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Depression is a relatively common form of serious psychiatric illness that produces powerful mood disturbances and leaves affected individuals feeling unusually sad, hopeless, helpless, and, in some cases, suicidal. Current medical consensus says that on a chemical level, the presence of depression is linked at least in part to abnormally low levels of a substance called serotonin. According to the results of a study published in 2013 in the journal Nature Neuroscience, that theory may prove incorrect. Instead, the authors of the study believe that depression may result from a disruption in the normal rates of communication between the nerve cells (neurons) that form the brain’s functional core.

Serotonin Basics

Serotonin is one of several different chemicals produced inside the brain and/or body that function as both hormones and neurotransmitters. Hormones are substances found throughout the body that help maintain everyday health by regulating a range of reactions that occur inside individual cells. Neurotransmitters help the brain’s neurons communicate with each other by serving as chemical messengers that circulate between individual neurons and change levels of neuron activity; they also encourage neurons to release a variety of substances (including other neurotransmitters) needed to power the brain’s ongoing processes. While many hormones come from a glandular network in the body called the endocrine system, serotonin comes from several different sources, including certain neurons in the brain, blood components called platelets, and cells contained in various portions of the human digestive tract.

Current Consensus on Serotonin’s Role

Among its other roles in human health and well-being, serotonin helps maintain a workable balance in your daily mood and keep you from feeling too “low” or too “high.” Because of this acknowledged function, doctors and pharmaceutical researchers developed a theory of depression that points to abnormally low serotonin levels as an underlying cause of seriously depressed moods. Acceptance of this theory has led to the development of a number of antidepressant medications that achieve their effects by boosting the brain’s serotonin supply. One class of these medications, called selective serotonin reuptake inhibitors or SSRIs, contains drugs that work by blocking the brain’s normal tendency to break down individual serotonin molecules after their immediate, short-term use. Another class of antidepressants, known as selective serotonin and norepinephrine reuptake inhibitors or SSNRIs, contains drugs that block serotonin breakdown and the breakdown of another important neurotransmitter, called norepinephrine.

Problems with the Serotonin Theory

Only roughly 30 to 50 percent of people who take SSRIs or SSNRIs experience significant drops in their depression symptoms. The lack of a higher rate of response has caused some doctors and researchers to wonder whether serotonin levels really play a fundamental role in the onset or continuation of depression. Some researchers have theorized that the serotonin-boosting effects of SSRIs and SSNRIs may  play only secondary roles in a larger process that leads to the easing of depression symptoms.

An Alternative Explanation

In the study published in Nature Neuroscience, researchers from the University of Maryland School of Medicine found an alternative explanation for serotonin’s role in depression treatment. With the help of rat and mice experiments designed to mimic the stressful events that commonly lead to bouts of depression in humans, the researchers initially sought to determine whether serotonin levels fall in test subjects with symptoms of depression. On this question, they concluded that stress does not trigger a drop in serotonin production.

Unexpectedly, the researchers also found that serotonin has a previously unidentified role in normal brain function. Essentially, the presence of serotonin helps the brain’s neurons maintain a health-supporting rate of communication in specific brain areas associated with both emotion and higher-level mental function. Normal communication in these areas is apparently critical to avoiding or easing depression. Based on this finding, the researchers concluded that effective communication between the neurons acts as the determining factor here, not a specific level of serotonin.

If the researchers’ findings are correct, they strongly imply that anything that helps the neurons communicate more effectively can help ease depression symptoms. In the current medication model, the role of “anything” is frequently played by serotonin-boosting SSRIs and SSNRIs, but any other treatment that improved brain communication could also work. The researchers’ findings also strongly imply that serotonin levels don’t play a crucial role in depression treatment in and of themselves. Essentially, any change in brain chemistry that improved communication rates between neurons affected by depression would serve just as well.


The authors of the study in Nature Neuroscience emphasize the preliminary nature of their current findings. Extensive further research would be required to confirm their conclusions and start the process of identifying new medications that could improve neuron communication in people affected by depression. It’s important to note that no one should change his or her current depression treatment regimen without the express approval of a qualified mental health professional.

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