Depressing brain scans

The first study of its kind has used MRI to demonstrate how changes in cortical thickness may surprisingly relate brain structure to major clinical depression. The large-scale US study suggests that a thinning of the right hemisphere of the brain could be a risk factor for depression.

Myrna Weissman of Columbia University Medical Center and the New York State Psychiatric Institute, working with Bradley Peterson, director of MRI Research have now published details of their study in an early online edition of the Proceedings of the National Academy of Sciences. The researchers found that people at high risk of developing depression had a 28% percent thinning of the outermost surface, the right cortex, of their brains.

The team used MRI to compare the thickness of the cortex of 131 subjects, aged 6 to 54 years-old, with and without a family history of depression. The study includes grandparents, their children and grandchildren and were recruited from the "Children at High and Low Risk of Depression" study, begun almost three decades ago by Weissman while at Yale University. They observed structural differences in the biological offspring of subjects with depression but not those children of parents without the disorder.

One of the primary goals of the research was to determine whether structural abnormalities in the brain predispose people to depression or are themselves a cause of the illness, explains Peterson. "Because previous biological studies only focused on a relatively small number of individuals who already suffered from depression, their findings were unable to tease out whether those differences represented the causes of depressive illness, or a consequence," he explains.

The stark difference in cortical thickness between those at risk and those not surprised the researchers who explain that this kind of change is on a par with the loss of brain tissue associated with Alzheimer's disease and schizophrenia. "The difference was so great that at first we almost didn't believe it," Peterson says. "But we checked and re-checked all of our data, and we looked for all possible alternative explanations, and still the difference was there."

Peterson suggests that the thinner cortex may be associated with an increased risk of developing depression because it disrupts a person's ability to pay attention to, and interpret, social and emotional cues from other people. Additional tests measured each person's level of inattention to and memory for such cues. The less brain matter a person had in the right cortex, the worse they performed on the attention and memory tests.

However, the research did not reveal a direct link between depression and thinning on the right side of brain. Indeed, it was subjects who exhibited an additional reduction in brain matter on the left side, who went on to develop depression or anxiety.

"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," Peterson adds, "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 next step will be to use functional MRI with 152 subjects, aged 12 to 50, with and without a family history of depression. From that planned study, Peterson and Weissman hope to learn more about the pattern of thinning by observing the circuits of functional activation during attention-based tasks to look at how these groups differ.

"If the mechanism, or pathway to illness, indeed runs from the thinning of the cortex to these cognitive problems that affect a person's attention and their ability to interpret social and emotional cues, it would suggest that there may be potential treatments or novel uses of already existing treatments for intervention," concludes Peterson.

Behavioural therapies aimed at improving attention and memory or stimulant medications usually used for attention-deficit/hyperactivity disorder (ADHD) might be useful in treating familial depression. This is pure conjecture on the part of the researchers at this time, but their work does suggest a logical hypothesis for further investigation.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.