Lesch, KP; Bengel, D; Heils, A; et al.

The validity of the hospital anxiety and depression scale: An updated literature review

Bjelland, I; Dahl, AA; Haug, TT; et al.

Common polygenic variation contributes to risk of schizophrenia and bipolar disorder

Purcell, Shaun M; Wray, Naomi R; Stone, Jennifer L; et al.

Mechanisms and functional implications of adult neurogenesis

Zhao, Chunmei; Deng, Wei; Gage, Fred H

抑郁障礙的核心腦機(jī)制——基于fMRI元分析的證據(jù)

劉耀中，柳均哲，林碗君，何振宏，張丹丹，關(guān)青，羅躍嘉

雙相障礙的診療現(xiàn)狀及相關(guān)研究進(jìn)展

王勇，趙雅娟，符浩，吳彥

浙江省15歲及以上人群精神疾病流行病學(xué)調(diào)查

石其昌，章健民，徐方忠，等

心境障礙

·編者按·

世界衛(wèi)生組織將今年的世界衛(wèi)生日活動(dòng)主題定為“一起來聊聊抑郁癥”，國(guó)家衛(wèi)生計(jì)生委對(duì)近年來精神障礙的主要趨勢(shì)做了總結(jié)并指出：以抑郁癥為主的心境障礙和焦慮障礙患病率呈現(xiàn)持續(xù)上升的趨勢(shì)。

2017年4月，國(guó)家衛(wèi)生部公布了全國(guó)精神障礙流行病調(diào)查結(jié)果，調(diào)查數(shù)據(jù)得出我國(guó)心境障礙患病率為4.06%，按照中國(guó)人口13.8億計(jì)算，相當(dāng)于是5600萬人，而且4.06%這個(gè)數(shù)字是12個(gè)月的患病率，也就是說，只是統(tǒng)計(jì)在過去的12個(gè)月內(nèi)有沒有得過心境障礙疾病，如果計(jì)算終身患病率，這個(gè)數(shù)字會(huì)變成7.37%，也就是1億人。這次的調(diào)查并沒有涉及青少年和兒童，雖然沒有數(shù)據(jù)統(tǒng)計(jì)，但是很多精神科研究人員表示，在近五六年的時(shí)間內(nèi)，兒童和青少年抑郁癥的上升趨勢(shì)十分驚人。

心境障礙也稱情感性精神障礙，是指由各種原因引起的以顯著而持久的情感或心境改變?yōu)橹饕卣鞯囊唤M疾病。臨床上主要表現(xiàn)為情感高漲或低落，伴有相應(yīng)的認(rèn)知和行為改變和有幻覺妄想等精神病性癥狀。包括：抑郁癥、心境惡劣、抑郁障礙未特定、雙向I性障礙、雙向II型障礙、其他雙向障礙、物質(zhì)所致心境障礙、軀體疾病所致心境障礙8個(gè)二級(jí)分類，則抑郁癥是心境障礙中最為常見的類型，現(xiàn)患病率為2.10%。目前，在臨床上無法通過化驗(yàn)或儀器來檢測(cè)診斷患者是否有心境障礙類疾病，一些檢查也是為了排除其他疾病，如：甲狀腺功能減退、腦部腫瘤引發(fā)的激素異常也會(huì)讓人表現(xiàn)出抑郁的癥狀。出現(xiàn)的一些復(fù)雜的腦成像技術(shù)只用于研究領(lǐng)域，離真正的臨床還有一定距離。心境障礙治療方面，中重度以藥物治療為主，心理治療和其他治療為輔。

目前與心境障礙相關(guān)的疾病的醫(yī)療花費(fèi)高昂，給社會(huì)和家庭帶來沉重負(fù)擔(dān)和嚴(yán)重危害。心境障礙的發(fā)病和病情發(fā)展除遺傳和環(huán)境等因素外，可能存在更深層次的機(jī)制，目前的研究還遠(yuǎn)未闡明其具體機(jī)制，發(fā)現(xiàn)新的藥物治療靶點(diǎn)，開發(fā)更加有效、不良反應(yīng)更小的藥物，是人類對(duì)心境障礙的認(rèn)識(shí)翻開新的篇章具有重要作用。

本專題得到專家羅躍嘉教授（深圳大學(xué)腦疾病與認(rèn)知科學(xué)研究中心）、王勇教授（上海交通大學(xué)醫(yī)學(xué)院附屬精神衛(wèi)生中心）的大力支持。

·熱點(diǎn)數(shù)據(jù)排行·

截至2017年8月28日，中國(guó)知網(wǎng)（CNKI）和Web of Science（WoS）的數(shù)據(jù)報(bào)告顯示，以“心境障礙（mood disorder）”“情感性障礙（affective disorder）”“惡劣心境障礙（dysthymic disorder）”“雙相障礙（bipolar disorder）”“抑郁障礙（depression disorder）”為詞條可以檢索到的期刊文獻(xiàn)分別為34780條與154571條，本專題將相關(guān)數(shù)據(jù)按照：研究機(jī)構(gòu)發(fā)文數(shù)、作者發(fā)文數(shù)、期刊發(fā)文數(shù)、被引用頻次進(jìn)行排行，結(jié)果如下。

研究機(jī)構(gòu)發(fā)文數(shù)量排名（CNKI）

研究機(jī)構(gòu)發(fā)文數(shù)量排名（WoS）

作者發(fā)文數(shù)量排名（CNKI）

作者發(fā)文數(shù)量排名（WoS）

期刊發(fā)文數(shù)量排名（CNKI）

期刊發(fā)文數(shù)量排名（WoS）

根據(jù)中國(guó)知網(wǎng)（CNKI）數(shù)據(jù)報(bào)告，以“心境障礙（mood disorder）”“情感性障礙（affective disorder）”“惡劣心境障礙（dysthymic disorder）”“雙相障礙（bipolar disorder）”“抑郁障礙（depression disorder）”為詞條可以檢索到的高被引論文排行結(jié)果如下。

國(guó)內(nèi)數(shù)據(jù)庫高被引論文排行

國(guó)內(nèi)數(shù)據(jù)庫高被引論文排行（續(xù)表）

根據(jù)中國(guó)知網(wǎng)（CNKI）數(shù)據(jù)報(bào)告，以“心境障礙（mood disorder）”“情感性障礙（affective disorder）”“惡劣心境障礙（dysthymic disorder）”“雙相障礙（bipolar disorder）”“抑郁障礙（depression disorder）”為詞條可以檢索到的高被引論文排行結(jié)果如下。

國(guó)外數(shù)據(jù)庫高被引論文排行

·經(jīng)典文獻(xiàn)推薦·

基于Web of Science檢索結(jié)果，利用Histcite軟件選取LCS（Local Citation Score，本地引用次數(shù)）TOP50文獻(xiàn)作為節(jié)點(diǎn)進(jìn)行分析，得到本領(lǐng)域推薦的經(jīng)典文獻(xiàn)如下。

本領(lǐng)域經(jīng)典文獻(xiàn)

Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region

Lesch, KP; Bengel, D; Heils, A; et al.

The validity of the hospital anxiety and depression scale: An updated literature review

Bjelland, I; Dahl, AA; Haug, TT; et al.

來源出版物：Journal of Psychosomatic Research, 2002,52(2): 69-77

Common polygenic variation contributes to risk of schizophrenia and bipolar disorder

Purcell, Shaun M; Wray, Naomi R; Stone, Jennifer L; et al.

Abstract:Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations,delusions and cognitive deficits, with heritability estimated at up to 80%.We performed a genome-wide association study of 3322 European individuals with schizophrenia and 3587 controls.Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia.First, we implicate the major histocompatibility complex.Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect.We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

來源出版物：Nature, 2009, 460(7256): 748-752

Mechanisms and functional implications of adult neurogenesis

Zhao, Chunmei; Deng, Wei; Gage, Fred H

Abstract:The generation of new neurons is sustained throughout adulthood in the mammalian brain due to the proliferation and differentiation of adult neural stem cells.In this review, we discuss the factors that regulate proliferation and fate determination of adult neural stem cells and describe recent studies concerning the integration of newborn neurons into the existing neural circuitry.We further address the potential significance of adult neurogenesis in memory, depression, and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

Keywords:microcells; distributed antenna systems; handoff;high speed train; mobile communications; radio over fiber

來源出版物：Cell, 2008, 132(4): 654-660

·推薦綜述·

抑郁障礙的核心腦機(jī)制——基于fMRI元分析的證據(jù)

劉耀中，柳均哲，林碗君，何振宏，張丹丹，關(guān)青，羅躍嘉

抑郁癥又稱抑郁障礙，是情感障礙的主要類型之一其典型臨床癥狀包括心境低落、認(rèn)知功能損傷、思維遲緩、意志活動(dòng)減退等。普通人群中約13%～20%有過抑郁體驗(yàn)，6.1%～9.5%終身抑郁；多數(shù)病例有反復(fù)發(fā)作的傾向，70%～80%的患者存在多次復(fù)發(fā)，需要終身服藥。抑郁癥的病因復(fù)雜，受到生物、心理和環(huán)境等多因素的影響。近年隨著腦影像技術(shù)，特別是功能性磁共振（functional magnetic resonance imaging, fMRI）的發(fā)展，研究者對(duì)抑郁癥背后的神經(jīng)機(jī)制已經(jīng)有了很多了解。

腦結(jié)構(gòu)上，抑郁癥患者的邊緣系統(tǒng)，如杏仁核，海馬體積往往小于正常被試，其中病人杏仁核的體積大小與抑郁癥的首發(fā)年齡相關(guān)顯著，首發(fā)年齡越小，杏仁核體積越小，而海馬體積存在性別差異，男性患者的海馬體積萎縮表現(xiàn)得更加明顯。抑郁癥患者的前額葉各部分（背外側(cè)前額葉、腹內(nèi)側(cè)前額葉和前扣帶回皮層）也存在不同程度的萎縮，其中扣帶皮層體積大小與病人的愈后情況有關(guān)，擁有較大扣帶皮層的患者相對(duì)扣帶皮層較小的患者有更好的藥物治療結(jié)果。腦功能上，抑郁癥患者的三大功能網(wǎng)絡(luò)：認(rèn)知控制網(wǎng)絡(luò)（cognitive control network），默認(rèn)網(wǎng)絡(luò)（default mode network）和情感網(wǎng)絡(luò)（affective network）都有不同程度的損傷。認(rèn)知控制網(wǎng)絡(luò)主要包括額葉、頂葉皮層和前扣帶回皮層，負(fù)責(zé)自上而下的認(rèn)知加工，如注意、工作記憶，執(zhí)行功能如決策、運(yùn)動(dòng)檢測(cè)、沖突解決等。而默認(rèn)網(wǎng)絡(luò)主要包括腹內(nèi)側(cè)前額葉，負(fù)責(zé)自我參照加工，如評(píng)估內(nèi)外部線索，回憶過去和規(guī)劃未來。情感網(wǎng)絡(luò)，包括前扣帶皮層的前膝部和膝下部分，下丘腦，杏仁核，內(nèi)嗅皮質(zhì)和伏隔核等。其通過與其他腦區(qū)的廣泛連接，在恐懼、警覺、自主性神經(jīng)活動(dòng)中起重要作用，主要負(fù)責(zé)情緒加工。

雖然人們對(duì)抑郁障礙背后的神經(jīng)機(jī)制已有了很多了解，但越來越多的實(shí)驗(yàn)結(jié)果并沒有帶來聚斂性的證據(jù)。相反，更多的腦區(qū)被發(fā)現(xiàn)與抑郁障礙有關(guān)。例如，利用經(jīng)典的倫敦塔任務(wù)（Tower of London task），研究者發(fā)現(xiàn)高負(fù)荷下中等和重度抑郁癥患者的背外側(cè)前額葉表現(xiàn)為過度激活，而非激活減弱。一方面，這說明抑郁癥的確是多維度、多層次的情感障礙，其神經(jīng)機(jī)制無法由單一腦區(qū)的異常來解釋。但另一方面，當(dāng)前研究方法的局限性也值得考慮。單獨(dú)的腦成像研究往往效果量不足，如被試量不夠或有偏，容易得到假陽性結(jié)果，而不同課題組，獨(dú)立實(shí)驗(yàn)得到的一致結(jié)果則會(huì)相對(duì)穩(wěn)健，因此定量地綜合分析多個(gè)研究成果以獲得聚斂性實(shí)驗(yàn)證據(jù)即元分析（meta-analysis），顯得至關(guān)重要。本文基于元分析的結(jié)果，嘗試對(duì)目前尚不清楚的抑郁障礙的核心腦機(jī)制進(jìn)行探討。

當(dāng)前fMRI研究的元分析方法有3種，分別為ALE（activation likelihood estimate），MKDA（multilevel kernel density analysis）和Neurosynth。前兩者主要基于以往研究中激活區(qū)域一致性的程度，做出前向推論（forward inference），即辨別被試在進(jìn)行某一具體認(rèn)知過程中（如注意、記憶）一致激活的腦區(qū)；這兩種方法主要依靠研究者手動(dòng)挑選文獻(xiàn)，流程相對(duì)繁瑣，分析結(jié)果也可能存在選擇偏差。而Neurosynth是由Yarkoni等人基于自然語言處理（natural language processing, NLP）和機(jī)器學(xué)習(xí)開發(fā)的無偏的全自動(dòng)化分析技術(shù)，主要依靠python語言和多線程處理能力，能在短時(shí)間內(nèi)完成元分析流程。Neurosynth最重要的特點(diǎn)是可以根據(jù)現(xiàn)有的腦激活模式推斷相應(yīng)的心理認(rèn)知過程，即逆向推斷（reverse inference）。相對(duì)于前向推斷，逆向推斷可以提供更加關(guān)鍵和有價(jià)值的信息。前向推斷主要關(guān)注與某一特定認(rèn)知過程或情緒狀態(tài)相關(guān)的腦區(qū)。但值得注意的是并非所有相關(guān)腦區(qū)都特異于這個(gè)認(rèn)知過程，其反映的可能是更一般的加工過程。例如，前額葉在許多認(rèn)知過程中均被激活，但對(duì)特定認(rèn)知過程缺乏特異性。逆向推斷則彌補(bǔ)了這一缺陷，它能夠回答“逆向推斷”問題，即揭示抑郁癥患者哪些腦區(qū)的異常具有診斷意義。因此，本文使用Neurosynth方法以定位抑郁障礙的特異性腦區(qū)。

1 元分析方法

本文的文獻(xiàn)分析基于“Neurosynth”數(shù)據(jù)庫。截至2014年4月13日，該數(shù)據(jù)庫共有9721篇功能性磁共振成像（functional magnetic resonance imaging, fMRI）文獻(xiàn)。本元分析的起始時(shí)間為2014年12月9日，元分析所選取文獻(xiàn)的發(fā)表時(shí)間為1990年至2014年12月的相關(guān)文獻(xiàn)。具體而言：1）提取坐標(biāo)，通過NLP自動(dòng)提取數(shù)據(jù)庫中現(xiàn)存文獻(xiàn)的所有激活坐標(biāo)（全部轉(zhuǎn)化到標(biāo)準(zhǔn)（montreal neurological institute，MNI） 2 mm空間坐標(biāo)體系中）；2）離析全文，根據(jù)文中關(guān)鍵詞由使用者輸入，如“depression”或近義詞（如“depressive”“depressed”）的出現(xiàn)次數(shù)（至少出現(xiàn)20次）和占全文字?jǐn)?shù)的比例（至少大于0.1%，即至少平均1000字中就有一個(gè)關(guān)鍵詞出現(xiàn)）挑選出與關(guān)鍵詞直接相關(guān)的所有文獻(xiàn)；3）人工檢查（排除無關(guān)文獻(xiàn)11篇，其中沒有直接比較病人與正常人的文獻(xiàn)6篇；病人群體中不包含抑郁癥患者的文獻(xiàn)3篇；被試人數(shù)少于10人2篇），確保所挑選文獻(xiàn)確實(shí)與抑郁癥障礙相關(guān)；4）分類，根據(jù)關(guān)鍵詞，所有的激活坐標(biāo)分為兩類：與抑郁障礙有關(guān)和與抑郁障礙無關(guān)；5）元分析。前向推論：類似于ALE，映射出己有抑郁障礙研究中一致激活的區(qū)域P（activation|depression）。逆向推論：根據(jù)文獻(xiàn)分析，計(jì)算全腦每個(gè)voxel能推斷抑郁障礙的后驗(yàn)概率（P（activation|depression））。后驗(yàn)概率本質(zhì)是條件概率，在貝葉斯統(tǒng)計(jì)中，一個(gè)隨機(jī)事件或者一個(gè)不確定事件的后驗(yàn)概率是指在考慮和給出相關(guān)證據(jù)或數(shù)據(jù)后所得到的條件概率。因此，在這里，P（activation|depression）是指在考慮activation結(jié)果時(shí)，出現(xiàn)depression的概率，可以理解為當(dāng)出現(xiàn)了這種激活模式時(shí)，計(jì)算有多大概率其與抑郁癥有關(guān)；6）多重校正，標(biāo)準(zhǔn)為FDR（false discovery rate）校正P＜0.01，即平均而言有小于1%的voxel激活為假陽性；7）考慮到不同抑郁障礙的異質(zhì)性以及抑郁與焦慮的高并發(fā)性，依照上面方法也分別進(jìn)行了重度抑郁障礙（major depression disorder）（搜索關(guān)鍵詞為“major depression”）和焦慮障礙（anxiety disorder）（搜索關(guān)鍵詞為“anxiety”或者“anxious”）的元分析。最后確認(rèn)與抑郁障礙相關(guān)的fMRI研究有307篇，其中與重度抑郁障礙有關(guān)的研究為137篇；與焦慮障礙相關(guān)的研究有252篇。

