn),但有的綜述并沒有將該認(rèn)知偏向當(dāng)作核心論述主題,如Mathews等人的綜述(Mathews &MacLeod,2005); 另一些綜述則引證單一,且多集中于腦成像學(xué)的證據(jù)(Roiser,Elliott,&Sahakian,2012)。類似地,國內(nèi)也有一篇依據(jù)Beck抑郁認(rèn)知模型對該認(rèn)知偏向腦成像研究的綜述(楊娟,張小崔,姚樹橋,2014)。然而,該認(rèn)知偏向還有來自其他領(lǐng)域(行為學(xué)和電生理學(xué))不容忽視的研究證據(jù),且目前國外對該認(rèn)知偏向的一些新的研究動(dòng)態(tài)值得我們關(guān)注,比如工作記憶偏向,而這是先前理論模型所不曾包含的。因此,在介紹該認(rèn)知偏向時(shí)我們更多從實(shí)證角度出發(fā),結(jié)合行為、電生理以及腦成像等多方面證據(jù)總結(jié)抑郁病人在認(rèn)知加工過程中的偏向特點(diǎn),在驗(yàn)證相關(guān)的理論模型的同時(shí),為臨床診斷提供抑郁癥認(rèn)知過程異常的有關(guān)生物指標(biāo)(biomarker)。我們從三個(gè)基本的認(rèn)知加工領(lǐng)域(知覺、注意和記憶)以及較高級的認(rèn)知領(lǐng)域(認(rèn)知解釋),對抑郁癥的認(rèn)知偏向相關(guān)研究進(jìn)行系統(tǒng)回顧,并進(jìn)一步總結(jié)了該認(rèn)知偏向的三個(gè)特點(diǎn)和相應(yīng)的腦機(jī)制,提出該領(lǐng)域研究有待回答的問題和對未來研究的展望。

1 心境一致性知覺偏向

抑郁癥人群的知覺偏向表現(xiàn)為對負(fù)性刺激尤其是悲傷刺激有更好和更準(zhǔn)確的知覺加工,而對正性刺激則呈現(xiàn)相反模式。研究情緒知覺最常用的方法有面孔表情識別任務(wù)、面孔情緒強(qiáng)度判斷任務(wù)(intensity judgment tasks),以及測量前注意無意識加工的后掩蔽任務(wù)(backward masking)等。與正常人相比,抑郁病人對悲傷面孔有更長的反應(yīng)時(shí),由于癥狀影響了他們對負(fù)性刺激的強(qiáng)度知覺,因此病人更多地將中性面孔解讀為悲傷面孔,而將愉快面孔解讀為中性面孔(Bourke,Douglas,& Porter,2010; Elliott,Zahn,Deakin,& Anderson,2011; Gollan,Pane,McCloskey,& Coccaro,2008)。這種偏向悲傷情緒的面孔知覺甚至?xí)掷m(xù)到病癥的恢復(fù)期(Joormann & Gotlib,2007),增加了未來疾病復(fù)發(fā)的風(fēng)險(xiǎn)(Bouhuys,Geerts,& Gordijn,1999)。Delle等人總結(jié)了近年來抑郁癥情緒知覺研究發(fā)現(xiàn),病人對不愉快面孔有知覺偏向,并對憤怒面孔有過度反應(yīng)(Delle-Vigne et al.,2014)。而與此相應(yīng)的是,病人對快樂面孔的敏感度則降低：Jormann和 Gotlib讓被試識別不同強(qiáng)度的面孔情緒,發(fā)現(xiàn)抑郁病人要在情緒強(qiáng)度很高的情況下才能正確識別快樂面孔,而對于悲傷和憤怒面孔則不需要如此(Joormann & Gotlib,2006); Yoon等人則采用二擇一面孔情緒強(qiáng)度判斷任務(wù)發(fā)現(xiàn),抑郁病人很少將微快樂表情的情緒強(qiáng)度判斷為比中性表情更高(Yoon,Joormann,& Gotlib,2009)。

在事件相關(guān)電位(event-related potential,ERP)研究中,Dai和Feng采用情緒強(qiáng)度評價(jià)任務(wù)發(fā)現(xiàn),MDD病人對悲傷面孔有更大的P1和P2波幅,說明病人更容易被負(fù)性情緒面孔所喚起(Dai & Feng,2012)。Yang等人的研究發(fā)現(xiàn),與積極靶刺激相比,當(dāng)消極靶刺激出現(xiàn)時(shí)病人右后腦區(qū)的 P1潛伏期縮短,反映了一個(gè)非常早期的情緒知覺偏向(Yang,Zhu,Wang,Wu,& Yao,2011)。此外,Chang等人發(fā)現(xiàn)抑郁病人與面部表情有關(guān)的早期視覺失匹負(fù)波(visual mismatch negativity,vMMN)下降,表明抑郁病人在對表情信息的前注意加工中存在功能障礙(Chang,Xu,Shi,Zhang,& Zhao,2010)。

