Unravelling the Link: How Severe Depression is Associated with Inflammation in the Brain

New Connections Psychology


A recent study reveals a strong association between clinical depression and a 30% rise in brain inflammation, according to a new study published in JAMA Psychiatry.

Inflammation is a complex and multifaceted process that occurs in response to various forms of injury or disease. It is the body’s natural defense mechanism that aims to protect and heal damaged tissues. Inflammation can be acute, which is a short-lived response to injury, or chronic, which persists over time and can lead to tissue damage and dysfunction.

Although inflammation is a vital process, excessive or prolonged inflammation can have detrimental effects on the body. It can cause tissue damage, impair normal bodily functions, and contribute to the development of chronic diseases, such as cardiovascular disease, diabetes, and cancer.

Recently, there has been growing evidence that inflammation may play a role in the development of psychiatric disorders, particularly depression. Depressive symptoms, such as low mood, fatigue, loss of appetite, and sleep disturbances, are often observed in individuals with chronic inflammatory conditions.

To explore the relationship between inflammation and depression further, researchers from the Centre for Addiction and Mental Health’s (CAMH) Campbell Family Mental Health Research Institute in Toronto, Canada, conducted a study using positron emission tomography (PET) to scan the brains of individuals with depression and healthy controls.

The study aimed to investigate whether inflammation is a primary driver of clinical depression independent of other physical illnesses. The researchers focused on the activation of microglia, immune cells that play a critical role in the brain’s inflammatory response.

Microglia are the primary immune cells in the central nervous system and play a crucial role in maintaining brain health. They act as the first line of defense against injury and infection and are responsible for removing damaged cells and debris from the brain.

However, prolonged activation of microglia can cause chronic inflammation, which can contribute to the development of various neurological and psychiatric disorders, including depression.

By using PET imaging to measure the activation of microglia in the brains of depressed individuals and healthy controls, the researchers aimed to determine whether inflammation is a driver of depression, independent of other physical illnesses.

The findings of the study revealed that individuals with depression had increased microglial activation in specific brain regions compared to healthy controls. These results suggest that inflammation may be a crucial driver of depression, independent of other physical illnesses.

The PET scans conducted as part of the study revealed that individuals with depression had significantly higher levels of inflammation in specific areas of the brain compared to healthy participants. The severity of inflammation was also positively correlated with the severity of depressive symptoms, indicating a strong association between the two.

Notably, the brains of individuals with clinical depression exhibited a 30% increase in inflammation compared to healthy controls. These findings suggest that inflammation may be a critical contributor to the development and severity of depression, independent of other physical illnesses.

Previous research has explored the relationship between depression and inflammation, with some studies examining markers of inflammation in the blood of depressed individuals. These studies aimed to address the debate surrounding whether inflammation is a consequence of or contributor to depression.

One such study, conducted by Duke University Medical Center researchers and published in Biological Psychiatry in 2012, found a correlation between the number of depressive episodes experienced by participants and increased levels of C-reactive protein (CRP), a marker of inflammation, in their blood. This study provides further evidence of the relationship between inflammation and depression and suggests that inflammation may contribute to the development of depressive symptoms.

“Our results support a pathway from childhood depression to increased levels of CRP, even after accounting for other health-related behaviors that are known to influence inflammation. We found no support for the pathway from CRP to increased risk for depression,” said Duke study leader Dr. William Copeland.

According to the Duke University Medical Center researchers, their findings suggest that depression may be a primary contributor to inflammation in the body, rather than a consequence of inflammation.

Although the CAMH study did not provide information on whether individuals with depression exhibited brain inflammation before or after the onset of symptoms, the researchers noted that their study was the first to provide conclusive evidence of inflammation in the brains of individuals with depression.


Should future depression therapies target inflammation?

Dr. Jeffrey Meyer, a Canada Research Chair in the neurochemistry of major depression and senior author of the study, considers the finding as the most convincing evidence thus far of brain inflammation during a major depressive episode. The discovery has significant implications for developing new treatments for individuals suffering from depression. The findings suggest a new target for reversing brain inflammation or shifting it to a positive repair role that could potentially alleviate symptoms.

Severe depression impacts 4% of the general population, with more than half of individuals with major depression not responding to antidepressants. Dr. Meyer suggests that future studies should investigate the potential impact of anti-inflammatory drugs on depression symptoms.

Dr. Meyer emphasizes that depression is a complex illness that requires multiple biological changes to cause an episode. However, he believes that inflammation in the brain is one of the key changes and identifying it as such is an important step forward in understanding the mechanisms of depression.


Getting Help

If you are experiencing symptoms of depression, seeking help from a mental health professional can make a significant difference in your recovery journey. One option to consider is therapy, which provides a safe and supportive environment for you to explore your emotions and learn coping skills. In addition, online telehealth services have become increasingly popular in recent years, allowing individuals to receive mental health treatment from the comfort of their own homes. With the COVID-19 pandemic and its effects on mental health, telehealth has become a critical tool in providing access to care. By seeking therapy and utilizing telehealth services, individuals with depression can receive support and treatment, including the potential use of anti-inflammatory drugs that may alleviate their symptoms.



The discovery of brain inflammation in individuals with depression provides new insights into the complex nature of the condition. The study’s findings suggest that inflammation in the brain may be a primary contributor to depression, rather than a consequence of the condition. This discovery highlights the importance of continued research into the biological changes that occur in individuals with depression and provides potential new targets for treatment. Seeking help through therapy and telehealth services is a critical step in receiving the necessary support and care for individuals with depression. With the ongoing advancements in mental health treatment, individuals with depression can receive the care they need to lead fulfilling and healthy lives.

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