逐漸迷失在另一個世界的聲音裡──思覺失調症

文／安德魯．所羅門；譯／謝忍翾

思覺失調症殘酷之處在於，哪些事物會消失而哪些不會，毫無道理可言。思覺失調症可能是讓人喪失情感能力，因而無法和人建立關係、愛人或信任他人，可能是讓人無法完全運用理性來思考，也可能是失去專業工作能力。患者有可能失去自理生活的基本能力，還可能喪失自我察覺及清楚分析的大部分能力。

最廣為人知的一點，是患者會逐漸迷失在另一個世界的聲音中，誤以為這個聲音來自外界，而他和這些聲音的關係，會變得比真正的外在世界更真實、更重要。296這些聲音多半很殘酷，還經常鼓勵患者做出奇怪或不適當的舉動。聽到聲音的人多半很害怕，幾乎全都變得偏執。有時，患者還會同時出現幻視及幻嗅，他的世界因此變得充滿實際威脅，他像是陷入無間地獄，無從逃脫。奇怪的是，很多患者會逐漸和妄想的對象建立感情，不過雖然如此，非妄想的世界逐漸淡去仍讓他們孤單無比，彷彿永遠隱居於某個危險的私人星球，永世不得離開，也不得有客人來訪。約有五至十三％的思覺失調症患者會自殺。不過，從某個角度來說，死亡還是苦難中最輕微的部分。有個思覺失調症患者羅傑最後自殺了，他的妹妹就說：「最後，羅傑的死，我母親放下了；但他所經歷的人生，我母親永遠也放不下。」

世界上最悲慘的事，莫過於把夢境視為真實。能夠從睡夢中醒來，逃離那令人恐懼的噩夢，伸懶腰迎接嶄新的一天，那種大鬆一口氣的感覺實在幸福。精神疾病很可怕，會打亂患者區分自我和現實的能力。幻想與現實之間原本有層隔膜，而思覺失調症患者的隔膜卻千瘡百孔，因此想到一件事跟經歷一件事變得幾無二致。患者在早期往往有憂鬱症的症狀，這是因為精神疾病本身就讓人痛苦，同時也因為患者腦中的想法在本質上就很令人絕望。這個時期自殺的可能性最高。之後的階段，患者整體情緒反應的能力都降低了，看起來可能會很茫然且沒有喜怒哀樂。

訪問思覺失調症患者的時候，我發現狀況嚴重的人似乎都不會自艾自憐，這跟我接觸過的憂鬱症等精神失調患者大相逕庭，後者經常唉聲嘆氣，我本人也是其一。思覺失調症患者在初期階段確實會害怕、悲傷，但久病的人卻不會如此。他們會抱怨某個妄想，或因為無法自理生活而覺得內疚，卻很少怪罪疾病本身。很多人原本正要邁向美好人生，例如有個面貌姣好的女性，她父母總念念不忘她原本可以盡情談戀愛，但她本人卻似乎未這樣想。有個年輕人性情溫和、高中時人緣極佳，他父母告訴我，他若有一輩子的朋友會有多快樂，但他本人從不這麼說。有個男人首次發病時正在哈佛就讀，成績優異，但他從未抱怨自己錯過了大好事業，為此遺憾的是他的父母。疾病彷彿把這些患者和上述的人生完全切割開來，所以他們對人生渾然不覺。面對疾病，他們有種堅定的雍容，我無時無刻不覺得感動。297

