Abstract
Abnormalities in the complement system have been described in patients with schizophrenia, with those individuals having greater frequency of complement component 4A (C4A) alleles and higher C4A transcript levels in postmortem brain tissue. Importantly, abnormalities in C4A and other complement molecules have been associated with synaptic pruning abnormalities that occur during neurodevelopment. A few studies have investigated C4 levels in living patients with schizophrenia, but all of them did so using peripheral blood samples. No studies have examined C4 levels in cerebrospinal fluid (CSF), presumably a better biofluid choice given its intimate contact with the brain. Therefore, we report for the first time on C4 levels in CSF and plasma of patients with schizophrenia. In this study, we obtained CSF in 32 patients with schizophrenia spectrum disorders and 32 healthy volunteers and peripheral blood samples in 33 SSD and 31 healthy volunteers. C4 levels were measured using Abcam ELISA assays. Univariate analysis did not show a statistically significant difference in CSF C4 values between groups. However, a multivariable analysis showed a statistically significant increase in CSF C4 levels between groups after adjusting for sex and age. We also observed a high correlation between CSF C4 levels and age. By contrast, plasma C4 levels were not significantly different between groups. CSF and plasma C4 levels were not significantly correlated. Therefore, the use of CSF samples is critical and should be complementary to the use of peripheral blood samples to allow for a comprehensive understanding of complement C4 abnormalities in schizophrenia.
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Thanks to Juan Cordero and Yuan-Shan Zhu at the CTSC Weill Cornell Medicine.
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JAG collected all data, performed statistical analyses, and wrote the paper. EAB and CM assisted with data collection, data cleaning, and reviewed critically the paper. TL and AKM assisted with study design, data interpretation, and revised the paper critically for important intellectual content.
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Gallego, J.A., Blanco, E.A., Morell, C. et al. Complement component C4 levels in the cerebrospinal fluid and plasma of patients with schizophrenia. Neuropsychopharmacol. 46, 1140–1144 (2021). https://doi.org/10.1038/s41386-020-00867-6
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DOI: https://doi.org/10.1038/s41386-020-00867-6
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