作者：Caroline Cassels
出處：WebMD醫學新聞
August 29, 2008 — 懷孕第二個月的急性妊娠壓力，顯著地增加兒童日後發生精神分裂症的可能性，特別是女孩子。
紐約大學醫學院的研究團隊發現，懷孕第二個月時的急性妊娠壓力與兒童發生精神分裂的風險上升2.3倍有關；女孩子發生精神分裂的風險更達4倍。
根據主要研究者Dolores Malaspina醫師表示，精神分裂症已經與子宮內暴露在因為喪親之痛、飢餓或重大災難等引發的急性妊娠壓力有關，且最近的證據顯示，人類在懷孕的第一期時最容易因為這樣受傷。
我們的研究結果顯示，嚴重壓力本身就可以在沒有感染、營養不良或是環境變化下，造成之後發生精神分裂症；Malaspina醫師向Medscape精神學表示，除此之外，我們能夠準確地指出風險較高的時間，且顯示這有性別專一性，女孩子的風險比男孩子更高。
這項研究線上發表於8月21日的BMC精神學期刊。
【自然實驗】
直到最近，證據是非常有限且缺乏統計力量的；研究團隊表示，要區分短期精神壓力與不佳的環境、飲食或是生活型態所帶來長期的影響是不容易的，後者可以是兒童時期的慢性壓力源；除此之外，較早期的研究缺乏有關於壓力時間點與其特徵的專一性。
為了檢驗急性妊娠壓力對於兒童的影響，研究人員追蹤一群於1967年6月之間懷孕的後代，當時正處於為期六天的阿拉伯以色列戰爭。
Malaspina醫師表示，這個衝突（戰爭）非常的嚴重，但是並不長，因此給了研究者一個自然實驗的機會。
研究團隊將出生紀錄與以色列精神註冊試驗相連結，接著分析來自耶路撒冷出生前後研究的數據，這是一項群眾為基礎的研究族群，共有88,829位於1964年到1976年出生於耶路撒冷的民眾。
Malaspina醫師表示，我們針對個體的出生時間，逐月找出在她們的懷孕過程中，傷害發生的確切時間，接著與之後診斷罹患精神分裂症相連結。
【存活效應？】
在這個族群中共有88,829位民眾，其中有637位被確認與精神分裂症有關的診斷，676位被確定罹患其他精神疾病；根據這項研究，原始數據顯示出生於1968年1月的群眾，發生精神分裂症的風險高出2~3倍，而這些群眾的母親在1967年6月時正處於懷孕的第二個月。
研究團隊發現，兒童精神分裂症或是其他狀況的發生率異常在戰爭後三個月，或是戰爭前三個月。
校正分析後顯示，於1967年6月時懷孕第二個月的女性，其所產下的小孩，精神分裂症的整體發生率加倍；對於男孩子而言，這項疾病的發生率增加20%，但在女孩子身上，危險比值高達4.3。
女孩子精神分裂症發生率較高的原因未明；研究共同作者Susan Harlap醫學學士在訪談中表示，但至少有兩項假設，第一項是男孩子比較不容易罹患精神分裂症。
然而，有第二個比較可能的假設；動物與臨床研究顯示，處於嚴重壓力下的女性較容易自發性流產。除此之外，流行病學研究顯示，男性胚胎較女性胚胎容易流產。
Harlap表示，這可能具有存活效應，因此女性胚胎並不一定就比較容易受到妊娠時壓力，而增加精神分裂症風險，但是女性胚胎在妊娠壓力下較不容易自發性流產。
【冰山一角？】
根據Malaspina醫師表示，這項研究的發現低估了妊娠壓力對於發育中胚胎的潛在負面影響。
她指出，嚴重的壓力可能只是冰山一角，我們必須記住腦部並非從固定的藍圖發展而來，且懷孕時的壓力會塑造基因成為易發生特定疾病。
醫師必須建議計畫組成家庭的婦女們，在懷孕前就開始降低她們的壓力。
我相信，我們並未提供太多有關於懷孕前與懷孕時必須降低壓力的訊息給懷孕婦女，一定的妊娠壓力對健康胎兒的發育是絕對必需的，但是婦女應該被建議，儘量地維持健康生活，包括運動、適當的睡眠、良好的營養與減少壓力。她表示，我們希望我們所有的病患都有健康的生活型態，這就是一個最好的理由。
研究者表示無相關資金上的關係。
Maternal Stress in Early Pregnancy Raises Schizophrenia Risk for Offspring
By Caroline Cassels
Medscape Medical News
August 29, 2008 — Acute maternal stress in the second month of pregnancy significantly increases the likelihood that the child will develop schizophrenia in later life, particularly if that child is female.
