Schizophrenia and C-reactive protein

Discussions on the various studies hinting at a possible connection between inflammation (however you wish to define this) and autism, at least some of the autisms, have cropped up with increasing frequency on this blog (see here and here). I wouldn't go so far as to say that a causal link has been established yet; as in 'inflammation causes autism', or indeed 'autism cause inflammation' but inflammation. in it's various guises, is certainly one to watch.

Amusing the muses @ Wikipedia 

Outside of autism, and bearing in mind an increasingly vocal research voice suggesting common ground (see here) and connections between autism and other more psychiatrically-defined conditions such as the schizophrenia spectrum (see here), similar work also suggests a possible connection between inflammatory markers and other conditions.

Indeed today's post is dedicated to some of the cumulative work looking at schizophrenia and inflammation, and in particular one of the more reliable markers of inflammation, C-reactive protein (CRP) linked to all manner of health ills (see here for example).

I arrived at this post after reading the paper by Lin and colleagues* and their assertion that subject to much more confirmatory research being required, cases of schizophrenia which were also following a medication regime (antipsychotic meds) seemed more likely to present with elevations in CRP. The medication element to the study reflects some interest in how antipsychotics might be able to affect the CRP measure, bearing in mind the results are still fairly limited in this area (see this paper by Diaz and colleagues**).

The paper by Miller and colleagues*** provides a pretty good summary of the various research undertaken so far on CRP and schizophrenia. They concluded that there was "a 28% prevalence of an elevated CRP level in patients with schizophrenia and related disorders" and onwards quite a strong implication of increased inflammation being associated with schizophrenia. Importantly as per the autism example, this does not necessarily mean that inflammation is causative of schizophrenia or vice-versa.

It is noteworthy that a name which has appeared more than once on this blog has also thrown their research hat into the schizophrenia-CRP arena. Faith Dickerson (with a mention for Robert Yolken too), famous around these parts for her various studies on schizophrenia with the gondii in mind (see here) and a few other potential important associations (see here), also suggested that CRP levels tended to be on the higher side in cases of schizophrenia****. They reported that even after adjusting for various potentially modifying variables such as smoking status (see here) and body mass index (BMI) (see here), CRP levels were elevated in their participants with schizophrenia above and beyond asymptomatic controls and even those diagnosed with bipolar disorder. That bipolar disorder bit has also been explored a little bit more with CRP in mind too*****.

Importantly Dickerson and the other authors included in this mini-review post highlight how elevated CRP outside of any direct connection with either the onset or perpetuation of schizophrenia might place a person at enhanced risk of various health-related issues (see here). Without wishing to sound too morbid, heart health in schizophrenia for example, does not seem to have a great track record as per some previous discussions on this blog (see here). That finding perhaps as part of a greater package of issues with physical health screening and mental illness (see this paper from Barley and colleagues******) and some inequality which appears to be present.

Just before I go, I wonder if it would be worth mentioning a few other potential points of interest which perhaps require some further investigation. I touched upon the topic of homocysteine - the big 'H' - and schizophrenia in a previous post (see here) and also an intersecting area dealing with folate metabolism (see here). Homocysteine, whilst still the topic of some debate, was at one time talked about with issues related to things like cardiovascular health (see this paper by Wald and colleagues*******). Appreciating that humans are very complex creatures and sweeping generalisations about one compound = risk of one disease seem to serve little use, one might choose to enquire whether CRP levels might correlate with homocysteine and whether this clarifies any health-related relationship or not? Something along the lines of this paper but with larger participant numbers and without the interfering variables. Indeed as per another Dickerson paper******** whether CRP plus [insert variable of your choice here] might provide further insights into how CRP levels could even affect some of the facets of schizophrenia itself.

And very, very finally and quickly, I do wonder about the questions raised by Berk and colleagues********* (open-access) bearing in mind no medical advice is given or intended.

To close, are you just living for the weekend?

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* Lin CC. et al. Increased high-sensitivity C-reactive protein levels in Taiwanese schizophrenic patients. Asia Pac Psychiatry. 2013 Jun;5(2):E58-63. doi: 10.1111/appy.12078.

** Diaz FJ. et al. Possible effects of some antipsychotic drugs on C-reactive protein in a drug-naïve psychotic sample. Schizophr Res. 2010 Aug;121(1-3):207-12. doi: 10.1016/j.schres.2010.06.002.

*** Miller BJ. et al. C-Reactive Protein Levels in Schizophrenia. Clin Schizophr Relat Psychoses. 2013 Feb 21:1-22

**** Dickerson F. et al. C-reactive protein is elevated in schizophrenia. Schizophr Res. 2013 Jan;143(1):198-202. doi: 10.1016/j.schres.2012.10.041.

***** Dickerson F. et al. Elevated C-reactive protein and cognitive deficits in individuals with bipolar disorder. J Affect Disord. 2013 May 17. pii: S0165-0327(13)00340-6. doi: 10.1016/j.jad.2013.04.039.

****** Barley E. et al. Interventions to encourage uptake of cancer screening for people with severe mental illness. Cochrane Database Syst Rev. 2013 Jul 16;7:CD009641.

******* Wald DS. et al. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002 Nov 23;325(7374):1202.

******** Dickerson F. et al. Additive effects of elevated C-reactive protein and exposure to Herpes Simplex Virus type 1 on cognitive impairment in individuals with schizophrenia. Schizophr Res. 2012 Jan;134(1):83-8. doi: 10.1016/j.schres.2011.10.003.

********* Berk M. et al. Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. BMC Med. 2013 Mar 18;11(1):74.

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Lin CC, Chang CM, Liu CY, & Huang TL (2013). Increased high-sensitivity C-reactive protein levels in Taiwanese schizophrenic patients. Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists, 5 (2) PMID: 23857813