New research conducted on mice has uncovered why various therapies for depression likely work – because they target a protein that inhibits brain cell growth.
The study by Johns Hopkins University researchers found that the protein, called sFRP3, is affected by both antidepressant drugs and electroconvulsive therapy (ECT). After the gene that makes the protein was deleted in mice, their brains behaved as though they were on antidepressants, researchers said.
The brain must maintain a delicate balance, with complex chains of signals keeping various opposing processes in check. The protein sFRP3, which inhibits the growth of brain cells, is useful in controlling cell growth from getting out of hand, but could be harmful if it hampers necessary growth. Working with mice, Johns Hopkins researchers showed that antidepressant medications, ECT and even exercise all reduced levels of sFRP3.
The findings have been published in two journals, “Cell Stem Cell” and “Molecular Psychiatry.”
The latest findings are simply the most recent in over a decade’s worth of research into the causes of and treatments for depression. All of this work has led to a hypothesis that could help to explain the triggers for depressions and the treatments, which though varied and different, all seem to help relieve symptoms.
The accumulated research has led scientists to conclude that stress, especially extreme stress and particularly during childhood, causes the brain to release an excess amount of a neurotransmitter, or brain-signaling chemical, called glutamate. High levels of glutamate are known to damage and kill brain cells in the hippocampus region of the brain. The hippocampus is a part of the brain that is related to memory and its thinning has been shown to contribute to the onset of depression. Why this loss of cells in the hippocampus causes depression is still not understood, but treatments that promote new growth seem to alleviate the mental illness.
These earlier findings have led researchers to continue to investigate the role of new brain cell growth in treating depression. The study at Johns Hopkins included measuring the amount of sFRP3 in mice. The researchers used different antidepressants, from different classes, meaning they had different mechanisms of action, and all caused the amount of sFRP3 to be reduced, allowing for the creation of new brain cells, as well as new connections between cells in the hippocampus of the mice. Mice that were treated with electroconvulsive therapy and exercise also had lower levels of sFRP3.
To further implicate the effects of sFRP3 on depression, the researchers bred mice that did not have the protein. These mice were less likely to show symptoms of depression, giving more credence to the idea that the loss of brain cells contributes to the illness.
In humans, genes for this protein were seen to affect how they responded to treatments for depression. All of the evidence together suggests that high levels of sFRP3 make people susceptible to depression because the protein inhibits the growth of new brain cells in the hippocampus.
The next question is why these different types of therapies, medication, exercise, and electroconvulsive therapy, all affect sFRP3. What the researchers know is that they all stimulate one kind of cell in the brain, which must be related to the inhibition of sFRP3. More work will needed to confirm these findings and to answer questions that arise from it.
That the researchers were able to come up with explanations for why various treatments work to relieve symptoms of depression is important. Understanding the mechanism of action not only helps explain why certain people are depressed, it also helps lead to more and improved treatments. If a drug can be developed that stimulates brain cell growth in all depression patients, without producing side effects, many people will find relief. It may even be possible one day to prevent depression.