作者: Meredith Wadman / 4161次阅读 时间: 2018年1月05日
来源: science

Huge study of teen brains could reveal roots of mental illness, impacts of drug abuse
By Meredith Wadman
陈明 编译
Jan. 3, 2018 , 5:15 PM

Combining results from 628 children's brains, this MRI scan shows regions activated as faces are viewed (yellow and orange) and other areas (blue and cyan) activated during a demanding working memory task.


Chya (pronounced SHY-a), who is not quite 10 years old, recently spent an unusual day at the University of Maryland School of Medicine in Baltimore. Part of the time she was in a "cool" brain scanner while playing video games designed to test her memory and other brain-related skills. At other points, she answered lots of questions about her life and health on an iPad.


A slender Baltimore third grader who likes drawing, hip hop, and playing with her pet Chihuahua, Chya is one of more than 6800 children now enrolled in an unprecedented examination of teenage brain development. The Adolescent Brain Cognitive Development Study—or ABCD Study—will complete its 2-year enrollment period in September, and this month will release a trove of data from 4500 early participants into a freely accessible, anonymized database. Ultimately, the study aims to follow 10,000 children for a decade as they grow from 9- and 10-year-olds into young adults.


Supported by the first chunk of $300 million pledged by several institutes at the National Institutes of Health (NIH) in Bethesda, Maryland, teams at 21 sites around the United States are regularly using MRI machines to record the structure and activity of these young brains. They're also collecting reams of psychological, cognitive, and environmental data about each child, along with biological specimens such as their DNA. In addition to providing the first standardized benchmarks of healthy adolescent brain development, this information should allow scientists to probe how substance use, sports injuries, screen time, sleep habits, and other influences may affect—or be affected by—a maturing brain.

在马里兰州贝塞斯达的国立卫生研究院(NIH)提供的第一批3亿美元的资助下,分布在美国21个地点的研究小组定期使用MRI机器记录这些年轻大脑的结构和活动。他们还收集了每个孩子的心理,认知,和成长环境的大量数据,同时也收集了他们的生物标本,比如他们的DNA。除了提供健康青少年 大脑发展的第一个标准化的基准之外,这些信息还可以让科学家探索物质滥用、运动损伤、观看电子屏幕的时间、睡眠习惯,以及其他的情况如何潜在的影响了大脑的成长,或者大脑又是如何影响这些。

"A lot of studies in this area are plagued by the fact that we tend to capture teenagers after they have already started to misbehave in various ways. So, the fact that we are following kids from … before they engage in a lot of risk-taking behavior—it's going to be an incredibly rich data set," says clinical neuroscientist Monica Luciana of the University of Minnesota in Minneapolis, an ABCD Study site where she is a principal investigator (PI).

“这一领域的很多研究都困扰于以下的事实:我们倾向于在青少年已经开始出现各种不端行为之后拽住他们。所以,事实上,我们正在孩子们从事大量的冒险行为之前用就开始一直跟踪他们了。”明尼苏达大学的临床神经科学家Monica Luciana说,“这将是一个极为丰富的数据系统。”Monica Luciana是ABCD研究的某站点的首席研究员。

Clarifying the impacts of alcohol and drug use is a key goal for the study's leading funders: the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), both in Bethesda. "There is an urgency to try to address these questions," says NIDA Director Nora Volkow, the prime mover behind the study. The recent legalization of recreational marijuana in several states makes the study especially timely, she argues.

阐明酒精和药物滥用的影响是该研究主要投资者的一个关键目标:国家药物滥用研究所(NIDA)和国家酒精滥用和酒精中毒研究所(NIAAA)都在贝塞斯达。这项研究的主要推动者,NIDA的主任Nora Volkow说“有一种解决这些问题紧迫感”。她认为,最近几个州的大麻合法化使得这项研究特别适时。

Other studies have used MRI to follow teen brain development. Europe's IMAGEN enrolled 2000 14-year-olds and scanned them at intervals over the past decade. And NIAAA has been funding a study of alcohol's impacts, imaging the brains of more than 800 youths once a year for 4 years. But ABCD "is going to be by far the largest," Volkow says. "It's [also] longer-lasting, starts younger, and is much more comprehensive" in terms of testing.