研究者普遍認(rèn)為杏仁核涉及對情緒凸顯刺激(包括面孔)的無意識和快速檢測(Anderson & Phelps,2001; Morris,?hman,& Dolan,1998; Whalen et al.,1998),而抑郁癥患者對負(fù)性刺激的知覺偏向與杏仁核和腹內(nèi)側(cè)前額葉(ventromedial prefrontal cortex,VMPFC)的障礙有關(guān),這些腦區(qū)涉及自下而上的情緒加工(Ochsner et al.,2004; Phillips,Drevets,Rauch,& Lane,2003)。該障礙表現(xiàn)為杏仁核對負(fù)性信息過度激活,且與 VMPFC的連接性(connectivity)發(fā)生改變(Fales et al.,2008)。

綜上所述,大量行為學(xué)、電生理學(xué)研究均揭示了抑郁病人的心境一致性知覺偏向。該知覺偏向與杏仁核對負(fù)性情緒信息過度激活,以及杏仁核與VMPFC連接發(fā)生改變有關(guān)。

2 心境一致性注意偏向

研究情緒注意常用的任務(wù)包括負(fù)性情緒啟動(dòng)任務(wù)(negative affect priming task)、點(diǎn)探測任務(wù)(dot-probe task)、情緒詞Stroop任務(wù)和Oddball任務(wù)等。與正常人相比,抑郁病人對負(fù)性刺激注意增加,對正性刺激注意減少,病人會(huì)選擇與其心境一致的負(fù)性刺激進(jìn)行編碼,而過濾掉正性信息(Kellough,Beevers,Ellis,& Wells,2008; Peckham,McHugh,& Otto,2010)。在負(fù)性情緒啟動(dòng)任務(wù)中,抑郁病人表現(xiàn)出對悲傷面孔注意易化(attention facilitation)增加,即存在更強(qiáng)的情緒啟動(dòng)效應(yīng)(affective priming effect) (Dai & Feng,2011a),而注意抑制減少(Dai & Feng,2011a; Goeleven,De Raedt,Baert,& Koster,2006)。對于后者,Everaert等人認(rèn)為這是抑郁病人認(rèn)知控制受損的表現(xiàn)之一(Everaert et al.,2012)。此外,病人對負(fù)性刺激尤其是悲傷刺激的注意偏向甚至?xí)掷m(xù)到抑郁癥恢復(fù)期,表明抑郁病人對負(fù)性刺激的注意偏向是特質(zhì)性而不是狀態(tài)性的(Fritzsche et al.,2010)。值得一提的是,抑郁病人對負(fù)性刺激的注意偏向受到刺激呈現(xiàn)時(shí)長調(diào)節(jié)。Zhong等人在點(diǎn)探測任務(wù)中設(shè)置了100 ms和500 ms兩種線索呈現(xiàn)時(shí)長,在100 ms條件下,抑郁病人傾向于把更多的注意分配到負(fù)性刺激上,但也有把少量注意分配到正性刺激上的趨勢; 但在500 ms條件下,病人卻存在難以避免注意負(fù)性刺激的趨勢,也就是說刺激呈現(xiàn)時(shí)間越長,注意偏向就越有可能出現(xiàn)(Zhong,Zhu,Yi,Yao,& Atchley,2011)。因此,研究者認(rèn)為刺激呈現(xiàn)時(shí)間較長的負(fù)性注意偏向并非是病人在負(fù)性刺激上分配了更多的注意資源,而是由于他們本身對負(fù)性刺激就存在注意解除困難(de Raedt &Koster,2010; Yoon et al.,2009)。