Neurosynth的逆向推斷主要基于貝葉斯統(tǒng)計(jì)。貝葉斯流派認(rèn)為概率估計(jì)需要考慮之前的信息，并根據(jù)之前的信息改變更新概率估計(jì)。例如，假設(shè)有兩個(gè)事件A，B，那么事件A在另外一個(gè)事件B己經(jīng)發(fā)生條件下的發(fā)生概率即為條件概率或后驗(yàn)概率，可以表示為P（A|B），即“在B條件下A的概率”。其計(jì)算公式為：P（A|B）=P（B|A）*P（A）/P（B）。其中P（B）和P（A）為先驗(yàn)概率。具體到本文Neurosynth的逆向推斷中，首先通過自然語言處理離析文獻(xiàn)，已知不同腦區(qū)激活的分布，即P（activation），同時(shí)也知道了抑郁研究的在腦成像研究的分布，即P（depression），要求的是P（activation| depression），即當(dāng)出現(xiàn)了這種激活模式時(shí)，計(jì)算有多大概率其與抑郁癥有關(guān)。

2 元分析結(jié)果

3個(gè)元分析（抑郁障礙、重度抑郁障礙和焦慮障礙）結(jié)果中均涉及的腦區(qū)包括皮層下結(jié)構(gòu)—杏仁核（amygdala）、海馬（hippocampus）、尾狀核（caudate）；皮層結(jié)構(gòu)—梭狀回（fusiform face area，F(xiàn)FA）、前扣帶回（anterior cingulated cortex，ACC）、腹內(nèi)側(cè)前額葉（ventromedial prefrontal cortex，VMPFC）和背外側(cè)前額葉（dorsolateral prefrontal cortex，DLPFC）。針對(duì)這7個(gè)腦區(qū)，分別比較了前向推論和逆向推論的結(jié)果。

針對(duì)抑郁障礙，前向推論在杏仁核、海馬、尾狀核、扣帶前回、背外側(cè)前額葉和腹內(nèi)側(cè)前額葉發(fā)現(xiàn)了最一致的激活，與前人的元分析結(jié)果一致。而逆向推論表明只有杏仁核，背外側(cè)前額葉和腹內(nèi)側(cè)前額葉才特異于抑郁障礙。針對(duì)重度抑郁障礙，最主要的抑郁障礙亞型，本研究組也發(fā)現(xiàn)了類似結(jié)果：只有杏仁核，背外側(cè)前額葉和腹內(nèi)側(cè)前額葉特異于重度抑郁障礙。有趣的是，焦慮障礙的前向推論結(jié)果與抑郁和重度抑郁障礙結(jié)果相似，逆向推論也發(fā)現(xiàn)了杏仁核，腹內(nèi)側(cè)前額葉的特異性，但沒有背外側(cè)前額葉。綜上，與抑郁障礙直接相關(guān)的核心腦區(qū)為杏仁核、背外側(cè)和腹內(nèi)側(cè)前額葉，而相對(duì)于焦慮障礙，最特異于抑郁障礙的異常激活腦區(qū)為背外側(cè)前額葉。以下將重點(diǎn)討論在抑郁障礙中具有推斷價(jià)值的3個(gè)腦區(qū)，即杏仁核、背外側(cè)前額葉以及腹內(nèi)側(cè)前額葉。

3 討論

通過Neurosynth綜合分析了抑郁障礙、重度抑郁障礙和焦慮障礙的相關(guān)腦區(qū)，前向推斷和逆向推斷結(jié)果類似。抑郁障礙的逆向推斷明確的指向了3個(gè)核心腦區(qū)：杏仁核、背外側(cè)前額葉和腹內(nèi)側(cè)前額葉。抑郁癥患者的杏仁核反應(yīng)過激是目前公認(rèn)的結(jié)論。杏仁核是皮質(zhì)下情緒加工的核心腦區(qū)，與丘腦（thalamus）相連，主要參與刺激的顯著性檢測(cè)（salience detection），解析刺激的情緒意義。結(jié)構(gòu)上，相對(duì)于正常被試，抑郁癥患者的杏仁核體積較小，且其體積與抑郁癥的首發(fā)年齡顯著相關(guān)。功能上，相對(duì)于正常被試，抑郁癥患者的杏仁核在處理負(fù)性情緒時(shí)更加明顯的激活（能達(dá)到正常人的1.7倍），且反應(yīng)更加持久（持續(xù)時(shí)間為正常人的3倍）。抑郁癥患者的杏仁核反應(yīng)和負(fù)性情緒的強(qiáng)度成正比，例如，當(dāng)加工面孔的悲傷程度越來越高時(shí)，患者左側(cè)杏仁核的激活也越來越強(qiáng)。進(jìn)一步的研究發(fā)現(xiàn)，杏仁核的過激活是高度自動(dòng)化的，即在沒有意識(shí)到負(fù)性刺激存在時(shí)，閾下情緒加工也會(huì)過度激活抑郁癥患者的杏仁核，且反應(yīng)強(qiáng)度與患者的心理健康水平成反比。

但同時(shí)，元分析結(jié)果提示，杏仁核的異常激活模式并非是抑郁癥患者所獨(dú)有的，其他情感障礙如焦慮癥也會(huì)存在此種現(xiàn)象.本文的結(jié)果證明，杏仁核的功能異常也是焦慮障礙的核心腦機(jī)制之一研究發(fā)現(xiàn)相對(duì)于正常被試，焦慮癥患者處理情緒信息，特別是負(fù)性信息時(shí)其杏仁核也會(huì)過度激活，且激活強(qiáng)度與焦慮障礙的嚴(yán)重程度成正比。靜息狀態(tài)下焦慮患者的杏仁核與前額葉皮層如內(nèi)側(cè)前額葉的功能連接強(qiáng)度降低，其連接強(qiáng)度與患者焦慮程度成反比?？紤]到抑郁和焦慮的高并發(fā)現(xiàn)象，杏仁核異常激活可能是一般情感障礙的普遍神經(jīng)機(jī)制，如普遍對(duì)負(fù)性刺激敏感，對(duì)負(fù)性刺激的反應(yīng)過激等。

背外側(cè)前額葉與前運(yùn)動(dòng)皮層、眶額葉以及外側(cè)穎葉有豐富的雙向連接，該腦區(qū)主要負(fù)責(zé)執(zhí)行控制特別是抑制功能.研究發(fā)現(xiàn)靜息狀態(tài)下，相對(duì)于正常被試，抑郁癥患者的背外側(cè)前額葉活動(dòng)強(qiáng)度偏低，且與皮質(zhì)下的海馬和杏仁核的功能連接強(qiáng)度減弱任務(wù)狀態(tài)下，當(dāng)執(zhí)行stroop或n-back等需要執(zhí)行控制能力的任務(wù)時(shí)，抑郁癥患者為了達(dá)到與正常被試相同的行為成績(jī)需要付出更大的認(rèn)知努力，于是表現(xiàn)為更強(qiáng)的背外側(cè)前額葉的激活。而當(dāng)患者服用抗抑郁藥物（如百憂解）后，相對(duì)于服藥前，其背外側(cè)前額葉的激活顯著增強(qiáng)。這些結(jié)果表明，背外側(cè)前額葉的功能異?？赡苁菍?dǎo)致抑郁障礙的核心機(jī)制之一，但明確的因果關(guān)系還需借助fMRI以外的研究手段，如經(jīng)顱磁刺激（ranscranial magnetic stimulation,TMS）才能確定。本文基于文獻(xiàn)的逆向推斷表明，相對(duì)于其他心境障礙，如焦慮障礙，背外側(cè)前額葉的功能異常是特異于抑郁障礙的。腦損傷和干預(yù)方面的研究結(jié)果也支持這一結(jié)果，例如，雙側(cè)背外側(cè)前額葉損傷的病人更可能患抑郁癥，且患病程度更高，當(dāng)用TMS暫時(shí)興奮患者的背外側(cè)前額葉時(shí)，其抑郁癥狀顯著減輕。抑郁癥患者背外側(cè)前額葉的激活降低也常伴隨著杏仁核的過度激活，更進(jìn)一步的研究表明，背外側(cè)前額葉對(duì)杏仁核的激活具有抑制功能，這種抑制功能是個(gè)體自上而下情緒調(diào)節(jié)，控制注意和記憶的核心機(jī)制。Beck認(rèn)為，抑郁患者無法從負(fù)性刺激上轉(zhuǎn)移注意的缺陷正是其臨床癥狀上表現(xiàn)出過度反當(dāng)負(fù)性體驗(yàn)的主要原因。元分析結(jié)果也表明，最特異于抑郁障礙的異常腦區(qū)是背外側(cè)前額葉。因此相對(duì)于杏仁核的過度激活，抑郁患者對(duì)負(fù)性情緒的抑制能力下降可能才是最核心的問題。綜上，背外側(cè)前額葉對(duì)抑郁障礙具有臨床診斷和治療意義，該腦區(qū)功能異?？赡苁且钟粽系K的核心腦機(jī)制之一，針對(duì)背外側(cè)前額葉的治療可有效緩解抑郁癥狀。

另外，本文發(fā)現(xiàn)對(duì)抑郁癥同樣具有診斷意義的腦區(qū)還包括腹內(nèi)側(cè)前額葉的功能異常。腹內(nèi)側(cè)前額葉主要負(fù)責(zé)情緒整合和自我參照加工，其反向投射至下丘腦（hypothalamus），調(diào)節(jié)自動(dòng)化情緒加工；投射至腹側(cè)紋狀體（ventral striatum），調(diào)節(jié)獎(jiǎng)賞加工。另外，腹內(nèi)側(cè)前額葉還與杏仁核有豐富的雙向連接，參與威脅檢測(cè)和恐懼條件學(xué)習(xí)。靜息狀態(tài)下，抑郁癥患者腹內(nèi)側(cè)前額葉與丘腦的功能連接強(qiáng)度顯著高于正常被試，且與被試的主觀負(fù)性情感感受成正比。任務(wù)狀態(tài)下，當(dāng)執(zhí)行自我參照任務(wù)時(shí)（如判斷人格形容詞是否適合描述自己），抑郁癥患者腹內(nèi)側(cè)前額葉的激活相對(duì)于正常被試顯著減弱。抑郁癥患者的腹內(nèi)側(cè)前額葉異常主要與其過度的自我關(guān)注有關(guān)。當(dāng)腹內(nèi)側(cè)前額葉損傷時(shí)，病人的自我覺知能力也降低或喪失，對(duì)負(fù)性情感如羞愧、內(nèi)疚、尷尬和后悔（這些均屬于與自我相關(guān)的社會(huì)情緒）的感受顯著降低，同時(shí)抑郁癥狀也顯著改善。這一結(jié)果與尾核下神經(jīng)束切斷術(shù)（subcaudate tractotomy）結(jié)果非常吻合：切斷抑郁癥患者腹內(nèi)側(cè)前額葉后部與皮層下結(jié)構(gòu)相連的雙側(cè)白質(zhì)，顯著減緩了患者的抑郁癥狀，術(shù)后患者體驗(yàn)到欣快，對(duì)自我狀態(tài)漠不關(guān)心。但值得注意的是，與杏仁核的功能異常類似，腹內(nèi)側(cè)前額葉的過度激活模式也不完全特異于抑郁障礙。逆向推斷結(jié)果表明，腹內(nèi)側(cè)前額葉異常也能顯著推斷焦慮障礙。研究發(fā)現(xiàn)，與抑郁癥患者類似，相對(duì)于正常被試，焦慮癥患者的腹內(nèi)側(cè)前額葉在靜息狀態(tài)時(shí)反應(yīng)更強(qiáng)烈，與杏仁核的功能連接更弱，而在患者完成自我參照任務(wù)時(shí)激活減弱。臨床上，焦慮患者和其他情感障礙患者也同樣表現(xiàn)出對(duì)自我的過度關(guān)注和偏低的自我評(píng)價(jià)。因此，腹內(nèi)側(cè)前額葉的功能異常可能是情感障礙的共同表現(xiàn)。

雖然Neurosynth相對(duì)于傳統(tǒng)元分析方法有很大進(jìn)步，特別是能進(jìn)行逆向推斷。但是這種方法也不能完全避免元分析方法本身的不足。元分析的對(duì)象是己發(fā)表的文獻(xiàn)結(jié)果而不是原始數(shù)據(jù)，無法保證數(shù)據(jù)結(jié)果的有效性，更無法避免文章發(fā)表的偏倚性，如陰性結(jié)果難以發(fā)表，領(lǐng)域冷熱影響接收難度等。另外，Neurosynth只能分析其數(shù)據(jù)庫收集的文獻(xiàn)，但該數(shù)據(jù)庫只包含了主流神經(jīng)科學(xué)雜志（主要是英文為主的期刊），可能會(huì)忽視潛在的國(guó)別間差異。因此，本文的結(jié)論還需進(jìn)一步實(shí)證研究的支持。還有，本次元分析沒有考慮不同年齡發(fā)展階段的特性，抑郁癥在不同年齡段發(fā)病機(jī)制存在不同。盡管如此，仍可以看到本文基于抑郁障礙fMRI元分析的逆向推斷結(jié)果與前人的fMRI研究、腦損傷研究、干預(yù)研究結(jié)果都非常吻合，對(duì)未來抑郁癥腦機(jī)制的研究有一定指導(dǎo)意義。

綜上所述，抑郁障礙核心的腦機(jī)制為杏仁核、背外側(cè)前額葉和腹內(nèi)側(cè)前額葉的異常。杏仁核的過度激活體現(xiàn)了過敏化的情緒加工，而背外側(cè)前額葉的激活減弱則體現(xiàn)了抑郁患者自上而下的抑制功能障礙。另外，過度激活的腹內(nèi)側(cè)前額葉是抑郁患者過度自我關(guān)注的神經(jīng)機(jī)制。值得注意的是，杏仁核和腹內(nèi)側(cè)前額葉的過度激活也是焦慮障礙的核心機(jī)制，逆向推斷表明這兩個(gè)腦區(qū)均能推斷焦慮障礙和抑郁障礙。因此本文的結(jié)果提示，相對(duì)于焦慮障礙，最特異于抑郁障礙的神經(jīng)機(jī)制是背外側(cè)前額葉的功能異常，這表明無法抑制過敏化的情緒加工是抑郁障礙的核心機(jī)制，也是導(dǎo)致患者過度反當(dāng)負(fù)性情感的原因。本研究的主要貢獻(xiàn)是通過對(duì)3種抑郁分型分別進(jìn)行前向和逆向推斷的統(tǒng)計(jì)分析，最終確定了最特異于抑郁癥患者的一致性的腦機(jī)制損傷，即背外側(cè)前額葉。

這對(duì)當(dāng)前研究有重大的啟發(fā)和指導(dǎo)意義，特別是當(dāng)前研究中過分關(guān)注抑郁癥患者杏仁核或獎(jiǎng)賞系統(tǒng)缺陷，而一定程度上忽略了對(duì)抑郁癥患者記憶和情緒抑制腦機(jī)制的研究。?

