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UI researchers study depression

BY KAITLIN DEWULF | MAY 02, 2014 5:00 AM

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Depression is one of the top disabilities worldwide, but current medication does not meet everyone’s needs. Research started at the University of Iowa illustrates a new type of medicine that could one day help those left out.

Scientists linking depression to a hormone that controls hunger found that the hormone’s natural ability to fight depression is due to its ability to protect newborn neurons from death. This neuron survival is particularly critical in the hippocampus, the region of the brain that controls mood, memory, and eating behaviors. The hippocampus is one of the few regions in the adult brain that experiences neurogenesis — a process in which new neurons are continually produced.

Andrew Pieper, an associate professor of psychiatry and neurology at the UI, discovered a new class of molecules that protects neurons from dying, meaning the body’s hormones could better fight depression. Pieper and Jeffrey Zigman, a University of Texas associate professor of internal medicine and psychiatry, introduced the new “P7C3” class of neuroprotective compounds, and they appeared to show that they can treat depression-like behavior in mice by increasing the survival of brain cells.

“Our hope is that this work will lead to the development of a new class of drugs,” Pieper said. “That might prove useful for treating patients with depression.” Zigman said previous work from the group has shown that the hormone, ghrelin, has natural antidepressant effects that become apparent with calorie restriction or prolonged psychological stress — meaning when a person is hungry or stressed, the body releases a hormone to fight depression.

Without ghrelin receptors, the body is unable to fight depression effectively. In the current study, Pieper and Zigman investigated the creation of neurons in stress-exposed mice lacking ghrelin receptors. After being given the new compounds, the mice showed more social interaction. The mice that didn’t receive the new compound were more isolated, comparable to a person afflicted with depression.

UI psychiatry Professor James Potash said he’s eager to see these compounds tested in human patients. “The path to getting from success in an animal model to breakthrough medication is a long one,” Potash said. “It requires time, large financial investments, and some luck, but the payoff is enormous.”

Major depressive disorder is now the second leading cause of disability in the world, according to a recent study by the Global Burden of Disease. Potash said although there are 30 different antidepressants on the market, they all, more or less, work on the same brain mechanisms as the pills first introduced in the late 1950s to treat depression.

“While there are treatments that help many people diagnosed with depression, 30 percent of patients don’t respond to the available medications,” Potash said. Zigman said evidence from the study suggests that P7C3 may potentially have stronger antidepressant effects, and the onset may occur faster than those currently available.

From here, the researchers will apply for additional funding and test on humans before approaching the FDA for approval.


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