在ERP研究中,情緒詞Stroop任務(wù)研究發(fā)現(xiàn)負(fù)性情緒詞對 MDD病人有更強(qiáng)的干擾效應(yīng),即對消極信息的注意抑制能力受損,體現(xiàn)為病人的N1波幅降低,頂葉的N450波幅升高(Dai & Feng,2011b)。一些研究者認(rèn)為：由于病人注意分心作用的增加,這種注意抑制能力的受損會(huì)使得早期認(rèn)知加工階段注意資源變少,表現(xiàn)為在執(zhí)行負(fù)性情感啟動(dòng)任務(wù)時(shí),負(fù)性刺激在病人身上誘發(fā)了更低P2波幅(Yao et al.,2010)。這些研究從ERP角度證明了先前行為學(xué)的結(jié)果,即抑郁病人對負(fù)性刺激的注意抑制減少,那么當(dāng)病人注意正性刺激時(shí),相關(guān)ERP結(jié)果又能提供哪些啟示呢？前面提及的情緒詞Stroop任務(wù)的ERP結(jié)果就發(fā)現(xiàn)正性刺激出現(xiàn)時(shí)病人的P1波幅降低,這意味著他們對積極刺激給予較少的注意資源(Dai & Feng,2011b)。在一項(xiàng) Oddball任務(wù)中,正性靶刺激在病人額區(qū)誘發(fā)出更大的P2成分,作者認(rèn)為此結(jié)果反映了病人早期階段的情緒加工偏差可能包含有對正性刺激的注意缺陷(Yang et al.,2011)。Zhong等人點(diǎn)探測實(shí)驗(yàn)的ERP結(jié)果也發(fā)現(xiàn)：當(dāng)正性-中性圖片的有效試次呈現(xiàn)時(shí),與無效試次相比,病人沒有像正常人那樣出現(xiàn)更大的 P1波,且正性-中性圖片的注意偏向分?jǐn)?shù)為負(fù)值(正常人則為正值),表明抑郁病人缺少對正性刺激的注意(Zhong et al.,2011)。此外,ERP研究還證明了行為學(xué)支持的注意解除困難效應(yīng)能持續(xù)到抑郁癥的恢復(fù)期,比如當(dāng)一個(gè)任務(wù)需要個(gè)體把注意從負(fù)性面孔中解除出來時(shí),與正常人相比抑郁癥恢復(fù)期個(gè)體反應(yīng)更慢,且 N450波幅降低,說明抑郁癥的注意解除困難也是特質(zhì)性的(Vanderhasselt et al.,2012)。

腦成像研究發(fā)現(xiàn),與正常人相比抑郁癥病人右側(cè)腹外側(cè)前額葉(ventral lateral prefrontal cortex,VLPFC)、右側(cè)背外側(cè)前額葉(dorsal lateral prefrontal cortex,DLPFC)和右側(cè)頂上皮質(zhì)對負(fù)性刺激激活減少(Beevers,Clasen,Stice,& Schnyer,2010;Fales et al.,2008),這些區(qū)域的活動(dòng)減退可能是促成病人對負(fù)性刺激注意解除困難的原因(Disner,Beevers,Haigh,& Beck,2011)。當(dāng)正常人成功地抑制了對積極刺激的注意時(shí),他們的前扣帶回喙部(rostral anterior cingulate cortex,rACC)比抑郁病人有更大的激活; 相反的,當(dāng)抑郁病人成功地抑制了對消極刺激的注意時(shí),他們的相應(yīng)部位比正常人有更大激活(Elliott,Rubinsztein,Sahakian,&Dolan,2002; Eugène,Joormann,Cooney,Atlas,&Gotlib,2010; Mitterschiffthaler et al.,2008)。這說明正常個(gè)體需要更多的認(rèn)知資源對積極刺激進(jìn)行注意解除,而抑郁個(gè)體則需要更多的認(rèn)知資源對消極刺激進(jìn)行注意解除(Disner et al.,2011)。在一個(gè)情緒線索任務(wù)中,當(dāng)要求被試的注意力從無關(guān)情緒線索轉(zhuǎn)移時(shí),癥狀越嚴(yán)重的病人其外側(cè)前額區(qū)與頂區(qū)激活越弱,而非情緒線索條件下則無此效應(yīng),說明抑郁病人在對情緒信息進(jìn)行認(rèn)知控制的腦區(qū)上出現(xiàn)了加工障礙(Beevers et al.,2010)。已知 rACC與自我參照加工有關(guān)(Nejad,Fossati,&Lemogne,2013)。研究發(fā)現(xiàn)抑郁病人的rACC在負(fù)性自我參照加工中有所激活,且激活程度與癥狀的嚴(yán)重程度有顯著相關(guān)(Wagner et al.,2013)。事實(shí)上,抑郁病人的自我聚焦(self-focus),即對自我的內(nèi)部注意是增加的,反映了病人的自我注意偏向(Nejad et al.,2013)。Disner等人在其認(rèn)知模型中總結(jié)：抑郁個(gè)體在刺激選擇(與 DLPFC功能降低有關(guān))、對負(fù)性刺激的注意解除(與DLPFC和前扣帶回功能降低有關(guān))以及映射到其他潛在適應(yīng)性刺激的注視轉(zhuǎn)移(gaze shift) (與頂上皮層功能降低有關(guān))等認(rèn)知功能中缺乏效率(Disner et al.,2011)。

綜上所述,抑郁癥患者對負(fù)性刺激的注意偏向表現(xiàn)在對負(fù)性刺激注意增加且抑制減少,對正性刺激注意減少,以及對負(fù)性刺激的注意解除困難上,該偏向與額區(qū)、頂區(qū)以及前扣帶回功能異常有關(guān)。