【作者單位：暨南大學(xué)管理學(xué)院；北京師范大學(xué)認(rèn)知神經(jīng)科學(xué)與學(xué)習(xí)國(guó)家重點(diǎn)實(shí)驗(yàn)室；深圳大學(xué)情緒與社會(huì)認(rèn)知科學(xué)研究所；深圳大學(xué)醫(yī)學(xué)部；成都醫(yī)學(xué)院四川養(yǎng)老與老年健康協(xié)同創(chuàng)新中心】

（摘自《中國(guó)科學(xué)：生命科學(xué)》2015年第12期）

雙相障礙的診療現(xiàn)狀及相關(guān)研究進(jìn)展

王勇，趙雅娟，符浩，吳彥

雙相障礙是一種嚴(yán)重精神疾病，具有高患病率、高復(fù)發(fā)率、高致殘率、高死亡率、高共病率和低齡化的特點(diǎn)。目前，臨床上對(duì)雙相障礙的認(rèn)識(shí)還不一致，其流行病學(xué)數(shù)據(jù)也有較大差異。隨著“雙相譜系障礙”的概念日益獲得精神科醫(yī)師的認(rèn)可，除傳統(tǒng)意義上的I型和II型雙相障礙外，有學(xué)者提出了“軟雙相障礙”和“閾下雙相障礙”的概念，甚至情緒不穩(wěn)或煩躁等亦被歸入了雙相譜系障礙。從雙相障礙所致疾病負(fù)擔(dān)來看，在世界衛(wèi)生組織1993年報(bào)告的傷殘調(diào)整生命年（disability adjusted life years，DALY）減少最多的前10種疾病中，精神疾病占5種，雙相障礙列第3位；中國(guó)數(shù)據(jù)顯示，在DALY減少1%的前25種疾病中，雙相障礙列第13位。因此，雙相障礙的臨床診療研究函待重視與加強(qiáng)。

1 診療現(xiàn)狀

1.1 識(shí)別率低

雙相障礙的識(shí)別率低。歐美國(guó)家的資料顯示，患者自首次出現(xiàn)肯定的雙相障礙臨床癥狀后，平均要經(jīng)8年才能得到確診；在現(xiàn)癥雙相障礙患者中，69%曾被誤診為單相抑郁、焦慮障礙、精神分裂癥、人格障礙和物質(zhì)依賴/濫用等。

1.2 治療率低

美國(guó)1994年的調(diào)查顯示，雙相障礙患者發(fā)病后平均要經(jīng)10年才能得到首次治療，50%以上的現(xiàn)癥患者在長(zhǎng)達(dá)5年以上的時(shí)期內(nèi)未接受過治療，其中36%甚至在長(zhǎng)達(dá)10年以上的時(shí)期內(nèi)未接受過治療。

1.3 治療不規(guī)范

臨床醫(yī)師治療雙相障礙時(shí)“亂拳迭出”，難言規(guī)范。對(duì)雙相抑郁的治療方法包括藥物治療（心境穩(wěn)定劑、抗精神病藥物、抗抑郁藥物）、改良的電休克治療（modified electroconvulsive therapy，MECT）和心理健康教育等。面對(duì)多樣治療選擇，臨床醫(yī)師往往表現(xiàn)為無所適從，導(dǎo)致多種治療方法聯(lián)合應(yīng)用的不合理和治療方法的頻繁更替，影響患者的預(yù)后。一項(xiàng)對(duì)歐洲精神科醫(yī)師的調(diào)查顯示，超過60%的雙相障礙患者在病情穩(wěn)定前至少經(jīng)歷了2次治療方法變更，平均治療方法變更次數(shù)為2.4次。

1.4 療效不令人滿意

雙相障礙急性期的治療療效仍然不能令人滿意，尤其是雙相抑郁的治療，患者的各種殘留癥狀和社會(huì)功能損害往往較單相抑郁更常見，抗抑郁藥物的不當(dāng)使用也非常普遍。由于多種藥物的聯(lián)用和更替，導(dǎo)致藥物不良反應(yīng)問題更為突出，患者的治療依從性亦差。而雙相障礙的臨床特征決定了對(duì)其維持治療和預(yù)防復(fù)發(fā)同等重要，但此卻未引起臨床醫(yī)師的足夠重視，全病程管理措施的缺失往往導(dǎo)致患者病情多次反復(fù)、頻繁發(fā)作，嚴(yán)重影響患者的社會(huì)功能。此外，雙相障礙在特殊人群（如兒童、老年人、孕產(chǎn)婦、絕經(jīng)期婦女、同時(shí)患有軀體或其他精神疾病患者）中的臨床癥狀常不典型，影響因素也更復(fù)雜，臨床識(shí)別和治療的難度都趨增加，需要強(qiáng)調(diào)個(gè)體化治療的重要性。

2 原因分析

2.1 疾病自身特點(diǎn)

雙相障礙的臨床表現(xiàn)復(fù)雜、癥狀多種多樣，既有各種情感癥狀，又有精神病性癥狀、軀體癥狀、認(rèn)知癥狀等，且往往與多種疾病同時(shí)存在，因此臨床識(shí)別和治療的難度較高。從縱向病程來看，雙相障礙呈現(xiàn)躁狂、輕躁狂、抑郁、輕抑郁、混合狀態(tài)、正常情緒等多種極性的無規(guī)律交替起伏變化，尤其是輕躁狂、輕抑郁與正常情緒之間很難區(qū)分，導(dǎo)致臨床識(shí)別困難。然而，無論是躁狂發(fā)作、還是抑郁發(fā)作，都無法改變雙相障礙的“永不穩(wěn)定”和“反復(fù)搖擺”的疾病性質(zhì)。

2.2 醫(yī)療相關(guān)因素

由于雙相障礙的復(fù)雜性、相關(guān)研究發(fā)現(xiàn)及概念處于動(dòng)態(tài)變化中和臨床醫(yī)師專業(yè)背景及經(jīng)驗(yàn)的差異，綜合醫(yī)院和基層醫(yī)院的臨床醫(yī)師對(duì)雙相障礙的基礎(chǔ)知識(shí)、尤其是最新進(jìn)展的了解不足。即使在?？漆t(yī)院，不同亞?？坪筒煌Y歷背景的臨床醫(yī)師對(duì)雙相障礙的認(rèn)識(shí)也有很大差異。此外，由于對(duì)雙相障礙危害的認(rèn)識(shí)不足、缺乏相關(guān)專業(yè)培訓(xùn)和受到時(shí)間緊、工作量大等客觀因素的制約，雙相障礙早期識(shí)別和規(guī)范化治療的重要性往往被臨床醫(yī)師忽視。醫(yī)療機(jī)構(gòu)對(duì)雙相障礙等精神疾病知識(shí)的宣傳及普及也不夠。

2.3 患者相關(guān)因素

目前，精神衛(wèi)生醫(yī)療資源的分布不均衡，主要集中于三級(jí)精神疾病?？漆t(yī)院和綜合醫(yī)院的精神或心身科，這些醫(yī)院的臨床醫(yī)師或有雙相障礙早期識(shí)別和規(guī)范化治療的能力，但其他醫(yī)院臨床醫(yī)師的專業(yè)水平不足。同時(shí)，客觀條件也使得精神衛(wèi)生服務(wù)的可及性受到限制。對(duì)上海地區(qū)社區(qū)居民精神衛(wèi)生知識(shí)知曉率和服務(wù)需求狀況的調(diào)查結(jié)果顯示，盡管逾70%的居民認(rèn)為精神衛(wèi)生知識(shí)很重要，但近90%的居民對(duì)精神衛(wèi)生信息來源渠道的便利性表示不滿意。由于時(shí)間、地域、交通、經(jīng)濟(jì)狀況等客觀條件的制約，患者對(duì)精神衛(wèi)生服務(wù)的需求往往得不到滿足。而且，患者對(duì)雙相障礙的認(rèn)識(shí)往往不足，多在抑郁發(fā)作時(shí)才可能主動(dòng)求醫(yī)，嚴(yán)重躁狂發(fā)作時(shí)往往就需家屬強(qiáng)制送醫(yī)，而輕躁狂發(fā)作時(shí)又往往不認(rèn)為自己有病。此外，病恥感、癥狀不典型（尤是雙相抑郁時(shí)）、個(gè)體就醫(yī)偏好（首診于綜合醫(yī)院或基層醫(yī)院）等因素也阻礙了雙相障礙的早期識(shí)別和規(guī)范化治療。

3 相關(guān)研究進(jìn)展

3.1 識(shí)別與評(píng)估

雙相障礙是一種慢性致殘性疾病，《中國(guó)雙相障礙防治指南（第二版）》強(qiáng)調(diào)了充分評(píng)估、量化監(jiān)測(cè)和全病程治療原則，建議臨床上采用“基于評(píng)估的治療（measurement-based care，MBC）”策略。MBC的實(shí)施流程應(yīng)當(dāng)包括篩查、初始治療、監(jiān)測(cè)疾病進(jìn)展并調(diào)整治療方案、長(zhǎng)期監(jiān)測(cè)及維持治療4個(gè)步驟。MBC應(yīng)當(dāng)體現(xiàn)在雙相障礙全病程的管理中，其中對(duì)疾病的量化評(píng)估是MBC實(shí)施的基礎(chǔ)。目前，一些雙相障礙的篩查量表已在臨床上得到廣泛使用，包括《犯項(xiàng)輕躁狂癥狀清單》《心境障礙問卷》《雙相抑郁指數(shù)量表》《雙相譜系診斷量表》《雙極性指數(shù)》和簡(jiǎn)版《氣質(zhì)評(píng)定量表》等。有助于提高雙相障礙的識(shí)別率與正確診斷率。

但是，服務(wù)對(duì)象多、成本高、流程繁瑣、對(duì)臨床醫(yī)師要求高等因素在很大程度上制約了MBC在臨床上的推廣實(shí)施。近年來“移動(dòng)健康（mobile health）”發(fā)展迅速，其整合了即時(shí)通訊、互聯(lián)網(wǎng)和移動(dòng)傳感3項(xiàng)關(guān)鍵技術(shù)，可即時(shí)提供各種服務(wù)和信息資源，尤其適用于醫(yī)療資源不足的地區(qū)。隨著新媒體技術(shù)的快速發(fā)展，電子化精神衛(wèi)生服務(wù)成為對(duì)公眾健康教育的主要形式之一。上海市精神衛(wèi)生中心于2014年發(fā)布、上線了手機(jī)應(yīng)用軟件“心情溫度計(jì)”，可篩查焦慮、抑郁情緒以及早期識(shí)別雙相障礙，幫助心境障礙高危人群或患者自我監(jiān)測(cè)情緒變化并提供醫(yī)學(xué)指導(dǎo)或建議，宣傳、普及心境障礙疾病知識(shí)，對(duì)提高公眾對(duì)情緒問題和雙相障礙的認(rèn)識(shí)、規(guī)范臨床診療行為將起到良好的促進(jìn)作用。

3.2 診斷與治療

有關(guān)雙相障礙的診療問題一直備受關(guān)注。自2007年中國(guó)《雙相障礙防治指南（第一版）》發(fā)布以來，雙相障礙的臨床診斷和治療水平有了一定的改善，但與國(guó)際水準(zhǔn)和現(xiàn)實(shí)需求還有相當(dāng)?shù)牟罹唷?010年9月—2011年2月，中華醫(yī)學(xué)會(huì)精神病學(xué)分會(huì)發(fā)起、組織了一項(xiàng)“中國(guó)雙相障礙患者診斷評(píng)估服務(wù)”調(diào)查，對(duì)在全國(guó)13家精神衛(wèi)生機(jī)構(gòu)（6家綜合醫(yī)院的精神/心身科和7家精神疾病?？漆t(yī)院）中的1487例被診斷為抑郁癥并正按抑郁癥治療的住院或門診成年患者重新應(yīng)用《簡(jiǎn)明國(guó)際神經(jīng)精神訪談》予以診斷，結(jié)果發(fā)現(xiàn)雙相障礙總體及I，II型雙相障礙被誤診為抑郁癥的比例分別為20.8%，7.9%，12.8%。美國(guó)精神醫(yī)學(xué)學(xué)會(huì)出版的《精神障礙診斷與統(tǒng)計(jì)手冊(cè)（第五版）》中除將雙相障礙與精神分裂癥、抑郁癥等并列為大類疾病外，還有以下4個(gè)方面的變化：1）納入了物質(zhì)/藥物（包括抗抑郁藥物）及其他醫(yī)學(xué)狀況引起的雙相及相關(guān)障礙，而不再作為排除標(biāo)準(zhǔn)；2）將活動(dòng)增加或精力旺盛與心境高漲、易激惹并列為A類核心癥狀；3）明確了“其他特定的雙相及相關(guān)障礙”的含義，包括有抑郁發(fā)作史的短暫輕躁狂發(fā)作（2～3 d）、有抑郁發(fā)作史的不充分輕躁狂發(fā)作癥狀、無抑郁發(fā)作史的輕躁狂發(fā)作和短暫環(huán)性心境（＜24個(gè)月）；4）以“伴混合特征”的標(biāo)注替代混合發(fā)作，并增加了“伴焦慮困擾特征”等標(biāo)注。隨著腦科學(xué)的發(fā)展，今后雙相障礙的分類診斷會(huì)更趨向于病因?qū)W診斷，會(huì)更細(xì)化和精確，與精神分裂癥和抑郁癥等疾病的界線會(huì)更明晰、鑒別更科學(xué)化，由此治療也會(huì)相應(yīng)地更精準(zhǔn)。

盡管國(guó)內(nèi)外發(fā)布的基于循證醫(yī)學(xué)證據(jù)的雙相障礙治療指南數(shù)不少，但臨床實(shí)踐與治療指南推薦的不一致現(xiàn)象仍很普遍?？傮w上看，臨床醫(yī)師治療雙相抑郁時(shí)與治療指南推薦的符合率明顯低于治療躁狂發(fā)作時(shí)，治療疾病嚴(yán)重程度較輕者時(shí)與治療指南推薦的符合率也較低。中國(guó)雙相障礙協(xié)作組開展的“中國(guó)雙相躁狂路徑調(diào)查”結(jié)果顯示，在3906例雙相障礙患者中，11.1%的輕躁狂、躁狂或混合發(fā)作患者的藥物治療與加拿大的雙相障礙治療指南推薦不符，而雙相抑郁患者藥物治療的不符率更高達(dá)50.2%，雙相障礙維持期藥物治療的不符率也達(dá)35.6%。2015年8月，《中國(guó)雙相障礙防治指南（第二版）》正式問世，其更新內(nèi)容參考了國(guó)際上最新的雙相障礙治療指南并結(jié)合了我國(guó)的實(shí)際情況及最新研究成果。

3.3 病因與發(fā)病機(jī)制

雙相障礙的病因不明。自從全球“腦計(jì)劃”研究啟動(dòng)以來，神經(jīng)科學(xué)工作者對(duì)雙相障礙、孤獨(dú)癥（自閉癥）等被認(rèn)為是最具生物學(xué)基礎(chǔ)的精神疾病開展了全方位、多層面的病因?qū)W與發(fā)病機(jī)制探索。研究表明，遺傳和環(huán)境因素對(duì)雙相障礙發(fā)病均有重要影響。

但是，雙相障礙的遺傳方式尚不明晰，普遍認(rèn)為是一種復(fù)雜的多基因遺傳病。近年來，國(guó)內(nèi)學(xué)者積極開展雙相障礙的遺傳學(xué)機(jī)制探索，多聚焦于神經(jīng)營(yíng)養(yǎng)失衡假說和神經(jīng)遞質(zhì)紊亂假說。相關(guān)研究結(jié)果顯示：1）雙相障礙的易患性和臨床特征與miRNA 206基因的多態(tài)性及表達(dá)水平無關(guān)；2）雙相障礙的易患性和治療療效與腦源性神經(jīng)營(yíng)養(yǎng)因子（brain-derived neurotrophic factor，BDNF），基因的多態(tài)性rs6265相關(guān)，但與BDNF血漿濃度的相關(guān)性不明顯；3）雙相障礙的易患性與神經(jīng)營(yíng)養(yǎng)性酪氨酸激酶受體-2（neurotrophic tyrosine kinase receptor type 2，NTRK2）基因的多態(tài)性rs1387923相關(guān)，I型雙相障礙的治療療效與NTRK2基因的多態(tài)性s2769605相關(guān)；4）miRNA 206與BDNF/NTRK2基因的多態(tài)性及外周表達(dá)無關(guān)。

隨著神經(jīng)影像學(xué)從結(jié)構(gòu)影像學(xué)向功能影像學(xué)發(fā)展，我們對(duì)精神疾病的認(rèn)識(shí)不再僅限于神經(jīng)結(jié)構(gòu)方面的顯著異常，而可更多地關(guān)注各個(gè)腦區(qū)和神經(jīng)環(huán)路中的更為細(xì)微的功能異常。近期，雙相障礙的神經(jīng)影像學(xué)研究主要聚焦于雙相抑郁和單相抑郁、雙相躁狂和雙相抑郁、雙相障礙和精神分裂癥之間在各個(gè)與情緒和認(rèn)知相關(guān)的腦區(qū)以及不同腦區(qū)之間連接的異同點(diǎn)。

此外，人們?cè)诶^續(xù)研究神經(jīng)遞質(zhì)（如5-輕色胺、去甲腎上腺素、多巴胺等）系統(tǒng)和神經(jīng)內(nèi)分泌系統(tǒng)（如下丘腦-垂體-腎上腺軸、下丘腦-垂體-甲狀腺軸等）與雙相障礙發(fā)病間的關(guān)聯(lián)。近年來，神經(jīng)內(nèi)分泌系統(tǒng)以及與此相關(guān)的神經(jīng)免疫學(xué)標(biāo)志物（如炎性細(xì)胞因子α-腫瘤壞死因子、白介素類物質(zhì)等）與雙相障礙的關(guān)系成為新的研究熱點(diǎn)。

4 小結(jié)

綜上所述，雙相障礙發(fā)病的生物學(xué)機(jī)制非常復(fù)雜，是生物學(xué)因素和環(huán)境因素交互作用的結(jié)果。隨著研究的技術(shù)手段的不斷發(fā)展以及對(duì)雙相障礙臨床現(xiàn)象學(xué)的深入研究，人們正在逐漸歸納并整理出一些相對(duì)集中的線索，這些線索的相互借鑒及驗(yàn)證可能有助于我們不斷接近雙相障礙發(fā)病的真諦，而此對(duì)臨床上更規(guī)范化、個(gè)體化地治療雙相障礙也具有重要的指導(dǎo)意義。雙相障礙治療指南往往是基于最新的研究成果和專家建議制定出來的，因此也是現(xiàn)階段最有借鑒價(jià)值的雙相障礙診療工具，值得更好地推廣應(yīng)用。?

