Brain atrophy responsible for depression in people battling multiple sclerosis

Jul 02, 2010

Study finds hippocampus is affected by imbalance in neuroendocrine system

Adding to all that ails people managing their multiple sclerosis is depression — for which multiple sclerosis sufferers have a lifetime risk as high as 50%.

Yet despite its prevalence, the cause of this depression is not understood. It's not related to how severe one's multiple sclerosis is, and it can occur at any stage of the disease. That suggests it is not simply a psychological reaction that comes from dealing with the burden of a serious neurologic disorder.

Now, in the first such study in living humans, researchers at UCLA suggest a cause, and it's not psychological, but physical: atrophy of a specific region of the hippocampus.

Reporting in the early online edition of the journal Biological Psychiatry, senior study author Dr Nancy Sicotte, a UCLA associate professor of neurology, Stefan Gold, lead author and a postdoctoral fellow in the UCLA Multiple Sclerosis Program, and colleagues used high-resolution MRI to identify 3 key subregions of the hippocampus that were found to be smaller in people with multiple sclerosis when compared with the brains of healthy individuals.

The researchers also found a relationship between this atrophy and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, a complex set of interactions among 3 glands. The hypothalamic-pituitary-adrenal axis is part of the neuroendocrine system that controls reactions to stress and regulates many physiological processes. It's thought that this dysregulation may play a role in the atrophy of the hippocampus and the development of depression.

"Depression is one of the most common symptoms in patients with multiple sclerosis," Gold said. "It impacts cognitive function, quality of life, work performance and treatment compliance. Worst of all, it's also one of the strongest predictors of suicide."

The researchers examined 3 subregions of the hippocampus region — CA1, CA3, and the dentate gyrus area of the hippocampal region called CA23DG. They imaged 29 patients with relapsing remitting multiple sclerosis and compared them with 20 healthy control subjects who did not have multiple sclerosis. They also measured participants' cortisol level 3 times a day.

In addition to the difference between multiple sclerosis patients and healthy controls, the researchers found that the multiple sclerosis patients diagnosed with depression showed a smaller CA23DG subregion of the hippocampus, along with excessive release of cortisol from the hypothalamic-pituitary-adrenal axis.

"Interestingly, this idea of a link between excessive activity of the HPA axis and reduced brain volume in the hippocampus hasn't received a lot of attention, despite the fact that the most consistently reproduced findings in psychiatric patients with depression (but without MS) include hyperactivity of the HPA axis and smaller volumes of the hippocampus," Sicotte said.

"So the next step is to compare MS patients with depression to psychiatric patients with depression to see how the disease progresses in each," she said.

Funding was provided by the National Multiple Sclerosis Society, the National Institutes of Health, the UCLA Cousins Center for Psychoneuroimmunology, and Claire and William Vaughn. The authors report no conflicts of interest.

Source: News Release
University of California - Los Angeles
July 1, 2010