3 心境一致性記憶偏向

抑郁癥患者以外顯長時(shí)記憶偏向?yàn)闃?biāo)志性認(rèn)知偏向(Everaert et al.,2012)。它一方面表現(xiàn)為患者對負(fù)性信息有回憶偏向(Mathews & MacLeod,2005),且在回憶與自我相關(guān)的負(fù)性信息時(shí),這種偏向效應(yīng)表現(xiàn)得更強(qiáng)(Wisco,2009)。另一方面則表現(xiàn)為患者不具備正常人那樣的對積極事件的正性記憶偏向(Harmer et al.,2009)。然而除了外顯層面,負(fù)性記憶偏向在內(nèi)隱記憶層面也有表現(xiàn)。抑郁病人在檢測閾下呈現(xiàn)的負(fù)性詞時(shí)的速度比正常人更快(Phillips,Hine,& Thorsteinsson,2010),同時(shí)在曾有抑郁史(formerly depressed)個(gè)體中也出現(xiàn)了此種效應(yīng)(Romero,Sanchez,& Vazquez,2014)。元分析(meta-analysis)發(fā)現(xiàn),抑郁病人對負(fù)性信息存在內(nèi)隱回憶偏向,而正常人則對正性信息有內(nèi)隱回憶偏向; 病人在編碼自我相關(guān)信息時(shí),這種偏負(fù)性的內(nèi)隱回憶更加明顯(Gaddy & Ingram,2014)。抑郁癥的負(fù)性記憶偏向還存在于錯(cuò)誤記憶之中。研究發(fā)現(xiàn)病人在錯(cuò)誤記憶任務(wù)中比正常人更傾向于把負(fù)性情境下的新詞誤認(rèn)為是舊詞; 同樣,自我相關(guān)性因素在病人的錯(cuò)誤記憶偏向中占有重要位置(Wittekind et al.,2014)。

近年來,抑郁癥患者的工作記憶成為心境一致認(rèn)知偏向研究的熱點(diǎn)。工作記憶是一個(gè)容量有限的系統(tǒng)(Baddeley,1996),它在情緒調(diào)節(jié)中維持與任務(wù)相關(guān)的情緒內(nèi)容而排除與任務(wù)不相關(guān)的情緒內(nèi)容,并且可以影響積極和消極情緒(Vanderhasselt et al.,2012)。然而,大量研究表明抑郁病人存在從工作記憶中消除無關(guān)負(fù)性想法或記憶的困難(Berman et al.,2011; Foland-Ross et al.,2013;Joormann & Gotlib,2008; Levens & Gotlib,2010;Yoon,LeMoult,& Joormann,2014)。作為認(rèn)知控制受損的又一大表現(xiàn),患者在工作記憶涉及轉(zhuǎn)移(shifting)和更新(updating)情緒及非情緒表征的過程中也存在異常(Lissnyder,Koster,& de Raedt,2012; Lo & Allen,2011)。這導(dǎo)致太多的負(fù)性信息在抑郁病人的工作記憶容量中沒有得到及時(shí)轉(zhuǎn)移和更新且一直堆積下去,使得病人沉浸在負(fù)性情緒內(nèi)容中并表現(xiàn)出對負(fù)性無關(guān)信息的提取增加,因而維持了抑郁心境(Yoon et al.,2014)。有意思的是,當(dāng)無關(guān)信息為正性時(shí),抑郁病人并不存在工作記憶解除困難,相反對它的解除比正常人更快(Levens & Gotlib,2010)。

