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Exploring the Link Between Depression and Cholesterol-lowering Medications

Long-term use of statin medications may sometimes result in symptoms of depression and anxiety because of the drug's impact on serotonin.

Researchers from the American Chemical Society (ACS), led by Amitabha Chattopadhyay, department of cell biology at the Scripps Research Institute, have discovered a possible explanation for the symptoms of depression and anxiety that sometimes occur in patients taking the statin family of anti-cholesterol drugs and in patients on low-cholesterol diets.

Using the medication mevastatin, the researchers found that long-term use of the drug resulted in significant changes in the structure and function of serotonin cell receptors. In the ACS journal Biochemistry, the team wrote that “a significant reduction in the level of specific ligand binding and G-protein coupling to serotonin1A receptors upon chronic cholesterol depletion” was observed during the study. When cells expressing serotonin1A were treated with mevastatin, it led to a “decrease in the diffusion coefficient and an increase in the mobile fraction of the receptor, as determined by fluorescence recovery after photobleaching measurements.” The team then replenished the mevastatin-treated cells with cholesterol, which “resulted in the recovery of specific ligand binding and G-protein coupling.”

According to the team, this study is the first to describe “the effect of long-term cholesterol depletion on this type of cell receptor, and suggest that chronic, low cholesterol levels in the brain might trigger anxiety and depression,” although they do note that the results “assume significance in view of recent reports highlighting the symptoms of anxiety and depression in humans upon statin administration, and the role of serotonin1A receptors in anxiety and depression.”