本帖最後由 lsc0019 於 2009-6-29 23:36 編輯
作者：Janis Kelly
出處：WebMD醫學新聞
June 9, 2009 — 新研究顯示，有血管張力素轉化酶（ACE）對偶基因以及低ACE活性的男性，可能比較容易自殺，且以跳樓這種典型比較常見於女性的自殺模式。除此之外，研究結果顯示，這個亞群男性如果使用降低ACE活性藥物（例如ACE抑制劑、血管張力素受體阻斷藥物[ARBs]）風險更高。
試驗研究者，來自波蘭Warsaw醫學大學的Rafal Ploski醫師向Medscape精神學表示，此時，根據這些發現做出結論時我將會非常謹慎。血管張力素受體抑制劑可能是自殺風險的流行病學證據是非常微弱的，且有鑑於這些藥物對許多病患的強烈好處，在沒有進一步數據的情況下，建議停止使用將是不智的。
唯一一個我可能會仔細考慮的狀況是，執著嘗試自殺（特別是跳樓）但沒有憂鬱症病史的男性。她附帶表示，即使是這樣，或許一個較好的選擇是使用不會通過血腦障壁的藥物。
這項研究發表在6月號的神經精神學期刊上。
【結果再現了日本的研究發現】
Ploski博士的數據再現了波蘭受試者之間自殺行為與ACE基因殖入（I）及去除（D）基因多型性基因型的關連，相關的研究報告之前由Hishimoto與其同事在日本進行的研究報告（Hishimoto A等人，J Neuro Transm. 2006；113:1915-1920）。
Ploski博士表示，目前，ACE活性與自殺之間的連結是非常複雜的，現在最重要的研究對象是進一步描述有I對偶基因是其危險因子的病患，因此使得阻斷ACE潛在是危險的。
波蘭研究包括了150位自殺與165位年齡及性別相符控制組的ACE基因型。研究者們發現男性受害者ACE I對偶基因，相較於男性控制組、女性自殺組、與綜合控制組，發生頻率顯著較高。ACE I對偶基因與女性自殺之間並無關連。
研究者們發現男性ACE I對偶基因複製數目與跳樓自殺之間有顯著關係，而ACE I對偶基因數目與上吊自殺卻有負向的關係。研究者們表示，低ACE活性也與憂鬱症風險較低有關，這可能解釋了ACE抑制劑Captopril用於憂鬱症的好處。
【全新的發現】
Ploski博士表示，這是個全新的發現，特別是當合併在我們的病患族群與整個波蘭族群後的數據，更是吸引人，女性較男性更常發生以自高處跳下的自殺方式。
他指出，這些發現顯示，跳樓自殺的男性可能代表一些未知的、或許是精神上的特徵，這些特徵在女性身上比男性典型，以及對ACE II基因型效應的特別敏感度。
這項研究的結果與Hishimoto研究及Sparks等人的不同，他們發現ACE I對偶基因量與自殺之間有反向關係（Sparks DL等人，Am J Med Genet B Neuropsychiatr Genet. 2009;150B:290-294）。
Ploski博士認為，他們的研究有一個非常有趣的地方，在於如何處理這些數據。他們假設D對偶基因（高ACE活性）是罹患憂鬱症病患自殺的一個危險因子（比女性這個危險因子更為典型），然而，I對偶基因（低ACE活性）對於沒有憂鬱症影響下（主要是男性）的病患來說是更危險的。
Ploski與Hishimoto研究都專注在已完成研究的基因型。Sparks的數據絕大多數是取自於有自殺危險因子的精神病患。
作者們表示沒有相關資金上的衝突。
Genetic Predisposition Plus Use of ACE-Activity-Lowering Drugs May Increase Suicide Risk in Men
By Janis Kelly
Medscape Medical News
June 9, 2009 — Men who have an angiotensin-converting-enzyme (ACE) allele associated with low ACE activity may be more likely to commit suicide and to do so by jumping from a high place, a method more typically associated with female suicides, new research suggests. Further, the study findings raise the possibility that this subgroup of men might be at even greater risk if they are taking drugs lowering ACE activity (eg, ACE inhibitors, angiotensin-receptor blockers [ARBs]).
"I would be very cautious [about drawing clinical conclusions about these findings] at this moment," study investigator Rafal Ploski, MD, PhD, from Warsaw Medical University, in Poland, told Medscape Psychiatry. "The epidemiological evidence that angiotensin-receptor blockers might be a risk factor for suicide is very?weak, and given the proven strong benefits of these drugs for many patients, it would not be wise to recommend their discontinuation without further data."
"The only situation in which I might perhaps reflect on it would be a male without a history of depression who had seriously tried to commit suicide (in particular by jumping from a height). Even then, perhaps a better option would be to go for a drug that does not penetrate the blood-brain barrier," he added.
The study is published in the June issue of Neuropsychobiology
Results Replicate Japanese Findings
Dr. Ploski's data replicate in Polish subjects the link between suicide and the ACE II genotype of the ACE insertion (I)/deletion (D) polymorphism previously reported by Hishimoto and colleagues in Japanese subjects (Hishimoto A et al. J Neural Transm. 2006;113:1915-1920).
"At present, the link between ACE activity and suicide looks very complex, and the most important subject to?study now is?to further delineate?the subset in whom the I allele is the risk factor, thus making ACE blockade potentially dangerous," Dr. Ploski said.
The Polish study included ACE genotype analysis in 150 completed suicides and 165 age- and sex-matched controls. The researchers found an increase in the frequency of the ACE I allele among male victims of suicide compared with male controls, female suicides, and pooled controls. There was no association between the ACE I allele and suicide in females.
The researchers found a striking association in males between the number of copies of the ACE I allele and suicide by jumping from a height, as well as a negative association between ACE I allele numbers and risk of suicide by hanging. Low ACE activity is also associated with lower risk of depression, which may explain reports of the beneficial effects of the ACE inhibitor captopril in depression, the researchers note.
Novel Observation
Dr. Ploski said this is "a novel observation that is particularly interesting when combined with the data showing that both in our samples and in a whole Polish population, jumping from a height as a means of suicide was significantly more frequent in women than men.
"These findings suggest that males committing suicide by jumping may represent a distinct subset characterized by some unknown, perhaps psychological, features that are more typical of females than males, as well as by a particular sensitivity to the effect of the ACE II genotype," he said.
The results of this and the Hishimoto studies are at odds with data reported by Sparks et al, who found a negative correlation between amount of the ACE I allele and suicide (Sparks DL et al. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:290-294).
"I think a very interesting aspect of our work is a suggestion how to reconcile these data,” Dr. Ploski said. “We propose that the D allele (high ACE activity) is a suicide risk factor in persons with depression (more typical of females), whereas the I allele (low ACE activity) may be more dangerous in patients who do not act under influence of depression (mainly males)."
The Ploski and Hishimoto studies both focused on genotypes in completed suicides. The Sparks data were largely drawn from a study of risk factors for suicide attempts in psychiatric patients.
The authors report no relevant conflicts of interest.
Neuropsychobiology. 2009;59:151-158. |
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