腦成像研究發(fā)現(xiàn),當(dāng)編碼負(fù)性刺激時(shí),抑郁病人在右側(cè)杏仁核的激活上比正常人更大,且杏仁核與海馬及尾狀核-殼核的功能連接(functional connectivity)也更強(qiáng),病人右側(cè)杏仁核在編碼負(fù)性刺激時(shí)的活動(dòng)與同側(cè)海馬及尾狀核-殼核的活動(dòng)有更高的相關(guān)(Hamilton & Gotlib,2008)。Arnold等人采用彌散張量成像對恢復(fù)期抑郁病人進(jìn)行研究,也發(fā)現(xiàn)杏仁核與海馬、小腦、腦干的連接增強(qiáng),并認(rèn)為這可能導(dǎo)致情緒記憶偏向; 他們還發(fā)現(xiàn)這些病人內(nèi)側(cè)前額葉皮質(zhì)(medial prefrontal cortex,mPFC)的神經(jīng)元密度減少,可能反映了自上而下加工的減弱,即額區(qū)損傷弱化了對杏仁核的調(diào)節(jié),使得杏仁核向海馬等皮質(zhì)下區(qū)域的輸出失調(diào),因而間接誘發(fā)了負(fù)性記憶偏向(Arnold et al.,2012)。Arnold等人的另一個(gè)研究也說明情緒性記憶偏向相關(guān)的神經(jīng)改變會(huì)持續(xù)到抑郁癥的恢復(fù)期(Arnold et al.,2011),因此這種神經(jīng)改變可能是抑郁復(fù)發(fā)的原因(Arnold et al.,2012)。Disner等人在其認(rèn)知模型中總結(jié)：抑郁癥的記憶偏向可能起因于編碼負(fù)性刺激時(shí)杏仁核活動(dòng)的增加,而回憶時(shí)海馬(負(fù)責(zé)情節(jié)記憶)、尾狀核-殼核活動(dòng)(負(fù)責(zé)技能學(xué)習(xí))增加(Disner et al.,2011)。此外,對于工作記憶中無關(guān)負(fù)性信息解除困難現(xiàn)象,功能性核磁共振成像(functional magnetic resonance imaging,fMRI)研究發(fā)現(xiàn),當(dāng)要求被試把負(fù)性詞從工作記憶中移除時(shí),病人的前扣帶回、頂上小葉以及雙側(cè)腦島都有更大激活,相反的是,當(dāng)把正性詞從工作記憶中移除時(shí)正常人的相應(yīng)腦區(qū)有更大激活(Foland-Ross et al.,2013)。此外,抑郁病人在進(jìn)行工作記憶任務(wù)時(shí)存在皮質(zhì)-邊緣系統(tǒng)-皮質(zhì)下神經(jīng)環(huán)路的功能異常,主要表現(xiàn)為額區(qū)、前扣帶回、頂葉、顳葉和枕葉等腦區(qū)的異常激活,但受限于被試的異質(zhì)性和研究方法的不同,目前尚未得到一致的激活模式(Wang et al.,2015)。

綜上所述,抑郁病人更容易回憶與自己抑郁心境一致的內(nèi)容,這種記憶偏向在內(nèi)隱記憶、錯(cuò)誤記憶中也都有表現(xiàn),負(fù)性內(nèi)容一旦與自我相關(guān)性結(jié)合還會(huì)增強(qiáng)該記憶偏向效應(yīng)。該記憶偏向主要由邊緣系統(tǒng)(杏仁核、海馬)調(diào)節(jié),但在皮層區(qū)也有激活異常。此外,病人在消除、轉(zhuǎn)換和更新工作記憶中的負(fù)性信息時(shí)還存在困難,這是認(rèn)知控制損傷的一大表現(xiàn)。

4 心境一致性解釋偏向

Beck的負(fù)性圖式模型和新近的抑郁認(rèn)知理論都提到抑郁癥與解釋偏向(interpretation bias)有關(guān)(Beck,2008; Mathews & MacLeod,2005),即抑郁癥患者傾向于消極地解釋模棱兩可事件。早期研究曾證實(shí)了該偏向的存在(Butler & Mathews,1983),但也有研究并未發(fā)現(xiàn)這一現(xiàn)象(Bisson &Sears,2007; Lawson & MacLeod,1999)。然而Lawson等人用情緒模棱兩可文字誘發(fā)意象,通過測量被試的驚反應(yīng)(the startle response)大小發(fā)現(xiàn)了解釋偏向在抑郁個(gè)體身上的存在證據(jù),并認(rèn)為解釋偏向是抑郁的一個(gè)認(rèn)知易感性因子(Lawson,MacLeod,& Hammond,2002)。Rude等人則在大學(xué)生群體中發(fā)現(xiàn)解釋偏向的大小能預(yù)測后續(xù)抑郁癥狀的嚴(yán)重程度(Rude,Wenzlaff,Gibbs,Vane,&Whitney,2002)。

目前僅發(fā)表了一篇探討抑郁癥解釋偏向的ERP研究。該研究使用了語法判斷任務(wù)(The grammar decision task)作為實(shí)驗(yàn)任務(wù),在聽完模棱兩可句子的前半部分后,被試會(huì)看到不同情緒類別的句尾詞,然后判斷該詞在所聽到的句子中是符合語法規(guī)則的(grammatical)還是不符合語法規(guī)則的(non-grammatical) (Moser,Huppert,Foa,& Simons,2012)。結(jié)果發(fā)現(xiàn)正性句尾詞和負(fù)性句尾詞在抑郁病人身上所誘發(fā)的 N4波幅無顯著差異,表明病人對結(jié)尾的正性或負(fù)性有同樣的期待,即不存在正性解釋偏向; 回歸分析還發(fā)現(xiàn)抑郁癥狀與 N4解釋偏向效應(yīng)有關(guān),這為抑郁癥存在負(fù)性解釋偏向提供了部分證據(jù)(Moser et al.,2012)。