自閉加上妄想

思覺失調可大致分為正性、負性和認知的症狀。正性症狀是出現精神幻覺，負性症狀和認知症狀則包含精神混亂、缺乏動力、情感遲鈍、失語、退縮、記憶限縮以及自理能力下降。有個專家這樣跟我形容，說這是「自閉加上妄想」。這種說法雖不完全貼切，卻也不無道理。有個病患這樣形容她的正性症狀：「可怕的畫面不斷向我襲來，一刻也不得喘息，這些畫面栩栩如生，我的身體都有確實的感覺。我無法說自己真正看到了影像，因為這些『影像』背後並沒有真正的事物。但我確實能感覺到，我的嘴裡似乎真的塞滿了鳥兒，然後我用牙齒把鳥咬碎，鳥羽、鳥血、碎鳥骨滿滿我的喉嚨。或是我看到人，我把這些人埋在牛奶瓶裡，任其腐爛，然後我吃下這些腐爛的屍體。或是我大口吞下一顆貓頭，然後貓頭同時也啃食我的重要器官。太血腥、太難忍受了。」

另一位病人則如此描述自己所經歷的負性及認知症狀：「不論何時，我對任何東西都沒有情緒反應，包括我自己。唯一剩下的，只有對四周事物還有我內心事件的抽象概念。就連這個刺穿我生命核心的疾病，我也只能客觀看待。我清醒地全程旁觀一名天資聰穎、教養良好的人就這麼漸漸毀壞，沒有什麼事比這更恐怖。而這，就是發生在我身上的事。」諾貝爾生理醫學獎得主坎德爾論及思覺失調症如何讓人失去對愉悅的期待，他說：「試想，有個人只要上館子用餐就會十分開心，卻提不起興趣上館子。」心理學的享樂原則說，人總是趨樂避苦，但對於有思覺失調症的人來說，這句話有一半不符合事實。

艾蜜莉．狄更生如此描述逐漸墮入精神疾病的狀態，刻畫鮮明得令人不寒而慄。

我感覺到心智劈出一道裂口── 猶如大腦裂開── 我試圖拼起──裂縫對上裂縫──303 卻無法吻合對接。 之後的思想，我努力將其 與之前的相接── 但次序散亂不成調 像球一顆顆── 散落在地。

雖然思覺失調症出現時，大多數人的感覺就像是有東西突然把腦袋劈開，但思覺失調症其實是一種發展型的失調，出生之前就已刻入大腦。這是種退化型的症狀，相較之下，自閉症雖然全面且持久，但多半不會隨著時間惡化。思覺失調症的症狀鮮少出現在童年或青春期早期。

一般而言，思覺失調症有五個可預測的階段，但在青春期發病之前是無跡可循的。然而晚近的研究指出，較晚走路及說話、喜歡自己玩、學業表現不佳、有社交焦慮，以及口語短期記憶較差都是徵兆。之後，正性症狀開始浮現，這是平均為時四年的前驅症狀期。這個階段的青少年或成人會開始改變認知、知覺、意志及運動機能，偶爾會有奇怪的念頭一閃而過，必須努力分辨不合邏輯的想法是真是假，也會變得猜疑而小心。有些患者似乎從小就和現實世界有些脫節，令人不太理解，後來他們逐漸陷入精神疾病。但大部分的人都是突然就變了，有時是因為創傷，有時則沒有明顯的觸發因素，突然就變了一個人。此時他們會進入思覺失調的發病期，開始出現幻覺或奇異的妄想，例如被控制妄想、思想插入、思想傳播、思想抽離。此階段好發於十五到三十歲之間，多半維持兩年。

目前還無法得知，究竟是成熟期的什麼事件觸發了精神病發作。主要有三種可能：一是青少年體內荷爾蒙激增，改變了腦內基因的表現。二是青少年時期大腦會以一層物質包覆神經纖維，使其功能發揮到最好，此過程稱為「髓鞘化」，而思覺失調症患者的髓鞘化出了問題。第三則是「突觸消除」（或突觸削減）出了狀況。嬰兒時期正常大腦發育的過程中，新的細胞會不斷游移、就定位，然後發展出突觸相連，此時會產生過多突觸。到了青春期，只有對特定個人十分有用的突觸會反覆加強，並因此保留下來，成為長久的神經架構。在不健康的大腦中，突觸可能會過度修剪、修剪不足或者修剪錯誤。304

