王超逸 高 博 楊慶雄 李勇輝

(1中國(guó)科學(xué)院心理健康重點(diǎn)實(shí)驗(yàn)室, 中國(guó)科學(xué)院心理研究所, 北京 10010)(2中國(guó)科學(xué)院大學(xué), 北京 100049) (2貴州師范大學(xué), 貴陽(yáng) 550001)

個(gè)體由于經(jīng)歷或目睹對(duì)生命具有威脅的事件后, 往往會(huì)導(dǎo)致一系列的生理和心理癥狀, 創(chuàng)傷后應(yīng)激障礙(posttraumatic stress disorder, PTSD)作為創(chuàng)傷事件后長(zhǎng)期持續(xù)的精神障礙(Li, Murakami,Wang, Maeda, & Matsumoto, 2006)具有以下主要癥狀表現(xiàn)：持續(xù)的再體驗(yàn)創(chuàng)傷事件(re-experiencing)、對(duì)創(chuàng)傷事件相關(guān)的刺激回避及對(duì)一般事物反應(yīng)麻木(avoidance & emotional numbing )、高喚醒狀態(tài)(hyperarousal) (American Psychiatric Association diagnostic and statistical manual of mental disorders,Forth edition, DSM-IV, 1994)。PTSD癥狀具有延遲出現(xiàn)的特點(diǎn), 一般在遭受創(chuàng)傷數(shù)日、數(shù)周甚至數(shù)月后才出現(xiàn)(Everly, 2000)。在長(zhǎng)達(dá)數(shù)年的病程中其癥狀的形成和發(fā)展也不是一蹴而就的, 同很多精神障礙一樣, 隨著時(shí)間的發(fā)展PTSD患者普遍存在非適應(yīng)性的泛化現(xiàn)象(Lissek et al., 2010;Lissek, 2012)。創(chuàng)傷相關(guān)的刺激或情境引發(fā)的恐懼情緒反應(yīng)及行為表現(xiàn)會(huì)逐漸被相似的刺激或情境引發(fā), 隨著時(shí)間的推移能夠引發(fā)PTSD癥狀的刺激和情境的邊界甚至?xí)幽：?Grillon &Margan,1999; Fendt & Koch, 2013)。

針對(duì)于PTSD泛化現(xiàn)象的研究集中在兩個(gè)方面。一方面, 有研究者將泛化現(xiàn)象作為PTSD引起的繼發(fā)現(xiàn)象(Gorman & Sloan, 2000)。他們將恐懼泛化現(xiàn)象和安全信號(hào)恐懼抑制失敗作為PTSD的核心特征(Jovanovic et al., 2010; Jovanovic,Kazama, Bachevalier, & Davis, 2012; Jovanovic &Ressler, 2010)。非適應(yīng)性泛化現(xiàn)象的產(chǎn)生原因是在PTSD形成之后, 與記憶相關(guān)的神經(jīng)系及腦結(jié)構(gòu)發(fā)生了一系列的改變, 這些改變導(dǎo)致創(chuàng)傷事件相關(guān)記憶出現(xiàn)扭曲, 與此同時(shí)個(gè)體的記憶、學(xué)習(xí)能力也遭到了破壞(Jovanovic et al., 2009, 2010;Jovanovic et al., 2012), 因此, PTSD患者會(huì)對(duì)創(chuàng)傷事件相關(guān)的刺激和環(huán)境出現(xiàn)恐懼泛化, 并且在安全信號(hào)和情境中恐懼抑制失敗, 對(duì)安全信號(hào)和危險(xiǎn)信號(hào)不能夠準(zhǔn)確的分辨, 從而引起高度警覺(jué)和過(guò)度的生理反應(yīng)等臨床表現(xiàn)(Lissek et al., 2010;Lissek, 2012)。另一方面, 也有研究者將泛化這種學(xué)習(xí)現(xiàn)象當(dāng)作引起和推動(dòng)PTSD發(fā)生發(fā)展的原因。由于PTSD的癥狀出現(xiàn)較為遲緩(Everly, 2000),所以非適應(yīng)性泛化被認(rèn)為是引起PTSD發(fā)生發(fā)展的一個(gè)可能原因, 泛化是學(xué)習(xí)過(guò)程中的一種普遍現(xiàn)象(Kimble, 1985), 在創(chuàng)傷事件發(fā)生后, 泛化從適應(yīng)性向非適應(yīng)性發(fā)展, PTSD的癥狀可能是在這個(gè)過(guò)程中逐漸形成的。以Mowrer的雙因素理論(two-factor learning theory)為基礎(chǔ)發(fā)展出泛化和二次交替學(xué)習(xí)是PTSD發(fā)生和發(fā)展的機(jī)制(Mowrer, 1960; Boudewyns & Hyer, 1996; Keane,Zimmering & Caddell, 1985)。

對(duì)于PTSD和非適應(yīng)性泛化之間的相互關(guān)系目前尚無(wú)定論, 由于PTSD具有延遲發(fā)生、病程持續(xù)時(shí)間長(zhǎng)、與其他精神障礙共病的特點(diǎn), 將非適應(yīng)性泛化現(xiàn)象作為研究對(duì)象, 明確其在PTSD發(fā)生發(fā)展中扮演的角色具有重要意義, 討論兩者之間的關(guān)系對(duì)于PTSD的診斷和治療都具有必要性?；诜沁m應(yīng)性泛化是PTSD核心表現(xiàn)的觀點(diǎn),首先, 通過(guò)對(duì)該現(xiàn)象的研究可以幫助人們進(jìn)一步認(rèn)識(shí)PTSD的各個(gè)癥狀簇及它們之間的關(guān)系; 其次, 在與其他的精神障礙進(jìn)行比較時(shí), 泛化現(xiàn)象可以作為PTSD區(qū)分于其他精神障礙的一項(xiàng)重要指標(biāo), 通過(guò)泛化現(xiàn)象是否發(fā)生、在發(fā)展中存在的異同給PTSD的診斷提供更可靠的依據(jù)?；诜沁m應(yīng)性泛化引起PTSD發(fā)生并推動(dòng)PTSD發(fā)展的觀點(diǎn), 了解非適應(yīng)性泛化發(fā)展變化的動(dòng)態(tài)特點(diǎn)可以幫助預(yù)測(cè)PTSD的發(fā)生, 為PTSD的早期識(shí)別與干預(yù)提供依據(jù)。