綜上所述,抑郁癥患者的負(fù)性解釋偏向雖然得到一些理論模型的支持,且已存在部分行為學(xué)與電生理學(xué)證據(jù),然而該領(lǐng)域相關(guān)研究并未達(dá)成一致的結(jié)論,因此該偏向及有關(guān)的神經(jīng)機(jī)制值得深入挖掘。

5 認(rèn)知偏向的三個(gè)特點(diǎn)及腦機(jī)制

根據(jù)以上研究,結(jié)合 Rottenberg等人提出的負(fù)性增強(qiáng)假設(shè)(negative potentiation hypothesis)(該觀點(diǎn)認(rèn)為抑郁病人對負(fù)性情緒刺激反應(yīng)敏感)與正性衰減假設(shè)(positive attenuation hypothesis)(該觀點(diǎn)認(rèn)為抑郁病人對正性情緒刺激反應(yīng)遲鈍)(Rottenberg,Gross,& Gotlib,2005),我們總結(jié)出抑郁癥心境一致性認(rèn)知偏向存在三個(gè)主要特點(diǎn),且推斷該認(rèn)知偏向是這些特點(diǎn)背后的腦機(jī)制協(xié)同作用的產(chǎn)物。(1)加工偏向負(fù)性：該特點(diǎn)在知覺、注意、記憶以及解釋等認(rèn)知環(huán)節(jié)層面均存在,而原因可能是大腦杏仁核對負(fù)性信息存在過度激活。杏仁核的功能包括將注意指向情緒信息、易化情緒記憶以及產(chǎn)生自主的情緒反應(yīng)(Pessoa,2010)。當(dāng)抑郁癥患者對情緒性刺激進(jìn)行知覺、評估和反應(yīng)時(shí),負(fù)性情緒刺激(如悲傷和恐懼面孔)能使大腦自下而上的反應(yīng)增強(qiáng)(杏仁核、梭狀回等腦區(qū)過度激活) (Arnone et al.,2012; Monk et al.,2008; 廖成菊,馮正直,2010),甚至在無意識條件下也是如此(Suslow et al.,2010; Victor,Furey,Fromm,?hman,& Drevets,2010); (2)加工偏離正性或積極偏向缺失：該特點(diǎn)與負(fù)性偏向一樣,也存在于抑郁病人的各個(gè)認(rèn)知環(huán)節(jié)中,而原因則是紋狀體對正性信息激活減弱,這可能是抑郁癥核心癥狀之一——快感缺失的神經(jīng)機(jī)制(Epstein et al.,2006)。眾所周知,紋狀體是獎(jiǎng)賞環(huán)路的重要組成部分,與積極情緒的加工有關(guān)(Groenewold,Opmeer,de Jonge,Aleman,& Costafreda,2013),而 MDD病人的獎(jiǎng)賞環(huán)路以紋狀體和邊緣區(qū)活動(dòng)減少以及額區(qū)激活增加為特征(Demenescu et al.,2011)。Heller等人對抑郁病人進(jìn)行2個(gè)月的藥物治療發(fā)現(xiàn),病人伏隔核激活越大以及腦內(nèi)額中回-紋狀體環(huán)路連接增加得越多,病人體驗(yàn)到的積極情緒也越多。作者認(rèn)為抑郁癥可能部分源于伏隔核持續(xù)活動(dòng)和額區(qū)-紋狀體連接性的缺失(Heller et al.,2013); (3)認(rèn)知控制的損傷：表現(xiàn)為抑郁病人對負(fù)性信息存在抑制和解除困難,這在注意和工作記憶環(huán)節(jié)均有體現(xiàn)。原因是抑郁病人負(fù)責(zé)認(rèn)知控制的腦區(qū)激活模式異常,比如額區(qū)對負(fù)性表情激活減少,而對正性表情激活增加,這可能反映了由心境不一致刺激所觸發(fā)的情緒調(diào)節(jié)需要的增加(Demenescu et al.,2011)。DLPFC和前扣帶回對認(rèn)知控制的缺乏可能危害自上而下的情緒監(jiān)控,從而使得患者大腦調(diào)節(jié)杏仁核反應(yīng)的能力減弱(Beck,2008; Pizzagalli,2011)。此外,病人對于未知情緒效價(jià)的事件的負(fù)性預(yù)測偏向也可能是認(rèn)知控制損傷所致。Herwig等人讓被試根據(jù)線索預(yù)期并知覺具有情緒效價(jià)以及未知情緒效價(jià)的圖片,結(jié)果發(fā)現(xiàn)在預(yù)期未知情緒效價(jià)的情緒圖片時(shí),抑郁病人在DLPFC和mPFC等腦區(qū)的神經(jīng)激活模式與預(yù)期負(fù)性情緒圖片時(shí)相同(Herwig et al.,2010)。