思覺失調是神經病理學家的墳墓

思覺失調症和自閉症一樣，只是統稱。思覺失調症一詞由布魯勒於一九○八年首創，當時他指的其實是多種思覺失調的症狀。一九七二年，傑出神經科學家普拉姆說了一句名言：「思覺失調是神經病理學家的墳墓。」意思是過去沒有人了解病原，未來也不會有。雖然我們對思覺失調症的了解已多於自閉症，但仍不清楚這種病症應該根據生物性（基因型）還是行為模式（表現型）來分類。雖然思覺失調症的基因型和表現型有很多種，卻找不出特定形式或發展過程與特定遺傳標記的關聯。有些人沒有基因缺陷，也得了此病；有些人有基因變異，卻沒患病。基因標記指的是可能的風險，但不是絕對會得。家族裡有某個人得了思覺失調症，有相同缺陷基因的另一人卻可能罹患雙極情感疾患或重度憂鬱。

思覺失調症顯然有家族遺傳。要預知未來是否會罹病，最可靠的方法就是看是否有一等親罹患此症。然而，大部分的思覺失調症患者都沒有家人得病。

哈佛大學教授列維也是執業心理師，她表示：「事實一，大部分思覺失調症患者的父母都沒有思覺失調症。事實二，思覺失調症的案例並未減少，有些地方甚至增加。事實三：思覺失調症患者的生育率很低。如此一來，我們該如何解釋造成思覺失調症的基因為何一直存在？有個可能的解釋是，帶有並將思覺失調基因遺傳給後代的人，大部分都未罹患此症。」306同卵雙胞胎的共病率僅略高於五十％，顯示兩人都有極高的罹病風險，卻不見得都會發作。雙胞胎不論有無患病，下一代罹患思覺失調的風險都一樣高。換言之，某個人可能攜帶了容易發病的基因，卻沒有發病，然後又把基因遺傳給孩子，而孩子就可能有思覺失調症。某些身上帶有基因的人是受到什麼保護才沒有發病，目前還無從得知。精神病的發病機制之一是神經傳導物質（尤其是多巴胺）失衡。思覺失調症患者的大腦前額葉及海馬體的體積都縮小了，而且還有紋狀體失調的現象。很可能是基因搭配環境因素，導致體內生物化學改變，然後對大腦構造產生退化性的影響。新的研究顯示，高風險基因很可能會因為某種寄生蟲而活化。

每個人的基因圖譜裡都有三千個左右的基因，但基因的表現如何，取決於染色體的設定，還取決於外在因素如何壓抑或增進基因表現。體內生化反應決定了基因是否活化，以及活化時間、方式還有程度。思覺失調的基因可能並未表現出來，而有保護作用的基因則可能過度表現。思覺失調和自閉症一樣，大部分的案例並非由單一基因異常所造成，而是由多個所謂「單一族系變異」，也就是「多個拷貝數變異」，每個變異很可能都足以造成此病。若父母是高齡得子，孩子較常出現這類變異，尤其是高齡的父親。另一套發病模式則是自發性基因突變，就和唐氏症產生的過程一樣。現在逐漸發現，思覺失調、自閉症、雙極情感疾患等患者都有某些自發性基因缺陷，可能是拷貝數突變，也可能是單一基因突變。精神疾病是否都位於同一光譜上，而不是一組組各不相干的疾病？耶魯大學精神病學主任暨著名期刊《生物精神病學》編輯克里斯托表示：「要我說，這比較像是格網。」