1 泛化的適應(yīng)性和非適應(yīng)性

1.1 適應(yīng)性泛化

泛化(generalization)在心理學(xué)研究中的定義極其廣泛, 最被大家所了解的是巴甫洛夫經(jīng)典條件學(xué)習(xí)理論中學(xué)習(xí)的泛化現(xiàn)象(Pavlov, 1972)。經(jīng)典條件作用中, 條件刺激(conditioned stimulus,CS)與非條件刺激(uncoditioned stilulus, US)匹配呈現(xiàn)多次后, 單獨(dú)呈現(xiàn)CS也能夠引起個(gè)體與非條件反應(yīng)(unconditioned response, UR)相同的條件反應(yīng)(conditioned response, CR), 一段時(shí)間后, 個(gè)體對(duì)與CS相似的刺激(generalized stimulus, GS)也會(huì)出現(xiàn)相似的反應(yīng)。泛化是長(zhǎng)期進(jìn)化過(guò)程的產(chǎn)物, 個(gè)體在學(xué)習(xí)的過(guò)程中都會(huì)出現(xiàn)一定程度的泛化現(xiàn)象, 該現(xiàn)象的存在會(huì)讓個(gè)體對(duì)于可能引發(fā)相同結(jié)果的事物做出類似反應(yīng)(比如, 我們被某種蛇咬傷之后, 會(huì)對(duì)所有蛇產(chǎn)生一定的警惕), 泛化在進(jìn)化的層面屬于一種適應(yīng)性現(xiàn)象。適應(yīng)性泛化(adaptive generalization)對(duì)正常個(gè)體具有諸多益處,首先, 可以幫助個(gè)體對(duì)刺激和情境進(jìn)行分類提高學(xué)習(xí)效率; 其次, 加快個(gè)體對(duì)刺激的反應(yīng)速度、節(jié)省精力和注意資源; 再次, 幫助個(gè)體總結(jié)經(jīng)驗(yàn),對(duì)于恐懼經(jīng)歷來(lái)說(shuō), 泛化可以使我們避免一些類似危險(xiǎn)信號(hào)的刺激引發(fā)的不良后果, 并有助于個(gè)體基于經(jīng)驗(yàn)對(duì)線索可能引發(fā)的結(jié)果進(jìn)行預(yù)測(cè)(Mclaern & Mackintosh, 2002)。

1.2 非適應(yīng)性泛化

對(duì)于PTSD和其他一些心理障礙(mental disorder)患者都會(huì)出現(xiàn)非適應(yīng)性泛化(maladaptive generalization)的表現(xiàn), 這種非適應(yīng)性泛化在心理障礙中普遍存在, 最初可能是由于涉及恐懼發(fā)生的腦區(qū)調(diào)節(jié)異常所引發(fā)的, 在發(fā)展過(guò)程中能引起患者心理生理癥狀的刺激及情境范圍不斷擴(kuò)大(Lesile & Anthony, 1994)。

動(dòng)物需要通過(guò)學(xué)習(xí)識(shí)別威脅信號(hào), 并基于先前的經(jīng)驗(yàn)對(duì)可能存在安全隱患的情境做出適應(yīng)性反應(yīng)。對(duì)于刺激線索, 非適應(yīng)性泛化首先表現(xiàn)為刺激泛化(stimulus generalization), 一個(gè)被廣泛使用的實(shí)驗(yàn)范式證明了該現(xiàn)象的存在(Kalish, 1969;Lissek et al., 2008), 固定半徑的圓圈(CS)與電擊刺激(US)相匹配形成條件作用之后, 要求實(shí)驗(yàn)組(PTSD患者)與對(duì)照組(健康被試)對(duì)一系列直徑由小到大依次排列的同心圓(包括CS, 與CS不同相似度的GS)進(jìn)行辨認(rèn), 發(fā)現(xiàn)PTSD患者泛化梯度(generalization gradient)的變化幅度較健康被試小,表現(xiàn)為對(duì)直徑相差較大和較小的同心圓的分辨力沒(méi)有明顯的差別, 同時(shí)在分辨刺激時(shí)所用的反應(yīng)時(shí)(reaction time)長(zhǎng)于對(duì)照組, 這說(shuō)明PTSD患者對(duì)同心圓之間的差異的辨別能力弱, 不能很好的區(qū)分那些與危險(xiǎn)線索(danger cue)相似度高的泛化刺激(GS), 這可能意味著他們?cè)诂F(xiàn)實(shí)生活中風(fēng)險(xiǎn)感知能力較低, 不易察覺(jué)危險(xiǎn)情況。Lissek和他的同事將該范式應(yīng)用于對(duì)焦慮障的研究中, 包括：PTSD (Lissek et al., 2010; 2012)、GAD (Lissek &Grillon, 2010)及PD (Lissek & Grillon, 2010)。隨著病程的增加, 患者會(huì)普遍出現(xiàn)對(duì)新刺激和其他與原始引起厭惡反應(yīng)線索并不相似的刺激產(chǎn)生反應(yīng), 這種現(xiàn)象被稱作刺激的交叉敏感化(cross sensitization)(Post et al., 1999; Bonne, Grillon, Vythilingam,Neumeister, & Charney, 2004)。

對(duì)于情境而言, 正常個(gè)體在某個(gè)環(huán)境中遭遇厭惡刺激, 但改變環(huán)境中的某些線索或更換環(huán)境后厭惡刺激引起的反應(yīng)不再出現(xiàn), 健康個(gè)體能夠區(qū)分線索與環(huán)境之間的聯(lián)系, 能夠區(qū)別日常生活環(huán)境與創(chuàng)傷情境之間的不同, 并在適當(dāng)?shù)那榫诚伦龀鲞m當(dāng)?shù)姆磻?yīng)。然而, 非適應(yīng)性情境記憶的泛化會(huì)導(dǎo)致個(gè)體將情境條件作用中習(xí)得的反應(yīng)遷移到安全的環(huán)境(Flor & Wessa, 2010; Garner et al.,2012), 甚至個(gè)體在能明確區(qū)分新情境與引起不良反應(yīng)情境的情況下, 仍然會(huì)產(chǎn)生不可抑止的異常行為及情緒反應(yīng), 比如焦慮障礙患者所具有的持續(xù)性的焦慮反應(yīng)(Woody & Rachman, 1994)。

在心理咨詢與治療中, 非適應(yīng)性泛化通常被認(rèn)為是區(qū)分一般心理障礙和嚴(yán)重心理障礙的重要標(biāo)準(zhǔn), 該現(xiàn)象的出現(xiàn)會(huì)大大降低個(gè)體學(xué)習(xí)的準(zhǔn)確性; 使個(gè)體面對(duì)新的刺激和環(huán)境做出錯(cuò)誤的預(yù)測(cè);對(duì)于某些刺激和情境無(wú)法做出適當(dāng)反應(yīng), 同時(shí)引發(fā)過(guò)度的不良行為和情緒反應(yīng), 對(duì)生理和心理均產(chǎn)生巨大的負(fù)面影響。

