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作者：Pam Harrison  
出處：WebMD醫學新聞

　　January 11, 2010 — 根據為期30年的「Dunedin Multidisciplinary Health and Development Study」研究結果，成年時發生精神分裂症者，在孩童時期已經顯示出一些徵兆，在7歲時有認知障礙，在記憶、注意力、處理速度等測量上，比他們的同儕慢成熟。
　　
　　線上登載於1月4日美國精神醫學期刊(American Journal of Psychiatry)的研究中，英國倫敦國王學院精神科研究中心的Abraham Reichenberg博士等人發現，成年時發生精神分裂症者，在孩童時與同儕相較，評估語言和視覺知識獲取、推理以及概念化的認知測驗中，比同儕早出現一些發育障礙徵兆，且維持穩定，這些孩童在評估處理速度、注意力、解決視覺-空間問題、操作記憶上也比同儕慢。
　　
　　在後來發生反覆憂鬱症的孩童中，也有這些發病前認知模式。
　　
　　研究者、Avshalom Caspi博士向Medscape Psychiatry表示，這個精神分裂症神經發展模式認為，這些神經障礙有許多在診斷前幾年已經出現，我們特別希望瞭解的是，這些認知障礙對於智商之外的本質。我認為，這些發現強調了一個事實，成人精神分裂症在生命早期即有跡可循。
　　
　　【縱向研究】
　　「Dunedin Multidisciplinary Health and Development Study」是一個縱向研究，研究對象是在1972至1973年間於紐西蘭Dunedin出生的所有孩童，研究者探討他們的健康與行為。
　　
　　這個世代中，總共有1,037名孩童參與在3歲時的追蹤評估，成為本研究的基礎樣本。在這些研究對象7、9、11、13歲生日的1個月內，使用Wechsler氏兒童智力量表-修定版( Wechsler Intelligence Scale for Children–Revised[WISC-R])，測量WISC-R 中的8組問題。如同之前報告的，這個世代中，孩童期智商較低者，成年時診斷有精神分裂症或憂鬱的風險顯著增加，控制社會階級因素之後也是如此[Am J Psychiatry. 2009;166:50-57]。
　　
　　目前的分析中，成年時發生精神分裂症的孩童，在資訊、類同測驗、詞彙、完成圖畫這四個認知檢測中，有早發的認知障礙。研究作者指出，計算心智年紀而言，這些檢測結果相當於0.4-0.8歲的差異。
　　
　　成年時發生反覆憂鬱症的孩童中，發育障礙也很明顯，只是沒有這麼顯著。
　　
　　測量專心注意以及解決視覺-空間問題的檢測中，後來發生精神分裂症的孩童，在發展上平均較慢，研究者觀察發現，在7-13歲中的每一年，後來發生精神分裂症者的心智年齡比健康者落後0.17-0.26歲。
　　
　　同樣的，後來反覆憂鬱症的孩童中，一樣有這類延遲，只是較不明顯。
　　
　　【精神病學的「聖杯」】
　　共同研究者、北卡羅來納杜克大學醫學中心的Richard Keefe博士向Medscape Psychiatry表示，試著確定哪些小孩在未來會發生精神分裂症，可以說是精神科的「聖杯」，但是就目前而言，提早確認後來會發生精神分裂比單純辨識低智商孩童還要複雜許多。
　　
　　的確，研究作者強調，他們不建議用孩童的智商檢測作為提早判斷哪些人有精神分裂症的風險，因為所有孩童的認知發展會隨著時間有相當大的改變，而每一年檢測一次也不會有幫助。
　　
　　Keefe博士表示，我們已經知道認知障礙會使人比較容易發生精神病，而這些資料顯示的是，這些孩童在某些方面比同儕差，這些障礙使得他們隨著時間惡化，同時採用早期障礙以及隨著時間惡化這兩項，似乎是目前瞭解精神病發生可能性的最敏感指標。
　　
　　【累積的證據】
　　英國劍橋大學的Peter Jones博士表示，該研究指出發生精神分裂症方面的累積證據。
　　
　　他向Medscape Psychiatry表示，在類似的研究中，精神分裂症的早期認知與發展異常在15年前就已經知道了，不過，這個研究在這方面更進一步，因為它從比較動態的觀點檢視認知功能，換句話說，是這些事情隨著時間改變，而不是孩童在任一時間點異於他人。
　　
　　他也認為，有這些障礙和發展遲緩的孩童，在成人時發生精神分裂症「並不意外」。
　　
　　Jones博士表示，我們知道腦中的不同部位代表不同的認知功能，因此，如果腦中的不同部位有別於正常的發展，那麼就可以預期會發生一些不同的異常，這類研究的「真正重要的目標」是要比原本的認知還要更佳瞭解這些缺陷的神經生物學。
　　
　　英國醫學研究委員會資金支持本研究。國家心智健康研究中心資金中的國家老化研究中心資金以及Royal Society-Wolfson Merit獎，資助紐西蘭健康研究委員會的「Dunedin Multidisciplinary Health and Development」研究小組。Reichenberg博士接受AstraZeneca藥廠的發言人獎金。
　　
　　Keefe博士擔任Cortex、Schering-Plough、Abbott、Acadia、AstraZeneca、BiolineRx、Bristol-Myers Squibb、Cephalon、Dainippon Sumitoma Pharma、Eli Lilly、Johnson and Johnson、Lundbeck、Memory Pharmaceuticals、Merck、NeuroSearch、Orexigen、Orion、Otsuka、Pfizer、Roche、Sanofi/Aventis、Targacept、Wyeth與Xenoport等藥廠的顧問。Caspi博士宣告沒有相關財務關係。 Jones博士接受Bristol-Myers-Squibb、Otsuka與Eli Lilly等藥廠的講座獎金，在前一年也接受GlaxoSmithKline藥廠的研究資金。
　　
　　Am J Psychiatry. 線上發表於2010年1月4日。


