Ketamine May Help With Depression Linked to Overeating

Processed foods rich in saturated fat have become a major part of the American diet. Two-thirds of American adults are overweight or obese. 

Type 2 diabetes is one of the over 60 chronic diseases linked to obesity. Diets rich in fat also impair cognitive functions, shrinks the hippocampus, and increase one’s risk of developing depression. 

People with type 2 diabetes are 54 percent more likely to develop depression than those without type 2 diabetes, according to a 2008 study in the Journal of the American Medical Association. Diabetes is a risk factor for depression. More surprisingly, depression is a risk factor for diabetes. 

Researchers at Yale wanted to examine the impact of a high-fat diet on the biological processes that contribute to the development of type-2 diabetes, depression, and anxiety. They put one group of rats on a high-fat diet by feeding the group six times the normal amount of fat.

The scientists found that, after four months on the high-fat diet, the rats exhibited signs of depression and anxiety, and their synaptic plasticity and metabolism were disrupted.

The scientists found that a single dose of ketamine, more popularly known as the illicit drug "Special K," reversed the symptoms quickly. Ketamine has been shown to reduce symptoms of chronic depression in bipolar and depressed patients who have not responded to other antidepressants. The drug works in just two hours. 

Depression and chronic stress damage synaptic connections in the brain. The effects of a high-fat diet overlap with the effects of chronic stress, said neurobiologist and senior study author Ronald Duman. These effects could be a contributing factor in depression and type 2 diabetes.

Ketamine targets a different part of the brain than traditional antidepressants. Instead of focusing on serotonin, norepinephrine or dopamine neurotransmitters, ketamine activates the mTORC pathway and focuses on a glutamate neurotransmitter.
 
Glutamate accounts for more than 90 percent of all synapses in the human brain. The single dose of ketamine was found to reverse the disruption of mTORC signaling pathways caused by the high-fat diet. 

The mTORC pathway is also involved in cellular responses to energy and metabolism.

Further studies need to be done to figure out the effects of ketamine on the metabolism. In addition, scientists must figure out how patients can use the drug without experiencing the dangerous side effects, such as addiction and severe bladder inflammation. Thus, they will have to find the proper dosage as an antidepressant. The use of Ketamine as an antidepressant is still a subject of clinical trials.

The study was published in the journal Neuropharmacology. 

Sources: press release via EurekAlert! and Yale University, study in Neuropharmacology, Diabetes Forecast, Scientific American