Gregory Ordway

According to stats, South Appalachia suffers the highest rate of depression and suicide than anywhere else in the United States. Clinical depression is marked by a constant sense of hopelessness and depressed mood, and this makes it difficult for a person to participate in normal, daily activities and relationships. Symptoms must occur for at least two weeks before being diagnosed. Clinical depression is a major health problem that leads to suicide and morbidity.

For the last three decades, Dr. Gregory Ordway’s laboratory at ETSU has been studying the biological basis of clinical depression. Research has shown 30 percent of patients with clinical depression receive no benefit from antidepressant drugs that are currently available and many others only partially respond to the antidepressants. This is why they are currently searching to develop new and better treatments for depression. The ultimate goal of their research is to improve the health and well-being of our region and country.

Recently, Ordway’s laboratory discovered that depression and suicide are associated with elevated gene expression of an enzyme known as PARP1. PARP1 activity is increased during inflammation and events that cause DNA damage, and there is growing evidence that inflammation in the brain is linked to clinical depression.

“We reasoned that if PARP enzyme activity is elevated in depression, then inhibition of this enzyme may produce antidepressant effects,” Ordway said.

His laboratory partnered with the laboratory of Dr. Russ Brown, a behavioral neuroscientist at ETSU, to explore the possibility that PARP inhibitors have antidepressant activity.

Using rodent behavioral models, they tested their theory and the results demonstrate that PARP inhibitors have robust antidepressant activity. Using the same rodent models, that also discovered that PARP inhibitors boost the antidepressant activity of fluoxetine, Prozac, a commonly prescribed antidepressant.

Their findings could lead to the development of new antidepressant drugs that could lead to improved treatment for depression in millions of people.

“We have recently partnered with a Houston biotech startup company, Drugshoppe LLC, to develop novel antidepressant compounds with PARP inhibitory activity,” Ordway said.

“Additionally, we are continuing our research to determine how PARP contributes to the behaviors of depression, and how PARP inhibitors change brain biology to produce antidepressant effects.”

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