How Does Trauma Impact the Immune System?
Researchers are exploring the effects of trauma on the immune system in the search for potential new treatments.
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It is estimated that over 70% of the population is exposed to at least one traumatic event in their lifetime. Experiences of trauma have been shown to have profound implications on health including increased risk for obesity, diabetes, cardiovascular disease and poor mental health.
In the book, The Myth of Normal, renowned physician and author Dr. Gabor Maté explains that the word “trauma”, in its Greek origin, means “wound”. He states that an individual's woundedness or how they cope with it determines much of our behavior, shapes our social habits and informs our ways of thinking about the world. Maté argues in the book that "psychological trauma, woundedness, underlies much of what we call disease."
Individuals with trauma-related disorders have been found to experience an array of physiologic alterations, including disruption of the autonomic nervous system which in turn may influence multiple bodily systems such as immune function.
In this article, we examine some of the latest findings on how trauma impacts the immune system, how post-traumatic stress disorder (PTSD) may increase the risk of autoimmune disease and some of the efforts being made to combat inflammation to treat trauma and stress-related disorders.
The effect of early life trauma on immune function
Researchers have found that losing a parent or caregiver can impact the body’s response to cytomegalovirus (CMV), a virus that reactivates under stress and can strain the immune system. The findings were published in the journal PLOS One.
Using nationally representative data from the Health and Retirement Study, scientists examined the association between experiencing parental/caregiver death or separation before age 16 and several indicators of immune function: C-reactive protein, interleukin-6 (IL-6), soluble tumor necrosis factor and immunoglobulin G (IgG) response.1
Consistent associations were found between experiencing parental/caregiver loss and separation and poor immune function as measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups.
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Subscribe for FREEExposure to adverse childhood experiences (ACE) has also been associated with long-term changes in brain structure as a result of inflammation. A study, published in Brain, Behavior, & Immunity – Health, investigated the interplay between ACE, inflammation and white matter in the brain of bipolar disorder (BD) and major depressive disorder (MDD) patients.2
A sample of 200 patients (100 BD, 100 MDD) underwent 3T magnetic resonance imaging (MRI) scans and ACE assessments using the Childhood Trauma Questionnaire. A subgroup of 130 patients (75 MDD and 55 BD) underwent blood sampling to assess immune/inflammatory markers.
Increased immune/inflammatory markers were found in patients suffering from BD but not MDD. Additionally, ACE was found to affect white matter microstructure differently in the two diagnostic groups, with analysis showing a significant indirect effect of ACE on white matter microstructure mediated by higher interleukin-2 levels in BD patients.
“Our findings suggest that inflammation may mediate the detrimental effect of early experiences on brain structure and different mechanisms underlying brain alterations in BD and MDD,” the researchers concluded.
How are PTSD and autoimmune diseases linked?
PTSD is unique among psychiatric disorders in that it requires trauma exposure to develop. While it is still not clear what causes some individuals to develop PTSD because of trauma, studies have shown that PTSD commonly co-occurs with autoimmune disease and immune-related conditions.
What is PTSD?
PTSD is a psychiatric disorder that can result from experiencing or witnessing a traumatic event, such as a serious accident or violent assault. Individuals with PTSD often relive the traumatic event through nightmares and flashbacks. It is estimated to affect one in every three people who have a traumatic experience, but it's not clear why some people develop the condition and others do not.
A study of 120,572 active military personnel in the United States found that the risk of developing select autoimmune diseases was 58% higher for those with a history of PTSD.3 The primary endpoints measured in the study were rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases and multiple sclerosis. The findings were published in the journal BMC Psychiatry.
A large-scale study in Sweden, published in the journal JAMA, found exposure to a stress-related disorder was significantly associated with an increased risk of subsequent autoimmune disease.4
Further explaining these findings, the researchers suggest that under stress, the activated autonomic nervous system might induce the dysregulation of immune function and disinhibition of inflammatory response.
Pointing to findings that patients with PTSD have low cortisol levels, the authors explain that this may cause amplified production of proinflammatory cytokines leading to accelerated immune cell aging and an overactive immune system.
“An alternative mechanism is a potential change in lifestyle after trauma exposure, such as sleep disruption, alcohol or substance abuse and increased smoking, which may indirectly alter the risk of autoimmune disease,” the researchers said.