Every 2 years, researchers will image the brain structures of Chya and other subjects, and record their neural activity as they perform tasks involving memory, rewards, and face recognition. Every year, the participants will have their height, weight, and waist measured, and answer questions designed to assess psychological symptoms. They will also be asked annually about environmental influences—things like family conflict and neighborhood crime.


The study aims to describe a normal trajectory of adolescent brain development—similar to the height and weight charts in pediatricians' offices—and use that to begin to answer the many chicken-and-egg questions that correlational studies can't. For instance, people who smoke marijuana heavily beginning in adolescence or young adulthood show markedly less connectivity between the neuronal axons of the hippocampus, a brain region important to long-term memory formation and learning, than do nonusers. But were the users' brains wired differently to begin with, leading them to smoke cannabis heavily? Or did the smoking cause the changes?


"At age 9 and 10 you can get a nice clean baseline assessment on these kids," says Hugh Garavan, a neurobiologist who is the PI at the ABCD Study site at the University of Vermont (UVM) in Burlington. "Then, when someone develops psychosis at 16, we can go back and look at their brains and psychological assessments at 9, 10, 11, and 12. Were there markers of risk there?"

伯灵顿佛蒙特大学ABCD研究站的首席研究员,神经生物学家Hugh Garavan说:“你可以在这些孩子9岁和10岁的时候,对他们做一个很好的基准评估。”那么,当有人在16岁时出现精神病时,我们可以回头看看他们在9, 10, 11岁和12岁时的大脑和心理评估。在那些时候标记了风险么?”

Such markers, it's hoped, will ultimately allow much earlier diagnosis, treatment, or prevention of substance abuse, mental illness, and other conditions. A key strength of the study is that it will enroll enough children—including 800 pairs of twins—to answer questions that require large numbers of subjects, such as whether there are age windows when the brain is particularly vulnerable to use of a given drug.


The study intends to reflect the United States's socioeconomic, geographical, racial, and ethnic diversity. Planners want the study pool to be 6% Asian-American, 16% black, and 24% Hispanic. As of early January, with 8 months left in recruitment, they are falling short on Asian-American and black enrollment, at 2% and 12%, respectively, but were close to meeting the Hispanic target, at 22%. And the "other" category, which includes mixed-race kids and Native Americans, accounts for fully 11% of enrollees, more than double the organizers' 5% target.


The ABCD Study crystallized at an inauspicious time. In May 2014, when its planners held their first meeting, the National Children's Study, an NIH effort to follow 100,000 children from the womb to age 21, was collapsing as a result of daunting logistics, overambitious objectives, and a projected cost of more than $3 billion. "We were very, very aware, because of the Children's Study, that we didn't want to load up the Christmas tree with too many ornaments," recalls George Koob, NIAAA director since 2014.

ABCD研究计划的成形遇上了一些不顺利的情况。在2014年5月,当它的规划者们举行第一次会议时,NIH的一项国家儿童研究试图跟踪10万名从子宫到21岁的孩子,由于后勤工作令人望而生畏,目标超出预期,以及超过预计的成本30亿美元而失败。NIAAA董事George Koob回忆说:“我们非常,非常清楚,因为这项儿童研究,我们不想在圣诞树上挂太多的饰品。”

By September 2016, under a tightly designed protocol dictated by the attention spans and wiggles of 9- and 10-year-old children, the ABCD Study was enrolling. The organizers are assuming 15% of the planned 11,500 enrollees will drop out over the decade, leaving the desired 10,000 participants. Some fear that may be optimistic, but Garavan is bullish. "Because it's a longitudinal study, we have to make sure the kids enjoy the experience," he says.


Garavan has succeeded with at least one recruit. "You had to drool into two vials, not spit. And it was fun," recalls Afton, who had his brain scanned at UVM last September, a day before his 10th birthday. "Eventually they are going to learn how to track if someone has depression or something else, or not, by just looking at their brain in an MRI machine. I thought that was cool. And I wanted to help."


Chya, for her part, left the Baltimore study site last month with a picture of her brain and an ABCD T-shirt. She plans to return at the same time next year.


*The ABCD Study keeps participants anonymous; the families of the kids in this article allowed the use of their first names.

* ABCD研究的参与者都是匿名的;本文中的孩子们允许使用他们的名字。

Posted in: Brain & Behavior 发表于《大脑与行为》


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