2 創(chuàng)傷后應(yīng)激障礙中的非適應(yīng)性泛化現(xiàn)象

PTSD中的非適應(yīng)性泛化現(xiàn)象包括：能引起PTSD生理及心理癥狀的刺激和環(huán)境范圍的不斷擴(kuò)大, 區(qū)分界限逐漸模糊, 對(duì)個(gè)體適應(yīng)環(huán)境造成不利影響的泛化現(xiàn)象(Kleim, Ehring, & Ehler,2012; Ehler & Clark, 2000)。PTSD泛化范圍隨著PTSD病程的持續(xù)而逐漸擴(kuò)大, 并且這種擴(kuò)大化的趨勢(shì)在三大癥狀簇(再體驗(yàn)、回避及情感麻木、高喚醒)中都有體現(xiàn)(Bonne et al., 2004)。

2.1 PTSD三大癥狀簇具有一致的泛化趨勢(shì)

分別對(duì)PTSD三大癥狀簇進(jìn)行觀察, 都伴隨非適應(yīng)性泛化的發(fā)生。再體驗(yàn)表現(xiàn)為患者缺少能力將與威脅相關(guān)的線索和那些無(wú)關(guān)線索相互區(qū)分(Bonne et al., 2004)。PTSD建模成功的實(shí)驗(yàn)動(dòng)物不僅會(huì)對(duì)恐懼條件作用中與電擊相匹配的聲音刺激產(chǎn)生恐懼反應(yīng), 而且對(duì)與之相似卻從未呈現(xiàn)的刺激也會(huì)產(chǎn)生相似程度的恐懼反應(yīng)(Kaouane et al.,2012), 對(duì)于人類而言, PTSD患者從開始與創(chuàng)傷刺激相關(guān)的線索引起記憶閃回逐漸變?yōu)闊o(wú)明確線索提取的創(chuàng)傷再體驗(yàn)和夢(mèng)魘(LeDoux, 2000; Maren,2001); 回避的泛化出現(xiàn)的時(shí)間較其他兩種癥狀的泛化出現(xiàn)的時(shí)間晚, 隨時(shí)間的發(fā)展PTSD患者由對(duì)于恐懼線索情境的回避發(fā)展到社交回避, 在人類身上體現(xiàn)出情感麻木、對(duì)事物普遍興趣缺失(Maier, 2001); 高喚醒這一癥狀伴有持續(xù)性的焦慮和過(guò)度的反應(yīng), 驚跳反應(yīng)、警覺(jué)(失眠癥)、易激惹, 高喚醒與焦慮之間存在著緊密的關(guān)系, 由于恐懼與焦慮共同作用導(dǎo)致惡性循環(huán)使得條件作用加劇, 患者對(duì)周圍的環(huán)境喪失了基本的安全感(Janoff-Bulman,1992)。

2.2 PTSD泛化現(xiàn)象隨時(shí)間發(fā)展而加劇

PTSD患者的恐懼反應(yīng)具有依時(shí)間改變的特點(diǎn), 脫離應(yīng)激事件的一段時(shí)間后對(duì)于恐懼線索的反應(yīng)有所加劇(McAllister & McAllister, 1967),PTSD患者所表現(xiàn)出的泛化現(xiàn)象也具有隨時(shí)間改變而發(fā)生變化的特點(diǎn), 經(jīng)歷著適應(yīng)性泛化發(fā)展為非適應(yīng)性泛化, 非適應(yīng)性泛化嚴(yán)重程度加劇的過(guò)程。

2.2.1 PTSD中非適應(yīng)性泛化的延遲出現(xiàn)

PTSD作為一種慢性焦慮障礙, 其癥狀出現(xiàn)具有延遲性, 維持的時(shí)間較長(zhǎng), 病程甚至可達(dá)數(shù)年, 在這個(gè)過(guò)程中泛化現(xiàn)象隨著時(shí)間的發(fā)展也呈現(xiàn)出范圍逐漸擴(kuò)大的趨勢(shì)(Frueh, Grubaugh,Gusack & Elhai, 2009)。

個(gè)體經(jīng)歷創(chuàng)傷事件之后, PTSD的癥狀往往不會(huì)立即出現(xiàn), 有研究者解釋PTSD的形成有延遲性(Pickens, Navarre & Nair, 2010), 也有研究者認(rèn)為PTSD在創(chuàng)傷事件后立即形成, 存在PTSD的潛伏期(incubation)使癥狀在數(shù)日甚至數(shù)月后得以表現(xiàn)并加劇, 在此期間患者并沒(méi)有再次暴露于創(chuàng)傷事件相關(guān)的線索之下(Frueh et al., 2009; Smid et al., 2011; Everly, 2000)。Wotjak和他的同事在研究中發(fā)現(xiàn)在創(chuàng)傷發(fā)生的最初實(shí)驗(yàn)動(dòng)物并沒(méi)有泛化現(xiàn)象產(chǎn)生, 一段時(shí)間之后才出現(xiàn)對(duì)相似刺激的泛化(stimulus generalization) (Wotjak, 2011), 這一現(xiàn)象在人類和實(shí)驗(yàn)動(dòng)物的研究中反復(fù)得到驗(yàn)證(Schreurs,Smith-Bell, & Burhans, 2011; Balogh & Wehner, 2003;Houston, Stevenson, McNaughton, & Barnes, 1999)。

對(duì)于PTSD中非適應(yīng)性泛化現(xiàn)象的延遲出現(xiàn)與PTSD癥狀出現(xiàn)所具有的潛伏期存在著時(shí)間維度上的共同點(diǎn), 但二者之間的關(guān)系尚無(wú)研究結(jié)論,明確PTSD是否在創(chuàng)傷事件發(fā)生后就立即形成在一定程度上可以解答這一疑問(wèn)。

2.2.2 創(chuàng)傷后應(yīng)激障礙中非適應(yīng)性泛化現(xiàn)象逐漸加劇

巴浦洛夫曾提出伴隨著時(shí)間的增加, 恐懼反應(yīng)的范圍會(huì)向與原初引起恐懼的刺激相類似的刺激延展(Pavlov, 1972)。動(dòng)物實(shí)驗(yàn)顯示在條件作用之后實(shí)驗(yàn)動(dòng)物很容易對(duì)應(yīng)激的環(huán)境和改變了條件的相似環(huán)境進(jìn)行區(qū)分, 但在一段時(shí)間間隔后動(dòng)物就很難區(qū)分出這兩個(gè)環(huán)境了, 這就是泛化現(xiàn)象,泛化的程度隨著時(shí)間的增加而逐漸加大(Balogh,Radcliffe, Logue, & Wehner, 2002; Wiltgen & Silva,2007), 引起恐懼反應(yīng)的刺激所覆蓋的范圍也越廣泛, 對(duì)認(rèn)知加工層次的影響也越深。