A 2022 review article highlighted findings that PTSD patients exhibit elevated concentrations of inflammatory markers such as C-reactive protein, IL-6 and tumor necrosis factor alpha. The authors suggest in the paper that factors such as lifetime trauma burden, biological sex, genetic background and metabolic conditions may contribute to inflammation in PTSD.
Targeting inflammation to treat trauma
Currently, only two selective serotonin reuptake inhibitors (SSRIs), paroxetine and sertraline, are approved by the US Food and Drug Administration (FDA) for the treatment of PTSD. The response rates of these SSRIs are approximately 50–60%, leading researchers to seek out new treatments to be used as an adjuvant to SSRIs or in combination with behavioral approaches.
The link between trauma, the immune system and the brain may pave the way for potential anti-inflammatory treatment or preventative therapies. Given the low cortisol levels in individuals with PTSD, clinical studies have examined the effectiveness of synthetic glucocorticoids for treatment. These studies have provided preliminary evidence for reduced PTSD incidence in glucocorticoid-treated patients.
Researchers from University College London (UCL) tested whether a pill form of the stress hormone cortisol could accelerate the process of forgetting intrusive memories when given immediately after a traumatic event.5
“Early treatment with glucocorticoids may reduce PTSD risk, although the effect of such treatment on the etiologically critical step of traumatic memory formation remains unclear,” the researchers said.
Published in Translational Psychiatry, the findings showed that the anti-inflammatory drug hydrocortisone acts to weaken the emotions that underly painful memories, such as those experienced in PTSD.
The medication was tested on 120 healthy participants. 60 were given hydrocortisone and 60 were given a placebo.
The group given hydrocortisone a few minutes after being shown several upsetting videos seemed to “forget” the event more quickly compared to the placebo group.
Individuals responded differently to the drug depending on the levels of sex hormones in their system. For example, men who had high levels of estrogen seemed to have the fewest upsetting memories for a week after watching the video. High levels of estrogen seemed to make women more susceptible to involuntary bad memories if they were treated with hydrocortisone.
Currently, hydrocortisone has only been found to be effective when given to trauma patients in the hours directly following trauma when the memory is consolidated. However, researchers hope that similar treatments with an added behavioral element could limit long-term psychological distress.
Looking to the future of research on trauma and the immune system
Trauma can cause changes to the immune system including increased inflammatory markers and reduced anti-inflammatory markers. Trauma-related disorders such as PTSD have also been linked to an increased risk of autoimmune disease.
Maté explains in the Myth of Normal, “One of the things many diseases have in common is inflammation, acting as kind of a fertilizer for the development of illness. We’ve discovered that when people feel threatened, insecure – especially over an extended period of time – our bodies are programmed to turn on inflammatory genes.”
Further studies on various potential therapies that target trauma-induced inflammation are of great significance not only to potentially alleviate the symptoms of traumatic stress disorders but also to prevent further health decline.
References
1. Noppert GA, Duchowny KA, Stebbins R, Aiello AE, Dowd JB, Clarke P. Biological expressions of early life trauma in the immune system of older adults. PLOS ONE. 2023;18(6):e0286141. doi: 10.1371/journal.pone.0286141
2. Poletti S, Paolini M, Ernst J, et al. Long-term effect of childhood trauma: Role of inflammation and white matter in mood disorders. Brain, Behavior, & Immunity - Health. 2022;26:100529. doi: 10.1016/j.bbih.2022.100529
3. Bookwalter DB, Roenfeldt KA, LeardMann CA, Kong SY, Riddle MS, Rull RP. Posttraumatic stress disorder and risk of selected autoimmune diseases among US military personnel. BMC Psychiatry. 2020;20:23. doi: 10.1186/s12888-020-2432-9
4. Song H, Fang F, Tomasson G, et al. Association of stress-related disorders with subsequent autoimmune disease. JAMA. 2018;319(23):2388-2400. doi: 10.1001/jama.2018.7028
5. Hennessy VE, Troebinger L, Iskandar G, Das RK, Kamboj SK. Accelerated forgetting of a trauma-like event in healthy men and women after a single dose of hydrocortisone. Transl Psychiatry. 2022;12(1):354. doi: 10.1038/s41398-022-02126-2
