Presentation Prenatal environmental factor and schizophrenia

大西, 新

Emerging literature has provided epidemiological evidence that maternal immune activation (MIA) during the first half of gestation increases the risk of schizophrenia in offspring: On the basis of the fact that the increased schizophrenia risks in offspring are correlated not only with influenza infection at pregnancy but with other maternal infectious diseases such as poliovirus, rubella and T. gondii, it seems that not a specific viral infection but MIA itself would increase the risks in offspring. We demonstrated that MIA rat models have GABAergic interneuronal loss together with dopamine D2 receptors dysfunction in the anterior cingulate cortex by both positron emission tomography and neurochemical analysis. The results obtained in our study were similar to several publications on patients with schizophrenia. Our findings suggest that MIA produce cortical neuronal abnormality similar to patients with schizophrenia.  It is estimated that 30% of schizophrenia cases could be prevented if certain prenatal infections were entirely eliminated from the pregnant population, and therefore it seems likely that there is a subgroup of sporadic schizophrenia patients with MIA background within overall population of the disease. Although a number of studies have been published that searched for clues to serodiagnostic markers of schizophrenia, serodiagnostic biomarkers for the patient with MIA background have yet to become entrenched. Although the whole picture of the MIA model animal phenotype has not yet been clarified, we herein suggest its usefulness in our quest for serodiagnostic biomarkers of sporadic schizophrenia with MIA background. We found augmentation of immunoglobulin (Ig) κ light chain in the serum proteome of the MIA model rats. We thereby studied Ig light chain contents in the commercially available sera of patients with sporadic schizophrenia to find elevation of both free Ig light chains (FLC). We also measured the contents of such pro-inflammatory cytokines as IL-6, IL-1β and TNF-α, all of which were below the detection limits of the ELISA reagents. Our results imply that serum FLC assay together with pro-inflammatory cytokine measurements would be of use to stratify the MIA-associated subgroup among schizophrenia patient population and thereby to realize a serodiagnostic test for diagnosis of sporadic schizophrenia subpopulation.

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