The World Health Organization projects that depression will cause more years in life lost to disability than any other illness by 2030 (WHO 2008, cited in Blume et al. 2011). Perhaps many of these lives lost will be affected by a weakened immune system stemming from a mental illness? This newly researched topic is opening the door for the health community and those afflicted by clinical depression to better understand the link between depression and its subsequent dysfunctional immune system.
Nearly 20 million adults in the United States alone suffer from Major Depressive Disorder, and that number is only representational of the patients who actively report their occurrence of symptoms.
Many more are unable to afford or even find the aid they need to treat their mental health disorders. According to Kiecolt-Glaser and Glaser (2002), “Depression is the most common psychiatric illness.” Clinical depression has long been understood and treated solely as a psychiatric illness, however more research has emerged about its somatic ramifications.
Depression includes a variety of both psychological and somatic symptoms that differs with every case.
Psychiatrists and doctors often utilize the Diagnostic and Statistical Manual of Mental Disorders (“DSM”) to diagnose mental health disorders and suggest a treatment journey. Because the mind is so complex, there are a wide array of treatment plans and medications for nearly every psychological disorder. Antidepressants medication and talk-therapy are among the most commonly prescribed treatments for mental health afflictions.
According to WebMD (2018), Major Depressive Disorder affects twice as many women than men, traced back to female changes in hormones and pregnancy.
Historically, however, women exhibiting these symptoms were treated as hysterical by psychiatrists until fairly recently. Today, a general stigma around mental illness remains and permeates through society, namely the United States. Depression and other mental illnesses are often treated without the same urgency as physical ailments. This country also lacks many public mental healthcare facilities, such as rehab centers and psychiatric wards for those unable to afford treatment. It is important to highlight new research on depression and raise awareness around mental illness in order to evolve the healthcare system to include more of those suffering from mental disorders and trauma.
Depression is widely treated solely in a psychiatric manner, yet treating depression with a holistic approach will improve the body’s overall somatic health. In this paper, research about the interconnection of immunology and depression will be presented in order to better understand the effects and possible treatments. Clinical depression has a similar effect on the immune system to chronic stress, causing a hyperactive inflammatory response and degrading the success of the immune system, even to the point of vaccination potency.
To understand the effects of depression on the body’s immune system, one must first be introduced to the diverse symptoms of depression, the basic operations of the human immune system, and the body’s reaction to stress.
Symptoms and severity of such symptoms vary among people, however most with depression report feeling in a generally low mood and loss of interest throughout their daily activities. Although most people experience instances of sadness or periods of difficulty, clinical depression is more serious and chronic. According to the DSM-5, symptoms of depression must present themselves for at least a two-week period in order to be clinically diagnosable. Other symptoms of depression include hypersomnia or insomnia, restlessness or sluggishness, fatigue, inability to concentrate, anhedonia, weight loss or weight gain, and thoughts of suicide or self-harm (Mayo Clinic Staff 2018). Symptoms may escalate others, such as an untreated depression case spiraling into a drug or alcohol addiction. Likewise, lack of motivation and constant fatigue may lead to social isolation. This interconnectedness of symptoms perpetuates the depressive cycle and feelings of hopelessness. These symptoms may amount to a single depressive episode or appear chronically throughout a patients’ life, which is more detrimental to the immune system functioning, much like chronic stress.
Because of the wide range of symptoms and complexity of the human psyche, depression may be caused by many variables. The most common perceived causation of depression is a biochemical imbalance of the neurotransmitters in the brain needed to function properly (Leonard 2001), including serotonin, norepinephrine, and dopamine. Antidepressant medication is a leading treatment for clinical depression; typically, neurotransmitter reuptake inhibitors maintain a higher level of mood-boosting chemicals in the brain, seemingly easing the symptoms of depression (Leonard 2001). This chemical imbalance can be triggered through traumatic experiences or genetically inherited. Other sources of depression arise from hormonal imbalances, notably in females, and environmental circumstances such as seasonally affective depression.
The body’s immune system is an intricate network of barriers and defense mechanisms protecting against unwanted foreign invaders like bacteria and viruses. In this system there are three key processes in protecting the body: the innate immune system, the antibody-mediated response, and the cell-mediated response.
The innate immune system is the first line of defense, including the body’s physical and chemical barriers. A key response in this system is inflammatory response, which is likewise a notable aspect in the stress response that will be covered next. As the body is invaded by an unwanted substance, it ignites the inflammatory response to attack the intruder and speed up healing. Four aspects of inflammation are pain, swelling, redness, and heat; each of these responses force further blood flow into the area and encourage the presence of cytokines. Pro-inflammatory cytokines are small proteins released by cells to signal other helpers, like phagocytes ad Natural Killer Cells, to mobilize.
