Inflammatory and Oxidative Pathways Are New Drug Targets in Multiple Episode Schizophrenia and Leaky Gut, Klebsiella pneumoniae, and C1q Immune Complexes Are Additional Drug Targets in First Episode Schizophrenia

In Schizophrenia, Chronic Fatigue Syndrome- and Fibromyalgia-Like Symptoms are Driven by Breakdown of the Paracellular Pathway with Increased Zonulin and Immune Activation-Associated Neurotoxicity

“…The third major finding of the present study is that a considerable part of the variance in the total FF score and the severity of physiosomatic FF symptoms is explained not only by the PARA/TRANS ratio and IgM to zonulin, but also by immune activation as indicated by increased levels of IL-6, TNF-α, MIP-1, and IL-10, and CCL11, and by lowered IgM responses to OSEs. These cytokines/chemokines are all increased during an immune-inflammatory response with IL-6 and TNF-α displaying inflammatory, CCL11 and MIP-1 chemotaxic, and IL-10 immuneregulatory effects (Maes et al, 2021b). These results extend those of previous reports which showed that a larger part of the variance in the FF score in schizophrenia is accompanied by increased levels of CCL11 and high mobility group box 1 protein (HMGB1) (Mousa et al, 2020).…”

“…Our finings that the total FF and physiosomatic FF scores were highly significantly associated with the BCPS-worsening index indicate that those FF symptoms are another feature of BCPS-worsening and should routinely be screened in schizophrenic patients to estimate the worsening of the illness. The results also suggest that FF symptoms and physiosomatic symptoms are driven, at least in part, by the same pathways that underpin aberrations in the connectome and neuroplasticity and which cause BCPS-worsening, namely "the prefronto-striato-thalamic, prefronto-parietal, prefronto-temporal, and dorsolateral prefrontal cortex, hippocampus and amygdala Orellana and Slachevsky, 2013;Maes et al, 2021b;Maes and Kanchanatawan, 2021).…”

“…Moreover, treatment with specific antioxidants, which are known to improve leaky gut (zinc, glutamine, and N-acetylcysteine) improves these indicants of leaky gut in association with a significant improvement in the severity of FF symptoms (Maes and Leunis, 2008). Part of the schizophrenia patients, especially those with first episode schizophrenia, show leaky gut and increased bacterial translocation an, therefore, those patients may benefit from treatments for leaky gut (Maes et al, 2021b).…”

“…The phenomenome of schizophrenia was conceptualized as the first factor extracted from selfrated scores of physical health, psychological health, and social and environmental responsible behaviors as scored with the World Health Organization Quality of Life Instrument-Abbreviated version (WHO-QoL-BREF) (Kanchanatawan et al, 2019). Moreover, we also constructed a new index which captures the severity of deterioration or the deficit in schizophrenia namely the behavioral-cognitive-physical-psycho-social-(BCPS)-worsening index conceptualized as the first factor extracted from the symptomatome, cognitome (G-CoDe), and QoL-phenomenome (Maes et al, 2021b).…”

False Dogmas in Schizophrenia Research: Toward the Reification of Pathway Phenotypes and Pathway Classes

“…Partial, vs. non-responders may also be differentiated by increased IL-6, endogenous opioid system biomarkers and inhibition of the Wnt signaling pathway (21). Schizophrenia phenotypes may also be differentiated by affective symptoms, fatigue and physiosomatic (formerly psychosomatic) symptoms, all of which are associated with immune/cytokine/TRYCAT/O&NS/gut-brain pathways, clearly indicating the achievability of pathway-phenotype differentiation of people classed with schizophrenia phenotypes (22,23).…”