Wednesday, 23 July 2014

Trauma and PTSD raise risk of autoimmune disorders?

I admit to some head scratching when I first read the paper by Aoife O’Donovan and colleagues [1] reporting that among war veterans of the Iraq and Afghanistan campaigns, "trauma exposure and PTSD [post-traumatic stress disorder] may increase risk of autoimmune disorders".

It wasn't that I didn't believe the results, but rather that the idea that a physical event with a psychological consequence could impact on a somatic condition with an autoimmune element to it seemed to open up some new avenues particularly pertinent to this blog and its focus on psychology and biology intersecting. That there may be consequences for other conditions from the O'Donovan findings was something else that piqued my interest.
Sunset in Rio @ BBC 1

Anyway, a few details first:

  • A retrospective study based on the analysis of several thousands of medical records of US troops deployed into active theatre in Iraq or Afghanistan was the study starting point. The idea being that outside of PTSD being "associated with endocrine and immune abnormalities" [2] there may be more to see when it comes to autoimmune disease - conditions characterised by a breakdown in the immune system distinguishing self from other. The types of autoimmune disorder included for study ranged from inflammatory bowel disease (IBD) to lupus erythematosus.
  • From an initial cohort of 666,269 veterans, 203,766 (30%) were diagnosed with PTSD and just shy of 20% were diagnosed with a psychiatric disorder other than PTSD. Comparing those with PTSD with those without, authors reported a "significantly higher adjusted relative risk (ARR) for diagnosis with any of the autoimmune disorders alone or in combination compared to veterans with no psychiatric diagnoses... and compared to veterans diagnosed with psychiatric disorders other than PTSD".
  • Both men and women with PTSD seemed to be equally affected by autoimmune disorders. Military sexual trauma exposure was also "independently associated with increased risk in both men and women" of autoimmune disorders.

The first thing that struck me about the O'Donovan findings was the observation that nearly a third of all veterans were diagnosed with PTSD. I've talked before about concepts like shell shock and how thousands of troops suffered psychological trauma during the First World War (see here). In the modern era where trench warfare has to some extent been overtaken by the digital battlefield, it appears that the psychological harms of war still persist and still inflict a terrible burden.

As intrigued as I was about the PTSD - autoimmune disorder connection included in the O'Donovan paper, a quick trawl through some of the other research in this area tells me this is not the first time that such an association has been made. The results from Boscarino [3] hinted that "chronic sufferers of PTSD may be at risk for autoimmune diseases" based on an analysis of Vietnam war veterans. The comparison between veterans who operated in different theatres of conflict (Iraq/Afghanistan vs. Vietnam) also to some degree negates any individual geographical effect from the war zone itself as influencing the results. The paper by Zung and colleagues [4] looking at paediatric type 1 diabetes frequency and psychological stress associated with the 2006 Lebanon War concluded that war trauma might play a role in the increased numbers of cases situated near the conflict. One wonders what the outcome of current events might be too. Such data also implies that age and occupation (i.e. a military career) are not going to be able to account for the PTSD - autoimmunity link either.

So then to the question of what mechanism might be driving this association. Outside of the general area of immune response and something like inflammation [5], the paper by Sommershof and colleagues [6] reported data pointing to a "profoundly altered composition of the peripheral T cell compartment [which] might cause a state of compromised immune responsiveness" in relation to traumatic stress and physical health. I'm no expert on T cells but I gather that they do play an important role in the issue of autoimmunity [7] (open-access) so perhaps there is more research to do there. O'Donovan et al also list "lifestyle factors" as also influencing the trauma exposure / PTSD - autoimmune disease relationship which brings into play a whole host of issues ranging from drug and/or alcohol abuse to less extreme environmental factors. I'd also be minded to suggest that culturally-related issues might also play a role in any relationship as per studies like the one from Whealin and colleagues [8] talking about "risk and resilience correlates of PTSD" as a function of ethnicity. I might also draw your attention to the important paper by Alessio Fasano on gut permeability and autoimmune disease [9] which might very well link PTSD to other physiological events as per other descriptions [10].

Whichever way you look at the O'Donovan paper, their findings present some stark facts about caring for war veterans. They also emphasise how war really can be hell.

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[1] O'Donovan A. et al. Elevated Risk For Autoimmune Disorders In Iraq And Afghanistan Veterans With Posttraumatic Stress Disorder. Biological Psychiatry. 2014. June 28.

[2] Pace TW. & Heim CM. A short review on the psychoneuroimmunology of posttraumatic stress disorder: from risk factors to medical comorbidities. Brain Behav Immun. 2011 Jan;25(1):6-13.

[3] Boscarino JA. Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies. Ann N Y Acad Sci. 2004 Dec;1032:141-53.

[4] Zung A. et al. Increase in the incidence of type 1 diabetes in Israeli children following the Second Lebanon War. Pediatr Diabetes. 2012 Jun;13(4):326-33.

[5] Tursich M. et al. Association of trauma exposure with proinflammatory activity: a transdiagnostic meta-analysis. Translational Psychiatry. 2014. July 22.

[6] Sommershof A. et al. Substantial reduction of naïve and regulatory T cells following traumatic stress. Brain Behav Immun. 2009 Nov;23(8):1117-24.

[7] Dejaco C. et al. Imbalance of regulatory T cells in human autoimmune diseases. Immunology. Mar 2006; 117: 289–300.

[8] Whealin JM. et al. Evaluating PTSD prevalence and resilience factors in a predominantly Asian American and Pacific Islander sample of Iraq and Afghanistan Veterans. J Affect Disord. 2013 Sep 25;150(3):1062-8.

[9] Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012 Feb;42(1):71-8

[10] Berk M. et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013 Sep 12;11:200.

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ResearchBlogging.org O’Donovan, A., Cohen, B., Seal, K., Bertenthal, D., Margaretten, M., Nishimi, K., & Neylan, T. (2014). Elevated Risk For Autoimmune Disorders In Iraq And Afghanistan Veterans With Posttraumatic Stress Disorder Biological Psychiatry DOI: 10.1016/j.biopsych.2014.06.015