In schizophrenia, the effects of the IL-6/IL-23/Th17 axis on health-related quality of life and disabilities are partly mediated by generalized cognitive decline and the symptomatome

Abstract Schizophrenia patients show increased disabilities and lower quality of life (DisQoL). Nevertheless, there are no data whether, in schizophrenia, activation of the interleukin (IL)-6, IL-23, T helper (Th)-17 axis and lowered magnesium and calcium levels impact DisQoL scores. This study recruited 90 patients with schizophrenia (including 40 with deficit schizophrenia) and 40 healthy controls and assessed the World Health Association QoL instrument-Abbreviated version and Sheehan Disability scale, Brief Assessment of Cognition in Schizophrenia (BACS), IL-6, IL-23, IL-17, IL-21, IL-22, tumor necrosis factor (TNF)-α, magnesium and calcium. Regression analyses showed that a large part of the first factor extracted from the physical, psychological, social and environmental HR-QoL and interference with school/work, social life, and home responsibilities was predicted by a generalized cognitive deterioration (G-CoDe) index (a latent vector extracted from BACs scores), and the first vector extracted from various symptom domains (“symptomatome”), whereas the biomarkers had no effects. Partial Least Squares analysis showed that the IL6IL23Th17 axis and magnesium/calcium had highly significant total (indirect + direct) effects on HR-QoL/disabilities which were mediated by G-CoDe and the symptomatome (a first factor extracted from negative and positive symptoms). The IL6IL23Th17 axis explained 63.1% of the variance in a single latent trait extracted from G-CoDe, symptomatome, HR-QoL and disability data. The latter features are manifestations of a common core, namely the behavioral-cognitive-psycho-social worsening index, which is caused by the neuroimmunotoxic effects of the IL6IL23Th17 axis in subjects with lowered antioxidant defenses (magnesium and calcium) thereby producing damage to neuronal circuits underpinning deficit schizophrenia.