New Depression Research May Yield Novel Therapies

by James Cavuoto, editor
February 2012

New research into the brain mechanisms leading to clinical depression may pave the way for new therapeutic approaches to treating the disorder. In particular, increased understanding of the brain networks and pathologies in neural communication that accompany depression offer hope for pinpointing new neuromodulation strategies.

Clinical depression brings with it a number of symptoms that can include anxiety, poor attention and concentration, memory issues, and sleep disturbances. Traditionally, depression researchers sought to identify the individual brain areas responsible for causing these symptoms. But the combination of so many symptoms suggested that the multiple symptoms of depression may be linked to a malfunction involving brain networks. UCLA researchers recently showed that people with depression have increased connections among most brain areas. Indeed, their brains are widely hyperconnected.

Their report, published 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, 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 researchers studied the functional connections of the brain in 121 adults diagnosed with major depressive disorder. They measured the synchronization of electrical signals from the brain 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. “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 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.”

During depression, the brain becomes less plastic and adaptable, and thus less able to perform certain tasks, like storing memories. Researchers at Karolinska Institutet recently traced the brain’s lower plasticity to reduced functionality in its support cells, and believe that learning more about these cells can pave the way for radical new therapies for depression.

Writing in the journal Molecular Psychiatry, a team led by Mia Lindskog reported they were able to cure memory dysfunction in “depressed” rats with D-serine. The team also studied the synaptic activity in the hippocampus of the rats. They found that there was a much higher degree of synaptic activity in the brains of the depressed rats than in the controls.

However, when the researchers tried to increase the level of signal transmission, they found the brains of the depressed rats to be unresponsive, which indicated that they had a lower plasticity that rendered them unable to increase neuronal activity when needed—unlike the brains of the healthy rats. When the brain samples were soaked in D-serine, the plasticity of the depressed rats’ brains improved.