6 現(xiàn)階段有待回答的問題與未來展望

抑郁癥人群的心境一致性偏向在認(rèn)知加工的各個(gè)環(huán)節(jié)(知覺、注意、記憶、解釋)都有發(fā)生。根據(jù)目前的相關(guān)研究,我們發(fā)現(xiàn)此認(rèn)知偏向的特點(diǎn)為偏向負(fù)性刺激、偏離正性刺激,以及認(rèn)知控制受損。該認(rèn)知偏向在腦成像研究中表現(xiàn)為邊緣系統(tǒng)(包括杏仁核、海馬等)對負(fù)性刺激的異常激活,紋狀體對正性刺激激活不足,以及額區(qū)對皮質(zhì)下區(qū)域認(rèn)知控制的減弱,總體反映了自下而上加工的增強(qiáng)以及自上而下加工的減弱。然而,抑郁癥人群心境一致性偏向的研究仍有諸多問題有待回答?？偨Y(jié)起來主要有以下三點(diǎn)：

第一,各環(huán)節(jié)的認(rèn)知偏向間是否存在聯(lián)系？Everaert等人認(rèn)為現(xiàn)階段研究的一個(gè)主要局限是抑郁病人的認(rèn)知偏向被單獨(dú)地、孤立地在相當(dāng)特定的信息加工階段內(nèi)進(jìn)行研究(Everaert et al.,2012)。他們的研究已證明,不同的認(rèn)知偏向(知覺、解釋、注意、認(rèn)知控制)是相互聯(lián)系的,但哪一種或哪幾種認(rèn)知偏向?qū)τ诤罄m(xù)癥狀發(fā)作更具有預(yù)測力仍然不得而知(Everaert et al.,2012)。當(dāng)前已有研究表明抑郁癥的注意偏向和記憶偏向具有密切的聯(lián)系,注意偏向的改變會(huì)影響情緒刺激的精細(xì)加工,并且是心境一致性記憶偏向的原因之一(Blaut,Paulewicz,Szastok,Prochwicz,& Koster,2013)。解釋偏向也會(huì)影響外顯記憶,積極解釋偏向訓(xùn)練還可能是改變負(fù)性記憶偏向的一個(gè)有效手段(Salemink,Hertel,& Mackintosh,2010; Tran,Hertel,& Joormann,2011)。那么,各認(rèn)知偏向之間若有聯(lián)系,這種聯(lián)系又是什么樣的關(guān)系,是序列關(guān)系還是平行關(guān)系？迄今為止這些問題還沒有得到有效解決。

第二,心境一致性認(rèn)知偏向與抑郁癥的關(guān)系是什么？具體而言,是認(rèn)知偏向?qū)е铝艘钟舭Y,還是抑郁癥導(dǎo)致了認(rèn)知偏向(戴琴,馮正直,2008)？研究表明,認(rèn)知偏向是抑郁癥狀產(chǎn)生、持續(xù)和發(fā)展的重要原因之一(Taylor & John,2004)。這么看來似乎是認(rèn)知偏向?qū)е铝艘钟舭Y,但上述很多研究已經(jīng)證明：恢復(fù)期個(gè)體抑郁癥狀雖早已消失,卻仍然存在認(rèn)知偏向和相應(yīng)神經(jīng)變化。這該作何解釋？那可以認(rèn)為是抑郁癥導(dǎo)致了認(rèn)知偏向嗎？恐怕不能。Singh等人通過考察有家族抑郁風(fēng)險(xiǎn)的兒童發(fā)現(xiàn),認(rèn)知偏向以及結(jié)構(gòu)和功能性的神經(jīng)改變早在抑郁癥狀發(fā)作之前就已出現(xiàn)(Singh& Gotlib,2014)。與健康母親的健康女兒相比,罹患抑郁癥母親的健康女兒會(huì)選擇性地注視負(fù)性情緒面孔,表現(xiàn)出注意偏向(Joormann,Talbot,&Gotlib,2007),且會(huì)把模棱兩可的詞語和故事解釋得更消極,表現(xiàn)出解釋偏向(Dearing & Gotlib,2009)。這些患病家庭的健康兒童在產(chǎn)生認(rèn)知偏向的同時(shí)還伴隨有相應(yīng)的神經(jīng)改變：當(dāng)出現(xiàn)消極情緒時(shí),病人母親的女兒在涉及消極情緒體驗(yàn)的腦區(qū)(杏仁核與 VLPFC)比正常母親的女兒有更大的激活; 相反在回憶積極情緒時(shí),正常母親的女兒在涉及對情緒自上而下調(diào)節(jié)的區(qū)域(DLPFC與背側(cè)前扣帶回)比病人母親的女兒有更大的激活(Joormann,Cooney,Henry,& Gotlib,2012)。由此可知這些來自有抑郁風(fēng)險(xiǎn)家族的兒童雖并未被診斷有抑郁癥,卻也會(huì)出現(xiàn)抑郁癥所特有的認(rèn)知偏向和相應(yīng)腦激活改變,意味著認(rèn)知偏向并非由抑郁癥直接引起。目前看來,這個(gè)問題相當(dāng)復(fù)雜,國內(nèi)學(xué)者暫把認(rèn)知偏向視作抑郁癥的一個(gè)特征(戴琴,馮正直,2008)。