After the antigen has been destroyed, anti-inflammatory cytokines, with the assistance of suppressor T-cells, are activated and this signals the body’s immune defense to retreat from the healed area. (Pearson Learning Solutions 2017) Thus, cytokines and their role in inflammation, if in balance, protect the body from pathogens and boost overall immunity. Both the antibody-mediated immune response and the cell-mediated immune response rely on a multitude of similar-functioning cells to discern non-self cells or abnormally-functioning self cells and destroy them. Each of these intricate processes rely heavily on the strength and proper operation of the immune system and health of the individual, which is why any ailment like depression can negatively impact these important defenses.
Another active aspect of the immune system is the implementation of life-saving vaccinations. These relatively new innovations present a nontoxic antigen, in the form of its protein, into the human body. Its memory cells are then exposed to and stimulate the antibody response to generate immunity to the harmful form of the antigen should the body ever be exposed to it (Pearson Learning Solutions 2017). Without vaccinations, millions would be afflicted with illness like polio and tetanus.
The right amount of stress a person experiences can be beneficial to the body. Unfortunately, many people in the United States experience high volumes of chronic stress that eventually degrades overall immune efficacy. There are many interesting findings from different studies on numerous categories of stress and how they affect the immune system. For example, according to Leonard and Song (1996), several researchers have concluded that divorced or separated individuals have poorer immune function overall than those who are married. So, how does the stress reaction work in the body?
Under stress, the body deactivates certain functions and heightens others in an effort to prepare the body for a perceived attack. This includes an inhibition of the digestive tract and reproductive functions and an increase in alertness and heart rate. Notably, under chronic stress, large aspects of the immune system are compromised. All of these activations and pauses are controlled primarily by the hypothalamus, amygdala, and brain stem, termed the HPA axis, in the central nervous system (Leonard and Song 1996). Each produce several neurotransmitters that are vital to the jumpstart of the stress reaction- cortisol and adrenaline. Both of these neurochemicals are components of the sympathetic nervous system, the central player in the body’s reaction to stress. The hypothalamus activates this system and the chemicals like cortisol begin to circulate through the body as a multitude of effects take place. Chronic stress maintains this activation throughout the body for longer than is typically healthy.
According to Harvard Medical School (2018), chronic stress can contribute to high blood pressure, hormonal changes, or even weight gain/weight loss. Another important consequence of chronic stress is its link to excessive inflammation in the body (Liu et al. 2017). In more direct terms, chronic stress prolongs a heightened sympathetic nervous system that can break down the homeostasis of the body. The parasympathetic nervous system calms down the stress reaction and ignites the normal functioning of the body’s different systems. However, this system is not often activated in someone who experiences chronic stress. Breathing and meditative techniques that help lower blood pressure and heart rate, as well as physical activity are often promoted as helpful tactics to combat the effects of chronic stress (Harvard Medical School 2018).
Clinical depression’s repercussions in the body often mirror that of a chronic stress reaction. Both depression and chronic stress induce the release of biochemical hormones, like cortisol, that can degrade the immune system (Blume et al. 2011). Debate remains around the causation of the comorbidity between chronic stress and depression- whether one causes the other. However, research exhibits that there is an obvious interconnectedness between depression, the chronic stress reaction, and chronic inflammation.
So, how does the connection between clinical depression and the immune system work? A key place to begin this understanding is in the research behind raised cytokines levels in depressed patients. Kiecolt-Glaser and Glaser (2002) researched this connection specifically in regards to depressed and chronically stressed patients. Their research revealed that not only does syndromal depression produce heightened levels of cytokines, but so does merely suffering from depressive symptoms. These cytokine levels enhance the inflammatory response and eventually decrease the immune system’s response to pathogens- the body is stuck in stress mode.
A chronic inflammatory response is linked to aging, primarily to a higher risk of cardiovascular disease, type 2 diabetes, and various cancers (Kiecolt-Glaser and Glaser 2002). Thus, clinical depression directly alters the amount of pro-inflammatory cytokines in the blood which may speed the internal aging process. Because depressed patients are more likely to experience depression-related symptoms such as poor sleep and poorer nutrition choices, this also builds into poor immune function and inadvertently causes higher risk for consequences like cardiovascular plaque. Each of these side behaviors related to depression have their own detrimental effects on immunity.
Another vital aspect of clinical depression’s impact on the immune system is its triggering of adrenal hormones. According to (Leonard 2001), cytokines hinder the release of certain helpful neurotransmitters, such as serotonin, and trigger the hypothalamus to increase biochemical release of cortisol from the adrenal glands. In understanding the stress response explained above, elevated cortisol levels are vital to acute stress for a short-term response but can become destructive in the long-term. These adrenal hormones, like cortisol, eventually wear down parts of the body like the kidneys and cardiovascular regions.
