From The Quarterly, Winter 2011

Mental illness is a major risk factor for cardiovascular disease and early death. People with depression and diabetes experience very high rates of stroke, heart attacks and renal failure. Current research is focused on finding novel ways to treat people with this double threat to their health and happiness before trouble begins.

Major risk factors for diabetes and heart disease are insulin resistance and obesity, the key components of the so-called metabolic syndrome. Interestingly, recent studies have shown that depression and diabetes travel a two-way street: each is a risk factor for the other. Researchers have found that patients displaying full-blown metabolic syndrome go on to develop depression at a rate 140 percent higher than average. Based on these and other observations, researchers are trying a reverse approach that attempts to treat depression by treating the metabolic syndrome.

Most current antidepressant medications target neurotransmitters in the brain, such as dopamine, serotonin and norepinephrine, whose dysfunction is believed to be involved in depression. Yet many patients with depression who are given these medications fail to improve fully or at all. Research is aimed at going beyond or around the current paradigm, based on findings that suggest targeting insulin-signaling pathways directly affects the activity of the neurotransmitters.

Pioglitazone is a drug used in the treatment of type 2, adult-onset diabetes to decrease metabolic syndrome and obesity. It also decreases some immune-system chemicals involved in inflammation that are abnormally activated in diabetes. In a small pilot study, the effectiveness of pioglitazone has been tested in patients who do not have diabetes, but do have altered insulin sensitivity or insulin resistance and depression. As expected, they showed improvement in metabolic symptoms, including reduced insulin levels. They also showed correlated improvement in symptoms of depression: those who had the largest decrease in insulin resistance also experienced the greatest abatement of depression severity. Additionally, patients with the most improvement in depression symptoms showed the largest drop in inflammatory markers. While this pilot study with pioglitazone is in its very early stages, it will lead to support for expanded studies to confirm the efficacy of this approach.

David E. Kemp, M.D.

NARSAD Young Investigator

Assistant Professor of Psychiatry and Director, Mood and Metabolic Clinic,

Case Western Reserve University