Wednesday, 21 August 2013

Blood biomarkers and suicide

Science can be a pretty cold thing.

Take for example some of the discussions on the recent paper by Helen Le-Niculescu and colleagues* (open-access) on the potential for a suite of blood biomarkers to predict suicidal behaviour (see here for some more commentary). The very complicated tragedy that is suicide - whether attempted or completed - [potentially] boiled down to genes, and in particular the product expression of one gene, SAT1 described by the authors as "head and shoulders above the rest" in terms of its [potential] predictive capability.

The Good Samaritan @ Wikipedia 
With my science hat on, I was obviously interested in this research, and how despite the relatively small participant group "In each of the suicide completers, the increase in SAT1 was at least three s.d. above the average levels".

But then as I read the words again, the realisation set in that these 'completers' were not just mice or rats in a cage, they were people. People who only 24 hours prior to their inclusion in the study were alive. And then for whatever reasons decided to end their life and with it the hopes and dreams of their parents, siblings, partners, extended family and friends.

Don't get me wrong, I'm not saying that we shouldn't be actively engaging in research looking at how we might eventually predict those at greatest risk from suicide. On the contrary, if this work pans out and survives replication the potential savings both in terms of that most precious commodity (life) and beyond could be enormous. But it is still an 'if' and those were real people.

The Le-Niculescu paper is open-access so I'm not going to go through it with a fine-toothed comb on this occasions. Suffice to say that this study, following previous interest from this authorship group (see here), set out to explore whether it was possible to predict and track suicidal states, particularly in those at high-risk for suicide as per their selection of participants diagnosed with "a major mood disorder (bipolar disorder)".

This involved first looking at blood gene expression in participants focused specifically on those who "switched from having no suicidal thoughts to scoring highly on a suicide-risk scale". The myriad of data this generated was then subject to analysis via an author favourite technique called Convergent Functional Genomics (see here**) used "to identify and prioritize from the list of differentially expressed gene biomarkers of relevance to suicidality". It was then a process of checking the top ranking gene biomarkers in those suicide completers (drawn from a different population) and "Niculescu's team was left with six which they was reasonably confident were indicative of suicide risk". More boiling down of the biomarkers was accomplished by looking at a further group of those hospitalised for suicide (attempts) and "SAT1, PTEN, MARCKS and MAP3K3 might be not only state biomarkers but trait biomarkers as well".

In all the chatter about this study, one particular question was floating around my mind: if these biomarkers are verified, does this mean we could eventually affect gene or biochemistry and somehow alter the behaviour of those attempting or thinking of attempting suicide?

Actually the authors do mention some potentially important information about this. They report for example, that the drug clozapine might affect expression of some of the biomarkers "in opposite direction to our human suicidality data in previous independent animal model pharmacogenomics studies conducted by us". Clozapine as they note is indicated for suicidality under certain circumstances (see here). Fair enough, an antipsychotic might help, bearing in mind it is an antipsychotic and carries some of the usual side-effects (see here).

But they also mention another possibility that requires some further study, as per this quite long quote:

"Several of the biomarkers from our current study (SAT1, S100A8, IL1B and 16 others) were changed in expression by omega-3 treatment in the blood of the circadian clock gene DBP (D-box binding protein) knock-out mouse model in opposite direction to our human suicidality data".

So, fatty acids, particularly those of the omega-3 variety might [might!] also impact on some of those biomarkers too? This point in particular is of real interest to me and this blog. A quick trawl of the literature looking at measured fatty acids and suicidality turns up some interesting data as per studies like this one*** and this one****. I don't think anyone has convincingly said that fatty acids 'cause' suicide because suicide is a very complicated process reliant on more than just biology, but the association is an interesting one. Some recent coincidental literature on suicides in prison (see here) confirms the multi-faceted nature of suicide.

Indeed, I've talked previously on this blog about how nutrition, in many forms, has been associated with suicide risk as per the vitamin D and independently, the lithium research (see here) reported in the scientific literature. To stress again, these are associations; so one has to be cautious not to say too much at the present time about causation.

I started this post by saying how cold science is when it comes to its operation. I suppose I should end by saying that science is cold, at least in the way it is carried out and reports, because it has to be. It has to be cold and objective. Assuming that the Le-Niculescu findings are successfully replicated however, science then can start to move out of the freezer and into something rather 'warmer' approaching real-life with regards to its translation into potentially saving lives.

To close, just in case you need to talk to someone, remember that these guys are only a phone call or email away (similar organisations are also in the US and other parts of the world).


* Le-Niculescu H. et al. Discovery and validation of blood biomarkers for suicidality. Molecular Psychiatry. 20 August 2013. doi: 10.1038/mp.2013.95

** Le-Niculescu AB. & Le-Niculescu H. Convergent Functional Genomics: what we have learned and can learn about genes, pathways, and mechanisms. Neuropsychopharmacology. 2010 January; 35(1): 355–356.

*** Lewis MD. et al. Suicide deaths of active-duty US military and omega-3 fatty-acid status: a case-control comparison. J Clin Psychiatry. 2011 Dec;72(12):1585-90. doi: 10.4088/JCP.11m06879.

**** Vaz JS. et al. Omega-6 fatty acids and greater likelihood of suicide risk and major depression in early pregnancy. J Affect Disord. 2013 May 30. pii: S0165-0327(13)00346-7. doi: 10.1016/j.jad.2013.04.045.

---------- Le-Niculescu H (2013). Discovery and validation of blood biomarkers for suicidality Molecular Psychiatry DOI: 10.1038/mp.2013.95