Tuesday, 11 August 2015

Schizophrenia and CRP meta-analysed

"CRP [C-reactive protein] levels were moderately increased in persons with SZ [schizophrenia] regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ."

That was the conclusion reached by Fernandes and colleagues [1] as part of their meta-analysis "of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects."

CRP, just in case you didn't know, is one of the molecules of choice when it comes to looking at systemic inflammation as a result of infection or injury. A member of the pentraxins, there has been quite a bit of scientific interest in CRP with schizophrenia in mind down the years as a result of various lines of investigation hinting at possible links between schizophrenia and inflammatory processes (see here).

I've already covered CRP and schizophrenia a few times on this blog (see here and see here) and some of the intricacies of a possible relationship between elevations in CRP and the signs and symptoms of schizophrenia. Research discussions have also entertained the thought that maternal levels of CRP might also show some connection to subsequent offspring risk of schizophrenia too (see here).

In their meta-analysis, Fernandes et al assessed over 25 studies cumulatively including some 85,000 participants. Alongside the idea that CRP might be elevated in cases of schizophrenia, authors also suggested that "the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms." Positive and negative symptoms of schizophrenia are discussed further here but can generally be described as symptoms not normally seen in the general population (positive) such as hallucinations and delusions, and symptoms that 'disrupt normal emotions and behaviours' (negative) such as anhedonia or a general lack of self-help skills.

Interestingly, body mass index (BMI) and age also showed something of a modifying relationship with CRP levels in schizophrenia. Increasing BMI was linked, sorry "aligned", to rising CRP levels which follows something of a trend in weight research [2] accepting that BMI is not necessarily the best way to categorise a person as overweight or obese. Such an observation seems to tie into a growing tide of research suggesting that facets of metabolic syndrome - in whole or in part - might be quite closely linked to at least some cases of schizophrenia [3] and beyond.

Finally, Fernandes and colleagues make an important point about the use of medication with schizophrenia and CRP in mind: "CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics." This would tend to confirm that (a) CRP levels are probably already elevated in medication-naive patients with schizophrenia and (b) various classes of antipsychotics are not 'inflammatory' in terms of their pharmacological effects.

"In summary, our study provides further evidence of the inflammatory hypothesis of SZ." Further: "Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified." On that last point, I'd be minded to suggest that research into other markers of inflammation in cases of schizophrenia might also be revealing (see here and see here for example). The next question is: what happens when inflammation is 'treated' in cases of schizophrenia [4] in terms of symptom presentation?

Music: Toploader - Dancing in the Moonlight.

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[1] Fernandes BS. et al. C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications. Mol Psychiatry. 2015 Jul 14.

[2] Visser M. et al. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999 Dec 8;282(22):2131-5.

[3] Lasić D. et al. Metabolic syndrome and inflammation markers in patients with schizophrenia and recurrent depressive disorder. Psychiatr Danub. 2014 Sep;26(3):214-9.

[4] Cox D. et al. The potential of immune biomarkers to advance personalized medicine approaches for schizophrenia. J Nerv Ment Dis. 2015 May;203(5):393-9.

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ResearchBlogging.org Fernandes, B., Steiner, J., Bernstein, H., Dodd, S., Pasco, J., Dean, O., Nardin, P., Gonçalves, C., & Berk, M. (2015). C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications Molecular Psychiatry DOI: 10.1038/mp.2015.87