從感覺(jué)層面觀察, 出現(xiàn)刺激泛化的個(gè)體對(duì)不同相似程度的刺激風(fēng)險(xiǎn)感知變化幅度大大低于正常個(gè)體, 對(duì)相似度低的刺激比常人的風(fēng)險(xiǎn)評(píng)分高,相反對(duì)相似性高的刺激風(fēng)險(xiǎn)評(píng)估則低于常人(Lissek & Grillon, 2010)。有研究對(duì)該現(xiàn)象的出現(xiàn)給出了可能的解釋, Resnnik測(cè)試個(gè)體在經(jīng)歷負(fù)性的聽覺(jué)刺激后聽覺(jué)差別閾限的變化, 發(fā)現(xiàn)負(fù)性刺激會(huì)使差別閾限增大, 對(duì)于相同感覺(jué)通道的兩個(gè)刺激更不容易分辨(Resnik, Gray & Borgia, 2011),所以PTSD患者可能更容易對(duì)創(chuàng)傷相關(guān)線索這種負(fù)性的刺激產(chǎn)生泛化。

隨著時(shí)間的發(fā)展, PTSD患者的恐懼反應(yīng)可能更容易被很多無(wú)害的中性線索所引發(fā), 與此同時(shí)創(chuàng)傷記憶被一次次提取鞏固, 由此帶來(lái)的負(fù)性體驗(yàn)強(qiáng)化了中性線索與創(chuàng)傷事件本身的聯(lián)結(jié), 產(chǎn)生次級(jí)條件學(xué)習(xí)效應(yīng)。次級(jí)條件作用還可能引發(fā)PTSD患者對(duì)更多無(wú)關(guān)中性刺激的恐懼反應(yīng), 這些刺激已經(jīng)不再滿足和與創(chuàng)傷事件相關(guān)線索相似的條件, 即交叉敏感化(Post et al., 1999)。

在比感覺(jué)加工更高層次的知覺(jué)認(rèn)知加工過(guò)程中, 與創(chuàng)傷事件相關(guān)刺激的特征被抽提概念化,導(dǎo)致PTSD患者對(duì)于創(chuàng)傷相關(guān)信息具有注意偏向(Amri, Ogwuegbu, Boujrad, Drieu, & Papadopoulos,1996), 對(duì)概念上相近的事物更容易發(fā)生泛化(Dunsmoor, Prince, Murty, Kragel, & LaBar, 2011)。

無(wú)論從三大癥狀簇泛化趨勢(shì)的表現(xiàn), 還是從能夠引起患者恐懼反應(yīng)的刺激的范圍, 乃至認(rèn)知加工的不同層次都能夠觀察到PTSD的非適應(yīng)性泛化在時(shí)間維度上具有階段性, 程度隨時(shí)間發(fā)展不斷加重。

3 創(chuàng)傷后應(yīng)激障礙與非適應(yīng)性泛化二者之間的關(guān)系

PTSD癥狀的發(fā)展與非適應(yīng)性泛化現(xiàn)象的變化之間有著不可分離的關(guān)系, 現(xiàn)有的研究結(jié)果從不同的角度對(duì)二者的關(guān)系進(jìn)行著描述和解釋, 對(duì)非適應(yīng)性泛化在PTSD中扮演的角色進(jìn)行探索。

3.1 PTSD非適應(yīng)性泛化現(xiàn)象的特殊性

雖然非適應(yīng)性泛化的形成都是以條件反射為基礎(chǔ)的, 導(dǎo)致的結(jié)果都是個(gè)體對(duì)與CS相似的刺激GS或不相關(guān)的中性刺激產(chǎn)生與US引起的一致反應(yīng), 但不同精神疾病產(chǎn)生過(guò)程中的US是截然不同的, 泛化后能夠引起患者產(chǎn)生癥狀的刺激和情境不同, 無(wú)論是外部反應(yīng)還是內(nèi)部認(rèn)知都不盡相同(Bouton, Mineka, & Barlow, 2001; Foa, Steketee,& Rothbaum, 1989), 比如, 引發(fā)PTSD焦慮癥狀的刺激范圍很廣, 單一(特定)恐懼癥所針對(duì)的事物卻很具體固定, 在無(wú)關(guān)刺激和情境中不會(huì)產(chǎn)生泛化(Lissek et al., 2010), 對(duì)于表達(dá)安全意義的信號(hào), PTSD患者不能進(jìn)行恐懼抑制(Jovanovic et al.,2009, 2010), 特質(zhì)性焦慮(Torrents-Rodas et al., 2013),抑郁癥(Jovanovic et al., 2010)患者卻可以抑制恐懼反應(yīng)。

3.2 非適應(yīng)性泛化推動(dòng)了PTSD的發(fā)展

經(jīng)典條件作用、次級(jí)操作條件作用和非適應(yīng)性泛化三者相互作用是導(dǎo)致PTSD癥狀不斷加劇的重要原因。首先, 經(jīng)典條件作用使中性刺激具有了引起恐懼反應(yīng)和提取創(chuàng)傷記憶的能力, 泛化現(xiàn)象將引起反應(yīng)的范圍擴(kuò)大到相似刺激, 經(jīng)過(guò)次級(jí)的條件作用將更多的中性刺激與創(chuàng)傷事件相聯(lián)系。Mowrer的雙因素理論認(rèn)為個(gè)體回避與創(chuàng)傷有關(guān)的刺激, 一方面阻止了恐懼記憶的消退, 另一方面操作條件化了回避行為(Mowrer, 1947), 并且在與泛化的共同作用下造成了持續(xù)性廣泛焦慮的形成(Boudewyns & Hyer, 1996; Keane et al., 1985),敏感化則會(huì)使得PTSD患者在新環(huán)境中處于高喚醒狀態(tài), 甚至引發(fā)焦慮等其它負(fù)性情緒加固條件作用(Siegmund & Wotjak, 2006; Stam, 2007)。

PTSD具有非適應(yīng)性泛化現(xiàn)象并且相比于其他精神障礙具有自身的特點(diǎn), 非適應(yīng)性泛化在PTSD癥狀的發(fā)展變化中具有重要作用, 但尚無(wú)研究報(bào)告對(duì)PTSD如何引起特異化的非適應(yīng)性泛化產(chǎn)生或適應(yīng)性的泛化向非適應(yīng)性泛化過(guò)渡是否是PTSD產(chǎn)生的原因做出定論, 但實(shí)驗(yàn)和臨床研究都認(rèn)為二者的產(chǎn)生與個(gè)體的學(xué)習(xí)記憶功能損傷有著直接的聯(lián)系。

4 PTSD中非適應(yīng)性泛化現(xiàn)象的神經(jīng)機(jī)制

不同腦結(jié)構(gòu)的相互聯(lián)系形成的神經(jīng)網(wǎng)絡(luò)是個(gè)體的行為表現(xiàn)的基礎(chǔ), 杏仁核、海馬、前額葉等腦結(jié)構(gòu)通常被認(rèn)為在PTSD和非適應(yīng)性泛化的形成中有重要作用。了解這些區(qū)域的功能和它們之間的關(guān)系可能進(jìn)一步幫我們理解PTSD與非適應(yīng)性泛化及二者之間的關(guān)系。

