Scientists have for the first time obtained evidence for the link between cholesterol-lowering drugs and depression in people taking these drugs to prevent heart attack.
They have found that cholesterol-lowering drug may affect the activity of a brain chemical that controls mood and behavior and thereby trigger anxiety and depression.
Cholesterol, a wax like substance, is the main culprit in heart disease. Although the body needs it, a high level of serum cholesterol causes blockage of coronary arteries thereby reducing blood circulation to the heart muscles leading to heart attack. A class of drugs called 'statins' which lower the cholesterol level -- by inhibiting a key enzyme responsible for its biosynthesis in the body - are the highest selling drugs in the global market and in clinical history with an estimated sale of 25 billion USD annually. They are extensively used as oral drugs to treat "hypercholesterolemia." Although they are very effective in reducing cholesterol levels in humans, there is a growing concern that chronic use of statins causes depression and anxiety in patients. "In the last few years, a number of publications in medical journals have reported apparent symptoms of anxiety and major depression in patients upon long-term statin administration," says Amitabha Chattopadhyay at the Centre for Cellular and Molecular Biology in Hyderabad.
Why should change in the level of a small greasy molecule in the body lead to changes in complex behavioral manifestations such as mood and anxiety has been a puzzle and there has been no molecular evidence to explain this till date. But a paper by Chattopadhyay's group just published in the journal Biochemistry sheds novel insight into the link between use of statins and mood disorders.
The scientists have shown that chronic cholesterol depletion by statins impairs the function of the receptors for serotonin, a neurotransmitter in the brain that controls mood and behavior. Chattopadhyay's group has previously shown that maintaining normal cholesterol levels is important for the function of cell membrane receptors for serotonin. Their latest study showed that cholesterol depletion in the brain affects the function of serotonin receptors leading to depression and anxiety.
The scientists demonstrated this in a test-tube experiment by studying the effect of statin on human serotonin receptors expressed in animal cells called "Chinese Hamster Ovary" cells. Their results showed that long-term treatment with the drug caused significant changes in the structure and function of serotonin receptors. Adding cholesterol to cells treated with statin restored the function of the receptor to normal level.
These novel results represent the first report describing the effect of long-term cholesterol depletion on this type of neurotransmitter receptor and suggest that chronic, low cholesterol levels in the brain may trigger anxiety and depression.