Evidence of neurotransmitter hindrance may also contribute to the longevity and severity of symptoms of one’s depression. New and innovative research is actually showing that a dysfunctional immune system may cause depressive symptoms or even clinical depression itself. Consequently, the depression-immunity cycle may work in a way that both pathways of depression and immunity effect one another. Although the existence of cytokines suggests an active immune function, the system is deprived of an off-switch, causing a hyperactive HPA axis, therefore damaging immunity operation (Leonard 2001).
This stress response, and possibly just having a negative mood for a day, may likewise decrease the amount of Natural Killer cells in the body, impairing a key aspect of the innate immune response (Glaser et al. 2002). NKC’s function as immunity against cancerous cells and virus-infected cells by perforating these toxic cell membranes and causing apoptosis, or cell suicide; Natural Killer cells are vital in fighting abnormal cells and antigens in the body. Thus, it is important to treat clinical depression as it may impact the healthy levels of NK cells in the suffering individual. Patients with clinical depression may also face longer infections (Glaser et al. 2002). Several factors may influence prolonged infectious episodes including a lower rate of NK cells and chronic inflammation. It is possible that longer infections and episodes of sickness may catalyze more depressive symptoms; this cycle is detrimental to both psychological and somatic wellbeing.
Luckily in studies conducted like Glaser et al. (2002), individuals who were treated with antidepressants manifested normalized levels of pro-inflammatory cytokines as well as other biochemicals. Interestingly, different types of antidepressants have varying effects on the levels of cytokines. For example, tricyclic antidepressants have less of an effect on diminishing pro-inflammatory cytokines than SSRI antidepressants. Tricyclic antidepressants are an older form of antidepressant therapy, and SSRI antidepressants are more commonly prescribed for clinical depression.
Other studies show that techniques like breathing and meditation exercises, consistent physical exercise, and maintaining a healthy diet can all improve both the symptoms of clinical depression and overall somatic function. Treatment of depression with a holistic approach in regards to bettering both mind and body may be more effective than solely focusing on the psychological level of depression. However, if patients can only afford psychiatric care, this research is helpful in proving that antidepressants may be enough to boost immune function and relieve many symptoms of depression.
Many engrossing studies have found that depression can hamper the effectiveness of vaccinations, exhibiting the direct ramifications of depression on the immune system. Studies have been conducted on both the shingles vaccine and vaccinations for rabies. Fairly recent UCLA research conducted in 2013 studied the link between depression and its hampering of the shingles virus.
This study measured a group of middle-age patients who suffered from clinical depression and a group of similarly matched control patients. Over two years, the two groups were tested for levels of the T-cells that targeted the shingles virus. Interestingly enough, the study found that those patients with major depressive disorder that were not being treated with antidepressant therapy showed a lesser response to the virus and thus potency of the vaccination; those treated with antidepressants had been better protected by the vaccination. (Wheeler 2013). This information suggests a correlation with relatively balanced biochemical markers in the brain and a better performing immune system.
Wheeler (2013) noted that once the patients who suffered from clinical depression were treated with antidepressant medication, the effectiveness of the vaccine and its levels actually stabilized even if the patients still experienced symptoms of depression. Again, this study reiterates the importance of antidepressant treatment for not only treating the psychological aspects of depression, but also boosting immune function and vaccination potency. Even in active forms of immunity that doctors have synthesized in a lab to save millions of lives may be impacted by clinical depression.
Research noted above does not suggest that every individual experiences all of these occurrences simultaneously as clinically depressed, rather that many of these can happen in different individuals at different times in their struggle with clinical depression. Several of these studies have had difficulty defining what chronic stress and depression mean exactly, because these occurrences vary so much between people. The problems with definition have caused issues in relating a conclusive causation between clinical depression and a dysfunctional immune system. Nevertheless, the studies conducted do show explicit correlation between clinical depression and either a hyperactive HPA axis, low neurotransmitter levels, high pro-inflammatory cytokine and adrenal hormone levels, and longer sickness periods. This research additionally reveals how clinical depression may influence the success of vaccination efforts against specific antigens.
Doctors and patients may use this significant information in order to treat clinical depression with a newer, more holistic outlook, treating both the body and the mind. Clinical depression in the United States is extremely widespread, effecting over 20 million people, but is still treated less seriously than physical ailments because of the extensive stigmas around mental health in this country. In studying the extreme effects of depression on the immune system, perhaps these conclusions will drive more funding and discussion around mental health in the United States. Perhaps better aid for those with mental disorders like clinical depression will lead to a decline in the current opioid crisis. The repercussions of treating mental health more shamelessly may not only help those suffering with mental disorders like addiction and depression, but as stated above it will improve those suffering with physical ailments and sicknesses, like cancers and autoimmune disorders.