前額葉皮層負(fù)責(zé)高級(jí)認(rèn)知功能, 與情景記憶,工作記憶, 自我抑制能力有關(guān)。MRI研究表明PTSD患者的腹內(nèi)側(cè)前額葉皮層(ventromedial prefrontal cortex, vmPFC)體積減小(Fennema-Notestine, Stein,Kennedy, Archibald, & Jernigan, 2002; Rauch et al.,2003), 嚴(yán)重的PTSD患者vmPFC在條件作用消退階段的活動(dòng)程度遠(yuǎn)低于正常人(Shin et al., 2004;Williams et al., 2006)。前額葉皮層(medial prefrontal cortex, MPFC)在泛化的形成中起到關(guān)鍵作用, 損壞其神經(jīng)突觸連接會(huì)引起情境恐懼記憶的過(guò)度泛化(Xu et al., 2012)。

在學(xué)習(xí)記憶中起到關(guān)鍵作用的杏仁核、海馬均與MPFC有著密切的神經(jīng)聯(lián)系。杏仁核是加工創(chuàng)傷事件情緒信息的核心核團(tuán), 腹內(nèi)側(cè)及外側(cè)前額葉皮層抑制杏仁核對(duì)刺激的反應(yīng)(Davidson et al., 2002; Quirk & Beer, 2006), 因此, MPFC機(jī)能失調(diào)導(dǎo)致不能通過(guò)抑制杏仁核產(chǎn)生對(duì)恐懼反應(yīng)的控制可能是PTSD癥狀形成的原因之一, 人類神經(jīng)影像學(xué)研究報(bào)告PTSD患者杏仁核活躍程度高于健康個(gè)體(Lorberbaum et al., 2004; Phan, Britton,Taylor, Fig, & Liberzon, 2006)。

影像學(xué)研究結(jié)果同樣驗(yàn)證了PTSD可能與海馬的機(jī)能失調(diào)有關(guān), PTSD患者海馬的活動(dòng)減少(Bremner & Brett, 1997; Shin et al., 1999), 且海馬體積變小(Bremner et al., 1995)。丘腦連結(jié)核(nucleus reuniens, NR)在生理解剖結(jié)構(gòu)上與 MPFC、海馬連接, 是調(diào)節(jié)泛化形成的核心腦結(jié)構(gòu)(Xu &Sudhof, 2013), NR不同的神經(jīng)活動(dòng)形式抑制或興奮中間神經(jīng)元(Dolleman-Van der Weel, daSilva, &Witter, 1997)對(duì)海馬的震蕩活動(dòng)產(chǎn)生影響(Zhang et al., 2012), 抑制其神經(jīng)傳出會(huì)使海馬CA1區(qū)以及MPFC的前扣帶回皮層(anterior cingulate cortex,ACC)的c-Fos蛋白的表達(dá)減少, 還會(huì)減少實(shí)驗(yàn)動(dòng)物情境性恐懼活動(dòng), 增強(qiáng)其活動(dòng)則剛好相反。

在記憶加工中, 杏仁核的特點(diǎn)是無(wú)意識(shí)的、自動(dòng)化的、泛化、加工速度快, 存儲(chǔ)在杏仁核中的情緒記憶是永久性的(Young, 2005), 海馬則以自傳體記憶形式儲(chǔ)存空間和事件的信息, 完整、中立、信息化, 表現(xiàn)為整體(Jacobs & Nadel, 1998),二者都受前額葉皮層的調(diào)控, PTSD患者vmPFC功能受損導(dǎo)致杏仁核活動(dòng)抑制失敗, 海馬的活動(dòng)性降低, 因此情境條件作用減弱, 個(gè)體不能形成情境線索相關(guān)學(xué)習(xí)的框架, 因而情緒性記憶占據(jù)主導(dǎo), 這種碎片化情緒相關(guān)記憶易泛化, 難消退(Grillon & Lissek, 2010; Wessa & Flor, 2007), 最終導(dǎo)致關(guān)于創(chuàng)傷事件記憶通常是分離的(Brewin,2007), 缺少聯(lián)系(Michael, Ehler, Halligan, & Clark,2005)或者過(guò)度概括化(Sch?nfeld, Ehlers, B?llinghaus,& Rief, 2007)。Kaouane及其同事在實(shí)驗(yàn)動(dòng)物完成線索學(xué)習(xí)和情境學(xué)習(xí)后對(duì)接受不同強(qiáng)度電擊的實(shí)驗(yàn)動(dòng)物進(jìn)行糖皮質(zhì)激素注射, 建立了嚙齒類動(dòng)物的PTSD樣恐懼記憶模型, 并驗(yàn)證了海馬和杏仁核在PTSD記憶泛化中有重要作用(Kaouane et al.,2012)。

輔助學(xué)習(xí)系統(tǒng)理論(complementary learning system theory) (McClelland, McNaughton, & O’Reilly,1995; Kumaran & McClelland,2012)將泛化的產(chǎn)生歸因于海馬的存儲(chǔ)記憶的特點(diǎn)：能夠儲(chǔ)存特異性記憶(McHugh et al.,2007)但不保存事物共同特征的相關(guān)信息, 該理論無(wú)法解釋在記憶獲得的階段泛化的產(chǎn)生和調(diào)控, Wu及同事在實(shí)驗(yàn)中分別在記憶的獲得、保持和提取階段對(duì)NR活性進(jìn)行抑制,發(fā)現(xiàn)NR對(duì)情境恐懼記憶的泛化發(fā)生在記憶的獲得階段, 彌補(bǔ)了這點(diǎn)不足(Xu & Sudhof, 2013)。

因此, MPFC作為動(dòng)機(jī)及情緒的控制中心(Wise,2008), 可以通過(guò)杏仁核控制情緒反應(yīng), 通過(guò)連接核控制海馬對(duì)記憶的重新編碼(Colgin, Moser &Moser, 2008), 對(duì)記憶形成的詳細(xì)程度或泛化程度進(jìn)行控制。值得注意的是, 泛化產(chǎn)生的機(jī)制不僅僅局限于此, Qin發(fā)現(xiàn)了藍(lán)斑去甲腎上腺素能神經(jīng)元(locus ceruleus-centered nor-epinephrine, LC-NE)與應(yīng)激相關(guān)情緒反應(yīng)有關(guān), 應(yīng)激發(fā)生時(shí)對(duì)海馬和中腦的繼發(fā)記憶效應(yīng)(Subsequent Memory effects,SMEs)產(chǎn)生影響繼而導(dǎo)致記憶特異性降低(Qin et al., 2012)。

