Featured on Psychology Today. Author: Marwa Azab, PhD
According to the World Health organization, depression is the leading cause of disability. Unfortunately, 30 to 60 percent of patients are not responsive to available antidepressant treatments (Krishnan & Nestler, 2008). In other words, 40 to 70 percent of patients are not helped by existing treatments. One area of research might shed light on why a sizable portion of patients is not helped by current antidepressants.
There is growing evidence that inflammation can give rise to or exacerbate depressive symptoms. The inflammatory response is a key component of our immune system. When our bodies are invaded by bacteria, viruses, toxins or parasites, the immune system recruits cells, proteins, and tissues including the brain to attack these invaders. The main strategy is to mark the injured body parts, so we can pay more attention to them. Local inflammation makes the injured parts red, swollen, and hot. When the injury is not localized, then the system becomes inflamed. These pro-inflammatory factors give rise to “sickness behavior.” These include physical, cognitiveand behavioral changes. Typically, the sick person experiences sleepiness, fatigue, slow reaction time, cognitive impairments and loss of appetite. This constellation of changes that take place when we are sick is adaptive. It compels us to get more sleep to heal and remain isolated so to not spread infections.
However, a prolonged inflammatory response can wreak havoc in our bodies and can put us at risk of depression and other illnesses. There is plenty of evidence solidifying the link between inflammation and depression. For example, markers of inflammation are elevated in people who suffer from depression compared to non-depressed ones (Happakoski et al., 2015). Also, indicators of inflammation can predict the severity of depressive symptoms. A study that examined twins who share 100 percent of the same genes found that the twin who had higher CRP concentration (measure of inflammation) was more likely to develop depression five years later.
Doctors noticed that their Cancer and Hepatitis C patients treated with IFN-alpha therapy (increases inflammatory response) also suffered from depression. This treatment increased the release of pro-inflammatory cytokines which gave rise to loss of appetite, sleep disturbance, anhedonia (loss of pleasure), cognitive impairment and suicidal ideation (Lotrich et al., 2007). The prevalence of depression in these patients was so high. These results add credence to the inflammation story of depression.
Subsequent careful studies showed that the increase in prevalence of depression in patients treated with IFN-alpha was not only because they were sick. Using a simple method of injecting healthy subjects with immune system invaders, researchers found higher rates of depressive symptoms in the ones who were exposed compared to the placebo group. The subjects who were induced to have an inflammatory response, complained of symptoms such as: negative mood, anhedonia, sleep disturbances, social withdrawal, and cognitive impairments.
The link between inflammation and depression is even more solid for patients who don’t respond to current antidepressants. Studies have shown that treatment resistant patients tend to have elevated inflammatory factors circulating at baseline than the responsive ones. This is clinically important; a clinician can utilize a measure like CRP levels which is a part of a routine physical to predict the therapeutic response to antidepressants. In one study, they found that increased levels of an inflammation molecule prior to treatment predicted poor response to antidepressants (O’Brien et al., 2007).
There are environmental factors that cause inflammation and therefore elevate risk for depression: stress, low socioeconomic status, or a troubled childhood. Also, an elevated inflammatory response leads to increased sensitivity to stress. The effect has been reported in multiple studies in mice. For example, mice that have gone under chronic unpredictable stress have higher levels of inflammation markers (Tianzhu et al., 2014). Interestingly, there are individual differences that make some mice more resistant to stress and therefore initiate a calmer immune response (Hodes et al., 2014).
Depression is a heterogeneous disorder. Each patient’s struggle is unique given his/her childhood, genetics, sensitivity of their immune system, other existing bodily illnesses and current status in society. Being on the disadvantageous end of these dimensions irritates our immune system and causes chronic inflammation. The brain is very responsive to these circulating inflammatory markers and initiates “sickness behavior.” When the inflammation is prolonged by stressors or other vulnerabilities, the sickness behavior becomes depression.
If you are a professional working with patients suffering from depression, I urge you to consider the health of your patients’ immune systems. If you are a patient suffering from an exaggerated immune disorder (e.g. arthritis), do not ignore the depressive symptoms that you might be experiencing. If you are suffering from depression, avoid anything that might exacerbate your immune response. This is another example of the beautiful dance between mind and body!