Chronic fatigue syndrome and fibromyalgia-like symptoms are an integral component of the phenome of schizophrenia: neuro-immune and opioid system correlates

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

“…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 immune-regulatory 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). HMGB1 is a DAMP (damage-associated molecular pattern) that may be released by necrotic and injured cells and stimulates the production and release of IL-6 and TNF-α, and T helper-(Th)-1 cytokines including interferon-γ (Yang et al, 2016; Lotze et al, 2005; Festoff et al, 2016).…”

“…The first major finding of this study is that schizophrenia is characterized by increased total FF scores and the severity of the physiosomatic symptoms of the FF and that the both FF scores are strongly associated with the BCPS-worsening index and its components, namely the symptomatome, G-CoDe, and QoL-phenomenome. Also, in other study groups, we found that FF symptoms as assessed with the FF scale, were part of the symptomatome of schizophrenia and belonged to a same latent factor as the PHEM and negative symptoms of schizophrenia (Almulla et al, 2020a; Mousa et al, 2020). This indicates that FF symptoms and physiosomatic symptoms are key manifestations of the symptomatome of schizophrenia.…”

“…Recently, we reported that a meaningful part of schizophrenia patients suffer from physiosomatic symptoms (formerly named psychosomatic symptoms) which are reminiscent of chronic fatigue syndrome and fibromyalgia (Kanchanatawan et al 2017; Almulla et al, 2020a; Mousa et al, 2021). We assessed these symptoms using the Fibromyalgia and Chronic Fatigue Rating (FF) Scale, including fatigue, muscle tension, cramps and pain, a flu-like malaise, headache, and autonomic and cognitive symptoms (Kanchanatawan et al 2017; Almulla et al, 2020a; Mousa et al, 2021). Moreover, the FF symptoms were strongly correlated with PHEM and negative symptoms, PMR, and FTD (Almulla et al, 2020a).…”

“…Importantly, increased expression of FF symptoms in schizophrenia is associated signs of immune activation, including elevated IgA responses to neurotoxic TRYCATs such as picolinic acid (PA), xanthurenic acid (XA), and 3-OH-kynurenine (3HK) (Kanchanatawan et al, 2019), and increased levels of IL-6, CCL11, and IL-1β (Mousa et al, 2021; Almulla et al, 2020a). Nevertheless, there are no data whether FF symptoms in schizophrenia are associated with indicants of the paracellular gut pathway, increased levels of zonulin and neurotoxicity, and lowered levels of protective IgM to OSEs.…”

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).…”