5 小結(jié)與研究展望

目前的研究結(jié)果表明PTSD與非適應(yīng)性泛化二者具有密切相關(guān), 但尚不能明確二者是否互為因果, 可以肯定的是二者的發(fā)生和發(fā)展有共同的神經(jīng)基礎(chǔ), 前額葉皮層、杏仁核、海馬、丘腦連接核在PTSD癥狀和泛化現(xiàn)象中都扮演者重要的角色, 創(chuàng)傷事件引起的與記憶相關(guān)的腦結(jié)構(gòu)功能活性的損傷或改變可能是導(dǎo)致PTSD癥狀和非適應(yīng)性泛化現(xiàn)象產(chǎn)生的根本原因, 結(jié)合對(duì)非適應(yīng)性泛化現(xiàn)象腦機(jī)制的研究可以不斷補(bǔ)充完善PTSD神經(jīng)基礎(chǔ)的構(gòu)型, 解答PTSD與非適應(yīng)性泛化之間的關(guān)系, 在此基礎(chǔ)上的深入研究, 可能幫助我們進(jìn)一步理解PTSD, 找到PTSD新的形成原因、易感因素或新的癥狀特點(diǎn), 也可能為我們提供新的PTSD的識(shí)別診斷標(biāo)準(zhǔn)、干預(yù)手段和治療方法,補(bǔ)充理論研究的同時(shí)完善臨床治療。

非適應(yīng)性泛化作用不僅對(duì)PTSD癥狀的形成有著推動(dòng)作用, 作為諸多精神障礙中一種普遍現(xiàn)象有很多當(dāng)今的研究沒(méi)有涉及和解答的問(wèn)題。泛化現(xiàn)象從適應(yīng)性向非適應(yīng)性發(fā)展是連續(xù)性的過(guò)程,不同的泛化程度可能對(duì)應(yīng)著個(gè)體不同的心理行為表現(xiàn), 泛化到何種程度才能算作是非適應(yīng)性泛化呢？非適應(yīng)性泛化現(xiàn)象廣泛存在于精神障礙中,是否它可能是一種引起嚴(yán)重心理問(wèn)題的原因？泛化現(xiàn)象在精神障礙中的共性, 在不同精神障礙中表現(xiàn)出其特殊性是如何形成的？是否能夠找到共同發(fā)展趨勢(shì)中決定特殊性的因素來(lái)診斷和控制精神障礙產(chǎn)生呢？這些問(wèn)題都值得進(jìn)一步研究。

對(duì)于非適應(yīng)性泛化的研究方向, 從局限的在某個(gè)精神障礙中的現(xiàn)象或某幾個(gè)精神障礙特異性的比較向該現(xiàn)象本身的成因和相關(guān)的腦機(jī)制發(fā)展可能具有重要意義。接受DSM-IV診斷的病人都可能符合不止一種病癥的診斷標(biāo)準(zhǔn), 大量的研究說(shuō)明了諸多精神障礙存在一些共病率較高的癥狀,研究者們?cè)絹?lái)越意識(shí)到添加更多層次精神障礙的分類, 能更好的推動(dòng)心理治療研究和應(yīng)用的發(fā)展,而更多層次精神障礙的分類意味著要通過(guò)連續(xù)的發(fā)展?fàn)顟B(tài)而不是非連續(xù)的類別來(lái)對(duì)心理疾病進(jìn)行劃分和定義, 泛化現(xiàn)象是具有連續(xù)變化特點(diǎn)的一個(gè)現(xiàn)象, 它包括正常個(gè)體的適應(yīng)性泛化, 精神障礙患者的非適應(yīng)性泛化以及從適應(yīng)性向非適應(yīng)性的過(guò)渡, 在研究對(duì)該現(xiàn)象相關(guān)問(wèn)題進(jìn)行研究的同時(shí), 也許可以幫助我們從新的角度理解精神障礙的形成。

American Psychiatric Association. (1994).Diagnostic and Statistical Manual of Mental Disorders(4th wd). Washington,DC: American Psychiatric Association.

Amri, H., Ogwuegbu, S. O., Boujrad, N., Drieu, K., &Papadopoulos, V. (1996). In vivo regulation of the peripheral-type benzodiazepine receptoand glucocorticoid synthesis by the Ginkgo biloba extract EGb761 and isolated ginkgolides.Endocrinology,137, 5707–5718.

Balogh, S. A., Radcliffe, R. A., Logue, S. F., & Wehner, J. A.(2002). Contextual and cued fear conditioning in C57BL/6J and DBA/2J mice: Context discrimination and the effects of retention interval.Behavioral Neuroscience, 116(6),947–957.

Balogh, S. A., & Wehner, J. M. (2003). Inbred mouse strain differences in the establishment of long-term fear memory.Behavioural Brain Research, 140(1–2), 97–106.

Bonne, O., Grillon, C., Vythilingam, M., Neumeister, A., &Charney, D. S. (2004). Adaptive and maladaptive psychobiological responses to severe psychological stress:Implications for the discovery of novel pharmacotherapy.Neuroscience & Biobehavioral Reiviews, 28(1), 65–94.

Boudewyns, P. A., & Hyer, L. A. (1996). Eye movement desensitization and reprocessing (EMDR) as treatment for post-traumatic stress disorder (PTSD).Clinical Psychology &Psychotherapy, 3(3), 185–195.

Bouton, M. E., Mineka, S., & Barlow, D. H. (2001). A modern learning theory perspective on the etiology of panic disorder.Psychological Review, 108(1), 4–32.

Bremner, J. D., & Brett, E. (1997). Trauma-related dissociative states and long-term psychopathology in posttraumatic stress disorder.Journal of Traumatic Stress, 10(1), 37–49.

Bremner, J. D., Randall, P., Scott, T. M., Bronen, R. A.,Seibyl, J. P., Southwick, S. M., ... Innis, R. B. (1995).Mri-Based measurement of hippocampal volume in patients with combat-related posttraumatic-stress-disorder.American Journal of Psychiatry, 152(7), 973–981.

Brewin, C. R. (2007).Posttraumatic stress disorder: malady or myth?New Haven: Yale University Press.

Colgin, L. L., Moser, E. I., & Moser, M. B. (2008).Understanding memory through hippocampal remapping.Trends in Neurosciences, 31(9), 469–477.

Davidson, J. R. T., Hewett, K., Bryson, H., Oldham, M.,Beebe, K., & Ruggiero, L. (2002). Post-traumatic stress disorder: Remission rates following paroxetine treatment.European Neuropsychopharmacology, 12, S347–S347.

Dolleman-Van der Weel, M. J., daSilva, F. H. L., & Witter, M.P. (1997). Nucleus reuniens thalami modulates activity in hippocampal field CA1 through excitatory and inhibitory mechanisms.Journal of Neuroscience, 17(14), 5640–5650.

Dunsmoor, J. E., Prince, S. E., Murty, V. P., Kragel, P. A., &LaBar, K. S. (2011). Neurobehavioral mechanisms of human fear generalization.Neuroimage, 55(4), 1878–1888.

