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Size of brain structure could signal vulnerability to anxiety disorders

July 12, 2005

Area appears smaller in those that continue to react to images associated with discomfort
The size of a particular structure in the brain may be associated with the ability to recover emotionally from traumatic events. A new study by researchers from Massachusetts General Hospital (MGH) finds that an area called the ventromedial prefrontal cortex is thicker in volunteers who appear better able to modify their anxious response to memories of discomfort. The report will appear in the Proceedings of the National Academy of Science and has received early online release on the PNAS website.

"We've always wondered why some people who are exposed to traumatic experiences go on to develop anxiety disorders like post-traumatic stress disorder and others do not," says Mohammed Milad, PhD, a research fellow in the MGH Department of Psychiatry, the study's lead author. "We think this study provides some potential answers."

In the classical model of conditioned fear, individuals respond with physical and emotional distress to situations that bring back memories of traumatic events. Such responses are normal and usually diminish over time, as those situations are repeated without unpleasant occurrences. But some people continue to respond with what can be overwhelming fear and may develop post-traumatic stress disorder (PTSD).

For example, it would not be unusual for a soldier who experienced a traumatic battlefield situation to become distressed when hearing noises that bring back those memories, such as the sound of a helicopter. Most commonly, repeated exposure to such sounds without additional trauma reduces or extinguishes the fearful response - a phenomenon called "extinction memory." But some individuals continue to experience anxiety, along with other symptoms characteristic of PTSD, when hearing the sounds.

Prior studies in animals have suggested that the ventromedial prefrontal cortex (vmPFC) - an area on the lower surface of the brain - may be involved in extinction memory. The vmPFC may help to quell potential fears by inhibiting the activity of the amygdala, an area known to be involved with fear. The current study was designed to see if the structure of the vmPFC is related to the ability to modify response to an unpleasant memory.

Over a period of two days, 14 volunteer study participants viewed a series of digital photos of two different rooms. Each room contained a lamp that was turned on - sometimes with a red light, sometimes a blue light. On the first day, participants viewed the photos several times, and then viewed them again with a mild electric shock - described as annoying but not painful - delivered to their hands right after a lamp with a blue light appeared. They then viewed a series of the photos with no shocks administered.

On the second day, measurements of skin conductance were taken while the volunteers once again viewed the photos with both colors of lights displayed but no shocks given. A measurement of anxiety level, skin conductance is determined by the amount of perspiration on the palm of the hand. After that part of the experiment, the volunteers had structural magnetic resonance (MR) images taken of their entire brains.

The MR studies showed that those participants who appeared to have less anxiety response upon viewing the blue lights the second day, as measured by skin conductance, also had a thicker vmPFC. "That was the only area of the brain that correlated with extinction memory," says Milad. "So, these results suggest that a bigger vmPFC may be protective against anxiety disorders or that a smaller one may be a predisposing factor. But exactly how that might work we just don't know."

Scott Rauch, MD, the senior author of the paper and director of the Psychiatric Neuroscience Research Division in MGH Psychiatry, notes that future research could look at genetic or environmental factors that may underlie these differences in brain structure and also investigate whether vmPFC size predicts the success of exposure-based therapies for anxiety disorders. Another factor to study would be whether vmPFC measurement should be used to screen those likely to be exposed to traumatic situations or to develop preventive strategies. Rauch is an associate professor of Psychiatry at Harvard Medical School.

Massachusetts General Hospital