【作者單位：上海交通大學(xué)醫(yī)學(xué)院附屬精神衛(wèi)生中心】

（摘自《上海醫(yī)藥》2017年第7期）

·高被引論文摘要·

被引頻次：356

浙江省15歲及以上人群精神疾病流行病學(xué)調(diào)查

石其昌，章健民，徐方忠，等

目的：了解浙江省15歲以上人群各類精神疾病的時(shí)點(diǎn)患病率和分布特點(diǎn)，為制定全省精神衛(wèi)生規(guī)劃提供科學(xué)依據(jù)。方法：2001年9至12月采用多階段分層整群抽樣方法隨機(jī)抽取14個(gè)縣（市）、70個(gè)鄉(xiāng)鎮(zhèn)（街道）、140個(gè)村（居委會(huì)）中15000名≥15歲的人為調(diào)查對(duì)象，由精神科護(hù)士用擴(kuò)展的一般健康問卷（GHQ12）將調(diào)查對(duì)象分為患精神疾病高、中、低危險(xiǎn)組，然后由精神科醫(yī)生以美國(guó)精神障礙診斷標(biāo)準(zhǔn)（DSMIV）依次對(duì)100%、40%、10%的調(diào)查對(duì)象進(jìn)行定式檢查（SCID），對(duì)各類精神障礙進(jìn)行診斷。結(jié)果14639人完成篩選，4788人完成診斷。調(diào)整后精神疾病總時(shí)點(diǎn)患病率為17.3%（95%CI為16.0%～18.7%），除外各類未特定障礙后，總時(shí)點(diǎn)患病率下降至13.4%（12.2%～14.7%）。最常見的疾病為心境障礙（8.6%，7.9%～9.5%）、焦慮障礙（4.3%，3.6%～5.1%）和物質(zhì)使用障礙（3.0%，2.4%～3.8%）。最常見的特定精神疾病為重性抑郁障礙（4.3%，3.7%～4.9%）、酒精使用障礙（2.9%，2.3%～3.7%）、心境惡劣障礙（1.6%，1.3%～1.9%）和特殊恐怖癥（1.2%，0.8%～1.8%）?？偦疾÷兽r(nóng)村高于城市（RR=1.23，95%CI為1.11～1.37），女性略高于男性（RR=1.11，1.00～1.22）。結(jié)論：精神障礙是嚴(yán)重影響浙江省社會(huì)經(jīng)濟(jì)發(fā)展的、迫切需要解決的公共衛(wèi)生問題，有必要在全省范圍內(nèi)開展和實(shí)施全面性的精神衛(wèi)生規(guī)劃并定期評(píng)估其效果。

精神障礙；流行病學(xué)研究

來源出版物：中華預(yù)防醫(yī)學(xué)雜志, 2005, 39(7): 229-236

被引頻次：218

產(chǎn)后抑郁癥發(fā)病因素的探討

張榮蓮，陳起燕，李艷華，等

摘要：目的：探討產(chǎn)后抑郁癥的發(fā)生率及其影響因素。方法：隨機(jī)抽取在本院產(chǎn)前門診初診并決定在本院分娩的1052例孕婦進(jìn)行醫(yī)院焦慮及抑郁情緒自評(píng)量表調(diào)查，其中以艾迪產(chǎn)后抑郁量表（EPDS）跟蹤調(diào)查至產(chǎn)后7 d內(nèi)共866例。結(jié)果：EPDS陽性率為15.01%（130/866，并用單因素和多元逐步回歸分析了產(chǎn)后抑郁癥的影響因素，發(fā)現(xiàn)孕婦健康狀況、孕期夫妻關(guān)系、分娩時(shí)醫(yī)務(wù)人員的態(tài)度、丈夫企盼生男孩的程度及孕婦孕期聽課次數(shù)、孕期焦慮情緒及抑郁情緒等7個(gè)因素與產(chǎn)后抑郁癥發(fā)生的關(guān)系最密切，其中孕期聽課次數(shù)與產(chǎn)后抑郁癥的發(fā)生呈負(fù)相關(guān)，余6項(xiàng)均與產(chǎn)后抑郁癥呈正相關(guān)。結(jié)論：孕期焦慮和抑郁情緒是發(fā)生產(chǎn)后抑郁癥的最主要因素。

關(guān)鍵詞：抑郁癥；產(chǎn)后；病因?qū)W

來源出版物：中華婦產(chǎn)科雜志, 1999, 34(4): 231-233

被引頻次：163

成年人心理幸福感的年齡差異研究

許淑蓮，吳志平，吳振云，等

摘要：目的：了解成年人心理幸福感的年齡差異和有關(guān)因素。方法：采用Ruff的心理幸福感量表對(duì)777名20～94歲的人進(jìn)行測(cè)查。結(jié)果：1）量表的信度合格，與抑郁癥患者反映的差異顯著。2）6個(gè)分量表除自主性無明顯年齡差異外，個(gè)人成長(zhǎng)較年青組均高于較年長(zhǎng)組；與他人積極關(guān)系及生活目的較年青三組均高于老老年組；環(huán)境掌握中年組與老年組高于老老年組；自我接受老年組顯著高于青年組。3）自主性、個(gè)人成長(zhǎng)、生活目的和自我接受分均男性顯著高于女性，與他人的積極關(guān)系分女性稍高于男性。4）影響心理幸福感的因素，青年組以工作學(xué)習(xí)、教育程度、疾病和心境，中年組以工作學(xué)習(xí)量、婚姻狀態(tài)以及人際交往，老年組以心境、健康情況，老老年組則以心境、人際交往、疾病情況、教育程度、家庭關(guān)系等因素為主；5）與美國(guó)比較，個(gè)人成長(zhǎng)結(jié)果基本一致；中國(guó)人生活目的、自我接受評(píng)價(jià)較低，可能受我國(guó)傳統(tǒng)的中庸之道影響。結(jié)論：心理幸福感受年齡影響，量表從積極心理功能角度考慮是合理的，但對(duì)除婚姻外的家庭關(guān)系涉及過少。

關(guān)鍵詞：健康心理學(xué)；心理幸福感；年齡差異；斷面調(diào)查；成人；中國(guó)人；美國(guó)人

來源出版物：中國(guó)心理衛(wèi)生雜志, 2003, 17(3): 167-171

被引頻次：156

心境障礙的神經(jīng)生物學(xué)研究進(jìn)展

張萍，王雪琦

摘要：近年的研究發(fā)現(xiàn)，心境障礙患者在腦、神經(jīng)細(xì)胞和信號(hào)分子水平都存在異常。邊緣-丘腦-皮質(zhì)環(huán)路和邊緣-皮質(zhì)-紋狀體-蒼白球-丘腦環(huán)路參與了心境障礙行為的發(fā)生，這些部位的糖代謝和腦血流量、皮質(zhì)容量、神經(jīng)元和膠質(zhì)細(xì)胞的數(shù)量和形態(tài)均發(fā)生改變，同時(shí)心境障礙患者腦內(nèi)磷酸肌醇環(huán)路、Wnt信號(hào)通路和神經(jīng)營(yíng)養(yǎng)因子下游信號(hào)轉(zhuǎn)導(dǎo)通路也有相應(yīng)變化。

關(guān)鍵詞：心境障礙；邊緣-丘腦-皮質(zhì)環(huán)路；邊緣-皮質(zhì)-紋狀體-蒼白球-丘腦環(huán)路；神經(jīng)元；膠質(zhì)細(xì)胞；信號(hào)轉(zhuǎn)導(dǎo)

來源出版物：中國(guó)神經(jīng)科學(xué)雜志, 2004, 20(1): 89-92

被引頻次：154

論肝郁與抑郁癥

楊林

摘要：認(rèn)為抑郁癥系情志致病，結(jié)合現(xiàn)代醫(yī)學(xué)和祖國(guó)醫(yī)學(xué)的病理生理理論論述其原發(fā)在肝，兼及脾腎，初期多實(shí)，久病兼虛?；静C(jī)為肝氣郁結(jié)，貫穿疾病始終。提出從肝郁辨證分型，調(diào)肝為主，兼顧他臟，結(jié)合辨病用藥，身心并治的治療模式。

關(guān)鍵詞：憂郁病/中醫(yī)藥療法；辨證論治；中醫(yī)學(xué)術(shù)發(fā)掘

來源出版物：陜西中醫(yī), 2000, 21(6): 260-261

被引頻次：147

綜合性醫(yī)院門診病人抑郁障礙的研究

肖澤萍，嚴(yán)和駿，肖世富，等

摘要：研究綜合性醫(yī)院門診病人抑郁障礙的患病率、識(shí)別和診治狀況。方法以兩步篩選法，對(duì)15個(gè)國(guó)家或地區(qū)共26969例門診病人進(jìn)行了GHD-12，GHQ-28、復(fù)合式國(guó)際診斷檢查（CI-DI）、內(nèi)科醫(yī)生檢查表等測(cè)定。在上海市共有583例完成以上量表測(cè)定，男、女比例分別為38.0%和62.0%。結(jié)果在檢查出的所有心理問題中，抑郁障礙患病率居首位；總樣本抑郁癥和心境惡劣的患病率分別為10.4%和2.1%。上海市則分別為4.0%和0.6%；上海市內(nèi)科醫(yī)生對(duì)抑郁障礙的識(shí)別率為21%，遠(yuǎn)低于15個(gè)國(guó)家資料的中位數(shù)55.6%；內(nèi)科醫(yī)生對(duì)抑郁障礙的治療不充分，在上海市內(nèi)科醫(yī)生未給予檢出病人任何抗抑郁劑治療。結(jié)論在綜合性醫(yī)院的內(nèi)科病人中，抑郁障礙是最常見的心理障礙。但抑郁障礙多未被內(nèi)科醫(yī)師檢出且治療不充分。內(nèi)科醫(yī)生的精神醫(yī)學(xué)知識(shí)再教育應(yīng)受到全社會(huì)的重視。

關(guān)鍵詞：抑郁障礙；門診病人

來源出版物：中華醫(yī)學(xué)雜志, 1999, 79(5): 329-331

被引頻次：129

河北省精神障礙的現(xiàn)況調(diào)查

栗克清，崔澤，崔利，等

摘要：目的：了解河北省≥18歲人群各類精神障礙的患病率和分布特點(diǎn)。方法：2004年10月至2005年3月采用多階段分層整群抽樣方法隨機(jī)抽取≥18歲人群，共24000名，以美國(guó)精神障礙診斷與統(tǒng)計(jì)手冊(cè)第4版（DSM-Ⅳ）軸Ⅰ障礙定式臨床檢查患者版進(jìn)行調(diào)查，用DSM-Ⅳ對(duì)各類精神障礙進(jìn)行診斷。結(jié)果：（1）患病率：20716人完成調(diào)查，精神障礙的時(shí)點(diǎn)患病率為162.43‰［95%可信區(qū)間（95%CI）為15.8%～16.7%］，排在前三位的是重性抑郁障礙（27.01‰）、未特定的焦慮障礙（25.09‰）和心境惡劣障礙（23.12‰）；終生患病率為185.12‰（95%CI為18.0%～19.0%），排在前3位的是重性抑郁障礙（47.47‰）、酒精依賴性和濫用性障礙（38.62‰）和未特定抑郁障礙（25.51‰）。（2）時(shí)點(diǎn)患病率：女性(167.95‰）高于男性（156.95‰），農(nóng)村（165.63‰）高于城市（144.31‰），P＜0.05～0.01；并隨年齡的增長(zhǎng)而不斷上升，其中30～49歲為137.17‰～156.71‰，50～≥70歲為201.44‰～285.41‰。結(jié)論：河北省精神 疾病的患病率較高，其中女性和農(nóng)村的患病率高；重性抑郁障礙是省內(nèi)患病率最高的精神疾病。

關(guān)鍵詞：精神障礙；流行病學(xué)方法；河北

來源出版物：中華精神科雜志, 2007, 13(1): 36-40

被引頻次：107

焦慮和抑郁三種理論模式的研究進(jìn)展

袁勇貴，張心保，吳愛勤

摘要：焦慮和抑郁是臨床上常見的兩組癥狀，二者常同時(shí)存在。目前，關(guān)于焦慮和抑郁的關(guān)系不外有三種觀點(diǎn)：（1）一元論：即連續(xù)譜論，認(rèn)為焦慮和抑郁是同一疾病的不同表現(xiàn)形式；（2）二分論：認(rèn)為焦慮障礙和抑郁障礙是兩種不同性質(zhì)的疾??；（3）共病論：認(rèn)為焦慮和抑郁共存時(shí)，是一種不同于焦慮障礙或抑郁障礙的獨(dú)特的疾病實(shí)體。

來源出版物：中華神經(jīng)科雜志, 2001, 34(1): 55-57

被引頻次：107

焦慮癥患者心理生理學(xué)反應(yīng)研究

李春波，吳文源，何康梅，等

摘要：目的：探討焦慮癥患者心理生理學(xué)指標(biāo)的特點(diǎn)。方法：對(duì)31例焦慮癥患者和23名健康志愿者應(yīng)用多導(dǎo)電生理儀對(duì)模擬應(yīng)激前后的心理生理學(xué)指標(biāo)進(jìn)行檢測(cè)，并在治療1月后復(fù)查。結(jié)果：焦慮癥患者的心率及低頻峰功率顯著高于對(duì)照組，其心理生理學(xué)指標(biāo)在治療前后無顯著性差別；低頻峰功率與高頻峰功率比值（靜息狀態(tài)）、脈搏圖血流量面積變化（模擬應(yīng)激前后）與HAMA分?jǐn)?shù)變化呈負(fù)相關(guān)。結(jié)論：焦慮癥患者存在交感神經(jīng)系統(tǒng)功能亢進(jìn)，可能是一種特性標(biāo)志，一些心理生理學(xué)指標(biāo)與臨床療效有一定的相關(guān)性。

關(guān)鍵詞：焦慮癥；心理生理學(xué)；模擬應(yīng)激

來源出版物：中國(guó)心理衛(wèi)生雜志, 2000, 14(5): 337-340

被引頻次：80

突發(fā)公共衛(wèi)生事件下心境障礙的特點(diǎn)與應(yīng)對(duì)

王一牛，羅躍

摘要：突發(fā)公共衛(wèi)生事件會(huì)給較大范圍的人群造成相當(dāng)?shù)男睦韷毫颓榫w問題。突發(fā)事件發(fā)生時(shí)，社會(huì)心理因素對(duì)突發(fā)事件控制效果和進(jìn)程的影響越來越顯著，因疫情、疾病、生活、工作以及社會(huì)和人際關(guān)系等因素而致的情緒問題非常突出。突發(fā)事件時(shí)情緒問題的表現(xiàn)有疑病、恐慌、焦慮、抑郁和強(qiáng)迫心理等，對(duì)此應(yīng)采取相應(yīng)的對(duì)策，而不同群體如罹患人群、隔離人群、家屬、普通就醫(yī)者及一般公眾的情緒問題有其獨(dú)特的表現(xiàn)和應(yīng)對(duì)措施。突發(fā)事件為情緒問題的研究提供了廣闊的前景。

關(guān)鍵詞：突發(fā)公共衛(wèi)生事件；重癥急性呼吸綜合征（SARS）；心境障礙；心理應(yīng)對(duì)

來源出版物：心理科學(xué)進(jìn)展, 2003, 11(4): 387-392

被引頻次：1587

A neurotrophic model for stress-related mood disorders

Duman, RS; Monteggia, LM

Abstract:There is a growing body of evidence demonstrating that stress decreases the expression of brainderived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress.Decreased levels of BDNF,as well as other neruotropbic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects, Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments.This review provides a critical examination of the neurotropbic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular(adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies.Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that up-regulation of BDNF plays a role in the actions of antidepressant treatment.

