Thinning of the right hemisphere of the brain could be a marker of an increased risk of depression. In one of the largest-ever imaging studies of depression, researchers at Columbia University Medical School and New York State Psychiatric Institute found that people at high risk of developing depression had a 28 percent thinning of the right cortex, the brain’s outermost surface, compared to people with no known risk.

 

Researchers were surprised by the drastic reduction in brain matter which was comparable to the observed loss with Alzheimer’s disease and schizophrenia. “The difference was so great that at first we almost didn’t believe it,” says Bradley Peterson, lead author of the study. “But we checked and re-checked all of our data, and we looked for all possible alternative explanations, and still the difference was there.”

 

The research was led by Myrna Weissman, professor of epidemiology in psychiatry at Columbia University College of Physicians and Surgeons, and director of the Division of Epidemiology at the New York State Psychiatric Institute, and Peterson, director of Child & Adolescent Psychiatry and director of MRI Research in the Department of Psychiatry at Columbia University Medical Center and the New York State Psychiatric Institute. Their findings were published in the online edition of the Proceedings of the National Academy of Sciences.

 

Depression is a leading cause of disability worldwide for persons 15 to 44 years of age, often leading to increased mortality from cardiovascular disease, poor personal care, and suicide. Early onset of depression, which occurs before young adulthood, tends to be familial and is often more chronic and severe. Until now there had been no studies of brain structure in depression that have focused on cortical thickness.

 

The study compared the thickness of the cortex by imaging the brains of 131 subjects, aged 6 to 54 years old, with and without a family history of depression. An average 28 percent reduction in the volume of the right cortex was observed in descendants of depressed parents and grandparents, whether or not the subjects had ever had a depressive episode or anxiety disorder. However, these structural brain differences were not found in the descendants of those who were not depressed.

 

The cerebral cortex is the region of the brain central to reasoning, planning, and mood.

One possibility is that the thinner cortex may increase the risk of developing depression by disrupting a person’s ability to pay attention to, and interpret, social and emotional cues from other people, the researchers surmise. Additional tests measured each person’s level of inattention to and memory for such cues. The less brain material a person had in the right cortex, the worse they performed on the attention and memory tests.

 

The study found that thinning on the right side of brain did not correlate with actual depression, only an increased risk for the illness. Only those individuals who also showed thinning on the left side of the brain went on to develop depression or anxiety.

 

One of the goals of the study was to determine whether structural abnormalities in the brain predispose people to depression or are a cause of the illness. Previous studies had focused on a relatively small number of individuals who already suffered from depression so their findings were unable to discern whether those differences represented the causes of depressive illness, or a consequence.

 

“Our findings suggest rather strongly that if you have thinning in the right hemisphere of the brain, you may be predisposed to depression and may also have some cognitive and inattention issues,” says Peterson. “The more thinning you have, the greater the cognitive problems. If you have additional thinning in the same region of the left hemisphere, that seems to tip you over from having a vulnerability to developing symptoms of an overt illness.”

 

The 131 participants in this study were taken from an earlier study begun 27 years ago by Weissman to examine the familial risk for depression in people with moderate to severe depression, as well as people with no mental illness. She followed them for more than 25 years and found that depression is transmitted across the generations in high-risk families. At the 20 year follow-up, she invited Peterson to collaborate on imaging the participants which now include grandparents, their children and grandchildren.

 

The researchers plan to continue their observations, using function magnetic resonance imaging to learn more about the pattern of thinning by observing the circuits of functional activation during tasks that require attention to look at how these groups differ. The will also try to identify more definitively the causal pathways that lead from thinning of the cortex to depression and whether the thinning relates to neurons or supporting cells known as glia.

 

A familial trait for depression is not necessarily genetic and could be a consequence of growing up with parents or grandparents who are depressed, noted Dr. Peterson. The researchers will also study their subjects’ DNA to see if there is a particular gene that contributes to having an elevated risk for depression. They can then investigate whether individuals with this depression risk gene also have more thinning in the cortex.