Inflammatory biomarkers in psychosis and clinical high risk populations

Background: Immunological, nutritional, and microbial factors have been implicated in the pathophysiology of schizophrenia, but the interrelationship among measures is understudied. In particular, an increase in the levels of the pro-inflammatory cytokine interleukin-6 (IL-6) is associated with all phases of the illness, and may be associated with other inflammatory markers. Vitamin D is a modulator of the immune system, and LPS antibodies are an indirect measure of gut barrier function. In this study we investigated potential contributing inflammatory mechanisms for IL-6 elevation. Methods: We compared the levels of vitamin D, C-reactive protein (CRP), antibodies to lipopolysaccharide (LPS), and IL-6 in children, adolescents and young adults with psychosis (n = 47), individuals at clinical high risk for psychosis (n = 17) and unaffected comparison controls (n = 33). Participants were diagnosed by a psychiatrist, using a structured interview, the MINI-Neuropsychiatric Interview. 25(OH)D was measured in serum using chemiluminescent micro particle immunoassay, and anti-LPS antibodies, CRP and IL-6 levels were measured by ELISA. Results: IL-6 and C-reactive protein levels were significantly elevated in the psychosis group relative to the unaffected control subjects. In the psychosis group, levels of IL-6 correlated positively with IgA anti-LPS antibodies and negatively correlated with vitamin D. Conclusions: Our findings show a significant correlation between IL-6, anti-LPS antibodies and vitamin D deficiency in psychosis, suggesting the existence of multiple potential pathways related to IL-6 elevation in psychosis, and therefore multiple potential strategies for risk mitigation. Collectively these findings support hypotheses regarding interrelated inflammatory contributions to the pathophysiology of psychosis.