要確定基因缺陷究竟會造成什麼影響，最好的辦法就是實驗，將缺陷基因植入老鼠身上，觀察老鼠是否出現類似人類疾病的症狀，接著研究人員再設法了解該基因如何影響腦部發展。我們當然無法得知老鼠是否有幻覺，但有些基因轉殖的老鼠變得離群索居、極具攻擊性或缺乏社交能力，有些不願接近異性老鼠，或看到陌生老鼠會退縮。很多有食物獎勵的事情，正常老鼠會樂意嘗試，基轉的老鼠卻拒絕不做，即使拿食物獎勵也沒用，這點和思覺失調症患者失去生活動力的情況十分類似。307坎德爾構思了這些架構龐大的研究方法，現在用他的話來說，已經找到「思覺失調症的典範轉移」。很多疾病都是因為某個基因持續表現所引起，關閉該基因，症狀就消失了。然而，思覺失調症的病原雖然也可能是基因，但是關閉基因並無助於減緩病症。思覺失調症一旦出現，就不會中止。

注釋

296 Statistics on suicide risk in schizophrenia come from Maurizio Pompili et al., “Suicide risk in schizophrenia: Learning from the past to change the future,” Annals of General Psychiatry 6 (March 16, 2007).

296 Statistics on suicide risk in schizophrenia come from Maurizio Pompili et al., “Suicide risk in schizophrenia: Learning from the past to change the future,” Annals of General Psychiatry 6 (March 16, 2007).

296 The quotation from the sister of a schizophrenic man comes from Carole Stone, “First person: Carole Stone on life with her schizophrenic brother,” Guardian, November 12, 2005.

297 This passage is based on an interview with Kitty and Pamela Watson in 2007 and on subsequent communications. All names in this passage are pseudonyms.

302 Useful general introductions to schizophrenia include Christopher Frith and Eve Johnstone, Schizophrenia: A Very Short Introduction (2003); Michael Foster Green, Schizophrenia Revealed: From Neurons to Social Interactions (2001); Rachel Miller and Susan E. Mason, Diagnosis: Schizophrenia (2002); E. Fuller Torrey, Surviving Schizophrenia (2006); and the NIH booklet Schizophrenia (2007).

302 The quotation from the schizophrenic woman describing her positive symptoms (“I could find no rest, for horrible images assailed me…”) occurs on page 37 of Marguerite Sechehaye, Autobiography of a Schizophrenic Girl: The True Story of “Renee” (1951).

302 The quotation from the patient describing negative symptoms of schizophrenia (“I am all the time losing…”) occurs on page 2 of Christopher Frith and Eve Johnstone, Schizophrenia: A Very Short Introduction (2003).

302 The quotation from Eric Kandel is from a personal communication in 2009.

302 The poem quoted is Emily Dickinson’s “I Felt a Cleaving in My Mind,” no. 937 in The Complete Poems of Emily Dickinson (1960).

303 The life course of schizophrenia is described in greater detail in Elaine Walker et al., “Schizophrenia: Etiology and course,” Annual Review of Psychology 55 (February 2004). See also figure 1 in Jeffrey A. Lieberman et al., “Science and recovery in schizophrenia,” Psychiatric Services 59 (May 2008).

303 The contribution of hormones to the development of schizophrenia is discussed in Laura W. Harris et al., “Gene expression in the prefrontal cortex during adolescence: Implications for the onset of schizophrenia,” BMC Medical Genomics 2 (May 2009); and Elaine Walker et al., “Stress and the hypothalamic pituitary adrenal axis in the developmental course of schizophrenia,” Annual Review of Clinical Psychology 4 (January 2008).

303 For more information on white matter in schizophrenia, see G. Karoutzou et al., “The myelin-pathogenesis puzzle in schizophrenia: A literature review,” Molecular Psychiatry 13, no. 3 (March 2008); and Yaron Hakak et al., “Genomewide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia,” Proceedings of the National Academy of Sciences 98, no. 8 (April 2001).

303 The synaptic-pruning hypothesis was originally proposed in I. Feinberg, “Schizophrenia: Caused by a fault in programmed synaptic elimination during adolescence?,” Journal of Psychiatric Research 17, no. 4 (1983). For a recent review article on the subject, see Gabor Faludi and Karoly Mirnics, “Synaptic changes in the brain of subjects with schizophrenia,” International Journal of Developmental Neuroscience 29, no. 3 (May 2011).