Early Cognitive Deficits, Developmental Delays, May Be a Harbinger for Adult-Onset Schizophrenia

By Pam Harrison
Medscape Medical News

January 11, 2010 — Children who develop schizophrenia as adults already show signs of cognitive deficits by the age of 7 years and lag behind their peers on measures of memory, attention, and processing speed as they mature, according to results of the 30-year Dunedin Multidisciplinary Health and Development Study.

In a study published online January 4 in the American Journal of Psychiatry, Abraham Reichenberg, PhD, Institute of Psychiatry, King’s College, London, United Kingdom, and colleagues, found that children who developed schizophrenia as adults had signs of development deficits relative to their peers that emerged early and remained stable on cognitive tests assessing verbal and visual knowledge acquisition, reasoning, and conceptualization. The same children also lagged behind their peers on tests assessing processing speed, attention, visual-spatial problem solving, and working memory.

Neither one of these premorbid cognitive patterns were seen in children who later developed recurrent depression.

"The neurodevelopmental model of schizophrenia says many of these neurological deficits appear years before the disorder is diagnosed, and what we specifically wanted to do was learn more about the nature of these cognitive deficits and go beyond the IQ," study investigator Avshalom Caspi, PhD, told Medscape Psychiatry. "And I think these findings underscore the fact that what we think about as adult psychiatric disorders have their origins much earlier in life."

Longitudinal Investigation

The Dunedin Multidisciplinary Health and Development Study is a longitudinal investigation of the health and behavior of a complete cohort of children born in Dunedin, New Zealand, between 1972 and 1973.

A total of 1037 children from this birth cohort participated in the follow-up assessment at 3 years of age and formed the base sample for the study. The Wechsler Intelligence Scale for Children–Revised (WISC-R) was administered to participants within 1 month of their birthdays at ages 7, 9, 11, and 13 years. Participants were also given 8 subtests of the WISC-R. As previously reported, lower childhood IQ among the same cohort of children significantly predicted an increased risk of being diagnosed as having schizophrenia or depression as an adult, even after controlling for social class [Am J Psychiatry. 2009;166:50-57].

