Hyperactivity in Brain May Explain Multiple Symptoms of Depression.

Brain hyperactivity. Maps showing the difference in the strength of brain connections between depressed subjects (left) and controls (right). Depressed subjects show much stronger connections, as evidenced by red colors in their maps. (Credit: Image courtesy of University of California - Los Angeles)

Source: Science Daily

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ScienceDaily (Feb. 27, 2012) — Most of us know what it means when it's said that someone is depressed. But commonly, true clinical depression brings with it a number of other symptoms. These can include anxiety, poor attention and concentration, memory issues, and sleep disturbances.

Traditionally, depression researchers have sought to identify the individual brain areas responsible for causing these symptoms. But the combination of so many symptoms suggested to UCLA researchers that the multiple symptoms of depression may be linked to a malfunction involving brain networks -- the connections that link different brain regions.
Now, for the first time, these UCLA researchers have shown that people with depression have increased connections among most brain areas. Indeed, their brains are widely hyperconnected. The report, published this week in the online journal PLoS One, sheds new light on the brain dysfunction that causes depression and its wide array of symptoms.
"The brain must be able to regulate its connections to function properly," said the study's first author, Dr. Andrew Leuchter, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA. "The brain must be able to first synchronize, and then later desynchronize, different areas in order to react, regulate mood, learn and solve problems."
The depressed brain, Leuchter said, maintains its ability to form functional connections but loses the ability to turn these connections off.
"This inability to control how brain areas work together may help explain some of the symptoms in depression," he said.
In the study, the largest of its kind, the researchers studied the functional connections of the brain in 121 adults diagnosed with major depressive disorder, or MDD. They measured the synchronization of electrical signals from the brain -- brain waves -- to study networks among the different brain regions.
While some previous studies have hinted at abnormal patterns of connections in MDD, the UCLA team used a new method called "weighted network analysis" to examine overall brain connections. They found that the depressed subjects showed increased synchronization across all frequencies of electrical activity, indicating dysfunction in many different brain networks.
Brain rhythms in some of these networks regulate the release of serotonin and other brain chemicals that help control mood, said Leuchter, who is also the director of UCLA's Laboratory of Brain, Behavior, and Pharmacology and chair of the UCLA Academic Senate.
"The area of the brain that showed the greatest degree of abnormal connections was the prefrontal cortex, which is heavily involved in regulating mood and solving problems," he said. "When brain systems lose their flexibility in controlling connections, they may not be able to adapt to change.
"So an important question is, to what extent do abnormal rhythms drive the abnormal brain chemistry that we see in depression? We have known for some time that antidepressant medications alter the electrical rhythms of the brain at the same time that levels of brain chemicals like serotonin are changing. It is possible that a primary effect of antidepressant treatment is to 'repair' the brain's electrical connections and that normalizing brain connectivity is a key step in recovery from depression. That will be the next step in our research."
Other authors of the study include Dr. Ian A. Cook, Aimee M. Hunter, Chaochao Cai and Steve Horvath, all of UCLA. Funding for the study was provided by the National Institutes of Health, Lilly Research Laboratories and Pfizer Pharmaceuticals.

In the Genes, but Which Ones? Studies That Linked Specific Genes to Intelligence Were Largely Wrong, Experts Say.

Source: Science Daily

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ScienceDaily (Feb. 24, 2012) — For decades, scientists have understood that there is a genetic component to intelligence, but a new Harvard study has found both that most of the genes thought to be linked to the trait are probably not in fact related to it, and identifying intelligence's specific genetic roots may still be a long way off.

Led by David I. Laibson '88, the Robert I. Goldman Professor of Economics, and Christopher F. Chabris '88, Ph.D. '99, assistant professor of psychology at Union College in Schenectady, N.Y., a team of researchers examined a dozen genes using large data sets that included both intelligence testing and genetic data. As reported in a forthcoming article in the journal Psychological Science, they found that in nearly every case, the hypothesized genetic pathway failed to replicate. In other words, intelligence could not be linked to the specific genes that were tested.
"It is only in the past 10 or 15 years that we have had the technology for people to do studies that involved picking a particular genetic variant and investigating whether people who score higher on intelligence tests tend to have that genetic variant," said Chabris. "In all of our tests we only found one gene that appeared to be associated with intelligence, and it was a very small effect. This does not mean intelligence does not have a genetic component, it means it's a lot harder to find the particular genes, or the particular genetic variants, that influence the differences in intelligence."
To get at the question of how genes influence intelligence, researchers first needed data, and plenty of it.
Though it had long been understood, based on studies of twins, that intelligence was a heritable trait, it wasn't until relatively recently that the technology emerged to allow scientists to directly probe DNA in a search for genes that affected intelligence.
The problem, Chabris said, was that early technology for assaying genes was very expensive, meaning that such studies were typically limited to, at most, several hundred subjects, who would take IQ tests and provide DNA samples for testing.
As part of their study, Chabris and his colleagues relied on several pre-existing data sets -- a massive study of Wisconsin high school graduates that began in the 1950s, the Framingham Heart Study, and an ongoing survey of all twins born in Sweden -- to expand that subject pool from a few hundred to many thousands.
"What we want to emphasize is that we are not saying the people who did earlier research in this area were foolish or wrong," Chabris said. "They were using the best technology they had available. At the time it was believed that individual genes would have a much larger effect -- they were expecting to find genes that might each account for several IQ points."
To identify genes that might play a role in intelligence, previous researchers used the "candidate gene approach," which requires identifying a gene that is already linked with a known biological function -- such as Alzheimer's disease or the production of a specific neurotransmitter. If people who scored high on intelligence tests shared a particular variant of that gene, it was believed, that demonstrated the gene's role in intelligence.
"These were reasonable hypotheses," said study co-author Daniel J. Benjamin '99, Ph.D. '06, assistant professor of economics at Cornell University. "But in retrospect, either the findings were false positives or the effects of the genes are much, much smaller than anyone had anticipated."
Chabris, however, emphasized that the results don't point to the idea that the dozen genes examined in the study play no role in intelligence, but rather suggest that intelligence may be tied to many genes and the ways in which they interact.
"As is the case with other traits, like height, there are probably thousands of genes and their variants that are associated with intelligence," he said. "And there may be other genetic effects beyond the single gene effects -- there could be interactions between genes, there could be interactions between genes and the environment. What our results show is that the way researchers have been looking for genes that may be related to intelligence -- the candidate gene method -- is fairly likely to result in false positives, so other methods should be used."