Researchers Investigate Association Between Metabolic Syndrome and Depression, and Resistance to Antidepressant Treatment; Ventral Dentate Gyrus May Be Key

Often, clinical depression has company; it shows up in the brain alongside metabolic abnormalities, such as elevated blood sugar, in the body. While studying an experimental antidepressant in rats, Rockefeller University researchers and their colleagues at Karolinska Institutet in Sweden found some molecular connections between the two disorders—depression and metabolic syndrome. “Many patients who suffer from depression do not respond to conventional antidepressant treatment, so we set out to examine the molecular changes that might explain this resistance,” says first author Benedetta Bigio, Ph.D., a bioinformatics specialist in Dr. Bruce McEwen’s Rockefeller lab. “Our results linked the activity of energy metabolism genes within one part of the brain to a predisposition to depression, as well as resistance to treatment,” she says. The research is described in a PNAS article titled “Epigenetics and Energetics in Ventral Hippocampus Mediate Rapid Antidepressant Action: Implications for Treatment Resistance.” That article was published in the July 12, 2016 issue of PNAS. It is not known why depression is often accompanied by metabolic syndrome, a constellation of conditions including abnormal levels of sugar and of a type of fat known as triglycerides in the blood. The team reports having found a molecular connection between the two diseases (metabolic syndrome and depression) that emerged from gene expression data they collected as part of their work on acetyl-L-carnitine (LAC). LAC is a compound naturally produced by the brain, liver, and kidneys. When given to rats and mice, it has been shown to rapidly alleviate depression-like symptoms by improving harmful imbalances in the brain’s glutamate signaling system.
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