Baseline high levels of complement component 4 predict worse clinical outcome at 1-year follow-up in first-episode psychosis

Background: Recent evidence has highlighted the potential role of complement component 4 (C4) in the development of schizophrenia. However, it remains unclear whether C4 is also relevant for clinical outcome and if it could be considered a possible therapeutic target. The aim of this naturalistic longitudinal study was to investigate whether baseline levels of C4 predict worse clinical outcome at 1-year follow-up in patients with first episode psychosis. Methods: Twenty-five patients with first episode psychosis were assessed at baseline and followed-up prospectively for their clinical outcome at 1 year from baseline assessment. Concentrations of complement component 4 (C4) were measured using ELISA methods from baseline serum samples. Twelve patients were classified as non-responders and 13 as responders. ANCOVA analyses were conducted to investigate differences in baseline C4 levels between responders and non-responders at 1-year covarying for baseline severity of symptoms and for levels of C reactive protein. Results: Non-responders show significantly higher baseline C4 levels compared with responders when controlling for baseline psychopathology and baseline levels of C reactive protein (552.5 +/- 31.3 vs 437.6 +/- 25.5 mcg/ml; p = 0.008). When investigating the ability of C4 levels to distinguish responders from non-responders, we found that the area under the ROC curve was 0.795 and the threshold point for C4 to distinguish between responders and non-responders appear to be around 490 mcg/ml. Conclusions: Our preliminary findings show that baseline C4 levels predict clinical outcome at 1-year follow-up in patients with first episode psychosis.