March 5, 2012

The Hyperactive Brain and Depression

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Chris Galloway, M.D. By:

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Brain network hyperconnectivity linked to depressive disorder

All of us feel sad from time to time, but true clinical depression brings with it a host of other symptoms, including anxiety, poor sleep, difficulty concentrating and memory problems.

Researchers have long tried to understand the causes of depression, moving more and more into the knowledge that it is a physical, chemical imbalance. Today, proof that depression is a chemical disorder is becoming more apparent.

New research from the University of California Los Angeles has established a link between depression and a malfunction in the connectivity of brain networks.

Previous research has been done to try and identify areas of the brain that play a role in depression. But the combination of all the multiple symptoms that usually go along with depression caused UCLA researchers to wonder if the disorder was created more by the connections between different brain regions.

The Depressed Brain can't shut off Electrical Connections

Dr. Andrew Leuchter, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA, led a team of researchers who discovered that people with depression have increased connections between most areas of the brain. In fact, depressed people have brains that are hyperconnected, with electrical signals that simply can't shut off.

Dr. Leuchter's study involved 121 adults who were diagnosed with major depressive disorder (MDD). It is the largest study of its kind, and sheds new light on the brain dysfunction that causes depression and its related symptoms.

UCLA researchers studied the functional connections in the brains of the participants, measuring the synchronization of brain waves in order to look at the networks and signals between the different regions of the brain.

Previous research has hinted at abnormal brain patterns in people with MDD, but the UCLA team used a new method called "weighted network analysis" to measure the brain connectivity. The depressed participants all showed increased synchronization across all the frequencies of electrical activity in the brain, which indicates dysfunction in many different brain networks.

"The brain must be able to regulate its connections to function properly," said Dr. Leuchter. "The brain must be able to first synchronize, and then later desynchronize, different areas in order to react, regulate mood, learn and solve problems." But the depressed brain does not have this ability; it can form the functional connections, but loses the ability to turn those connections off.

Regulation of Mood Chemicals Affected

The prefrontal cortex area of the brain, which is heavily involved in regulating mood, showed the greatest degree of abnormal connections in the depressed subjects. These brain rhythms regulate the release of serotonin and other chemicals that help control mood, and when they lose their ability to control these connections the brain may not be able to adapt.

Dr. Leuchter explained that antidepressant medications alter these electrical rhythms in the brain while chemicals such as 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."

Answering the question of what extent these abnormal rhythms drive the brain chemistry changes found in depressed people is the next step in the UCLA research.

"The more we understand about the biology and chemistry of the brain, the more we realize the power of the organic component behind symptom development and progression," says Dr. Russell Ricci. "However, it still is often not clear whether a specific change is the cause or result of the underlying disease process. The hope though is that whether cause or result, we can develop interventions that improve health."

Dr. Ricci compares antidepressants to the temporary supports under a bridge. "Antidepressant medications can help improve mood, but the challenge is determining how to safely wean a person from the medication."

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. Findings were published in the journal PLoS ONE in February 2012. The authors report no conflict of interest.

Image provided by UCLA: 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.

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Reviewed by: 
Chris Galloway, M.D.
Review Date: 
March 2, 2012

Last Updated:
March 12, 2012