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Depression’s Chemical Imbalance Explained

For over three decades, scientists have attributed a chemical imbalance in the brain as the source of major depression. Now, a new study provides an explanation of how this “chemical imbalance” occurs.

Major depression is a disease that impacts approximately 5% of people globally. For over 30 years, scientists believed that monoamines– mood-related chemicals such as serotonin, norepinephrine and dopamine– are low in the brain during major depressive episodes. This is commonly referred to as a “chemical imbalance”. However, no one had ever found a convincing explanation for monoamine loss, until now.

This study by the Canadian-based Centre for Addiction and Mental Health (CAMH) is published in the November Archives of General Psychiatry.

DepressionDr. Jeffrey Meyer investigated whether brain monoamine oxidase A (MAO-A) — an enzyme that breaks down chemicals like serotonin, norepinephrine and dopamine– was higher in those with untreated depression. The results showed that in major depression MAO-A was significantly higher in every brain region that the scientists investigated. On average, MAO-A was 34% higher.

According to Dr. Meyer, “In major depression, higher levels of MAO-A is the primary process that lowers monoamine levels. Having more MAO-A leads to greater breakdown of key chemicals like serotonin.”

This study by the Canadian-based Centre for Addiction and Mental Health (CAMH) includes a detailed new monoamine model of depression, based upon this work as well as four previous publications from Dr. Meyer and collaborators at CAMH.

Said Dr. Meyer, “A key barrier to making advances in treating depression is a lack of precise disease models. Having disease model is like having a map. Once you have that map you can really begin to understand how an illness like depression works, and offer more targeted and effective treatment.”

A second part of this new model is that monoamine transporters have an important role in removing monoamines away from active sites. Having more of a monoamine transporter is not helpful as it removes more monoamine — for example if one has more serotonin transporter, one would additionally lose more serotonin during depression.

“An important aspect of our advanced monoamine model is that individuals with depression lose chemicals like serotonin and dopamine at different rates based upon transporter density. This helps explain why one person with depression may experience loss of appetite while another may not. And some people have more severe symptoms than others,” said Dr. Meyer.

This advanced monoamine model of depression is a huge step forward in the disease frontier. It brings the study of mental illness closer to the advancements seen in research into physical illness such as cardiac disease, and offers one of the most comprehensive disease models in mental illness.

The next step for researchers will be to investigate why MAO-A levels are raised in the brain and consider prevention strategies. Prevention strategies are critical — according to the World Health Organization, major depression is currently the fourth leading cause of death and disability and is expected to rise to second by the year 2020.

Source: Centre for Addiction and Mental Health

Depression’s Chemical Imbalance Explained

Rick Nauert PhD

Rick Nauert, PhDDr. Rick Nauert has over 25 years experience in clinical, administrative and academic healthcare. He is currently an associate professor for Rocky Mountain University of Health Professionals doctoral program in health promotion and wellness. Dr. Nauert began his career as a clinical physical therapist and served as a regional manager for a publicly traded multidisciplinary rehabilitation agency for 12 years. He has masters degrees in health-fitness management and healthcare administration and a doctoral degree from The University of Texas at Austin focused on health care informatics, health administration, health education and health policy. His research efforts included the area of telehealth with a specialty in disease management.

APA Reference
Nauert PhD, R. (2018). Depression’s Chemical Imbalance Explained. Psych Central. Retrieved on March 23, 2019, from
Scientifically Reviewed
Last updated: 8 Aug 2018
Last reviewed: By a member of our scientific advisory board on 8 Aug 2018
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