PTSD Linked to Chronic Inflammation and Early Death
By John Gever, Staff Writer, MedPage Published: February 13, 2008; Reviewed by Zalman S. Agus, MD; Emeritus Professor University of Pennsylvania School of Medicine
DANVILLE, Pa., Feb. 13 -- Post traumatic stress disorder is a risk factor for early death, a study of Vietnam-era veterans showed. Veterans diagnosed with posttraumatic stress disorder in the mid-1980s were more than twice as likely to die by 2000 as those who did not have a PTSD diagnosis, reported Joseph A. Boscarino, Ph.D., M.P.H., of Geisinger Health System here, in the February issue of the Journal of Nervous and Mental Disease.
- Explain that the study found post traumatic stress disorder to significantly predict death within 15 years, independent of other risk factors. Explain that other factors also predicted early death, including markers of chronic inflammation, such as white blood cell count and erythrocyte sedimentation rate. Explain that the author suggested that clinicians screen for posttraumatic stress disorder as part of routine workups.
Dr. Boscarino found a hazard ratio for all-disease death in Vietnam-era veterans of 2.1 (95% CI 1.4 to 3.1, P<0.001) after adjusting for other risk factors, including markers of chronic inflammation and stress, as well as smoking, obesity, age, race, intelligence, Army intake status, alcohol abuse, depression, and antisocial personality disorder. High erythrocyte sedimentation rate, white blood cell count, an sulfate ratio were also significant and independent predictors of early all-disease death, Dr. Boscarino reported. "Although PTSD is a predictor of future disease mortality, there are other common biologic factors operative among trauma-exposed populations," he wrote. In an interview, he said that the increased death rates probably stemmed from multiple pathways. These include the effects of chronic, low-grade, systemic inflammation as well as drug-taking or other risky behaviors, he said. It's likely that these pathways interact, he added. Earlier research has linked post traumatic stress directly to chronic inflammation. The study involved 4,462 Vietnam-era Army veterans, including 2,490 who actually served in Vietnam, as well as 1,972 who served elsewhere.
At baseline, 323 of the veterans were diagnosed with post traumatic stress disorder, including 10.2% of those who served in Vietnam and 3.4% of those serving elsewhere. Study participants had undergone interviews and laboratory tests in 1985 and 1986 as part of an earlier study. Dr. Boscarino correlated the baseline findings in the 1980s with vital status through 2000.
Mortality rates in 2000 were 13.6% among those with post traumatic stress disorder at baseline versus 5% among those who did not have a PTSD diagnosis (P<0.001). In addition to predicting all-cause mortality, post traumatic stress disorder and high erythrocyte sedimentation rate at baseline were also significantly associated with death rates from cardiovascular conditions. Adjusted hazard ratios for cardiovascular death were 2.2 (95% CI 1.1 to 4.4) for posttraumatic stress disorder and 3.6 (95% CI 2.5 to 5.0) for high erythrocyte sedimentation rate.
A high cortisol: dehydroepiandrosterone sulfate ratio was significantly associated with all-disease death (HR 2.9, 95% CI 1.9 to 4.4) but not with cardiovascular mortality. When asked about clinical implications, Dr. Boscarino said that physicians treating veterans should consider routinely screening for post traumatic stress disorder, just as they do for conventional disease risk factors. "There is a very serious burden of illness associated with having this marker, this psychological marker," he said. "The general practitioner maybe needs to put that on his or her clinical inventory of assessment tools." He added that the social stigma attached to post traumatic stress disorder is an obstacle to testing for it, but it's important to try to overcome it. "If we can get beyond those barriers, we have treatments that work," Dr. Boscarino said.
He identified several limitations of the study. Cause of death was obtained from death certificates, which are known to be imperfect. Baseline diagnoses of post traumatic stress disorder were based on criteria now considered obsolete. Also, the number of deaths among study participants was low and reduced the statistical power. Dr. Boscarino said it would be important to confirm the findings in prospective studies, which are now being done with veterans of more recent wars. "The new studies will be more definitive," he said.