304 Statistics on response to antipsychotics over the short and long term come from Jeffrey A. Lieberman and T. Scott Stroup, “The NIMH-CATIE schizophrenia study: What did we learn?,” American Journal of Psychiatry 168, no. 8 (August 2011).

304 This passage is based on my interview with Connie and Steve Lieber in 2008 and subsequent communications.

304 Brain & Behavior Research Foundation (formerly NARSAD) website: http:// bbrfoundation.org/.

304 Figures on grant-making come from the Brain & Behavior Research Foundation (formerly NARSAD), “Our history” (2011), http://bbrfoundation.org/about/our -history. As of 2012, the most recent NARSAD grant statistics were: total given, $275,947,302.20; total number of grantees, 3,117; total number of grants given, 4,061; total number of institutions, 426; total number of countries (other than the United States), 30.

304 Herbert Pardes made this remark at a NARSAD gala in 2010.

305 Bleuler’s invention of the word schizophrenia is discussed in Paolo Fusar-Poli and Pierluigi Politi, “Paul Eugen Bleuler and the birth of schizophrenia (1908),” American Journal of Psychiatry, 165, no. 11 (2008).

305 Frederick Plum declared that “schizophrenia is the graveyard of neuropathologists” in his paper “Prospects for research on schizophrenia. 3. Neurophysiology: Neuropathological findings,” Neurosciences Research Program Bulletin 10, no. 4 (November 1972).

305 For more information on the genetics of schizophrenia, see Nancy C. Andreasen, Brave New Brain (2001); and Yunjung Kim et al., “Schizophrenia genetics: Where next?,” Schizophrenia Bulletin 37, no. 3 (May 2011).

305 The most comprehensive study of schizophrenia risk in relatives is the Roscommon (Ireland) Family Study; see Kenneth S. Kendler et al., “The Roscommon Family Study. I. Methods, diagnosis of probands, and risk of schizophrenia in relatives,” Archives of General Psychiatry 50, no. 7 (July 1993); and numerous subsequent reports published by Kendler and his colleagues from 1993 to 2001. For a review and synthesis of twin studies discussing the various sorts of environmental influences that might contribute to the differential development of schizophrenia in twins, see Patrick F. Sullivan, Kenneth S. Kendler, and Michael C. Neale, “Schizophrenia as a complex trait: Evidence from a meta-analysis of twin studies,” Archives of General Psychiatry 60, no. 12 (December 2003).

305 All quotations from Deborah Levy come from my interview with her in 2008 and subsequent communications.

306 Studies on dopamine function in schizophrenia include Anissa Abi-Dargham et al., “Increased baseline occupancy of D2 receptors by dopamine in schizophrenia,” Proceedings of the National Academy of Sciences 97, no. 14 (July 2000); and Philip Seeman et al., “Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis,” Proceedings of the National Academy of Sciences 102, no. 9 (March 2005).

306 For more information on hippocampal function in schizophrenia, see Stephan Heckers, “Neuroimaging studies of the hippocampus in schizophrenia,” Hippocampus 11, no. 5 (2001); and J. Hall et al., “Hippocampal function in schizophrenia and bipolar disorder,” Psychological Medicine 40, no. 5 (May 2010).

306 Epigenetics of schizophrenia is explored in Karl-Erik Wahlberg et al., “Geneenvironment interaction in vulnerability to schizophrenia,” American Journal of Psychiatry 154, no. 3 (March 1997); and Paul J. Harrison and D. R. Weinberger, “Schizophrenia genes, gene expression, and neuropathology: On the matter of their convergence,” Molecular Psychiatry 10, no. 1 (January 2005).

306 The question of parasites and schizophrenia, Jaroslav Flegr’s hypothesis that schizophrenia is exacerbated by toxoplasmosis, is described in Kathleen McAuliffe, “How your cat is making you crazy,” Atlantic, March 2012.

