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Inflammation and Depression: Is there A Link?

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Depression is one of the many mental disorders that impact millions of people worldwide.

Major depressive disorder (MDD) can immensely impact every aspect of your life, including your performance at work, relationships with other people, self-esteem, physical health, and your ability to participate in social activities [1]. 

Because of the increasing impact of mental disorders on numerous populations, experts hope to discover novel treatment strategies that will target the possible causes and treat various kinds of psychiatric diseases.

Does Inflammation Cause Depression?

Does inflammation cause depression? There is currently a growing body of research that tries to answer this question. Let's explore the plausibility of this connection and whether specific medications may combat both inflammation and depression.

How To Tell If You Have Depression?

Depression, or major depressive disorder (MDD), is a common and severe medical condition that will negatively impact your thoughts, actions, and behavior. 

Depression may cause you to feel sad frequently or lose interest and delight in activities you once found enjoyable and fulfilling. 

You might also notice alterations in your appetite, which can lead to weight disorder. At times, you may experience feelings of shame, guilt, worthlessness, or even have suicidal thoughts.

The poor sleeping quality or oversleeping disorder and the inability to focus on daily tasks are also possible symptoms of depression. 

The exact cause of depression is unknown. A combination of biological, environmental, psychological, and social factors may predispose an individual to a higher risk of getting MDD. 

Over the years, studies have analyzed the association between brain inflammation and MDD, seeing a potential to control depression by managing inflammation in the body.

What Causes Inflammation?

Inflammation is your immune system's response to pathogens, external injuries, and chemicals or radiation [3]. 

During an acute inflammatory response, your body will initiate a chemical signaling cascade to promote leukocyte recruitment from the general blood circulation to the site of injury. These activated leukocytes will then release inflammatory mediators to induce an inflammatory response [3, 4]. 

This acute inflammatory response will initiate the healing process and minimize the damage and injury to your cells and tissues. 

Hence, the inflammatory process is an essential biological response of the immune system that acts as a defense mechanism [4]. 

However, uncontrolled systemic or local inflammation is a significant cause of several diseases. Both acute and chronic inflammation-mediated injury can affect the tissues in various organs, including your heart, kidney, liver, and brain [4]. 

Learn more from our article on everyday foods to reduce inflammation naturally.


Is Depression Caused By Inflammation?

Brain inflammation Mechanisms

Inflammatory responses can occur in the brain as they do in the rest of the body. Inflammation in the brain is associated with increased neuronal excitability, cell injury, and enhanced blood-brain barrier (BBB) permeability to certain substances. 

Your brain possesses microglia. These are the primary immune cells in the brain capable of orchestrating strong inflammatory responses. The activation of these cells results in inflammatory occurrences in the brain [4, 5].

Alteration In Brain Regions Resulting From Inflammation Is Linked To Depression States

Studies link depression to significant alterations in various brain regions, including the frontal lobe, temporal lobe, thalamus, amygdala, striatum, and hippocampus [6]. 

Because inflammatory changes can occur in the brain parenchyma, researchers have investigated the association between these changes and the likelihood of depression [7]. 

The exact mechanism by which inflammatory mediators implicate the brain's pathways to cause depression is not entirely understood. However, some studies have suggested that inflammatory mediators are associated with increased glutamate levels resulting in neurotoxicity, decreased serotonin synthesis, and hippocampal atrophy [8].

Pro-Inflammatory Cytokines And Depression

Cytokines are a category of small proteins responsible for the communication between immune and non-immune cells. An increase in pro-inflammatory cytokines in some areas of the brain has also been associated with depression. 

TNFα is a cytokine that functions as a vital mediator of inflammation. During inflammation, there is a surge in the levels of TNFα in the hippocampus and striatum. The increased levels of TNFα in these regions of the brain have been associated with depressed behaviors in animal models [7, 9]. 

Central inflammation is not the only type of inflammatory response linked to changes in the brain. Peripheral inflammation can also lead to the alteration of the BBB, which allows the increased permeability of immune cells and pro-inflammatory cytokines into the brain. These cytokines and immune cells can alter the pathways in the brain as well [7, 8]. 

Overall, the brain itself can produce pro-inflammatory cytokines. In addition to that, peripheral cytokines released due to inflammatory responses in other parts of the body can also signal the brain. These cytokines can enter the brain through increased permeability of the BBB or active transport across the BBB.

Regardless of the exact mechanism, studies have suggested that inflammation-induced peripherally or centrally, or attained from external sources (such as diet), may lead to an increased risk of depression [8, 10].


What Are The Effects Of Pro-Inflammatory And Anti-Inflammatory Medications On Depression?

Patients with hepatitis C, malignant melanoma (skin cancer), some blood cancers, and multiple sclerosis are occasionally treated with interferon-alpha (INF-alpha), a potent inducer of pro-inflammatory cytokines. Collected data shows these patients to have a higher prevalence of depression than patients who did not undergo treatment with INF-alpha [8]. 

On the other hand, a meta-analysis demonstrated that anti-inflammatory medications, especially celecoxib, can decrease depressive symptoms. However, researchers were cautious about the risk of bias in this systemic review. Plus, depression affects people of the same and varying populations differently.

inflammation and depression

Hence, they concluded that anti-inflammatory medication could alleviate depressive symptoms, but further research is required to detect the subgroups of people more likely to benefit from anti-inflammatory drugs [11]. 


Inflammation And Depression: Summing Up

Research has suggested that inflammation may cause, worsen, or prolong depressive symptoms. Despite that, depression is a complex mental disorder that a combination of factors can bring about. Due to this, it is challenging to pinpoint inflammation as the exact or sole cause [8]. 

However, since a possible link is suspected, treatment targeted towards restoring the balance and proper functioning of the immune system and its inflammatory mediators can be considered a strategy for treating depression. Therefore, a group of anti-inflammatory drugs may be synthesized in the future to target inflammation in a specific subset of patients with depression. 

Future research directed towards exploring the association between inflammation and depression may also prove helpful to physicians. If the association is confirmed, they can carefully watch patients who have had a robust immune activation in response to infections or diseases since they may be more susceptible to experiencing depression or other psychiatric disorders.

References:

[1] https://www.who.int/health-topics/depression#tab=tab_2
[2] https://www.psychiatry.org/patients-families/depression/what-is-depression
[3] https://www.ncbi.nlm.nih.gov/books/NBK279298/
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805548/
[5] https://www.frontiersin.org/articles/10.3389/fncel.2018.00488/full
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489983/
[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658985/
[8] https://www.jneuropsychiatry.org/peer-review/depression-and-inflammation-disentangling-a-clear-yet-complex-and-multifaceted-link.html
[9] https://pubmed.ncbi.nlm.nih.gov/21255614/
[10] https://www.dovepress.com/diet-related-inflammation-is-associated-with-major-depressive-disorder-peer-reviewed-fulltext-article-JIR
[11] https://pubmed.ncbi.nlm.nih.gov/25322082/

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