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Joslin Researcher Studies Link Between Type 2 Diabetes and Depression

Monday, September 23, 2013

Physicians have long observed that mood disorders, including depression, occur more often in patients with diabetes, than even those with other chronic disease. However, the relationship between these two conditions has remained something of a mystery. One possible hypothesis is that patients become depressed as a result of being diagnosed with diabetes and the impact it has on their quality of life -- a reasonable assumption.

But others, such as André Kleinridders, Ph.D., a research fellow at Joslin, believes that type 2 diabetes can trigger a biological response that leads to depression. This is the focus of his research in the laboratory of Dr. C. Ronald Kahn. He uses a mouse model of diabetes to understand the development of depression, and how it can best be treated.

Usually, researchers perform experiments with relatively young mice. But diabetes is a chronic disease, and many disturbances of the brain, such as mood disorders, Parkinson´s or Alzheimer´s disease, often develop late in life.

So Dr. Kleinridders realized that if he were truly to study the effects of diabetes on mood disorders, he would have to follow the impact of brain insulin resistance, a hallmark of diabetes, on mood and behavioral disorders throughout the subjects’ lifetimes.

As the mice reached the young adult stage, which in mice is three months, the insulin-resistant mice showed signs of mitochondrial dysfunction. That is the part of the brain cell providing it with energy.

At first, the insulin-resistant mice were behaviorally indistinguishable from healthy mice. But by the time the mice reached sixteen months, the equivalent of a person in his or her forties to fifties, the behavioral differences were striking. Notably, the insulin resistant mice quickly gave up on tests that were designed to assess their depression levels. For example, when held by the tail, they stopped trying to escape after two minutes, while healthy mice continued trying even after six minutes.

Though all mice performed similarly during strength tests, the insulin resistant mice demonstrated significant motor skills impairments, their paws frequently slipping off a narrow beam during coordination exercises.

When Dr. Kleinridders studied the brain chemistry of the insulin-resistant subjects, he learned that they suffered from decreased dopamine and serotonin signaling (these are both neurotransmitters, or chemicals that send signals throughout the brain) compared to their healthy counterparts, and this could contribute greatly to their developing depression. Dr. Kleinridders believes that the early onset of mitochondrial dysfunction as a result of their brain insulin resistance may be largely at fault for their decreased neurotransmitter signaling.

Importantly, when Dr. Kleinridders treated these mice with antidepressants, they completely recovered from their depression, and began behaving just like healthy mice subjected to stress, suggesting that the depression associated with brain insulin resistance can be treated.  A similar treatment may be possible for people with type 2 diabetes suffering from depression and other mood disorders.

Page last updated: July 31, 2014