Ehlers, A., & Clark, D. M. (2000). A cognitive model of posttraumatic stress disorder.Behaviour Research and Therapy,38, 319–345.

Everly, G. S. Jr. (2000). Five principles of crisis intervention:Reducing the risk of premature crisis intervention.International Journal of Emergency Mental Health,2(1),1–4.

Fendt, M., & Koch, M. (2013). Translational value of startle modulations.Cell and Tissue Research,354(1), 287–295.

Fennema-Notestine, C., Stein, M. B., Kennedy, C. M., Archibald,S. L., & Jernigan, T. L. (2002). Brain morphometry in female victims of intimate partner violence with and without posttraumatic stress disorder.Biological Psychiatry, 52(11),1089–1101.

Flor, H., & Wessa, M. (2010). Memory and posttraumatic stress disorder.Zeitschrift für Psychologie/Journal of Psychology,218(2), 61–63.

Frueh, B. C., Grubaugh, A. L., Cusack, K. J., & Elhai, J. D.(2009). Disseminating evidence-based practices for adults with PTSD and severe mental illness in Public-Sector mental health agencies.Behavior Modification, 33(1), 66–81.

Foa. E. B., Steketee, G., & Rothbaum, B. (1989).Behaviorallcognitive conceptualizations of posttraumatic stress disorder.Behavior Therapy,20, 155–176.

Garner, A. R., Rowland, D. C., Hwang, S. Y., Baumgaertel,K., Roth, B. L., Kentros, C., & Mayford, M. (2012).Generation of a synthetic memory trace.Science, 335(6075),1513–1516.

Grillon, C., & Lissek, S. (2010). Overgeneralization of conditioned fear in the anxiety disorders.Zeitschrift für Psychologie / Journal of Psychology, 218(2), 146–148.

Grillon, C., & Margan, C. A. (1999), Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder.Journal of Abnormal Psychology, 108(1), 134–142.

Gorman, J. M., & Sloan, R. P. (2000). Heart rate variability in depressive and anxiety disorders.American Heart Journal,140(S4), 77–83.

Houston, F. P., Stevenson, G. D., McNaughton, B. L., &Barnes, C. A. (1999). Effects of age on the generalization and incubation of memory in the F344 rat.Learning &Memory, 6(2), 111–119.

Jacobs, W. J., & Nadel, L. (1998) Neurobiology of reconstructed memory.Psychology, Public Policy, and Law, 4(4), 1110–1134.

Janoff–Bulman, R. (1992).Shattered assumptions: Towards a new psychology of trauma. New York: Free Press.

Jovanovic, T., Kazama, A., Bachevalier, J., & Davis, M. (2012).Impaired safety signal learning may be a biomarker of PTSD.Neuropharmacology, 62(2), 695–704.

Jovanovic, T., Norrholm, S. D., Blanding, N. Q., Davis, M.,Duncan, E., Bradley, B., & Ressler, K. J. (2010). Impaired fear inhibition is a biomarker of PTSD but not depression.Depress Anxiety, 27(3), 244–251.

Jovanovic, T., Norrholm, S. D., Fennell, J. E., Keyes, M.,Fiallos, A. M., Myers, K. M., ... Duncan, E. J. (2009).Posttraumatic stress disorder may be associated with impaired fear inhibition: Relation to symptom severity.Psychiatry Research, 167(1–2), 151–160.

Jovanovic, T., & Ressler, K. J. (2010). How the neurocircuitry and genetics of fear inhibition may inform our understanding of PTSD.TheAmerican Journal of Psychiatry, 167(6),648–662.

Kalish, H. I. (1969).Stimulus generalization.In M. H. Marx(Ed.),Learning: Processes. Oxford, England: Macmillan.

Kaouane, N., Porte, Y., Vallee, M., Brayda-Bruno, L., Mons,N., Calandreau, L., ... Desmedt, A. (2012).Glucocorticoids can induce PTSD-like memory impairments in mice.Science, 335(6075), 1510–1513.

Keane, T. M., Zimmering, R. T., & Caddell, J. M. (1985). A behavioral formulation of posttraumatic stress disorder in Vietnam veterans.The Behavior Therapist,8(1), 9–12.

Kimble, G. A. (1985). Conditioning and learning. In S. Koch& D. E. Leary (Eds),A century of psychology as science(pp. 284–321). Washington, DC, US: American Psychological Association.

Kleim, B., Ehring, T., & Ehlers, A. (2012). Perceptual processing advantages for trauma-relatedvisual cues in post-traumatic stress disorder.Psychological Medicine,42,173–181.

Kumaran, D., & McClelland, J. L. (2012). Generalization through the recurrent interaction of episodic memories: A model of the hippocampal system.Psychological Review,119(3), 573.

LeDoux, J. E. (2000). Emotion circuitins the barin.Annual Review Neuroscience, 23, 155–184.

Lesile, F. L., & Anthony, J. C. (1994), Maintenance and generalization of behaviours after treatment of persons with traumatic brain injury.Brain Injury,8(6), 529–540.

Li, S., Murakami, Y., Wang, M., Maeda, K., & Matsumoto, K.(2006). The effects of chronic valproate and diazepam in a mouse model of posttraumatic stress disorder.Pharmaclogy Biochemistry Behavior, 85(2), 324–331.

Lissek, S. (2012). Toward an account of clinical anxiety predicated on basic, neurally mapped mechanisms of Pavlovian fear-learning: the case for conditioned overgeneralization.Depress Anxiety, 29(4), 257–263.

Lissek, S., Biggs, A. L., Rabin, S. J., Cornwell, B. R.,Alvarez, R. P., Pine, D. S., & Grillon, C. (2008).Generalization of conditioned fear-potentiated startle in humans: Experimental validation and clinical relevance.Behaviour Research and Therapy, 46(5), 678–687.

Lissek, S., Rabin, S., Heller, R. E., Lukenbaugh, D., Geraci,M., Pine, D. S., & Grillon, C. (2010). Overgeneralization of conditioned fear as a pathogenic marker of panic disorder.TheAmerican Journal of Psychiatry, 167(1), 47–55.

Lissek, S., & Grillon, C. (2010). Overgeneralization of conditioned fear in the anxiety disorders.Journal of Psychology,218(2), 146–148.

Lorberbaum, J. P., Kose, S., Johnson, M. R., Arana, G. W.,Sullivan, L. K., Hamner, M. B., ... George, M. S. (2004).Neural correlates of speech anticipatory anxiety in generalized social phobia.Neuroreport, 15(18), 2701–2705.

Maier, S. F. (2001). Exposure to the stressor environment prevents the temporal dissipation of behavioral depression/ learned helplessness.Society of Biological Psychiatry, 49,763–773.

Maren, S. (2001). Neurobiology of pavlovian fear conditioning.Annual Review of Neuroscience,24(1), 897–931.

McAllister, D. E., & Mcallister, W. R. (1967). Incubation of fear: An exmination of the concept.Journal of Experimental Research in Personality,2(3), 180–190.

