May 17, 2016

expert reaction to bacterial immunisation and PTSD-like symptoms in mice

The relationship between inflammatory diseases, stress and immunisation with dead bacteria is explored in a paper published in the journal PNAS in which the authors report that such immunisation in mice reduced effects associated with stress and fear.

Dr Sheena Cruickshank, British Society for Immunology spokesperson and Senior Lecturer in Immunology at The University of Manchester said:

“It is clear that, in developed countries, there is an increased incidence of allergy and inflammatory autoimmune disorders, although the reasons for this are not fully understood. One popular theory is that we have become too clean and the types of germs we are exposed to has changed, meaning that our immune system becomes ‘faulty’ and reacts inappropriately – this idea is sometimes called the ‘Old Friend’s’ hypothesis.

“In this study, Reber and colleagues have set out to investigate this ‘Old Friend’s’ hypothesis by repeatedly vaccinating mice using a heat-killed environmental microbe and then studying their response to stressful situations.

“The study’s findings that injecting mice with this particular bacterium can reduce stress and inflammation are intriguing, but it is early days yet. The gut inflammation characterised in this study appears to be only mild in nature.  Additionally, the outcomes observed between the different gut inflammation models used are inconsistent, making it hard to come to an overall conclusion on treatment effects.  The study was conducted over a relatively short time frame, so it remains to be seen whether there is any long-lasting protective effect, how wide-ranging any effects may be (particularly against other types of inflammation) and how applicable the findings are to humans.”

Prof. Neil Greenberg, Royal College of Psychiatrists’ lead on Military and Veterans’ Mental Health and Professor of Defence Mental Health, King’s College London:

“This seems to be a very interesting finding in an animal model that is suggestive of ‘old friends’ bacteria being linked to behavioural responses which [in an animal model] are positive in terms of apparent dealing with stressful situations. It’s interesting, but a very long way from a strong demonstration that immunisation with Myobacterium Vaccae (m.vacc) or equivalent in humans will treat [or prevent] PTSD or other mental health disorders. From what I can tell the methodology is decent in terms of demonstrating the effects described (e.g. mice being able to deal better with an aggressor) in mice. It’s not a surprise that immunisation with m.vacc leads to an alteration of the immune system in some way. I am not expert enough in immunology to form a view on whether the specific T cell changes are to be expected or not.

“I am not aware of any animal models of PTSD which have had an impact on our understanding of how PTSD affects people or in the treatment of PTSD. PTSD, and indeed many mental health problems, have substantial psychosocial elements to them (moral judgements, contemplation of mortality, loss of opportunity for career advancement, feeling let down by people etc.) which I can only imagine are very different to the life of a mouse.

“I think in essence, this is an interesting signal and with ethical clearance it might be possible to try and see what effect this might have in chronic (complex) PTSD suffers. But whilst I know m.vacc is used in cancer patients, I don’t know about the dosing and side effects etc that might occur in patients who have a significant mental health disorder; I suspect carrying out such a trial would have some good going ethical questions to answer and there may well be information from patients treated with m.vacc for cancer which might be of relevance to any human trial aiming to treat mental health problems.

Prof. Jamie Hacker-Hughes, Visiting Professor of Military Psychology, Anglia Ruskin University and Visiting Professor of Psychology, University of Hertfordshire and Vice President of British Psychological Society and Former Head of Defence Clinical Psychology and Defence Consultant Advisor in Psychology, Ministry of Defence, said:

“This is a robust study with a good sample size and reasonable effect sizes but one cannot yet extrapolate from animal models of anxiety to PTSD in humans. So while the discovery of a new agent for use in immunisation is, of course, good news the claim that it will prevent PTSD goes one step too far.

“The problem with this lies not in the research or its conclusion but in the headline to the accompanying press release. Of course it is excellent to find a new method of achieving immunity and the work of colleagues John Stanford and Graham Rook at UCL in isolating Myobacterium Vaccae and investigating its immunological properties is to be commended.

“But, and it’s a big ‘but’, it is a big leap to go from this very worthwhile discovery to link it, as the release does, to Eraly et al’s 2014 JAMA study linking plasma biomarkers of infection to a predisposition to US Marine Corps and Navy personnel developing Post Traumatic Stress Disorder.

“And the reason, of course, is that the development of PTSD is multifactorial – trauma severity, frequency, contact and duration, age, gender, occupation and role, previous traumatisation and, yes, infection, among many others. And did the mice really have PTSD in the first place anyway? Is there such a thing and how would we know if they had it? The research only mentions PTSD in passing and focuses rightly on anxiety and stress responses which are linked, but different.”

‘Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice’ by Reber et al. published in PNAS on Monday 16^th May. 

Declared interests

Dr Cruickshank: “No conflict of interests to declare.”

Prof. Greenberg: “I did collaborate with some of the researcher in the US a few years back to try and get a grant (to study this in military veterans) but with no luck! I have never actually met them.”

Prof Hacker-Hughes: “Has received grant funding from the Defence Healthcare Science and Technology Centre, BLESMA, Forces in Mind Trust, Royal British Legion. ”