- inflammation of cells in ptsd and Traumatic stress
Cortisol directly influences your insulin levels and metabolism. It also plays a role in chronic inflammation and your immune system. I’m sure you’ve seen this relationship in your own life: how many times have you worked endless hours only to go on vacation and get sick? Your body is good at keeping a lid on things, but it can’t do it forever. Coping with persistent stress takes a steady toll on your immune system, your adrenals, and your central nervous system.
Your body reacts to stressors universally, whether they are biological or psychological. The more acute the threat feels, the more dramatic the response will be. With inflammation, painful emotional baggage is as incendiary as physical stress. Think about asthma. An emotional shock will trigger an attack in some people as often as physical exertion or an allergen. Thoughts and internalized feelings are very powerful — and they manifest themselves physically all the time with symptoms of inflammation. Stress makes your skin break out. Your intestines go into revolt during a painful break-up. But the good news is your feelings can — and should — be enlisted as allies in the healing process. With all the other factors contributing to inflammation, coping with stress and emotional pain is often overlooked — but it’s really important. And it can play a big part in restoring your immune system’s balance before it gets overloaded.
Abstract BACKGROUND: Post traumatic stress disorder (PTSD) is a prevalent psychiatric disorder that develops following a traumatic event and has substantial health implications, including high rates of health morbidity and mortality, as well as significant health-related costs. Medical risks that are associated with PTSD often have an underlying inflammatory pathology, suggesting that inflammation contributes to these health declines.
OBJECTIVES AND DESIGN: In this critical literature review, the authors examine the medical risks associated with PTSD and the inflammatory mechanisms that likely underlie these risks.
RESULTS AND CONCLUSIONS: The authors offer a review of their "Cells to Society Resiliency Model" to motivate the development of integrative interventions that include factors of society, community, family, individual, physiological, and cellular factors to thereby reduce the health risks associated with PTSD.
Ashwaganda: Effects on Stress, Inflammation and Immune Cell Activation Ayurvedic medicine has been practiced in India for more than 2,500 years. Ashwagandha (Withania somnifera) is one of the most widely utilized herbs in the system. It is thought to affect the endocrine, immune, nervous, and cardiopulmonary systems. This study was designed as a preliminary investigation of the effects of Ashwagandha on stress, inflammation, and immune modulation. Participants took the liquid extract in cow’s milk twice a day for five days. The results of initial, one-day, and final blood draws were compared to determine participant’s beginning and ending levels of cortisol, inflammatory cytokines, and immune-cell activation (CD4 T-cells, CD8 T-cells, B cells and natural killer cells). Measurements were completed using flow cytometry and ELISA assay. The purpose of this study is to determine which effects of Ashwagandha are most suitable for further investigation.
Research Examines Link Between PTSD and Inflammation
BETHESDA, MD—The science into the biological mechanisms behind the psychological symptoms of PTSD is still in its infancy, but studies have linked PTSD to other serious health problems, including cardiovascular disease, chronic pain, fatigue, and metabolic disorders. Research funded by NIH is suggesting that the cause of this link might have its roots in endocrine and immune function differences in patients with PTSD and most significantly in those with co-morbid major depressive disorder.
Inflammation and PTSD
“PTSD and major depressive disorder (MDD) share a common vulnerability along the experience of a trauma, such that they are highly comorbid. Depression is a significant risk factor for the onset of PTSD following a trauma,” explained Jessica Gill, PhD, RN, an assistant clinical investigator at the National Institute of Nursing Research, during an NIH clinical center lecture last month. “When the two diseases are comorbid, additional medical conditions present, including conditions that have an inflammatory pathology.”
Gill’s research over the last few years has led her to describe the endocrine and immune function differences in patients with PTSD and MDD, and to link inflammatory risks in those patients with subsequent physical health decline. “We need to understand why PTSD is often related to low levels of cortisol, especially when MDD is comorbid,” Gill said. “It’s counterintuitive to what we would think since stress such as trauma is associated with high levels of cortisol and over-activation of that system.”
It is also counterintuitive to find lower levels of cortisol—a glucocorticoid produced by the adrenal gland in times of stress—in patients with PTSD and MDD, since depression alone is associated with higher levels of plasma cortisol, Gill added. And yet in individuals who experience early life trauma and have MDD without PTSD, studies show lower levels of cortisol in their systems.
