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‌Brain study seeks roots of suicide

Ed Kashi/VII/Corbis

There is evidence that genetics influences a person’s suicide risk

Suicide is a puzzle. Fewer than 10% of people with depression attempt suicide, and about 10% of those who kill themselves were never diagnosed with any mental-health condition.

Now, a study is trying to determine what happens in the brain when a person attempts suicide, and what sets such people apart. The results could help researchers to understand whether suicide is driven by certain brain biology — and is not just a symptom of a recognized mental disorder.

The project, which launched this month, will recruit 50 people who have attempted suicide in the two weeks before enrolling in the study. Carlos Zarate, a psychiatrist at the US National Institute of Mental Health in Bethesda, Maryland, and his colleagues will compare these people's brain structure and function to that of 40 people who attempted suicide more than a year ago, 40 people with depression or anxiety who have never attempted suicide and a control group of 40 healthy people. In doing so, the researchers hope to elucidate the brain mechanisms associated with the impulse to kill oneself.

Zarate's team will also give ketamine, a psychoactive ‘party drug’, to the group that has recently attempted suicide. Ketamine, which is sometimes used to treat depression, can quickly arrest suicidal thoughts and behaviour — even in cases when it does not affect other symptoms of depression1. The effect is known to last for about a week.

To some researchers, such findings suggest that ketamine affects brain circuits that are specific to suicidal thinking. But John Mann, a psychiatrist at Columbia University in New York City, says that abnormal brain chemistry and genetics could also predispose a person to attempt suicide in times of great stress, such as after a job loss. “They’re part of the person, they're a trait,” Mann says. “They just get more important when the person gets ill.” Written in the genes?

There is evidence that genetics influences a person’s suicide risk. For instance, biological relatives of adopted children who kill themselves are several times more likely to take their lives than the general population2.

Fabrice Jollant, a psychiatrist at McGill University in Montreal, Canada, suggests that this genetic influence is related to impulsivity and flawed judgement, rather than a specific mental illness. He has found that close relatives of people who killed themselves were more impulsive than a control group when playing a gambling game designed to test decision-making3. “It seems that this is something transmitted,” Jollant says.

Other researchers are seeking biomarkers that would allow clinicians to spot people most at risk of suicide. Alexander Niculescu, a psychiatrist at Indiana University in Indianapolis, and his colleagues have identified a set of six genes whose expression is altered in the blood of people who have killed themselves4. The team has found that combining these biomarkers with data from an app that tracks mood and risk factors can predict, with more than 90% accuracy, whether people with bipolar disorder or schizophrenia will eventually be hospitalized for a suicide attempt.

And Mann is using positron emission tomography to track the best-studied biomarker, for the signalling molecule serotonin, in the brains of people who have attempted suicide5. Their altered serotonin patterns are similar to those seen after death in the brains of those who have killed themselves, says Mann.

Although serotonin levels are altered in people with depression, Mann has found differences between people who attempt suicide and those who are depressed but have no history of suicide attempts. He has also shown that serotonin levels are altered to a greater degree in those who make more serious suicide attempts — such as taking an entire bottle of painkillers — than in those whose attempts are less drastic6.

Ethical challenges

Researchers hope that a better understanding of the biology underlying suicide will lead to more effective treatments for suicidal impulses. But studies such as Zarate’s present difficult logistical and ethical challenges. Researchers must consider whether a person who has just attempted suicide can make informed decisions about whether to participate in research.

Michael Minzenberg, a psychiatrist at the University of California, San Francisco, knows these concerns all too well: he studies suicidal people with schizophrenia. Many of these people struggle with basic life skills, such as keeping a job or finding housing. “They’re a challenging group to treat, let alone to study,” Minzenberg says.

He and other researchers who study suicidal people say that they treat them with special care — and that the overall benefits of such studies outweigh any risks. “In most clinical trials, people at high risk of suicide are excluded, so we don’t know how to treat them,” Jollant says. “We need to assess this population, not just say ‘exclude them from trials’.”

