Depression: The Role of Chronic Inflammation

Depression is a common mental disorder affecting around 4% of the world’s population. Evidence suggests that chronic inflammation plays an important role in the development of depression. Indeed, around one third of individuals with depression show signs of chronic inflammation. Depression is associated with inflammation-related changes in the brain. Obesity and cigarette smoking are both associated with inflammation and depression.

What is chronic inflammation?

“[…] inflammation that persists over a long period of time can be problematic.”

Inflammation is characterized by activation of the immune system which protects the body from threats (e.g. injury or infection) and stimulates tissue repair. Inflammation is usually temporary and disappears once the threat has been removed. This type of short-term inflammation is important for health; however, inflammation that persists over a long period of time can be problematic. This persistent, long-term inflammation, better known as chronic inflammation, can occur in the absence of threats and is characterized by continuous activation of the immune system. This can cause serious damage to the body over time. Increased risk of depression is therefore associated with the damage driven by chronic inflammation.

Chronic inflammation and development of depression

Certain inflammatory compounds can cross the blood brain barrier and contribute to depression through various changes in the brain. These changes include altered transmission of signals between neurons, reduced formation of new neurons, and changes to the “fight or flight” stress response.

Chronic inflammation can alter transmission of signals between neurons by affecting neurotransmitter levels. Neurons are the basic building blocks of the brain which communicate with each other by releasing different neurotransmitters. The signals from neurotransmitters such as serotonin, dopamine, and glutamate are important for brain function and mood regulation. Chronic inflammation may contribute to damage in the brain by decreasing the levels of serotonin and dopamine in neurons. Chronic inflammation can also prevent glutamate from re-entering neurons, causing further damage. The damage associated with imbalance of neurotransmitter levels can result in neuron cell death, which has been implicated in the development of depression. Formation of new neurons in adults is vital for memory, learning, and other brain functions. Damage caused by chronic inflammation can also lead to reduced formation of new neurons in the brain, which predisposes to depression.

“Changes to cortisol levels in the brain can impact serotonin levels and promote further chronic inflammation.”

The effect of inflammatory compounds on the “fight or flight” stress response system may further contribute to increased risk for depression. Cortisol is the body’s main stress hormone which is released in response to stress. Cortisol helps the body respond to stress and one of its functions is to inhibit inflammation. However, chronic inflammation can interfere with cortisol release and leave the body unable to properly respond to stress. Changes to cortisol levels in the brain can impact serotonin levels and promote further chronic inflammation. These inflammation-mediated changes appear to be important in the development of depression.

Chronic inflammation and recovery from depression

Chronic inflammation is not only associated with the development of depression but also presents a barrier to recovery and a lack of response to treatment. Recovery from depression is associated with a return to typical levels of inflammatory compounds. Chronic inflammation may hinder recovery from depression because the brain remains in a state of high stress. Evidence also demonstrates that chronic inflammation plays a role in treatment-resistant depression. Anti-inflammatory drugs may therefore help some individuals recover from depression. Antidepressants have been shown to reduce inflammation and to stimulate the formation of new neurons in specific brain regions. However, the effect of antidepressants in individuals with particularly severe depression may not be enough to reduce inflammation to an appropriate level. Understanding the role of chronic inflammation in depression development and recovery may support the development of effective personalized treatments.

Sources of inflammation

Other conditions are also associated with both depression and inflammation, including obesity and cigarette smoking. These relationships appear to be bidirectional and may be associated with other environmental and social factors. However, it is worth noting that not all people with obesity also have depression and not all people with depression have obesity. The same goes for individuals who smoke.

Obesity is associated with the release of high levels of inflammatory compounds. Obesity is also associated with a 55% increased risk for depression. The increase in inflammatory compounds associated with obesity may explain the simultaneous increase risk for depression. In addition, diet quality can influence the immune system and inflammation levels, as well as the risk for depression. Consumption of a diet rich in fat or refined sugar is associated with higher production of inflammatory compounds. There is evidence to suggest that depression may also increase risk for subsequent obesity. Symptoms of depression such as low energy and motivation are related to low levels of exercise and weight gain, which may contribute to sustained chronic inflammation and worsening of depressive symptoms. Inflammation, obesity and depression may therefore exist in a self-perpetuating cycle that can be difficult to break.

“Cigarettes contain many chemicals which may increase susceptibility for depression by increasing inflammation.”

Cigarette smoking has also been associated with a 52% increase in risk for depression. Cigarettes contain many chemicals which may increase susceptibility for depression by increasing inflammation. Depressed smokers have higher levels of inflammation than non-depressed smokers, suggesting a cumulative effect of inflammation between cigarette smoking and depression. Cigarette smoking can interfere with serotonin, dopamine, glutamate, and other neurotransmitter levels in the brain, which may affect mood regulation and the stress response. These changes may be linked with the development of depression. In addition, rates of cigarette smoking are higher in individuals with depression compared to individuals without depression. One possible reason for this is the use of cigarette smoking as form of self-medication to relieve certain depressive symptoms. Increased risk for depression due to cigarette smoking may differ between individuals based on the frequency and the number of cigarettes smoked as well as the presence of smoking-related health and social consequences.



Written by Anna Chaplin
Image by Sumana Shrestha
Translated by Elmer Sandoval



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Arielle Hogan

Arielle Hogan received a B.S. in Biology and a B.A. in French from the University of Virginia. She is now pursuing a Ph.D. in Neuroscience in the NSIDP program at UCLA. Her research focuses on CNS injury and neural repair. Specifically, she is researching the differential intrinsic transcriptional programs that allow for PNS regeneration and investigating how these transcriptional programs can be induced in models of CNS injury to promote regeneration. She also enjoys learning about biomechatronics and brain-machine interface (BMI), as well as participating in science outreach and teaching. Outside of the lab, she spends time practicing her French, playing basketball, watching movies (even the bad ones), and traveling. For more information about Arielle Hogan, please visit her full profile.