Studies have also found that patients with PTSD and comorbid MDD have greater levels of the inflammatory marker interleukin-6 (IL-6). “Studies of Katrina survivors and survivors of myocardial infarctions show higher levels of IL-6 in those patients with PTSD and MDD. But when depression is controlled for, these findings are no longer significant,” Gill explained.
In a study published in 2008, Gill looked at baseline endocrine and immune function in women with PTSD, women with PTSD and comorbid MDD, and controls. She and her colleagues found that cortisol was significantly lower in those women with PTSD and inflammatory markers were significantly higher. There was also a trend of elevation in the PTSD and MDD group compared to PTSD alone. There were similar findings in a previous study of male and female refugees. However, in studies of male combat veterans with PTSD and no MDD, there were higher immune cell counts in relation to cortisol levels.
A 2009 study by Gill looked at overnight levels of endocrine and immune markers in PTSD and MDD patient populations, and added the injection of hydrocortisone upon waking. The study confirmed that individuals with PTSD and MDD had significantly reduced levels of cortisol, especially in the morning hours. The researchers focused on nocturnal levels because patients with PTSD frequently suffer from sleep/wake cycle disturbances that significantly impact health. Also, high levels of IL-6 prior to waking have been shown to be a significant risk factor for myocardial infarction. The study found IL-6 to be significantly elevated in the PTSD and MDD group. But it was the PTSD without MDD group that was hyper-responsive to the administration of hydrocortisone. For those patients with PTSD and MDD, even after administration of hydrocortisone, their IL-6 levels remained significantly higher. This could have significant impact on patient health, since inflammatory markers have been linked to significant risk for mortality and morbidity.
Predicting and Preventing PTSD
These results suggest not only that there is a differential function in the immune and endocrine systems in individuals with PTSD and MDD, but also that there might be insufficient regulation of the inflammatory actions of the immune system by the low levels of circulating cortisol. “These low levels may not be able to restrain the mechanisms of the immune system,” Gill declared. And an unrestrained immune system could lead to inflammation that could later lead to other health problems, such as CV disease and metabolic diseases.
But questions remain concerning whether treating cortisol levels can have a direct effect on the symptoms of PTSD. “We need more prospective studies to identify when biological changes occur following the advent of trauma, so that we can understand how they are linked to long-term consequences to physical and psychiatric health,” Gill explained. “This could inform the development of interventions to screen and prevent the onset of PTSD as well as the medical consequences associated with it.”
For example, could anti-inflammatories have a preventative effect on PTSD and its subsequent physical symptoms? “NSAIDs have not yet been used to prevent the onset of PTSD. But that’s something we’d like to look at,” Gill said. “There hasn’t been a lot of research to look at pharmaceutical agents to prevent the onset of PTSD. Hopefully future studies will be prospectives so we can look at the trends that may predict the onset of PTSD psychologically and biologically, as well as social factors. Right now we just don’t have enough prospective studies to understand that risk factor profile.”
Causes of inflammation
by Marcelle Pick, OB/GYN NP
Systemic or chronic inflammation has a domino effect that can seriously undermine your health. So how does it all begin?
The immune system and the inflammatory response. Many experts now see inflammation as arising from an immune system response that’s out of control. When you catch a cold or sprain your ankle, your immune system switches into gear. Infection or injury trigger a chain of events called the inflammatory cascade. The familiar signs of normal inflammation — heat, pain, redness, and swelling — are the first signals that your immune system is being called into action.
In a delicate balance of give-and-take, inflammation begins when pro-inflammatory hormones in your body call out for your white blood cells to come and clear out infection and damaged tissue. These agents are matched by equally powerful, closely related anti-inflammatory compounds, which move in once the threat is neutralized to begin the healing process.
Acute inflammation that ebbs and flows as needed signifies a well-balanced immune system. But symptoms of inflammation that don’t recede are telling you that the “on” switch to your immune system is stuck. It’s poised on high alert — even when you aren’t in imminent danger. In some cases, what started as a healthy mechanism, like building scar tissue or swelling, just won’t shut off.