Keywords:antidepressant; depression; neurogenesis;behavior; BDNF; VEGF

來源出版物：Biological Psychiatry, 2006, 59(12):1116-1127

被引頻次：1539

Common polygenic variation contributes to risk of schizophrenia and bipolar disorder

Purcell, Shaun M; Wray, Naomi R; Stone, Jennifer L; et al.

Abstract:Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations,delusions and cognitive deficits, with heritability estimated at up to 80%.We performed a genome-wide association study of 3322 European individuals with schizophrenia and 3587 controls.Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia.First, we implicate the major histocompatibility complex.Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect.We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

來源出版物：Nature, 2009, 460(7256): 748-752

被引頻次：1523

Subgenual prefrontal cortex abnormalities in mood disorders

Drevets, WC; Price, JL; Simpson, JR; et al.

Abstract:Pathological disturbances of mood may follow a ‘bipolar’ course, in which normal moods alternate with both depression and mania, or a ‘unipolar’ course, in which only depression occurs.Both bipolar and unipolar disorders can be heritable illnesses associated with neurochemical,neuroendocrine and autonomic abnormalities.The neurobiological basis for these abnormalities has not been established.Using positron emission tomographic (PET)images of cerebral blood flow and rate of glucose metabolism to measure brain activity, we have now localized an area of abnormally decreased activity in the pre-frontal cortex ventral to the germ of the corpus callosum in both familial bipolar depressives and familial unipolar depressives.This decrement in activity was at least partly explained by a corresponding reduction in cortical volume as magnetic resonance imaging (MRI)demonstrated reductions in the mean grey matter volume in the same area of 39% and 48% in the bipolar and unipolar samples, respectively.This region has previously been implicated in the mediation of emotional and autonomic responses to socially significant or provocative stimuli, and in the modulation of the neurotransmitter systems targeted by antidepressant drugs.

來源出版物：Nature, 1997, 386(6627): 824-827

被引頻次：1307

The role of childhood trauma in the neurobiology of mood and anxiety disorders: Preclinical and clinical studies

Heim, C; Nemeroff, CB

Abstract:Epidemiologic studies indicate that children exposed to early adverse experiences are at increased risk for the development of depression, anxiety disorders, or both.Persistent sensitization of central nervous system(CNS) circuits as a consequence of early life stress, which are integrally involved in the regulation of stress and emotion, may represent the underlying biological substrate of art increased vulnerability to subsequent stress as well as to the development of depression and anxiety, A number of preclinical studies suggest that early life stress induces long-lived hyper (re) activity of corticotrophin-releasing factor (CRF) systems as well as alterations in other neurotransmitter systems, resulting in increased stress responsiveness.Many of the findings from these preclinical studies are comparable to findings in adult patients with mood and anxiety disorders.Emerging evidence from clinical studies suggests that exposure to early life stress is associated with neurobiological changes in children and adults, which may underlie the increased risk of psychopathology.Current research is focused on strategies to prevent or reverse the detrimental effects of early life stress on the CNS The identification of the neurobiological substrates of early adverse experience is of paramount importance for the development of novel treatments for children, adolescents, and adults.

Keywords:stress; development; animal; human;depression; anxiety

來源出版物：Biological Psychiatry, 2001, 49(12): 1023-1039

被引頻次：1201

Cross-national epidemiology of major depression and bipolar disorder

Weissman, MM; Bland, RC; Canino, GJ; et al.

Abstract:Objective: To estimate the rates and patterns of major depression and bipolar disorder based on cross-national epidemiologic surveys.Design and Setting: Population based epidemiologic studies using similar methods from 10 countries: the United States, Canada, Puerto Rico, France,West Germany, Italy, Lebanon, Taiwan, Korea, and New Zealand.Participants: Approximately 38000 community subjects.Outcome Measures: Rates, demographics, and age at onset of major depression and bipolar disorder.Symptom profiles, comorbidity, and marital status with major depression.Results: The lifetime rates for major depression vary widely across countries, ranging from 1.5 cases per 100 adults in the sample in Taiwan to 19.0 cases per 100 adults in Beirut.The annual rates ranged from 0.8 cases per 100 adults in Taiwan to 5.8 cases per 100 adults in New Zealand.The mean age at onset shows less variation (range, 24.8-34.8 years).In every country, the rates of major depression were higher for women than men.By contrast, the lifetime rates of bipolar disorder are more consistent across countries (0.3/100 in Taiwan to 1.5/100 in New Zealand); the sex ratios are nearly equal; and the age at first onset is earlier (average, 6 years) than the onset of major depression.Insomnia and loss of energy occurred in most persons with major depression at each site.Persons with major depression were also at increased risk for comorbidity with substance abuse and anxiety disorders at all sites.Persons who were separated or divorced had significantly higher rates of major depression than married persons in most of the countries, and the risk was somewhat greater for divorced or separated men than women in most countries.Conclusions: There are striking similarities across countries in patterns of major depression and of bipolar disorder.The differences in rates for major depression across countries suggest that cultural differences or different risk factors may affect the expression of the disorder.

Keywords:channel modeling; composite transportation;cuttings and tunnels; high-speed railway (HSR); operation control system; train control data; viaducts

來源出版物：JAMA-Journal of the American Medical Association, 1996, 276(7): 293-299

被引頻次：1172

Transduction of psychosocial stress into the neurobiology of recurrent affective disorder

Post, RM

Abstract:Early clinical observations and recent systematic studies overwhelmingly document a greater role for psychosocial stressors in association with the first episode of major affective disorder than with subsequent episodes.The author postulates that both sensitization to stressors and episode sensitization occur and become encoded at the level of gene expression.In particular, stressors and the biochemical concomitants of the episodes themselves can induce the proto-oncogene c-fos and related transcription factors, which then affect the expression of transmitters,receptors, and neuropeptides that alter responsivity in a long-lasting fashion.Thus, both stressors and episodes may leave residual traces and vulnerabilities to further occurrences of affective illness.These data and concepts suggest that the biochemical and anatomical substrates underlying the affective disorders evolve over time as a function of recurrences, as does pharmacological responsivity.This formulation highlights the critical importance of early intervention in the illness in order to prevent malignant transformation to rapid cycling,spontaneous episodes, and refractoriness to drug treatment.

Keywords:high-speed railway; train-bridge system;dynamic interaction; experiment

來源出版物：Computers & Structures, 2005, 83(23-24):1891-1901

被引頻次：1141

The long-term natural history of the weekly symptomatic status of bipolar I disorder

Judd, LL; Akiskal, HS; Schettler, PJ; et al.

Abstract:Background: To our knowledge, this is the first prospective natural history study of weekly symptomatic status of patients with bipolar I disorder (BP-I) during long-term follow-up.Methods: Analyses are based on ongoing prospective follow-up of 146 patients with Research Diagnostic Criteria BP-1, who entered the National Institute of Mental Health (Bethesda, Md)Collaborative Depression Study from 1978 through 1981.Weekly affective symptom status ratings were analyzed by polarity and severity, ranging from asymptomatic, to subthreshold levels, to full-blown major depression and mania.Percentages of follow-up weeks at each level as well as number of shifts in symptom status and polarity during the entire follow-up period were examined.Finally,2 new measures of chronicity were evaluated in relation to previously identified predictors of chronicity for BP-I.Results: Patients with BP-I were symptomatically ill 47.3%of weeks throughout a mean of 12.8 years of follow-up.Depressive symptoms (31.9% of total follow-up weeks)predominated over manic/hypomanic symptoms (8.9% of weeks) or cycling/mixed symptoms (5.9% of weeks).Subsyndromal, minor depressive, and hypomanic symptoms combined were nearly 3 times more frequent than syndromal-level major depressive and manic symptoms(29.9% vs 11.2% of weeks, respectively).Patients with BP-I changed symptom status an average of 6 times per year and polarity more than 3 times per year.Longer intake episodes and those with depression-only or cycling polarity predicted greater chronicity during long-term follow-up,as did comorbid drug-use disorder.Conclusions: The longitudinal weekly symptomatic course of BP-I is chronic.Overall, the symptomatic structure is primarily depressive rather than manic, and sub-syndromal and minor affective symptoms predominate.Symptom severity levels fluctuate,often within the same patient over time.Bipolar I disorder is expressed as a dimensional illness featuring the full range (spectrum) of affective symptom severity and polarity.

來源出版物：Archives of General Psychiatry, 2002, 59(6):530-537

被引頻次：863

Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression

Drevets, Wayne C; Price, Joseph L; Furey, Maura L; et al.

Abstract:The neural networks that putatively modulate aspects of normal emotional behavior have been implicated in the pathophysiology of mood disorders by converging evidence from neuroimaging, neuropathological and lesion analysis studies.These networks involve the medial prefrontal cortex (MPFC) and closely related areas in the medial and caudolateral orbital cortex (medial prefrontal network), amygdala, hippocampus, and ventromedial parts of the basal ganglia, where alterations in grey matter volume and neurophysiological activity are found in cases with recurrent depressive episodes.Such findings hold major implications for models of the neurocircuits that underlie depression.In particular evidence from lesion analysis studies suggests that the MPFC and related limbic and striato-pallido-thalamic structures organize emotional expression.The MPFC is part of a larger “default system”of cortical areas that include the dorsal PFC, mid- and posterior cingulate cortex, anterior temporal cortex, and entorhinal and parahippocampal cortex, which has been implicated in self-referential functions.Dysfunction within and between structures in this circuit may induce disturbances in emotional behavior and other cognitive aspects of depressive syndromes in humans.Further,because the MPFC and related limbic structures provide forebrain modulation over visceral control structures in the hypothalamus and brainstem, their dysfunction can account for the disturbances in autonomic regulation and neuroendocrine responses that are associated with mood disorders.This paper discusses these systems together with the neurochemical systems that impinge on them and form the basis for most pharmacological therapies.

來源出版物：Brain Structure & Function, 2008, 213(1-2):93-118

被引頻次：830

Common genetic determinants of schizophrenia and bipolar disorder in Swedish families:A population-based study

Lichtenstein, Paul; Yip, Benjamin H; Bjork, Camilla; et al.

Abstract:Background: whether schizophrenia and bipolar disorder are the clinical outcomes of discrete or shared causative processes is much debated in psychiatry.We aimed to assess genetic and environmental contributions to liability for schizophrenia, bipolar disorder, and their comorbidity.Methods: We linked the multi-generation register, which contains information about all children and their parents in Sweden, and the hospital discharge register,which includes all public psychiatric inpatient admissions in Sweden.We identified 9009202 unique individuals in more than 2 million nuclear families between 1973 and 2004.Risks for schizophrenia, bipolar disorder, and their co-morbidity were assessed for biological and adoptive parents, offspring, full-siblings and half-siblings of pro-bands with one of the diseases.We used a multivariate generalized linear mixed model for analysis of genetic and environmental contributions to liability for schizophrenia,bipolar disorder, and co-morbidity.Findings First-degree relatives of pro-bands with either schizophrenia (n=35985)or bipolar disorder (n=40487) were at increased risk of these disorders.Half-siblings had a significantly increased risk (schizophrenia: relative risk [RR] 3.6, 95%CI2.3-5.5 for maternal half-siblings, and 2.7, 1.9-3.8 for paternal half-siblings; bipolar disorder: 4.5, 2.7-7.4 for maternal half-siblings, and 2.4, 1.4-4.1 for paternal half-siblings),but substantially lower than that of the full-siblings(schizophrenia: 9.0, 8.5-11.6; bipolar disorder: 7.9,7.1-8.8).When relatives of pro-bands with bipolar disorder were analyzed, increased risks for schizophrenia existed for all relationships, including adopted children to biological parents with bipolar disorder.Heritability for schizophrenia and bipolar disorder was 64% and 59%,respectively.Shared environmental effects were small but substantial (schizophrenia: 4.5%, 4.4%-7.4%; bipolar disorder: 3.4%, 2.3%-6.2%) for both disorders.The comorbidity between disorders was mainly (63%) due to additive genetic effects common to both disorders.Interpretation Similar to molecular genetic studies, we showed evidence that schizophrenia and bipolar disorder partly share a common genetic cause.These results challenge the current nosological dichotomy between schizophrenia and bipolar disorder, and are consistent with a reappraisal of these disorders as distinct diagnostic entities.Funding: Swedish Council for Working Life and Social Research, and the Swedish Research Council.

來源出版物：Lancet, 2009, 373(9659): 234-239

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北京市社區(qū)人群心境障礙、焦慮障礙及物質(zhì)使用障礙的現(xiàn)況調(diào)查

劉肇瑞，黃悅勤，陳曦，等

摘要：目的：描述北京市心境障礙、焦慮障礙及物質(zhì)使用障礙的流行病學(xué)特點(diǎn)。方法：按照現(xiàn)況調(diào)查多階段分層抽樣的方法于2010年選取北京市3387名16歲及以上社區(qū)居民，采用復(fù)合性國(guó)際診斷交談表3.0計(jì)算機(jī)版進(jìn)行入戶訪談，按美國(guó)精神病學(xué)協(xié)會(huì)診斷和統(tǒng)計(jì)手冊(cè)第4版的標(biāo)準(zhǔn)對(duì)心境障礙、焦慮障礙及物質(zhì)使用障礙進(jìn)行診斷。結(jié)果：接受訪談?wù)?469人，應(yīng)答率為72.9%。心境障礙30 d患病率和調(diào)整率分別為0.81%和0.87%，12月患病率和調(diào)整率分別為3.32%和3.40%，終生患病率和調(diào)整率分別為7.21%和6.55%。焦慮障礙30天患病率和調(diào)整率分別為3.16%和3.08%，12月患病率和調(diào)整率分別為3.93%和3.90%，終生患病率和調(diào)整率分別為5.95%和6.37%。物質(zhì)使用障礙30 d患病率和調(diào)整率分別為0.33%和0.37%，12月患病率和調(diào)整率分別為1.15%和1.92%，終生患病率和調(diào)整率分別為5.30%和5.58%。心境障礙、焦慮障礙以及物質(zhì)使用障礙間存在共病現(xiàn)象；首發(fā)年齡中位數(shù)分別為38歲、15歲和28歲。結(jié)論：本次調(diào)查顯示北京市9人中約有1人曾患有心境障礙、焦慮障礙或物質(zhì)使用障礙中的一種，應(yīng)大力加強(qiáng)精神衛(wèi)生知識(shí)宣傳和防治。

關(guān)鍵詞：心境障礙；焦慮障礙；物質(zhì)使用障礙；患病率；復(fù)合性國(guó)際診斷交談表；現(xiàn)況調(diào)查

來源出版物：中國(guó)心理衛(wèi)生雜志，2013, 27(2): 102-110

認(rèn)知療法提升惡劣心境障礙大學(xué)生心理韌性個(gè)案研究

王平

摘要：目的：初步探索認(rèn)知療法對(duì)提升惡劣心境障礙大學(xué)生心理韌性的效果。方法：1例惡劣心境障礙大學(xué)生接受連續(xù)9周、每周一次的認(rèn)知治療。采用青少年心理韌性量表、抑郁自評(píng)量表、焦慮自評(píng)量表和領(lǐng)悟社會(huì)支持量表在干預(yù)前、干預(yù)后和干預(yù)后3個(gè)月對(duì)患者分別實(shí)施測(cè)評(píng)，并收集患者的主觀報(bào)告。結(jié)果：患者經(jīng)過干預(yù)后，心理韌性水平提高，同時(shí)抑郁、焦慮水平下降。自我報(bào)告治療后社會(huì)支持感提高，生活滿意度提高，其效果在干預(yù)結(jié)束后3個(gè)月內(nèi)的跟蹤期間仍保持穩(wěn)定。結(jié)論：認(rèn)知治療對(duì)有效地提升惡劣心境障礙患者的心理韌性存在一定的可能性，但未來仍需更多的實(shí)證研究來證實(shí)。

