Tuesday, 10 July 2012

The trial of Toxoplasma gondii

Although self-directed harm and attempted suicide are probably not most people's favourite topic of conversation, it is a fact of life that they happen, and happen more regularly than many of us might think. The reasons for such behaviours are complex and to a large degree, unique to an individual's circumstances; acknowledging that external forces such as the economic downturn that we are all currently presented with, can play a role (see this post on Greece). It is indeed a sobering thought that even things like the work conditions of a father can conceivably impact on offspring risk of attempted and completed suicide* (full-text); such is the potential effect of the environment around us.

Not being an expert on the psychology of self-harm and suicide, I can't readily provide information on the intricate details of how a person arrives at such a situation. Up until a few years ago, I just assumed that the person themselves represents the starting point, and onwards how they cope (or not) with the situations they are presented with bearing in mind the various issues/conditions which can affect mental health. The suggestion that a person might not have as much control over such behaviours or ideations as we might think, seemed a little bit far-fetched; that is until I read a little more about organisms such as Toxoplasma gondii.

Toxoplasma gondii or T.gondii is one of nature's survivors. I don't want to go through all the details of its survival tricks or what it might conceivably do because they have to some extent already been covered in previous blog posts on rats being attracted to cats and mention of the possible link with cases of schizophrenia. Suffice to say that this is a parasite who knows how to keep its head above the water.

Indeed, having previously discussed some interesting data produced by Pedersen and colleagues** in this post on risk of schizophrenia spectrum disorders and T.gondii infection, I was equally interested in the latest paper from this research group*** (full-text) looking at self-directed violence and T.gondii infection. Sensational headlines like 'Are ‘Cat Ladies’ More Likely to Attempt Suicide?' are to be put to one side for now.

I'm not the first to cover this paper. I don't really want to regurgitate all the ins and outs of the latest study by Marianne Pedersen and colleagues (see Dr Emily Deans' post for a good dissection of the study), which by all accounts seemed to mimic their previous protocol: looking at more than 45,000 women giving birth in Denmark between 1992 and 1995, measuring IgG antibody levels to T.gondii and, on this occasion, seeing how this linked (or not) to the reports of suicide, attempted suicide and self-directed violence via hospital and death registers. Suffice to say that was a mammoth project both in terms of numbers and the work gone into the various studies.

There are several interesting parts to this study and its results which I do however want to mention. From a methodological point of view, the study highlights a potential 'predictive value' from IgG antibody levels to T.gondii and risk of self-directed violence and attempted suicide. Based on their statistics, the link between IgG antibodies and actual suicide showed the strongest relationship with a relative risk of 2.05 (95% CI, 0.78-5.20). Bear in mind however that out of the total 45,000+ women studied, only 18 women committed suicide, and 8 of them were seropositive for antibodies, so less than half.

The authors discuss the possible mechanism to account for the association found. I was interested in a couple of the ideas outlined:

  • Once again those letters and that number, IL-6, crop up as possibly being related to the findings. I wasn't aware that apparently there may be a relationship between IL-6 levels and suicide attempts**** and hence how inflammatory cytokines may show some critical relationship to the presence of T.gondii. I suppose it is what the immune system is designed to do.
  • Keeping with the inflammation theme, some discussion on a role for the enzyme indoleamine 2,3-dioxygenase (IDO) is also provided, taking us back to another previous dinner party guest, tryptophan. It doesn't stop at tryptophan however as kynurenic acid moves into the fray and its link to glutamatergic neurotransmission. I have a post scheduled fairly soon looking at the kynurenic acid hypothesis of schizophrenia***** just to give you a flavour of where this line of thought might lead.

This is an interesting area of work which although requiring a lot more investigation adds another layer to the idea that we might think we are in control of our destiny but perhaps not as much as we would like to be even outside of the various social nudging. As per my previous discussions on T.gondii there is also the issue of what we might be able to do if infection is picked up early enough, and importantly whether such intervention might actually in this case save lives. Again I link to this study by Goodwin and colleagues****** and their suggestion, to quote: "some agents used to treat schizophrenia have the ability to inhibit T. gondii proliferation in cell culture". Makes me wonder how many other medications and other products******* might have similar effects?

----------

* Aleck O. et al. The impact of fathers' physical and psychosocial work conditions on attempted and completed suicide among their children. BMC Public Health. 2006; 6: 77.

** Pedersen MG. et al. Toxoplasma infection and later development of schizophrenia in mothers. The American Journal of Psychiatry. 2011; 168: 814-821.

*** Pedersen MG, Mortensen PB, Norgaard-Pedersen B, & Postolache TT (2012). Toxoplasma gondii Infection and Self-directed Violence in Mothers. Archives of General Psychiatry, 1-8 PMID: 22752117

**** Lindqvist D. et al. Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity. Biological Psychiatry. 2009; 66: 287-292.

***** Erhardt S. et al. The kynurenic acid hypothesis of schizophrenia. Physiology & Behaviour. 2007; 92: 203-209.

****** Goodwin DG. et al. Evaluation of five antischizophrenic agents against Toxoplasma gondii in human cell cultures. The Journal of Parisitology. 2011; 97: 148-151.

******* Kavitha N. et al. In vitro Anti-Toxoplasma gondii activity of root extract/fractions of Eurycoma longifolia Jack. BMC Complementary & Alternative Medicine. 2012; 12: 91.