In the current analysis, children who developed schizophrenia as adults exhibited early cognitive deficits on 4 cognitive tests: information, similarities, vocabulary, and picture completion. "Calculated in terms of mental age, the extent of impairment on these tests ranged from 0.4 to 0.8 years," the study authors add.

Developmental deficits were also apparent, although less strikingly so, among children who developed recurrent depression as adults.

On tests measuring freedom from distractibility and visual-spatial problem solving, skills among children who would develop future schizophrenia were developmentally slower such that, on average, “for every year between the ages of 7 and 13, future schizophrenia case subjects fell behind healthy comparison subjects by an additional 0.17 to 0.26 mental age years,” the investigators observe.

Again, developmental lags were less apparent among children who later developed recurrent depression.

Psychiatry's "Holy Grail"

Coinvestigator Richard Keefe, PhD, Duke University Medical Center, Durham, North Carolina, told Medscape Psychiatry that trying to establish which child will develop future schizophrenia is really the "Holy Grail" in psychiatry, but so far early identification of future schizophrenia is more complex than simply identifying children with lower IQs.

Indeed, the study authors stress that they do not recommend testing IQ in children for the early identification of those at potential risk for schizophrenia because there is simply too much change in cognitive development over time in all children, and a single test at a single age will not be helpful.

"We’ve known for a while that cognitive deficits make an individual vulnerable to progression to psychoses, and what these data show are that vulnerable children perform worse on certain tasks than their peers, and these deficits make them vulnerable to worsening over time, and the combination of early deficit and worsening over time appears to be the most sensitive index we have of vulnerability to psychosis at this point in time," said Dr. Keefe.

Accumulating Evidence

Peter Jones, MD, PhD, University of Cambridge, United Kingdom, said the study adds to accumulating evidence for the developmental aspect of schizophrenia.

"The fact that there were early cognitive and developmental abnormalities in schizophrenia has really been known for more than 15 years from similar studies," he told Medscape Psychiatry. This study, however, "takes it a bit further because it examines cognitive function from a more dynamic point of view — in other words, the way things change over time rather than the fact that children are different from anyone at any one point in time."

He also suggests that it is "no surprise" that there are these sorts of deficits and development lags in children who develop schizophrenia as adults.

"We know that different parts of the brain subserve different cognitive function, so if those different parts of the brain develop in different ways, then you would expect that abnormalities that develop would be expressed in different ways,” he said. Dr. Jones added that the "really important goal" in this sort of research is to understand the neurobiology of these deficits, which, once better understood, "may suggest new interventions."

The study was supported by a United Kingdom Medical Research Council grant. National Institute of Mental Health grants, a National Institute on Aging grant, funding for the Dunedin Multidisciplinary Health and Development Research Unit from the New Zealand Health Research Council, and the Royal Society-Wolfson Merit Award. Dr. Reichenberg has received speaker’s honoraria from AstraZeneca. Dr. Keefe has served as a consultant to Cortex, Schering-Plough, Abbott, Acadia, AstraZeneca, BiolineRx, Bristol-Myers Squibb, Cephalon, Dainippon Sumitoma Pharma, Eli Lilly, Johnson and Johnson, Lundbeck, Memory Pharmaceuticals, Merck, NeuroSearch, Orexigen, Orion, Otsuka, Pfizer, Roche, Sanofi/Aventis, Targacept, Wyeth, and Xenoport. Dr. Caspi has disclosed no relevant financial relationships. Dr. Jones has received honoraria from Bristol-Myers-Squibb, Otsuka, and Eli Lilly for lectures and has received a research grant from GlaxoSmithKline within the previous year.

Am J Psychiatry. Published online January 4, 2010.