参考译文

通过大脑研究寻找自杀根源

自杀是一个谜。不到10%的抑郁症患者有自杀倾向，而与此同时，约有10%的自杀者从未被诊断出有任何心理健康问题。

现在，一项研究正在试图指出当一个人尝试自杀时大脑中究竟发生了什么，又是什么使得这些人如此“与众不同”。这些结果可能会帮助研究人员理解自杀是否不仅是一种公认的精神疾病症状，而是由某种特定大脑生物学反应引起。

该项目于本月启动，将会招募50位在参加研究前两周有过自杀尝试的参与者。来自美国国家心理健康研究所的精神病专家Carlos Zarate和他的同事将会比较这50名参与者和其他三组参与者的大脑结构以及功能，另外三组人分别由40个曾在一年前尝试自杀，40个患有抑郁症或焦虑症且并未尝试过自杀以及40个作为对照的健康人组成。研究人员希望借此研究可以阐释与自杀冲动相关联的大脑机制。

与此同时，Zarate团队将会为近期尝试过自杀的一组成员提供氯胺酮（一种致使精神兴奋的“派对药物”）。氯胺酮作为一种偶尔用来治疗抑郁症的药物，即便有些情况下它对抑郁症的其他症状没有影响，但却可以快速阻止自杀的想法和行为并将这一效果持续一周左右的时间。

对一些研究人员而言，这些发现表明氯胺酮影响了和自杀想法相关的特定大脑回路。但纽约市哥伦比亚大学精神病专家John Mann则认为非正常的脑化学和遗传基因也能让一个人在面临巨大压力时更易产生自杀倾向，比如在失业之后。Mann说：“它们是人遗传特性的一部分，在人生病时会变得更为重要。” 自杀倾向被刻入基因？

目前已有证据表明遗传基因会影响一个人的自杀风险。例如，和自杀者有亲缘关系的儿童比一般人自杀的可能性要高出几倍。

加拿大麦吉尔大学精神病专家Fabrice Jollant认为这种遗传影响并非是某种特殊的精神疾病而是与冲动和缺陷性判断有关。自杀者的亲属和对照组的一般人相比，在玩专为测试决策过程而设计的赌博游戏时更容易冲动。他表示：“似乎有某种东西被遗传了下来。”

另一些研究人员正在努力需找可以帮助临床医生判断病人自杀风险的生物标记物。印第安那大学的精神病专家Alexander Niculescu和他的同事已经鉴定出6个在自杀者血液中表达发生变化的基因，同时他们还发现将这些生物标记物与来自情绪及风险因子追踪应用的数据结合后可以预测躁郁症和精神分裂症患者是否最终会因自杀倾向而入院治疗，这一预测的准确率竟然高于90%。

Mann正在使用正电子放射断层扫描技术在那些有自杀倾向的人群中追踪目前研究最为深入的生物标记物——一种血清素的信号分子。他表示，这些人的血清素变化模式和自杀者死后大脑中的血清素变化模式非常相似。

Mann发现，尽管抑郁症患者的血清素水平都会发生变化，但有自杀倾向的患者和从未有过自杀倾向历史的患者之前还是有很大不同。另外，他也表示在这些有自杀倾向的患者中，自杀倾向严重者(比如喝下一整瓶止痛药)血清素水平的变化幅度也要比自杀倾向低的患者大很多。

伦理挑战

研究人员希望通过更好地理解潜在自杀生物学来为自杀冲动提供更加有效的治疗措施。但类似于Zarate所进行的这种研究正面临着艰难的逻辑和伦理挑战。研究人员不得不考虑一个刚刚企图自杀的人是否能够明智地决定要不要参加这类研究。

来自加州大学的精神病专家Michael Minzenberg也非常清楚这些担忧，他研究的是具有自杀倾向的精神分裂症患者，这些患者中大部分人都很难掌握基本的生活技能，譬如持有一份工作，找到一个住所之类。正如他所言：“治疗这些患者原本就已极具挑战性，更不要说研究他们了。”

他和其他研究自杀者的研究人员表示，他们必须要给予这些患者特别的护理和关心，而这些研究的整体利益则大于所能想到所有风险。Jollant表示：“在大多数临床试验中，具有高自杀风险的人都会被排除在外，因此我们并不知道该如何对待这些人。我们需要接近这个群体，而并非将他们拒之门外。”