Investigators at the New York University School of Medicine, in New York, found that acute maternal stress in the second month of pregnancy was associated with a 2.3-fold increased risk for schizophrenia in children; the risk was more than 4-fold among female children.
According to principal investigator Dolores Malaspina, MD, MPH, schizophrenia has been linked with intrauterine exposure to maternal stress due to bereavement, famine, and major disasters, and recent evidence suggests that humans are most vulnerable in the first trimester of gestation.
"We showed that severe stress alone, in the absence of infection, malnutrition, or environmental changes, is related to later schizophrenia. Furthermore, we were able to pinpoint the timing of this risk, and showed there was sex specificity and that female offspring are at much greater risk than males," Dr. Malaspina told Medscape Psychiatry.
The study was published online August 21 in BMC Psychiatry.
Natural Experiment
Until recently, the evidence has been limited by low statistical power. The researchers note that it has been difficult to separate short-term psychic stressors from the long-term influence of disrupted environments, diets, or lifestyles that can act as chronic stressors during childhood. Furthermore, earlier research lacked specificity regarding the timing of stress and its character.
To examine the consequences of acute maternal stress in children, the investigators followed a cohort of offspring whose mothers were pregnant in June 1967, during the 6-day Arab–Israeli war.
This conflict, said Dr. Malaspina, was extremely severe but relatively short-lived, so provided investigators with "a natural experiment."
The researchers linked birth records with Israel's Psychiatric Registry and then analyzed data from the Jerusalem Perinatal Study, a population-based research cohort of 88,829 individuals born in Jerusalem between 1964 and 1976.
"We looked at the timing of the individuals' birth to narrow down, month by month, the exact point [in their gestational life] the insult took place, and then correlated that information with a diagnosis of schizophrenia in later life," said Dr. Malaspina.
Survival Effect?
A total of 637 people in this cohort of 88,829 were identified with schizophrenia-related diagnoses, and 676 were identified with other psychiatric disorders. According to the study, the raw data suggest a 2- to 3-fold excess of schizophrenia in the cohort born in January 1968, whose mothers would have been in their second month of pregnancy in June 1967.
The researchers found no unusual incidence of schizophrenia or other conditions among children conceived in the 3 months after the war, or in those born in the 3 months before it.
Adjusted analyses revealed that the overall incidence of schizophrenia was more than double that for children who were in the second month of gestation in June 1967. In males alone, there was a 20% increased risk for the disorder; in females, the hazard ratio was 4.3.
The reason for the higher incidence of schizophrenia among females is not clear. But there are at least 2 potential hypotheses. The first is that males are less susceptible to schizophrenia, study coauthor Susan Harlap, MBBS, said in an interview.
However, she said, there is a second, and possibly more likely, explanation. Animal and clinical research shows that severely stressed females frequently spontaneously abort. In addition, epidemiologic studies show that male fetuses tend to be miscarried more frequently than females.
"There may be a survival effect at play, so it is not necessarily that female fetuses are more susceptible to schizophrenia due to maternal stress, but that they are less likely to be aborted in the presence of maternal stress," said Dr. Harlap.
Tip of the Iceberg?
According to Dr. Malaspina, the study's findings underscore the potential negative impact of maternal stress on the developing fetus.
"Severe stress may just be the tip of the iceberg. We must keep in mind that the brain doesn't develop from a blueprint, and stress during pregnancy can program genes for many medical conditions," she said.
Physicians need to advise women who are planning a family to reduce their stress levels well in advance of the actual pregnancy, she added.
"I believe there's very little information given to pregnant women about the need to reduce stress well before and during pregnancy. A certain amount of maternal stress is absolutely necessary for healthy fetal development, but women should be advised to, as much as they can, lead a healthy life that includes exercise, proper sleep, good nutrition, and reduced stress. We want all our patients to live a healthy lifestyle, and here's 1 more reason to," said Dr. Malaspina.
The researchers have disclosed no relevant financial relationships.
BMC Psychiatry. 2008; Published online before print August 21, 2008. Abstract
[ 本帖最後由 goodcat1111 於 2008-9-8 22:15 編輯 ] |
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