McClelland, J. L., McNaughton, B. L., O'Reilly, L. C. (1995).Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory.Psychological Review, 102(3), 419–457.

Michael, T., Ehlers, A., Halligan, S., & Clark, D. M. (2005).Unwanted memories of assault: What intrusion characteristics are associated with PTSD?Behaviour Research and Therapy,43(5), 613–628.

Mclaern, I. P. L., & Mackintosh. N. J.(2002). Associative learning and elemental representation:II. generalization and discrimination.Animal Learning & Behavior,30(3),177–200.

McHugh, T. J., Jones1, M. W., Quinn, J. J., Balthasar, N.,Coppari, R., Elmquist, J. K., … Wilson, M. A. (2007).Susumu tonegawa dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network.Science,317(5834), 94–99.

Mowrer, O. H. (1960).Learning theory and behavior.Hoboken, NJ, US: John Wiley & Sons Inc.

Mowrer, O. H. (1947). On the dual nature of learning a reinterpretation of "conditioning" and" problem–solving".Harvard Educational Review, 17, 102–148.

Pavlov, I. P. (1972).Conditioned reflexes(G. V. Anrep,Trans.). London: Oxford University Press, (Original work prblished 1927).

Pickens, C. L., Navarre, B. M., & Nair, S. G. (2010).Incubation of conditioned fear in the conditioned suppression model in rats: Role of food-restriction conditions, length of conditioned stimulus, and generality to conditioned freezing.Neuroscience, 169(4), 1501–1510.

Phan, K. L., Britton, J. C., Taylor, S. F., Fig, L. M., &Liberzon, I. (2006). Corticolimbic blood flow during nontraumatic emotional processing in Posttraumatic stress disorder.Archives of General Psychiatry, 63(2), 184–192.

Post, R. M., Kimbrell, T. A., McCann, U. D., Dunn, R. T.,Osuch, E. A., Speer, A. M., & Weiss, S. R. B. (1999).Repetitive transcranial magnetic stimulation as a neuropsychiatric tool: Present status and future potential.Journal ofElectroconvulsive Therapy, 15(1), 39–59.

Qin, L. D., Wang, Z., Sun.,Y. W., Su, S. S., Zhou, Y., & Xu, J.R. (2012). A preliminary study of alterations in default network connectivity in post-traumatic stress disorder patients following recent trauma.Brain Research, 1484(12),50–56.

Quirk, G. J., & Beer, J. S. (2006). Prefrontal involvement in the regulation of emotion: Convergence of rat and human studies. Current OpinioninNeurobiology, 16(6), 723–727.

Rauch, S. L., Shin, L. M., Segal, E., Pitman, R. K., Carson,M. A., McMullin, K., ... Makriss, N. (2003). Selectively reduced regional cortical volumes in post-traumatic stress disorder.Neuroreport, 14(7), 913–916.

Resnik, L., Gray, M., & Borgia, M. (2011). Measurement of community reintegration in sample of severely wounded servicemembers.Journal of Rehabilitation Research and Development, 48(2), 89–101.

Sch?nfeld, S., Ehlers, A., B?llinghaus, I., & Rief, W. (2007).Overgeneral memory and suppression of trauma memories in post-traumatic stress disorder.Memory,15(3), 339–352.

Schreurs, B. G., Smith-Bell, C. A., & Burhans, L. B. (2011).Incubation of conditioning-specific reflex modification:Implications for post traumatic stress disorder.Journal of Psychiatric Research, 45(11), 1535–1541.

Shin, L. M., McNally, R. J., Kosslyn, S. M., Thompson, W.L., Rauch, S. L., Alpert, N. M., ... Pitman, R. K. (1999).Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation.American Journal of Psychiatry, 156(4), 575–584.

Shin, L. M., Orr, S. P., Carson, M. A., Rauch, S. L., Macklin,M. L., Lasko, N. B., ... Pitman, R. K. (2004). Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD.Archives of General Psychiatry,61(2), 168–176.

Siegmund, A., & Wotjak, C. T. (2006). Toward an animal model of posttraumatic stress disorder.Annals of the New York Academy of Sciences, 1071, 324–334.

Smid, G. E., Lensvelt-Mulders, G. J. L. M., Knipscheer, J. W.,Gersons, B. P. R., & Kleber, R. J. (2011). Late-onset PTSD in unaccompanied refugee minors: Exploring the predictive utility of depression and anxiety symptoms.Journal of Clinical Child and Adolescent Psychology, 40(5), 742–755.

Stam, R. (2007). PTSD and stress sensitisation: A tale of brain and body Part 1: Human studies.Neuroscience &Biobehavioral Reiviews, 31(4), 530–557.

Torrent-Rodas, D., Fullana, M. A., Bonillo, A., Caseras, X.,Andion, O., & Torrubia, R. (2013). No effect of trait anxiety on differential fear conditioning or fear generalization.Biological Psychology, 92(2), 185–190.

Wessa, M., & Flor, H. (2007). Failure of extinction of fear responses in posttraumatic stress disorder: Evidence from second-order conditioning.American Journal of Psychiatry,164(11), 1684–1692.

Williams, L. M., Kemp, A. H., Felmingham, K., Barton, M.,Olivieri, G., Peduto, A., ... Bryant, R. A. (2006). Trauma modulates amygdala and medial prefrontal responses to consciously attended fear.Neuroimage, 29(2), 347–357.

Wiltgen, B. J., & Silva, A. J. (2007). Memory for context becomes less specific with time.Learning & Memory,14(4), 313–317.

Wise, S. P. (2008). Forward frontal fields: Phylogeny and fundamental function.Trends in Neurosciences,31(12),599–608.

Woody, S., & Rachman, S. (1994). Generalized anxiety disorder (GAD) as an unsuccessful search for safety.Clinical Psychology Review,14(8), 743–753.

Wotjak, C. T. (2011). Role of the cannabinoid receptor 1(CB1) in fear adaptation.Alcohol, 45(3), 270–270.

Xu, W., Morishita, W., Buckmaster, P. S., Pang, Z. P.,Malenka, R. C., & Sudhof, T. C. (2012). Distinct neuronal coding schemes in memory revealed by selective erasure of fast synchronous synaptic transmission.Neuron, 73(5),990–1001.

Xu, W., & Sudhof, T. C. (2013). A neural circuit for memory specificity and generalization.Science, 339(6125),1290–1295.

Young, J. E. (2005). Schema–focused cognitive therapy and the case of Ms. S.Journal of Psychotherapy Integration,15(1), 115–126.

Zhang, Y., McCord, R. P., Ho, Y. J., Lajoie, B. R., Hildebrand, D.G., Simon, A. C., ... Dekker, J. (2012). Spatial organization of the mouse genome and its role in recurrent chromosomal translocations.Cell, 148(5), 908–921.