關(guān)鍵詞：認(rèn)知治療；心理韌性；惡劣心境障礙；大學(xué)生；個(gè)案

來源出版物：中國(guó)臨床心理學(xué)雜志, 2013, 21(2): 334-338

雙相情感障礙：綜述

周淑新，李雯（譯）

摘要：雙相情感障礙為常見、致殘、反復(fù)發(fā)作、嚴(yán)重度不同的精神衛(wèi)生問題。常發(fā)生于兒童晚期或青春早期。雙相情感障礙患者患其他精神障礙及軀體疾病的比率較高。雙相情感障礙若能早期識(shí)別則可改善結(jié)果。心境發(fā)作治療取決于呈現(xiàn)的病程階段：躁狂、輕躁狂、混合狀態(tài)、抑郁或維持階段。雙相情感障礙常在出現(xiàn)癥狀數(shù)年后的青春期或成人早期才被診斷出來。癥狀包括躁狂、輕躁狂、精神病癥狀或相對(duì)健康期夾雜抑郁。雙相情感障礙的臨床病程呈多變性。單相發(fā)作的患者罕見，據(jù)報(bào)道其5年復(fù)發(fā)率＞70%。雖然雙相情感障礙用出現(xiàn)躁狂或輕躁狂癥狀來定義，但多數(shù)患者多數(shù)時(shí)間都處于抑郁狀態(tài)，這也是致殘的主要原因。

關(guān)鍵詞：雙相情感障礙；診斷；治療

來源出版物：中國(guó)全科醫(yī)學(xué), 2013, 16(2B): 473-477

抑郁癥的多機(jī)制發(fā)病

劉春林，阮克鋒，高君偉，等

摘要：抑郁癥（depression）是一種嚴(yán)重的精神疾病，對(duì)社會(huì)危害極大。最新研究表明抑郁癥病因復(fù)雜，涉及神經(jīng)系統(tǒng)和內(nèi)分泌系統(tǒng)的多種神經(jīng)遞質(zhì)與激素，以及相應(yīng)的受體。本文對(duì)近幾年抑郁癥發(fā)病機(jī)制的研究進(jìn)行了綜述。

關(guān)鍵詞：抑郁癥；機(jī)制；抗抑郁

來源出版物：生理科學(xué)進(jìn)展, 2014, 44(4): 253-258

雙相障礙的診治與研究——機(jī)遇與挑戰(zhàn)

方貽儒，吳志國(guó)，陳俊

摘要：雙相障礙臨床表現(xiàn)復(fù)雜、病程多變，常導(dǎo)致臨床識(shí)別不足、診斷不確定以及治療困難。由此，學(xué)界開展了一系列研究，探索該病的特征與本質(zhì)，并在循證醫(yī)學(xué)的基礎(chǔ)上踐行有關(guān)診斷標(biāo)準(zhǔn)的修正以及治療理念的糾正。該文從概念與診斷、神經(jīng)生物學(xué)研究進(jìn)展以及心境穩(wěn)定劑治療等方面對(duì)雙相障礙的探索現(xiàn)狀和前景進(jìn)行評(píng)述。

關(guān)鍵詞：雙相障礙；診斷；精神疾病診斷與統(tǒng)計(jì)手冊(cè)；神經(jīng)生物學(xué)；心境穩(wěn)定劑

來源出版物：上海交通大學(xué)學(xué)報(bào)（醫(yī)學(xué)版）, 2014, 34(4):413-416

長(zhǎng)沙地區(qū)社區(qū)人群酒精使用障礙與心境障礙共病調(diào)查

譚奔騰，楊梅，郭田生，等

摘要：目的：了解長(zhǎng)沙地區(qū)居民酒精使用障礙與心境障礙共病的患病情況。方法：采用多階段整群抽樣方法，對(duì)15歲及以上人群進(jìn)行入戶調(diào)查，共抽樣12475人。以增補(bǔ)后的一般健康問卷12（GHQ-12）為篩選工具，將調(diào)查對(duì)象分為患精神疾病高、中、低危險(xiǎn)組。以美國(guó)精神障礙診斷與統(tǒng)計(jì)手冊(cè)第4版（DSM-IV）軸Ⅰ障礙定式臨床檢查病人版（SCID-I/P）為診斷工具。12094人完成GHQ-12,2351人完成SCID-I/P，對(duì)這2351名居民中酒精使用障礙和心境障礙的共患情況進(jìn)行分析。結(jié)果：酒精使用障礙和心境障礙的時(shí)點(diǎn)患病率分別為1.76%（46/2351）和6.01%（141/2351）。酒精使用障礙患者有心境障礙者占60.9%（28/46），心境障礙患者有酒精使用障礙者為19.9%（28/141）。控制年齡、性別、居住地、受教育程度、家庭年收入以后，酒精使用障礙患者發(fā)生心境障礙的風(fēng)險(xiǎn)性高于非現(xiàn)患酒精使用障礙者（OR＝33.54, 95%CI: 17.52～64.20）；心境障礙患者發(fā)生酒精使用障礙的風(fēng)險(xiǎn)性高于非現(xiàn)患心境障礙者（OR＝35.11,95%CI: 18.02～68.39）。結(jié)論：酒精使用障礙與心境障礙容易發(fā)生共患，應(yīng)引起精神衛(wèi)生工作者的重視。

關(guān)鍵詞：酒精使用障礙；心境障礙；患病率；共??；現(xiàn)況調(diào)查

來源出版物：中國(guó)心理衛(wèi)生雜志, 2014, 28(5): 349-355

從“焦慮性抑郁癥”概念解析抑郁障礙的復(fù)雜性

吳志國(guó)，吳彥，方貽儒

摘要：抑郁障礙是一類極為復(fù)雜的精神疾病，目前已發(fā)展出諸多臨床描述亞型以試圖“精準(zhǔn)對(duì)焦”解析抑郁障礙的復(fù)雜化現(xiàn)象，其中焦慮性抑郁癥受到了越來越多的關(guān)注。該文將通過對(duì)以癥狀維度定義的焦慮性抑郁癥研究進(jìn)展進(jìn)行綜述，從共患焦慮的角度對(duì)抑郁障礙的復(fù)雜性進(jìn)行解析。

關(guān)鍵詞：抑郁障礙；焦慮性抑郁癥；焦慮障礙；共病

來源出版物：上海交通大學(xué)學(xué)報(bào)：醫(yī)學(xué)版, 2014, 34(4):450-454

抗炎性細(xì)胞因子與抑郁癥

徐說，林文娟

摘要：細(xì)胞因子假說是關(guān)于抑郁癥發(fā)病機(jī)理的重要假說，為探討抑郁癥的發(fā)病機(jī)理和臨床治療方法提供了新方向。細(xì)胞因子分為前炎性細(xì)胞因子和抗炎性細(xì)胞因子。前炎性細(xì)胞因子與抑郁癥的發(fā)病密切相關(guān)，而抗炎性細(xì)胞因子可能具有抗抑郁的作用。本文著重綜述抗炎性細(xì)胞因子與抑郁癥的關(guān)系?？寡仔约?xì)胞因子如白介素10、白介素1受體拮抗劑、白介素4、白介素13、轉(zhuǎn)化生長(zhǎng)因子β和脂聯(lián)素等，在抑郁癥中表達(dá)下降；補(bǔ)充外源抗炎性細(xì)胞因子則具有一定的抗抑郁作用?？寡仔约?xì)胞因子可通過拮抗前炎性細(xì)胞因子的作用，并與MAPK信號(hào)通路、神經(jīng)遞質(zhì)和糖皮質(zhì)激素相互作用而參與到抑郁癥中.抗抑郁藥能使抗炎性細(xì)胞因子的表達(dá)上升，這可能是藥物起效的機(jī)制之一?？寡撞呗栽谝钟舭Y的治療中有重要應(yīng)用前景。

關(guān)鍵詞：抑郁癥；細(xì)胞因子；抗炎性細(xì)胞因子；抗炎作用；抗抑郁藥

來源出版物：生物化學(xué)與生物物理進(jìn)展, 2014, 41(11):1099-1108

抑郁癥發(fā)病機(jī)制研究進(jìn)展

王睿，黃樹明

摘要：抑郁癥因其病因不清、致病因素復(fù)雜、發(fā)病機(jī)制不詳，一直是神經(jīng)科學(xué)領(lǐng)域的一個(gè)難題。近年來，國(guó)內(nèi)外對(duì)抑郁癥的研究方興未艾，并在發(fā)病機(jī)制的研究上取得了重要進(jìn)展。文中從神經(jīng)生化研究、神經(jīng)內(nèi)分泌研究、神經(jīng)可塑性研究等方面對(duì)抑郁癥的發(fā)生機(jī)制主流假說進(jìn)行簡(jiǎn)單闡述，以拓寬對(duì)抑郁癥的認(rèn)識(shí)。

關(guān)鍵詞：抑郁癥；神經(jīng)生化；神經(jīng)內(nèi)分泌；神經(jīng)可塑性

來源出版物：醫(yī)學(xué)研究生學(xué)報(bào), 2014, 27(12): 1332-1336

誤診為抑郁癥的雙相障礙Ⅱ型患者自殺風(fēng)險(xiǎn)的危險(xiǎn)因素分析

王君，陳林，吉振鵬，等

摘要：目的：探討誤診為抑郁癥的雙相障礙Ⅱ型患者自殺風(fēng)險(xiǎn)的社會(huì)人口學(xué)及臨床特征方面的危險(xiǎn)因素。方法：通過簡(jiǎn)明國(guó)際神經(jīng)精神訪談（the Mini International Neuropsychiatric Interview, MINI）5.0中文版，對(duì)來自全國(guó)13個(gè)中心的1478例最初診斷為抑郁癥的患者進(jìn)行重新診斷，其中190例被診斷為雙相障礙Ⅱ型，將這190例誤診患者按照有無自殺風(fēng)險(xiǎn)進(jìn)行分組，從性別、年齡等社會(huì)人口學(xué)資料及起病年齡、是否伴有自殺觀念等臨床特征方面探討被誤診患者自殺風(fēng)險(xiǎn)可能的危險(xiǎn)因素。結(jié)果：有自殺風(fēng)險(xiǎn)組共74例患者，無自殺風(fēng)險(xiǎn)組共116例。有自殺風(fēng)險(xiǎn)組與無自殺風(fēng)險(xiǎn)組相比,年齡更?。郏?4.45±11.18）vs.（37.23±13.22）］，起病年齡更早［（26.20±9.16）vs.（30.37±11.59）］，更常伴有自殺觀念（82.4% vs.53.4%），差異均具有統(tǒng)計(jì)學(xué)意義（P＜0.05）。Logistic回歸分析顯示，年齡（OR＝0.969, 95%CI: 0.945～0.993)、伴有自殺觀念（OR＝4.129, 95%CI:2.030～8.397）與誤診為抑郁癥的雙相障礙Ⅱ型患者發(fā)生自殺風(fēng)險(xiǎn)相關(guān)聯(lián)（P＜0.05）。結(jié)論：年齡小、伴有自殺觀念可能是誤診為抑郁癥的雙相障礙Ⅱ型患者自殺風(fēng)險(xiǎn)的獨(dú)立危險(xiǎn)因素。

關(guān)鍵詞：雙相障礙；抑郁癥；自殺風(fēng)險(xiǎn)；危險(xiǎn)因素；誤診

來源出版物：中國(guó)神經(jīng)精神疾病雜志, 2015, 41(2): 65-70

情感障礙患者的疾病感知

張萌，趙旭東

摘要：疾病感知是指患者利用以往獲取的疾病知識(shí)經(jīng)驗(yàn)來分析解釋當(dāng)前的癥狀或疾病的過程。本文對(duì)疾病感知的概念、測(cè)量工具、干預(yù)措施及其在情感障礙患者中的實(shí)證研究進(jìn)行綜述，以探討疾病感知與預(yù)后及求治行為、治療依從性等預(yù)后影響因素之間的關(guān)系。

關(guān)鍵詞：情感障礙；疾病感知；預(yù)后；求治行為；治療依從性

來源出版物：中國(guó)臨床心理學(xué)雜志, 2015, 23(1): 104-107

心境障礙和甲狀腺功能異常相關(guān)的研究進(jìn)展

黃立芳，尹超群

摘要：心境障礙是常見的精神障礙疾患，主要表現(xiàn)為心境和情感的改變，通常表現(xiàn)為持久的情感高漲或低落，其高致殘率對(duì)社會(huì)造成了極為嚴(yán)重的危害。甲狀腺激素異常見于心境障礙患者，并且甲狀腺功能異常加大了人群心境障礙的患病率。心境障礙患者甲狀腺功能障礙主要表現(xiàn)為甲狀腺激素水平的異常，甲狀腺素（T4）向三碘甲狀腺原氨酸（T3）轉(zhuǎn)化異常，下丘腦-垂體-甲狀腺（HTP）軸功能的亢進(jìn)或抑制。甲狀腺激素對(duì)于心境障礙患神經(jīng)遞質(zhì)有所影響，異常的甲狀腺激素水平對(duì)基因的調(diào)節(jié)和生化改變相關(guān)聯(lián)。甲狀腺抗體同樣是心境障礙發(fā)病的關(guān)聯(lián)因素。本文總結(jié)了心境障礙和甲狀腺功能異常相關(guān)的研究進(jìn)展，為進(jìn)一步研究心境障礙和甲狀腺功能異常提供一定的依據(jù)。

關(guān)鍵詞：心境障礙；甲狀腺功能；甲狀腺激素

來源出版物：中國(guó)全科醫(yī)學(xué), 2016, 19(10): 1225-1228

首發(fā)精神分裂癥與雙相障礙及抑郁障礙認(rèn)知功能比較

陳大春，陳科，張榮珍

摘要：目的：探討首發(fā)精神分裂癥、雙相障礙及抑郁障礙患者認(rèn)知功能差異。方法：納入首發(fā)精神分裂癥患者61例，雙相障礙患者57例，抑郁障礙患者48例，另設(shè)正常對(duì)照59名。所有研究對(duì)象采用重復(fù)性神經(jīng)心理測(cè)查系統(tǒng)（repeatable battery for the assessment of neuropsychological status，RBANS）評(píng)估認(rèn)知功能，首發(fā)精神分裂癥組采用陽性和陰性癥狀量表（positive and negative syndrome scale，PANSS）評(píng)定精神病性癥狀，雙相障礙組、抑郁障礙組采用漢密爾頓抑郁量表（Hamilton depression scale，HAMD）、漢密爾頓焦慮量表（Hamilton anxiety scale，HAMA）評(píng)估抑郁和焦慮癥狀，貝克-拉范森躁狂（Bech-Rafaelsen mania scale，BRMS）量表評(píng)估躁狂癥狀。結(jié)果：4組對(duì)象的RBANS總分（F＝5.18,P＜0.01）、即刻記憶（F＝4.09,P＜0.01）、言語功能（F＝9.53,P＜0.01）、注意（F＝3.87,P＝0.01）、延時(shí)記憶（F＝9.86,P＜0.01）因子得分差異具有統(tǒng)計(jì)學(xué)意義，其中首發(fā)精神分裂癥、雙相障礙組RBANS總分低于對(duì)照組（P＜0.01），首發(fā)精神分裂癥、雙相障礙、抑郁障礙組即刻記憶、言語功能、延時(shí)記憶得分低于對(duì)照組（P＜0.05），雙相障礙組言語功能得分低于首發(fā)精神分裂癥組（P＜0.01），首發(fā)精神分裂癥組注意得分低于抑郁障礙及對(duì)照組（P＜0.01）。結(jié)論：首發(fā)精神分裂癥、雙相障礙、抑郁障礙患者均存在認(rèn)知功能損傷，首發(fā)精神分裂癥認(rèn)知功能缺陷重于抑郁障礙，輕于雙相障礙。

