Depression Risk May Be Linked to a Thinner Cortex

by Jim Schnabel

June 22, 2009

A thinner cerebral cortex may be a sign of vulnerability to depression, according to a magnetic resonance imaging (MRI) study of 58 families. The researchers who conducted the study theorize that the thinning seems to disrupt brain networks that support social and emotional cognition.

“We think that those kinds of cognitive problems impair people’s social and emotional relationships, and that is ultimately what predisposes people to depression,” says Bradley Peterson, a pediatric psychiatrist at Columbia University Medical Center and first author on the study, which appeared first online March 26 in the Proceedings of the National Academy of Sciences.

“It certainly puts a light on something we need to investigate further,” says Martin Paulus, a psychiatrist at the University of California, San Diego, who also has done studies of the neurobiology of depression but did not participate in Peterson’s recent study.

The origins of depression, also known as major depressive disorder (MDD), are not well understood. While the disorder does run in some families, studies of identical twins suggest that environmental factors are often at work as well. And although brain-imaging studies have linked some differences in brain structure or activity to depression, most of that research involved only a small number of subjects. Such studies also have tended to provide only “snapshots” of depressive patients’ brain characteristics and could not determine whether those characteristics are the cause of depression or are its effects.

In the Columbia study, Peterson and his colleagues used a high-resolution MRI device to study the brains of 131 people ages 6 to 54. Researchers have been studying this particular group for years to try to understand how the vulnerability to depression plays out from one generation to the next.

The first-generation members of the group include people who in the late 1980s had been in treatment for moderate to severe depression. At that time, researchers matched them with a similar-age group from the same community that had no discernible lifetime history of depression and began to study how the two groups differed. The current study also includes the children and grandchildren of the first-generation groups, thus making up a potentially high-risk group, with a family history of depression, and a relatively low-risk group.

The most striking finding by Peterson and his colleagues was that in the high-risk group, compared with the low-risk group, broad areas of the rumpled outer sheet of the brain, the cerebral cortex, especially on the right side, were significantly thinner—by about 28 percent, on average. This large difference was evident regardless of age and was consistent even in members of the high-risk group who had never had depression or an anxiety disorder—implying that the abnormality was not a result of depression but, rather, preceded it.

Some previous studies of people with depression had found abnormalities in brain activity or test performance that suggested problems with right-hemisphere functions, including functions that relate to attention and the response to emotional faces or words. Peterson and his colleagues gave standard psychological tests to their 131 subjects and found that those in the high-risk group performed significantly worse on attention and visual-memory tasks involving images of people, including family members. “The thinner the cortex, the worse the cognitive problems in those areas,” Peterson says.

Those in the group who had symptoms of depression or an anxiety disorder also showed patches of cortical thinning in corresponding left-hemisphere areas and a similar link between the severity of symptoms and the overall thinning. Peterson suggests that a bilateral deficit in these areas might therefore “tip you over from having vulnerability to illness to expressing overt symptoms.”

The Columbia researchers plan to follow up with genetic studies of the group and also hope to develop an MRI-based system to help diagnose a person’s vulnerability to depression. “Four or five years ago I would have said we’re a long way from that. But through this study, and other [ongoing] studies in our laboratory, I feel we’re actually very close,” says Peterson.

However, Paulus cautions that before the cortical-thinning hypothesis gains broad acceptance, researchers will need to perform further studies involving a larger number of subjects. Such groups may be readily available.

“For example, in New Zealand there’s a cohort of several thousand people that researchers have followed since birth, and they’ve ascertained their mental health history very closely. It would be fantastic if in such a large group you could do something like this,” Paulus says.