The recurrence of illness (ROI) index is a key factor in major depression that indicates increasing immune-linked neurotoxicity and vulnerability to suicidal behaviors.

In this study, we aimed to investigate the associations between the recurrence of illness (ROI) and biomarkers related to an activated immune network, immune-linked neurotoxicity (INT), and a combined INT and atherogenicity index (METAMMUNE). The study involved 67 healthy controls and 66 outpatient MDD (OMDD) participants. We utilized a Multiplex method to measure 48 cytokines and examined INT and METAMMUNE composite scores in association with different ROI indices. Our findings revealed that a ROI index was successfully created by extracting a validated principal component, from the physician-rated or self-declared number of depressive episodes, the frequency of lifetime suicidal ideation and attempts. ROI was significantly associated with INT and METAMMUNE indices, neuroticism, lifetime and current suicidal behaviors, and the phenome. Our analysis also revealed that a significant portion of the variance in the OMDD phenome, which includes current suicidal behaviors, anxiety, and depression, can be accounted for by the regression on INT, ROI, and emotional neglect and abuse. A validated latent construct was successfully extracted from the three ROI components, INT and METAMMUNE indices. The results indicate that increasing ROI indicates heightened immune-metabolic abnormalities, increased risk of suicidal behaviors, and elevated severity of lifetime and current phenome features.

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.

Schizophrenia patients show increased disabilities and lower quality of life (DisQoL). Nevertheless, there are no data on whether the activation of the interleukin (IL)-6, IL-23, T helper (Th)-17 axis, and lower 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 the behavioral-cognitive-psycho-social (BCPS) worsening index a single latent trait extracted from G-CoDe, symptomatome, HR-QoL and disability data. In summary, the BCPS worsening index is partly caused by the neuroimmunotoxic effects of the IL6IL23Th17 axis in subjects with lowered antioxidant defenses (magnesium and calcium), thereby probably damaging the neuronal circuits that may underpin deficit schizophrenia.