306 Copy number variations in schizophrenia are the focus of Daniel F. Levinson et al., “Copy number variants in schizophrenia: Confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications,” American Journal of Psychiatry 168, no. 3 (March 2011); Jan O. Korbel et al., “The current excitement about copy-number variation: How it relates to gene duplication and protein families,” Current Opinion in Structural Biology 18, no. 3 (June 2008); and G. Kirov et al., “Support for the involvement of large copy number variants in the pathogenesis of schizophrenia,” Human Molecular Genetics 18, no. 8 (April 2009). The contribution of paternal age to schizophrenia is discussed in E. Fuller Torrey, “Paternal age as a risk factor for schizophrenia: How important is it?,” Schizophrenia Research 114, nos. 1–3 (October 2009); and Alan S. Brown, “The environment and susceptibility to schizophrenia,” Progress in Neurobiology 93, no. 1 (January 2011).

306 For more information on spontaneous mutations and schizophrenia, see Anna C. Need et al., “A genome-wide investigation of SNPs and CNVs in schizophrenia,” PLoS Genetics 5, no. 2 (February 2009); and Hreinn Stefansson et al., “Large recurrent microdeletions associated with schizophrenia,” Nature 455, no. 7210 (September 11, 2008).

306 John Krystal’s comments come from my interview with him in 2012.

306 The development of transgenic mice that display schizophrenia-associated traits was first described in Takatoshi Hikida et al., “Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans,” Proceedings of the National Academy of Sciences of the United States of America 104, no. 36 (September 4, 2007); and Koko Ishizuka et al., “Evidence that many of the DISC1 isoforms in C57BL/6J mice are also expressed in 129S6/SvEv mice,” Molecular Psychiatry 12, no. 10 (October 2007). For a recent review article on transgenic mouse research, see P. Alexander Arguello and Joseph A. Gogos, “Cognition in mouse models of schizophrenia susceptibility genes,” Schizophrenia Bulletin 36, no. 2 (March 2010).

307 The quotation from Eric Kandel comes from a personal communication. For a review of work by Kandel and his colleagues, see Christoph Kellendonk, Eleanor H. Simpson, and Eric R. Kandel, “Modeling cognitive endophenotypes of schizophrenia in mice,” Trends in Neurosciences 32, no. 6 (June 2009).

307 Maryellen Walsh’s observation (“The history of schizophrenia is the history of blame”) occurs on page 154 of her book Schizophrenia: Straight Talk for Family and Friends (1985).

307 Frieda Fromm-Reichman introduced the concept of the “schizophrenogenic mother” in her paper “Notes on the development of treatment of schizophrenics by psychoanalytic psychotherapy,” Psychiatry 11, no. 3 (August 1948); this was followed by the proliferation of the term throughout the scientific literature, e.g., Loren R. Mosher, “Schizophrenogenic communication and family therapy,” Family Processes 8 (1969).

307 The source of the quotation characterizing the schizophrenic patient as an “unsuccessful mediator” between parents is Murray Bowen et al., “The role of the father in families with a schizophrenic patient,” American Journal of Psychiatry 115, no. 11 (May 1959).

307 See Gregory Bateson et al., “Toward a theory of schizophrenia,” Behavioral Science 1, no. 4 (1956).

307 Examples of parent-blaming in the literature of systems-oriented family therapy include Ruth Wilmanns Lidz and Theodore Lidz, “The family environment of schizophrenic patients,” American Journal of Psychiatry 106 (November 1949); Murray Bowen, Robert H. Dysinger, and Betty Basamania, “The role of the father in families with a schizophrenic patient,” American Journal of Psychiatry 115, no. 11 (May 1959); and Gregory Bateson et al., “Toward a theory of schizophrenia,” Behavioral Science 1, no. 4 (1956). For an extended critique of parent-blame theories, see John G. Howells and Waguih R. Guirguis, The Family and Schizophrenia (1985).

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