Serum complement proteins rather than inflammatory factors is effective in predicting psychosis in individuals at clinical high risk

Abstract

Immunological/inflammatory factors are implicated in the development of psychosis. Complement is a key driver of inflammation; however, it remains unknown which factor is better at predicting the onset of psychosis. This study aimed to compare the alteration and predictive performance of inflammation and complement in individuals at clinical high risk (CHR). We enrolled 49 individuals at CHR and 26 healthy controls (HCs). Twenty-five patients at CHR had converted to psychosis (converter) by the 3-year follow-up. Inflammatory cytokines, including interleukin (IL)-1β, 6, 8, 10, tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor levels, and complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, factor B, D, I, H) were measured by enzyme-linked immunosorbent assay at baseline. Except for TNF- alpha, none of the inflammatory cytokines reached a significant level in either the comparison of CHR individuals and HC or between CHR-converters and non-converters. The C5, C3, D, I, and H levels were significantly lower (C5, p = 0.006; C3, p = 0.009; D, p = 0.026; I, p = 0.016; H, p = 0.019) in the CHR group than in the HC group. Compared to non-converters, converters had significantly lower levels of C5 (p = 0.012) and C5a (p = 0.007). None of the inflammatory factors, but many complement factors, showed significant correlations with changes in general function and symptoms. None of the inflammatory markers, except for C5a and C5, were significant in the discrimination of conversion outcomes in CHR individuals. Our results suggest that altered complement levels in the CHR population are more associated with conversion to psychosis than inflammatory factors. Therefore, an activated complement system may precede the first-episode of psychosis and contribute to neurological pathogenesis at the CHR stage.

Fig. 1. Sample flowchart.

CHR Clinical high risk for psychosis, CHR-converter CHR individuals who were converted to full psychosis, HC Healthy control.

Fig. 2. Comparisons for serum levels of complement factors in HC and CHR individuals with converter versus non-converter.

Bar shows the mean and standard error of complement factors. The Mann-Whitney U tests were performed for comparisons between groups. The level of statistical significance was set at a two-tailed P value of 0.05. Statistically significant p values are written above the bars. NS: non statistic significant. CHR Clinical high risk for psychosis, CHR-converter, CHR individuals who were converted to fully psychosis; HC Healthy control, ^*p < 0.05; ^**p < 0.01; ^***p < 0.001.

Fig. 3. Correlation analysis between functional and symptomatic changes and complement factors.

Correlation (Spearman) between functional and symptomatic changes from baseline to 1-year and complement factors. GAF Global Assessment of Functioning, ^*p < 0.05; ^**p < 0.01; ^***p < 0.001.

Fig. 4. Receiver operating characteristic curve profiles for complement factors in terms of discrimination of the CHR individuals from HC, and CHR non-converters from converters.

Abbreviations: AUC an area under the Receiver operating characteristic curve, CHR Clinical high risk for psychosis, CHR-converter, CHR individuals who were converted to fully psychosis, HC Healthy control.