第三,如何解決研究結(jié)果的不一致？在抑郁癥認(rèn)知偏向的諸研究中,結(jié)果的不一致時(shí)有發(fā)現(xiàn)。例如,對抑郁癥工作記憶的腦成像研究通常發(fā)現(xiàn)病人額葉神經(jīng)環(huán)路的功能失調(diào)(Wang et al.,2015),同樣采用與工作記憶相關(guān)的任務(wù),有研究發(fā)現(xiàn)病人 DLPFC激活增強(qiáng)(Matsuo et al.,2007;Walter,Wolf,Spitzer,& Vasic,2007),也有發(fā)現(xiàn)該區(qū)域激活減弱(Garrett et al.,2011; Kerestes et al.,2012),甚至還有研究未發(fā)現(xiàn)該腦區(qū)被激活(Sandstr?m et al.,2012)。多數(shù)研究者把結(jié)果不一致的問題歸結(jié)為被試和實(shí)驗(yàn)任務(wù)的異質(zhì)性,以及認(rèn)知本身的復(fù)雜性。除此之外,我們認(rèn)為還有兩個(gè)重要原因不容忽視：其一是實(shí)驗(yàn)范式的有效性。例如一個(gè)元分析研究發(fā)現(xiàn),在抑郁癥注意偏向的測量上,點(diǎn)探測范式比情緒 Stroop范式更有效,且效果量更大(Peckham et al.,2010)。其二,大部分研究只注重刺激材料的情緒效價(jià),卻忽視了刺激的自我相關(guān)性。事實(shí)上,抑郁癥不僅僅與負(fù)性偏向有關(guān),還與增加的自我聚焦(self-focus)有關(guān)(Nejad et al.,2013)。抑郁病人加工與自我有關(guān)的負(fù)性刺激時(shí),認(rèn)知偏向會(huì)增強(qiáng)(Gaddy & Ingram,2014)。部分研究極有可能讓自我相關(guān)因素混淆到實(shí)驗(yàn)刺激中,造成了與控制嚴(yán)格的實(shí)驗(yàn)研究所不一致的結(jié)果。

因此,未來研究可以從以下三個(gè)方向開展。首先,如前所述,雖然在知覺、注意、記憶和認(rèn)知解釋每個(gè)層面對抑郁癥的認(rèn)知偏向都有不少研究,但對兩個(gè)或三個(gè)環(huán)節(jié)之間的綜合性研究甚少,因此難以對抑郁癥的認(rèn)知偏向形成一個(gè)整體的認(rèn)識。所以今后對抑郁病人的知覺與注意、記憶以及解釋四個(gè)偏向進(jìn)行綜合研究是很有必要的。其次,需要進(jìn)行縱向研究以探討認(rèn)知偏向與抑郁癥的因果關(guān)系,以此確定認(rèn)知偏向究竟是抑郁癥的預(yù)測因子還是診斷標(biāo)準(zhǔn)之一。最后,亟需一個(gè)標(biāo)準(zhǔn)化的實(shí)驗(yàn)流程以盡量減少方法學(xué)、人口學(xué)上的變異,目前已有研究者在此方面作出了有益嘗試。例如Korgaonkar等人在fMRI中采用了標(biāo)準(zhǔn)化的成套測驗(yàn)和成像協(xié)議(imaging protocols),以此控制方法學(xué)和樣本所產(chǎn)生的變異,該研究發(fā)現(xiàn),抑郁病人在工作記憶更新和有意識的負(fù)性情緒加工期間,DLPFC的激活減少; 在工作記憶任務(wù)和反應(yīng)抑制任務(wù)中背內(nèi)側(cè)前額葉皮質(zhì)(dorsomedial prefrontal cortex,DMPFC)的激活增大; 在有意識的正性情緒加工期間,DMPFC激活減少(Korgaonkar,Grieve,Etkin,Koslow,& Williams,2013)。此外,檢測各研究范式的效果量,盡可能選擇大效果量的實(shí)驗(yàn)范式,排除刺激材料自我相關(guān)性對研究結(jié)果的干擾,進(jìn)而改善目前研究結(jié)論不一致的狀況。

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