Brains of Lonely People Work Differently
Lonely people have less activity in a part of the brain that normally lights up in association with reward, scientists have found. It’s not clear if social isolation diminishes the brain-reward response, however, or if people with less activity in that part of the brain tend toward loneliness.
More research will be need to sort out the findings, which come from a study of just 23 female college students. But the finding offers hope that scientists may improve their understanding of loneliness, a growing emotional problem in an increasingly scattered society and one known to raise the risks of several health problems.
The subjects were surveyed with standard questions to determine who felt socially isolated, or lonely, vs. those who did not. They then underwent fMRI brain scans while looking at photos of people enjoying themselves.
The ventral striatum — a region of the brain known from other research to light up in association with rewards such as food and money — was much less activated in the lonely group.
“Given their feelings of social isolation, lonely individuals may be left to find relative comfort in nonsocial rewards,” said John Cacioppo, a professor of psychology at the University of Chicago.
About one if five Americans experience loneliness, Cacioppo said. And it is a growing problem in modern society in part because the average household size is decreasing. By 2010, 31 million Americans — roughly 10 percent of the population — will live alone, Cacioppo and his colleagues say.
Previous work has suggested it can be as detrimental to health as smoking, Cacioppo said. In his book, “Loneliness: Human Nature and the Need for Social Connection” (W.W. Norton, 2008), he presented evidence that loneliness is related to less blood flow through the body, poorer immune systems, increased levels of depression and a faster progression of Alzheimer’s disease.
A 2006 study by a different research team, of people age 50 to 68, found that those who scored highest on measures of loneliness also had higher blood pressure, a major risk factor for heart disease. The potentially deadly health effect of loneliness accumulates gradually and faster as you get older, that study found.
Although loneliness may be influence brain activity, the research also suggests that activity in the ventral striatum may prompt feelings of loneliness, said Cacioppo’s colleague Jean Decety, a professor of psychology and psychiatry at the university. “The study raises the intriguing possibility that loneliness may result from reduced reward-related activity in the ventral striatum in response to social rewards,” Decety said.
The results are published in the current issue of the Journal of Cognitive Neuroscience. Cacioppo presented the findings today at the annual meeting of the American Association for the Advancement of Science, in Chicago.
What to do
In his 2008 book, Cacioppo and co-author William Patrick, former science editor at Harvard University Press, argue that loneliness creates a feedback loop that reinforces social anxiety, fear and other negative feelings. Getting out of the loop requires first recognizing it and overcoming the fear related with connecting with others.
“The process begins in rediscovering those positive, physiological sensations that come during the simplest moments of human contact,” Patrick said. “But that means overcoming the fear and reaching out.”
“Lonely people feel a hunger,” Cacioppo added. “The key is to realize that the solution lies not in being fed, but in cooking for and enjoying a meal with others.”
A Prenatal Link to Alzheimer’s?
New research at Genentech Inc. is challenging conventional thinking about Alzheimer’s disease, providing a provocative theory about its cause and suggesting potential new targets for therapies to treat it.
The researchers propose that a normal process in which excess nerve cells and nerve fibers are pruned from the brain during prenatal development is somehow reactivated in the adult brain and “hijacked” to cause the death of such cells in Alzheimer’s patients.
The dominant view of Alzheimer’s disease today is that it is caused by deposits called beta amyloid that accumulate in the brain because of bad luck or other unknown reasons, degrading and destroying nerve cells and robbing victims of their memory.
The new findings offer evidence that “Alzheimer’s is not just bad luck, but rather it is the activation of a pathway that is there for development purposes,” says Marc Tessier-Lavigne, executive vice president, research drug discovery, at Genentech. “It suggests a different way of looking at Alzheimer’s disease.”
The report, being published Thursday in the journal Nature, is based on laboratory and mouse experiments, and further study is needed to validate the hypothesis.
Genentech, a South San Francisco, Calif., biotech company, says it has identified potential drug candidates based on the findings, but even if they prove promising, it would take several years for any potential treatment to be developed.
Beta amyloid, a fragment of a larger molecule called amyloid precursor protein, or APP, has long been the dominant focus of Alzheimer’s research. Many drug companies have compounds in development that are intended to block or clear the buildup of beta amyloid plaques in the brain. But the track record for developing effective drugs has been unimpressive so far. Moreover, some people accumulate beta amyloid in the brain without any apparent effect on memory, adding to confusion about its role in Alzheimer’s.
During human development, the prenatal brain makes about twice the number of nerve cells it needs, Dr. Tessier-Lavigne explained. Those neurons, in turn, each make hundreds of nerve fibers that seek to make connections with other cells. The cells and nerve fibers that succeed in making connections survive — while those that don’t naturally trigger a self-destruction mechanism called apoptosis that clears out the unneeded cells.
“We make too many, and then we prune back,” Dr. Tessier-Lavigne said. “The system gets sculpted so you have the right set of connections.”
What he and his colleagues, including scientists from the Salk Institute, La Jolla, Calif., found is that the amyloid precursor protein linked to Alzheimer’s also plays a critical role in triggering the prenatal pruning process. But the beta amyloid that appears to kill nerve cells in Alzheimer’s patients isn’t involved in the developing embryo. Instead, the pruning is sparked by another fragment of APP called N-APP, causing a cascade of events that results in the death of excess nerve cells and nerve fibers.
“This suggests that APP may go through a novel pathway rather than beta amyloid to cause Alzheimer’s disease,” says Paul Greengard, a scientist at Rockefeller University, New York, and a Nobel laureate who wasn’t involved in the research. He called the paper “an important step” in understanding the pathology of Alzheimer’s — something that is necessary to develop better drugs.
Don Nicholson, a Merck & Co. vice president and author of a commentary that accompanies the Tessier-Lavigne study in Nature, said the paper doesn’t rule out a role for beta amyloid. He added that given the intense focus on the role of beta amyloid in the disease, the finding that another part of the precursor protein may be important in Alzheimer’s is “unexpected biology.”
Exactly what triggers the reappearance in the adult brain of a process fundamental to its early prenatal development isn’t clear and is the subject of continuing research, Dr. Tessier-Lavigne said. Meantime, there are several steps in the cascade of events that lead to the death of the developing neurons and nerve fibers. If the process reflects the unwanted death of such cells in Alzheimer’s, it presents several places where a drug could block or affect the process to possibly prevent the damage.
“We’ve identified a mechanism of nerve-cell death and degeneration involving amyloid precursor protein in the embryo,” he said. “What Alzheimer’s is doing is hijacking not only the molecule but the whole mechanism of degeneration.”
Meantime, a second paper published last month by a team including researchers at Buck Institute for Age Research, Novato, Calif., reported that a protein called netrin-1 appears to regulate production of beta amyloid. The finding, which appeared in the journal Cell Death and Differentiation, is behind the authors’ belief that Alzheimer’s is the result of normal processes going awry.
Together the papers add to intriguing evidence that beta amyloid is perhaps only part of the Alzheimer’s story. “What we’re seeing is a completely different view of the disease,” said Dale Bredesen, a Buck Institute researcher and co-author of the paper. The brain has to make connections and break connections all the time. Alzheimer’s, he suggests, is the result when that process is out of balance.