Allie WidmanAllie Widman presents at Discoveries in the Making at Homewood Public Library in December 2016. (Photo by Heather Dark)Major Depressive Disorder (MDD) is one of the most common mental illnesses in the United States, with approximately 6.7 percent of adults suffering at least one depressive episode in 2015. MDD is characterized by depressed mood, anhedonia, appetite changes, negative information processing, and a myriad of other debilitating characteristics.

While it is a mental illness, MDD has many complex underlying neurobiological mechanisms that contribute to its prevalence. Understanding these mechanisms may be the key to uncovering the processes through which symptoms of MDD develop and are maintained. There are numerous types of antidepressants used to treat MDD; however, these antidepressants can take months to work, and have a limited rate of complete symptom relief. Thus, finding more effective treatments is a primary aim of medical researchers.

Ketamine, an NMDA receptor antagonist, commonly used as an anesthetic, has attracted the attention of many researchers for its fast-acting antidepressant effects. Administered intravenously in clinical settings, ketamine has been found to significantly decrease depressive symptoms, like suicide ideation, anhedonia, and depressed mood in patients just hours after administration. These compelling effects have warranted further study into how ketamine works to relieve depressive symptoms.

Allie Widman, a 5th year Neuroscience Ph.D. student at UAB, examines the antidepressant effects of ketamine on the brain. She spoke about her research at Discoveries in the Making at Homewood Public Library in December. In the brain, neurons carry messages through electrochemical processes that affect the ways we think and behave. MDD is associated with greater neuronal atrophy in key regions like the hippocampus and amygdala, which decreases the communication and functioning of various brain regions. Impairments in communication in key regions can results in maladaptive thought patterns that characterize many symptoms of depression. In her research, Allie investigates the effects of ketamine on neuronal firing in the hippocampus, a region of the brain involved in learning and memory, and implicated in cognitive deficits in the pathophysiology of MDD.

In a series of studies using single cell recording in mice, Allie examined neuronal communication in the hippocampus after a dose of ketamine. She found that after one dose of ketamine, neuronal firing increased, suggesting an increase in communication between neurons. This finding supports previous research where ketamine has been found to reduced depressive symptoms in patients with MDD. In another study comparing ketamine to other FDA approved NMDA antagonists, she found that Scopolamine and Rapastinel had similar effects to ketamine; however, they were not as effective as ketamine in producing rapid neuronal firing. These findings suggest that ketamine has greater rapid-acting antidepressant effects relative to other NMDA receptors.

Findings from Allie’s research outline the important neurobiological effects of ketamine in reducing depressive symptoms. The fast-acting effects differ from current FDA approved antidepressants and other NMDA antagonists, and can drastically change the way MDD progresses and is maintained in patients. In the future, Allie hopes to extend her findings to large scale studies to examine the effects of ketamine over time.

Allie will speak again about her research at Discoveries in the Making Coffee Break on Sunday, January 29 at 2 p.m. at The Abbey Coffee Shop in the Avondale neighborhood of Birmingham.