Plasma marker inflames schizophrenia risk

By Eleanor McDermid, Senior medwireNews Reporter

Elevated plasma levels of the inflammatory molecule C-reactive protein (CRP) may be a marker of an increased risk for developing schizophrenia, a study suggests.

The research team says that these “novel findings” are in line with a previous report that patients hospitalized with autoimmune disease or severe infection (ie, conditions associated with elevated inflammation) had an increased risk for later schizophrenia.

However, Børge Nordestgaard (Copenhagen University Hospital, Denmark) and co-workers note that all 78,810 participants in their population-based study were at least 20 years old, so the postulated association may only apply to late-onset schizophrenia.

During follow-up, 36 patients were hospitalized with first-time schizophrenia, and 95 with schizophrenia-like psychosis. The risk for schizophrenia varied with baseline CRP levels, being elevated 1.7-fold for people in the second quartile (median=1.3 mg/L), 2.1-fold for those in the third quartile (1.9 mg/L), and 11.0-fold for those in the fourth quartile (4.3 mg/L), relative to people in the first quartile (0.8 mg/L).

The risk difference between the first and fourth quartiles was statistically significant, and remained so after accounting for multiple confounders, at a 5.9-fold increase, the team reports in Schizophrenia Bulletin.

However, this became nonsignificant on inclusion of people with schizophrenia-like psychosis, which the researchers suggest is because schizophrenia represents a chronic process, and therefore more likely to be associated with inflammation.

To test whether the observed risk could be causal, Nordestgaard and team also did a Mendelian randomization study, based on four single nucleotide polymorphisms in the gene encoding CRP. The theoretical risk for schizophrenia, assuming a causal relationship, was raised 8% and 15% among people who had two genotypes that resulted in elevated CRP levels, relative to those with a genotype that did not.

The actual risk for schizophrenia among these people during follow-up was elevated by about 20%. Although the observed risk increase was not statistically significant, it was broadly in line with the theoretical risk increase, leading the researchers to say that “we cannot exclude that elevated CRP levels per se may be causally associated with schizophrenia.”

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