CRP40 may have pathogenic role in schizophrenia

By Joanna Lyford, Senior medwireNews Reporter

Gene expression of catecholamine-regulated protein 40 (CRP40) is dysregulated in people with schizophrenia, study findings show.

The research builds on earlier work with post-mortem specimens and supports a potential functional role for this protein in the pathophysiology of schizophrenia.

CRP40 is expressed in the central nervous system and blood and is a 40-kDa heat shock-like splice variant of mortalin-2 - a mitochondrial 70-kDa heat shock protein involved in energy production and oxidative stress.

In vitro studies have shown that CRP40 may be neuroprotective, and a human post-mortem study found that CRP40 levels are lower in brain samples from schizophrenia patients than from healthy individuals.

To investigate further, Joseph Gabriele (McMaster University, Hamilton, Ontario, Canada) and team studied 28 individuals with chronic schizophrenia receiving antipsychotic medication, 13 treatment-naïve individuals with first-episode schizophrenia, and 17 healthy controls.

Blood from all participants was analyzed for absolute copy numbers of CRP40/mortalin-2 messenger (m)RNA. Levels were significantly lower in the first-episode and chronic schizophrenia patients than in healthy controls, report Gabriele and co-authors in Schizophrenia Research.

Furthermore, these differences remained significant after controlling for gender, age, and use of antipsychotic medication.

CRP40/mortalin-2 mRNA levels were also lower in first-episode schizophrenia patients than in those with chronic schizophrenia, although the difference did not reach statistical significance. The authors describe this finding as "hypothesis-generating."

"Our laboratory has previously reported a positive correlation between CRP40/mortalin-2 mRNA expression and the amount of antipsychotic drug treatment throughout total lifespan in post-mortem brains of schizophrenia patients," they note.

Postulating that CRP40 may have similar functions to mortalin-2 and be involved in the regulation of mitochondrial dysfunction and oxidative stress, the team concludes: "The results of this study present a solid starting point towards further investigation of CRP40 involvement in the pathophysiology of schizophrenia, and possibly other oxidative stress disorders."

They add: "It may be possible that CRP40 could be exploited as a dynamic marker of schizophrenia in the future."

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