關(guān)鍵詞：首發(fā)精神分裂癥；雙相障礙；抑郁障礙；認(rèn)知功能

來源出版物：中國(guó)神經(jīng)精神疾病雜志, 2016, 42(9): 518-522

情緒障礙及其干預(yù)：心理表象的視角

王銘，江光榮

摘要：心理表象在多種情緒障礙中均表現(xiàn)出病理性特點(diǎn)。研究者基于心理表象主要對(duì)創(chuàng)傷后應(yīng)激障礙、抑郁心境、雙相障礙情緒和社交焦慮進(jìn)行了心理病理學(xué)解釋，尤其關(guān)注閃回和過度概化記憶等兩種典型癥狀，并且重視心理表象在情緒癥狀維持中的作用。概括而言，研究者強(qiáng)調(diào)記憶形成與提取過程的異常、認(rèn)知與行為的保護(hù)性策略的負(fù)強(qiáng)化、對(duì)事件及自我的認(rèn)知偏差等三類因素對(duì)情緒障礙的致病作用。目前，針對(duì)或運(yùn)用心理表象的干預(yù)與訓(xùn)練方法包括減少消極表象、改變消極表象內(nèi)容、提高積極表象能力、提高記憶的具體性等四類。未來應(yīng)注重侵入性表象的功能分析以及相關(guān)的心理病理學(xué)模型研究，并拓展干預(yù)與訓(xùn)練研究。

關(guān)鍵詞：心理表象；情緒障礙；心理病理學(xué)；干預(yù)與訓(xùn)練

來源出版物：心理科學(xué)進(jìn)展, 2016, 24(4): 573-590

雙相抑郁的特點(diǎn)、危害及藥物治療研究進(jìn)展

袁銘，李素敏，王雪芹，等

摘要：雙相抑郁是一復(fù)發(fā)性疾病，不同情感形式的發(fā)作可能會(huì)對(duì)患者的心理、職業(yè)和社會(huì)福利產(chǎn)生持續(xù)的破壞作用。此外，雙相抑郁是一種嚴(yán)重的致殘性疾病，因與單相抑郁不易區(qū)分，極易被誤診，對(duì)患者及社會(huì)造成嚴(yán)重的負(fù)擔(dān)。抑郁癥狀是雙相抑郁的主要特征，該階段患者的自殺率較高，應(yīng)得到重視。本文將雙相抑郁的特點(diǎn)、危害及藥物治療研究進(jìn)展進(jìn)行綜述，為進(jìn)一步研究雙相抑郁的治療提供一定的依據(jù)。

關(guān)鍵詞：雙相情感障礙；危害；治療進(jìn)展

來源出版物：中國(guó)全科醫(yī)學(xué), 2016, 19(10): 1229-1233

雙相障礙患者對(duì)情緒信息的注意偏向

程玉琴，劉鐵榜

摘要：有關(guān)注意的研究為雙相障礙的病理性研究和治療研究提供了發(fā)展框架。已有研究表明對(duì)消極情緒的注意偏向可能是罹患雙相障礙的危險(xiǎn)因素。本文從雙相障礙患者對(duì)情緒注意偏向是狀態(tài)性還是素質(zhì)性、心境是否一致性，以及不同臨床相患者的注意偏向特征等方面進(jìn)行了探討，并提出了對(duì)患者注意偏向干預(yù)的行為學(xué)矯治方法。

關(guān)鍵詞：雙相障礙；注意偏向；情緒；綜述

來源出版物：中國(guó)心理衛(wèi)生雜志, 2017, 31(7): 528-532

重性抑郁障礙病人生活質(zhì)量及其影響因素

李峰，薄奇靜，趙燕，等

摘要：目的：評(píng)估重性抑郁障礙（major depressive disorder, MDD）病人的生活質(zhì)量，分析其影響因素。方法：對(duì)符合美國(guó)精神障礙診斷與統(tǒng)計(jì)手冊(cè)第4版（Diagnostic and Statistical Manual of Mental Disorders 4th edition, DSM-IV）診斷的92例成人重性抑郁障礙病人及80例健康對(duì)照使用世界衛(wèi)生組織生存質(zhì)量測(cè)定量表簡(jiǎn)表（World Health Organization Quality of Life Scale Brief, WHOQOL-BREF）、漢密爾頓抑郁量表17項(xiàng)（the 17-item Hamilton Depression Rating Scale, HAMD-17）、漢密爾頓焦慮量表（Hamilton Anxiety Scale, HAMA）、社會(huì)支持量表（Social Support Rating Scale, SSRS）進(jìn)行評(píng)估。結(jié)果重性抑郁障礙病人的WHOQOL-BREF各維度評(píng)分均低于健康對(duì)照（P＜0.05）；對(duì)病人組進(jìn)行Pearson相關(guān)分析顯示，WHOQOL-BREF各維度評(píng)分與HAMD-17、HAMA評(píng)分呈負(fù)相關(guān)，與SSRS評(píng)分呈正相關(guān)（P＜0.01）。性別與WHOQOL-BREF的社會(huì)關(guān)系領(lǐng)域呈負(fù)相關(guān)（P＜0.05），而病程與WHOQOL-BREF的環(huán)境領(lǐng)域呈負(fù)相關(guān)（P＜0.05）。對(duì)病人組進(jìn)行逐步多元線性回歸分析顯示，HAMD-17評(píng)分與WHOQOL-BREF的生理、心理領(lǐng)域得分呈負(fù)相關(guān)（P＜0.05）；SSRS的主觀支持評(píng)分與WHOQOL-BREF的心理、社會(huì)關(guān)系、環(huán)境領(lǐng)域呈正相關(guān)（P＜0.05）；SSRS中對(duì)支持的利用度、家庭收入等級(jí)與WHOQOL-BREF的心理領(lǐng)域也有影響（P＜0.01)。結(jié)論重性抑郁障礙病人的生活質(zhì)量低于一般人群，并且癥狀越重、病程越長(zhǎng)及社會(huì)支持度越差，生活質(zhì)量越差。而男性病人可能具有更差的生活質(zhì)量。具有穩(wěn)定的配偶也有助于提升生活質(zhì)量。

關(guān)鍵詞：重性抑郁障礙；生活質(zhì)量；世界衛(wèi)生組織生存質(zhì)量測(cè)定量表簡(jiǎn)表

來源出版物：首都醫(yī)科大學(xué)學(xué)報(bào), 2017, 38(2): 1860191

雙相心境障礙抑郁發(fā)作患病嚴(yán)重程度的影響因素分析

庚天琦，安妮，王喜今，等

摘要：目的：研究影響雙相心境障礙疾病抑郁發(fā)作期嚴(yán)重程度的危險(xiǎn)因素，為該病的有效預(yù)防提供理論依據(jù)。方法：收集2010—2015年某市精神?？漆t(yī)院的雙相心境障礙抑郁發(fā)作住院466名患者的病例信息，根據(jù)漢密爾頓抑郁量表將患者分為輕、中、重度，并選出年齡、性別、居住地、出生季節(jié)、遺傳史等15個(gè)可能危險(xiǎn)因素，進(jìn)行單因素和多因素條件Logistic回歸分析。結(jié)果：Logistic回歸分析篩選出7個(gè)影響雙相心境障礙疾病抑郁發(fā)作嚴(yán)重程度的危險(xiǎn)因素，即出生季節(jié)（冬季OR＝3.091、秋季OR=2.363）、高學(xué)歷（OR＝1.414）、婚姻離異（OR＝3.132）、長(zhǎng)期居住農(nóng)村（OR＝0.587）、排行老大（OR＝1.461）、性格內(nèi)向（OR＝1.705）、家族遺傳史（OR＝2.101）。結(jié)論：雙相心境障礙抑郁發(fā)作嚴(yán)重程度受多種因素的影響。

關(guān)鍵詞：雙相心境障礙；病例回顧分析；危險(xiǎn)因素；Logistic回歸

來源出版物：現(xiàn)代預(yù)防醫(yī)學(xué), 2017, 44(6): 1145-1148

From stress to inflammation and major depressive disorder: A social signal transduction theory of depression

Slavich, George M; Irwin, Michael R

Abstract:Major life stressors, especially those involving interpersonal stress and social rejection, are among the strongest proximal risk factors for depression.In this review, we propose a biologically plausible, multilevel theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of socialenvironmental stress with internal biological processes that drive depression pathogenesis.Central to this social signal transduction theory of depression is the hypothesis that experiences of social threat and adversity up-regulate components of the immune system involved in inflammation.The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia,fatigue, psychomotor retardation, and social-behavioral withdrawal.This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury.However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain,metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration.Insights from this theory may thus shed light on several important questions including how depression develops, why it frequently recurs, why it is strongly predicted by early life stress, and why it often co-occurs with symptoms of anxiety and with certain physical disease conditions.This work may also suggest new opportunities for preventing and treating depression by targeting inflammation.

Keywords:early life stress; social threat; cytokines;mechanisms; disease

來源出版物：Psychological Bulletin, 2014, 140(3): 774-815

Inflamed moods: A review of the interactions between inflammation and mood disorders

Rosenblat, Joshua D; Cha, Danielle S;Mansur, Rodrigo B; et al.

Abstract:Mood disorders have been recognized by the World Health Organization (WHO) as the leading cause of disability worldwide.Notwithstanding the established efficacy of conventional mood agents, many treated individuals continue to remain treatment refractory and/or exhibit clinically significant residual symptoms, cognitive dysfunction, and psychosocial impairment.Therefore, a priority research and clinical agenda is to identify pathophysiological mechanisms subserving mood disorders to improve therapeutic efficacy.During the past decade,inflammation has been revisited as an important etiologic factor of mood disorders.Therefore, the purpose of this synthetic review is threefold: 1) to review the evidence for an association between inflammation and mood disorders,2) to discuss potential pathophysiologic mechanisms that may explain this association and 3) to present novel therapeutic options currently being investigated that target the inflammatory-mood pathway.Accumulating evidence implicates inflammation as a critical mediator in the pathophysiology of mood disorders.Indeed, elevated levels of pro-inflammatory cytokines have been repeatedly demonstrated in both major depressive disorder (MDD)and bipolar disorder (BD) patients.Further, the induction of a pro-inflammatory state in healthy or medically ill subjects induces ‘sickness behavior’ resembling depressive symptomatology.Potential mechanisms involved include,but are not limited to, direct effects of pro-inflammatory cytokines on monoamine levels, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, pathologic microglial cell activation, impaired neuroplasticity and structural and functional brain changes.Anti-inflammatory agents, such as acetyl-salicylic acid (ASA), celecoxib, anti-TNF-alpha agents, minocycline, curcumin and omega-3 fatty acids, are being investigated for use in mood disorders.Current evidence shows improved outcomes in mood disorder patients when anti-inflammatory agents are used as an adjunct to conventional therapy; however,further research is needed to establish the therapeutic benefit and appropriate dosage.

Keywords:bipolar disorder; cytokines; inflammation;major depressive disorder; mood disorder; non-steroidal anti-inflammatory drug (NSAID)

來源出版物：Progress in Neuro-Psychopharmacology &Biological Psychiatry, 2014, 53: 23-34

A critical appraisal of neuroimaging studies of bipolar disorder: Toward a new conceptualization of underlying neural circuitry and a road map for future research

Phillips, Mary L; Swartz, Holly A

Abstract:Objective: In this critical review, the authors appraise neuroimaging findings in bipolar disorder in emotion-processing, emotion-regulation, and rewardprocessing neural circuitry in order to synthesize the current knowledge of the neural underpinnings of bipolar disorder and provide a neuroimaging research road map for future studies.Method: The authors examined findings from all major studies in bipolar disorder that used functional MRI, volumetric analysis, diffusion imaging,and resting-state techniques, integrating findings to provide a better understanding of larger-scale neural circuitry abnormalities in bipolar disorder.Results: Bipolar disorder can be conceptualized, in neural circuitry terms, as parallel dysfunction in prefrontal cortical (especially ventrolateral prefrontal cortical) hippocampal-amygdala emotionprocessing and emotion-regulation circuits bilaterally,together with an “overactive” left-sided ventral.striatalventrolateral and orbitofrontal cortical reward-processing circuitry, resulting in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability,emotional dysregulation, and heightened reward sensitivity.A potential structural basis for these functional abnormalities is gray matter volume decreases in the prefrontal and temporal cortices, the amygdala, and the hippocampus and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions.Conclusions:Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuits supporting emotion processing, emotion regulation, and reward processing, although there are several limitations to these studies.Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches;larger studies examining neurodevelopmental trajectories in youths with bipolar disorder or at risk for bipolar disorder; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful individual-level data.Such studies will help identify clinically relevant biomarkers to guide diagnosis and treatment decision making for individuals with bipolar disorder.

來源出版物：American Journal of Psychiatry, 2014, 171(8):829-843

Reward processing dysfunction in major depression,bipolar disorder and schizophrenia

Whitton, Alexis E; Treadway, Michael T;Pizzagalli, Diego A; et al.

Abstract:Purpose of reviewThis article reviews the recent literature on reward processing dysfunction in major depression (MDD), bipolar disorder and schizophrenia,with a focus on approach motivation, reward learning and reward-based decision-making.Recent findingsEmerging evidence indicates the presence of reward processing abnormalities across all three disorders, supporting a transdiagnostic approach.In particular, findings are consistent with a role of abnormal phasic striatal dopamine signaling, which is critical for reinforcement learning,efficient mobilization of effort to obtain reward and allocation of attention to reward-predictive cues.Specifically,reward-related striatal signaling appears blunted in MDD and the negative symptoms of schizophrenia, elevated in bipolar (hypo) mania, and contextually misallocated in the positive symptoms of psychosis.However, whether shared or distinct pathophysiological mechanisms contribute to abnormal striatal signaling across the three disorders remains unknown.Summary: New evidence of reward processing abnormalities in MDD, bipolar disorder and schizophrenia has led to a greater understanding of the neural processes associated with symptomatology common across these conditions (e.g., anhedonia).Dissecting various subcomponents of reward processing that map onto partially different neurobiological pathways and investigating their dysregulation in different psychiatric disorders holds promise for developing more targeted, and hopefully efficacious treatment and intervention strategies.

Keywords:bipolar disorder; dopamine; major depressive disorder; reward learning; schizophrenia

來源出版物：Current Opinion in Psychiatry, 2015, 28(1):7-12

Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: A systematic review and meta-analysis

Vancampfort, Davy; Stubbs, Brendon;Mitchell, Alex J; et al.

Abstract:Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases.The primary aim of this systematic review and meta-analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders,bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use.The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls.The pooled MetS prevalence in people with severe mental illness was 32.6% (95%CI:30.8%-34.4%;N=198;n=52678).Relative risk metaanalyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder.Only two studies directly compared people with schizophrenia and major depressive disorder,precluding meta-analytic calculations.Older age and a higher body mass index were significant moderators in the final demographic regression model (z=-3.6,P=0.0003,r2=0.19).People treated with all individual antipsychotic medications had a significantly (P＜0.001) higher MetS risk compared to antipsychotic-naive participants.MetS risk was significantly higher with clozapine and olanzapine(except vs.clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs.amisulpride).Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS(RR=1.58; 95%CI: 1.35-1.86;P＜0.001) and all its components, except for hypertension (P=0.07).These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness.Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients.Risks of individual antipsychotics should be considered when making treatment choices.

Keywords:Metabolic syndrome; severe mental illness;schizophrenia; bipolar disorder; major depressive disorder;antipsychotics

來源出版物：World Psychiatry, 2015, 14(3): 339-347

Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder

Mertens, Jerome; Wang, Qiuwen; Kim, Yongsung; et al.

Abstract:Bipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15% of patients commit suicide.Hence, it has been ranked by the World Health Organization as a top disorder of morbidity and lost productivity.Previous neuropathological studies have revealed a series of alterations in the brains of patients with bipolar disorder or animal models’, such as reduced glial cell number in the prefrontal cortex of patients,upregulated activities of the protein kinase A and C pathways and changes in neurotransmission.However,the roles and causation of these changes in bipolar disorder have been too complex to exactly determine the pathology of the disease.Furthermore, although some patients show remarkable improvement with lithium treatment for yet unknown reasons, others are refractory to lithium treatment.Therefore, developing an accurate and powerful biological model for bipolar disorder has been a challenge.The introduction of induced pluripotent stem-cell (iPSC) technology has provided a new approach.Here we have developed an iPSC model for human bipolar disorder and investigated the cellular phenotypes of hippocampal dentate gyrus-like neurons derived from iPSCs of patients with bipolar disorder.Guided by RNA sequencing expression profiling, we have detected mitochondrial abnormalities in young neurons from patients with bipolar disorder by using mitochondrial assays; in addition, using both patch-clamp recording and somatic Ca2+imaging, we have observed hyperactive action-potential firing.This hyperexcitability phenotype of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment.Therefore,hyperexcitability is one early endophenotype of bipolar disorder, and our model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment.

來源出版物：Nature, 2015, 527(7576): 95-99

Bipolar disorder

Grande, Iria; Berk, Michael; Birmaher, Boris

Abstract:Bipolar disorder is a recurrent chronic disorder characterised by fluctuations in mood state and energy.It affects more than 1% of the world's population irrespective of nationality, ethnic origin, or socioeconomic status.Bipolar disorder is one of the main causes of disability among young people, leading to cognitive and functional impairment and raised mortality, particularly death by suicide.A high prevalence of psychiatric and medical comorbidities is typical in affected individuals.Accurate diagnosis of bipolar disorder is difficult in clinical practice because onset is most commonly a depressive episode and looks similar to unipolar depression.Moreover, there are currently no valid biomarkers for the disorder.Therefore,the role of clinical assessment remains key.Detection of hypomanic periods and longitudinal assessment are crucial to differentiate bipolar disorder from other conditions.Current knowledge of the evolving pharmacological and psychological strategies in bipolar disorder is of utmost importance.

來源出版物：Lancet, 2016, 387(10027): 1561-1572

The genetics of stress-related disorders: PTSD,depression, and anxiety disorders

Smoller, Jordan W

Abstract:Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors.An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research.This review focuses on the genetic basis of three disorder categories-posttraumatic stress disorder (PTSD), major depressive disorder (MDD),and the anxiety disorders-for which environmental stressors and stress responses are understood to be central to pathogenesis.Each of these disorders aggregates in families and is moderately heritable.More recently,molecular genetics approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants.In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene-environment interaction.Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders.Progress in this area will likely require analysis of much larger sample sizes than have been reported to date.The phenotypic complexity and genetic overlap among these disorders present further challenges.The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research.

來源出版物：Neuropsychopharmacology, 2016, 41(1):297-319

Subcortical volumetric abnormalities in bipolar disorder

Hibar, DP; Westlye, LT; van Erp, TGM; et al.

Abstract:Considerable uncertainty exists about the defining brain changes associated with bipolar disorder(BD).Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis.Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate,hippocampus, globus pallidus, putamen, thalamus, lateral ventricles.In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohe’sd=-0.232;P=3.50×10-7) and thalamus (d=-0.148;P=4.27×10-3) and enlarged lateral ventricles (d=-0.260;P=3.93×10-5) in patients.No significant effect of age at illness onset was detected.Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls.However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume.This likely represents similar etiology between BD subtype classifications.Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium.We detected no significant differences between BDII patients and controls in the largest such comparison to date.Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

來源出版物：Molecular Psychiatry, 2016, 21(12):1710-1716

What are ‘good’ depression symptoms? Comparing the centrality of DSM and non-DSM symptoms of depression in a network analysis

Fried, Eiko I; Epskamp, Sacha; Nesse, Randolph M; et al.

Abstract:Background: The symptoms for Major Depression (MD) defined in the DSM-5 differ markedly from symptoms assessed in common rating scales, and the empirical question about core depression symptoms is unresolved.Here we conceptualize depression as a complex dynamic system of interacting symptoms to examine what symptoms are most central to driving depressive processes.Methods: We constructed a network of 28 depression symptoms assessed via the Inventory of Depressive Symptomatology (IDS-30) in 3463 depressed outpatients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.We estimated the centrality of all IDS-30 symptoms, and compared the centrality of DSM and non-DSM symptoms; centrality reflects the connectedness of each symptom with all other symptom.Results: A network with 28 interwined symptom emerged, and symptoms differed substantially in their centrality values.Both DSM symptoms (e.g., sad mood)and non-DSM symptom (e.g., anxiety) were among the most central symptoms, and DSM criteria were no mow central than non-DSM symptoms.Limitations: Many subjects enrolled in STAR*D reported comorbid medical and psychiatric conditions which may have affected symptom presentation.Conclusion: The network perspective neither supports the standard psychometric notion that depression symptoms are equivalent indicators of MD, nor the common assumption that DSM symptoms of depression are of higher clinical relevance than non-DSM depression symptoms.The findings suggest the value of research focusing On especially central symptoms to increase the accuracy of predicting outcomes such as the course of illness, probability of relapse, and treatment response.

Keywords:centrality; depression symptoms; major depression; network analysis

來源出版物：Journal of Affective Disorders, 2016,189:314-320

Resting-state connectivity biomarkers define neurophysiological subtypes of depression

Drysdale, Andrew T; Grosenick, Logan; Downar, Jonathan;et al.

Abstract:Biomarkers have transformed modern medicine but remain largely elusive in psychiatry, partly because there is a weak correspondence between diagnostic labels and their neurobiological substrates.Like other neuropsychiatric disorders, depression is not a unitary disease, but rather a heterogeneous syndrome that encompasses varied, co-occurring symptoms and divergent responses to treatment.By using functional magnetic resonance imaging (fMRI) in a large multisite sample (n=1188), we show here that patients with depression can be subdivided into four neurophysiological subtypes(‘biotypes’) defined by distinct patterns of dysfunctional connectivity in limbic and frontostriatal networks.Clustering patients on this basis enabled the development of diagnostic classifiers (biomarkers) with high (82%-93%)sensitivity and specificity for depression subtypes in multisite validation (n=711) and out-of-sample replication(n=477) data sets.These biotypes cannot be differentiated solely on the basis of clinical features, but they are associated with differing clinical-symptom profiles.They also predict responsiveness to transcranial magnetic stimulation therapy (n=154).Our results define novel subtypes of depression that transcend current diagnostic boundaries and may be useful for identifying the individuals who are most likely to benefit from targeted neurostimulation therapies.

來源出版物：Nature Medicine, 2017, 23(1): 28-38

Prevalence of depression in patients with mild cognitive impairment a systematic review and Meta-analysis

Ismail, Zahinoor; Elbayoumi, Heba; Fischer, Corinne E

Abstract:Depression is common in individuals with mild cognitive impairment (MCI) and may confer a higher likelihood of progression to dementia.Prevalence estimates of depression in those with MCI are required to guide both clinical decisions and public health policy, but published results are variable and lack precision.Depression is common in individuals with mild cognitive impairment(MCI) and may confer a higher likelihood of progression to dementia.Prevalence estimates of depression in those with MCI are required to guide both clinical decisions and public health policy, but published results are variable and lack precision.A search of literature from database inception to March 2016 was performed using Medline,Embase, and PsycINFO.Hand searching of all included articles was performed, including a Google Scholar search of citations of included articles.Articles were included if they (1) were published in English, (2) reported patients with MCI as a primary study group, (3) reported depression or depressive symptoms using a validated instrument, and(4) reported the prevalence of depression in patients with MCI.All abstracts, full-text articles, and other sourceswere reviewed, with data extracted in duplicate.The overall prevalence of depression in patients with MCI was pooled using a random-effects model.Heterogeneity was explored using stratification and random-effects meta-regression.The prevalence of depression in patients with MCI,reported as a percentage with 95% CIs.Estimates were also stratified by population source (community-based or clinicbased sample), method of depression diagnosis (clinicianadministered, informant-based, or self-report), and method of MCI diagnosis (cognitive vs global measure and amnestic vs nonamnestic).Of 5687 unique abstracts, 255 were selected for full-text review, and 57 studies, representing 20 892 patients, met all inclusion criteria.The overall pooled prevalence of depression in patients with MCI was 32%(95%CI, 27-37), with significant heterogeneity between estimates (I-2=90.7%).When stratified by source, the prevalence of depression in patients with MCI in community-based samples was 25%(95%CI, 19-30) and was 40% (95%CI, 32-48) in clinic-based samples, which was significantly different (P＜0.01).The method used to diagnose depression did not significantly influence the prevalence estimate, nor did the criteria used for MCI diagnosis or MCI subtype.The prevalence of depression in patients with MCI is high.A contributor to heterogeneity in the reported literature is the source of the sample, with greater depression burden prevalent in clinic-based samples.

來源出版物：Nonlinear Dynamics, 2016, 83(4): 2157-2169

Resting-state connectivity biomarkers define neurophysiological subtypes of depressionDrysdale, Andrew T; Grosenick, Logan;

Downar, Jonathan; et al.

Abstract:Biomarkers have transformed modern medicine but remain largely elusive in psychiatry, partly because there is a weak correspondence between diagnostic labels and their neurobiological substrates.Like other neuropsychiatric disorders, depression is not a unitary disease, but rather a heterogeneous syndrome that encompasses varied,co-occurring symptoms and divergent responses to treatment.By using functional magnetic resonance imaging(fMRI) in a large multisite sample (n= 1188), we show here that patients with depression can be subdivided into four neurophysiological subtypes (‘biotypes’) defined by distinct patterns of dysfunctional connectivity in limbic and frontostriatal networks.Clustering patients on this basis enabled the development of diagnostic classifiers (biomarkers) with high (82%-93%) sensitivity and specificity for depression subtypes in multisite validation (n=711) and out-of-sample replication (n=477) data sets.These biotypes cannot be differentiated solely on the basis of clinical features, but they are associated with differing clinicalsymptom profiles.They also predict responsiveness to transcranial magnetic stimulation therapy (n=154).Our results define novel subtypes of depression that transcend current diagnostic boundaries and may be useful for identifying the individuals who are most likely to benefit from targeted neurostimulation therapies.

來源出版物：Nature Medicine, 2017, 23(1): 28-38

The Healthy Activity Program (HAP), a lay counsellor-delivered brief psychological treatment for severe depression, in primary care in India: A randomised controlled trial

Patel, Vikram; Weobong, Benedict; Weiss, Helen A

Abstract:Background: Although structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care.We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings.Methods: In this randomised controlled trial, we recruited participants aged 18-65 years scoring more than 14 on the Patient Health Questionnaire 9(PHQ-9) indicating moderately severe to severe depression from ten primary health centres in Goa, India.Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible.Participants were randomly allocated (1:1) to enhanced usual care (EUC) alone or EUC combined with HAP in randomly sized blocks (block size four to six [two to four for men]), stratified by primary health centre and sex, and allocation was concealed with use of sequential numbered opaque envelopes.Physicians providing EUC were masked.Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression (PHQ-9 score of ＜10) at 3 months in the intention to-treat population, assessed by masked field researchers.Secondary outcomes were disability, days unable to work, behavioural activation, suicidal thoughts or attempts, intimate partner violence, and resource use and costs of illness.We assessed serious adverse events in the per-protocol population.This trial is registered with the ISRCTN registry, number ISRCTN95149997.Findings:Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 495 participants (247 [50%] to the EUC plus HAP group [two of whom were subsequently excluded because of protocol violations] and 248 [50%] to the EUC alone group), of whom 466 (95%) completed the 3 month primary outcome assessment (230 [49%] in the EUC plus HAP group and 236 [51%] in the EUC alone group).Participants in the EUC plus HAP group had significantly lower symptom severity (Beck Depression Inventory version II in EUC plus HAP group 19.99 [SD 15.70] vs 27.52 [13.26] in EUC alone group; adjusted mean difference -7.57 [95%CI-10.27 to -4.86];p＜0.0001)and higher remission (147 [64%] of 230 had a PHQ-9 score of ＜ 10 in the HAP plus EUC group vs 91 [39%] of 236 in the EUC alone group; adjusted prevalence ratio 1.61[1.34-1.93]) than did those in the EUC alone group.EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability (adjusted mean difference-2.73 [-4.39 to -1.06];p=0.001), days out of work (-2.29[-3.84 to -0.73];p=0.004), intimate partner physical violence in women (0.53 [0.29-0.96];p=0.04), behavioural activation (2.17 [1.34-3.00];p＜0.0001), and suicidal thoughts or attempts (0.61 [0.45-0.83];p=0.001).The incremental cost per quality-adjusted life-year gained was$ 9333 (95%CI3862-28 169; 2015 international dollars),with an 87% chance of being cost-effective in the study setting.Serious adverse events were infrequent and similar between groups (nine [4%] in the EUC plus HAP group vs ten [4%] in the EUC alone group;p=1.00).Interpretation:HAP delivered by lay counsellors plus EUC was better than EUC alone was for patients with moderately severe to severe depression in routine primary care in Goa, India.HAP was readily accepted by this previously untreated population and was cost-effective in this setting.HAP could be a key strategy to reduce the treatment gap for depressive disorders, the leading mental health disorder worldwide.

來源出版物：Lancet, 2017, 389(10065): 176-185

The PHQ-9：Validity of a brief depression severity measure

Kroenke, K; Spitzer, RL; Williams, JBW

While considerable attention has focused on improving the detection of depression, assessment of severity is also important in guiding treatment decisions.Therefore, we examined the validity of a brief, new measure of depression severity.The Patient Health Questionnaire (PHQ) is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders.The PHQ-9 is the depression module, which scores each of the 9 DSM-IV criteria as “0” (not at all) to“3” (nearly every day).The PHQ-9 was completed by 6000 patients in 8 primary care clinics and 7 obstetricsgynecology clinics.Construct validity was assessed using the 20-item Short-Form General Health Survey, selfreported sick days and clinic visits.and symptom-related difficulty.Criterion validity was assessed against an Independent structured mental health professional (MHP)interview in a sample of 580 patients.As PHQ-9 depression severity Increased, there was a substantial decrease in functional status on all 6 SF-20 subscales.Also,symptom-related difficulty, sick days, and health care utilization increased.Using the MHP reinters view as the criterion standard, a PHQ-9 score greater than or equal to 10 had a sensitivity of 88% and a specificity of 88% for major depression.PHQ-9 scores of 5, 10, 15 and 20 represented mild, moderate, moderately severe, and severe depression, respectively.Results were similar in the primary care and obstetrics-gynecology samples.In addition to making criteria-based diagnoses of depressive disorders, the PHQ-9 Is also a reliable and valid measure of depression severity.These characteristics plus Its brevity make the PHQ-9 a useful clinical and research tool.Results from instrumented test runs with a high-speed train on a soft soil site in Sweden are presented.It is shown that large dynamic amplifications appear in the dynamic response of the rail/embankment/ground system as the train speed approaches an apparently critical value.The measured dynamic response is analyzed in detail, and it is shown that the critical speed is controlled by the minimum phase velocity of the first Rayleigh mode of the soil and embankment profile at the site.Moreover, it is shown that the critical speed and the amount of dynamic amplification also depend on a coincidence between characteristic wavelengths for the site and the distances between bogies and axles in the train.The displacement response is found to consist of a speed-independent portion in quasi-static equilibrium with the train loads and a dynamic portion representing freely propagating Rayleigh waves.An efficient computer code for the prediction of ground response to high-speed trains has been developed and its ability to reproduce the observed behavior is demonstrated.

來源出版物：Journal of General Internal Medicine, 2001,16(9): 606-613

Abstract:Transporter-facilitated uptake of serotonin(5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and anti-anxiety drugs.Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region.The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts.Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sib ships.

來源出版物：Science, 1996, 274(5292): 1527-1531

Abstract:Objective: To review the literature of the validity of the Hospital Anxiety and Depression Scale (HADS).Method: A review of the 747 identified papers that used HADS was performed to address the following questions:(1) How are the factor structure, discriminant validity and the internal consistency of HADS? (2) How does HADS perforin as a case finder for anxiety disorders and depression? (3) How does HADS agree with other self-rating instruments used to rate anxiety and depression?Results: Most factor analyses demonstrated a two-factor solution in good accordance with the HADS subscales for Anxiety (HADS-A) and Depression (HADS-D),respectively.The correlations between the two subscales varied from 0.40 to 0.74 (mean 0.56).Cronbach’s alpha for HADS-A varied from 68 to 93 and for HADS-D from 67 to 90.In most studies an optimal balance between sensitivity and specificity was achieved when caseness was defined by a score of 8 or above on both HADS-A and HADS-D.The sensitivity and specificity for both HADS-A and HADS-D of approximately 0.80 were very similar to the sensitivity and specificity achieved by the General Health Questionnaire (GHQ).Correlations between HADS and other commonly used questionnaires were in the range 49 to 83.HADS was found to perform well in assessing the symptom severity and caseness of anxiety disorders and depression in both somatic, psychiatric and primary care patients and in the general population.

anxiety; depression; Psychiatric Status Rating Scales; psychometrics; reproducibility of results;sensitivity and specificity

責(zé)任編輯：衛(wèi)夏雯