In Schizophrenia, Chronic Fatigue Syndrome- and Fibromyalgia-Like Symptoms are Driven by Breakdown of the Paracellular Pathway..., 2022, Maes et al

Full title: 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.

Abstract

Background: A meaningful part of schizophrenia patients suffer from physiosomatic symptoms (formerly named psychosomatic) which are reminiscent of chronic fatigue syndrome and fibromyalgia (FF) and are associated with signs of immune activation and increased levels of tryptophan catabolites (TRYCATs).

Aims: To examine whether FF symptoms in schizophrenia are associated with breakdown of the paracellular pathway, zonulin, lowered natural IgM responses to oxidative specific epitopes (OSEs); and whether FF symptoms belong to the behavioral-cognitive-physical-psychosocial-(BCPS)-worsening index consisting of indices of a general cognitive decline (G-CoDe), symptomatome of schizophrenia, and quality of life (QoL)-phenomenome.

Methods: FF symptoms were assessed using the Fibromyalgia and Chronic Fatigue Rating scale in 80 schizophrenia patients and 40 healthy controls and serum cytokines/chemokines, IgA levels to TRYCATs, IgM to OSEs, zonulin and transcellular/paracellular (TRANS/PARA) molecules were assayed using ELISA methods.

Results: A large part (42.3%) of the variance in the total FF score was explained by the regression on the PARA/TRANS ratio, pro-inflammatory cytokines, IgM to zonulin, IgA to TRYCATs (all positively) and IgM to OSEs (inversely). There were highly significant correlations between the total FF score and G-CoDe, symtopmatome, QoL phenomenome and BCPS-worsening score. FF symptoms belong to a common core shared by G-CoDe, symtopmatome, and QoL phenomenome.

Discussion: The physio-somatic symptoms of schizophrenia are driven by various pathways including increased zonulin, breakdown of the paracellular tight-junctions pathway, immune activation with induction of the TRYCAT pathway, and consequent neurotoxicity. It is concluded that FF symptoms are part of the phenome of schizophrenia and BCPS-worsening as well.

Paywall, https://www.eurekaselect.com/article/125378

 

Similar studies
Chronic fatigue syndrome and fibromyalgia-like symptoms are an integral component of the phenome of schizophrenia, 2020, Maes et al
Chronic fatigue & fibromyalgia symptoms [] key components of deficit schizophrenia & [] associated w/activated immune-inflammatory.., 2020, Maes et al

and a thread on the Fibromyalgia and Chronic Fatigue Rating scale, A rating scale for fibromyalgia and chronic fatigue syndrome (the FibroFatigue scale), 2002, Zachrisson et al

 

It would be helpful if they were to descibe the physiosomatic symptoms which they are comparing. Perhaps they do in the full article. Do patients with schizophrenia really suffer from something comparable to PEM?

 

Physio-somatic symptoms in schizophrenia: association with depression, anxiety, neurocognitive deficits and the tryptophan catabolite pathway

Buranee Kanchanatawan & Sunee Sirivichayakul & Supaksorn Thika & Kiat Ruxrungtham & André F. Carvalho & Michel Geffard & George Anderson & Cristiano Noto & Rada Ivanova & Michael Maes

Abstract
"To investigate the frequency of physio-somatic symptoms (PS) symptoms in schizophrenia and their rela-tion to positive, negative and affective symptoms; neurocognitive deficits and impairments in the tryptophan catabolite (TRYCAT) pathway. Eighty four patients with schizophrenia and 40 healthy controls were assessed using the 12 item Fibromyalgia and Chronic Fatigue Syndrome Rating scale (FF) and scales for negative and positive symptoms, depression and anxiety. Cognitive functioning was tested using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Other assessments included: immunoglobulin (Ig)A and IgM responses to tryptophan catabolites (TRYCATs), namely quinolinic (QA), 3-OH-kynurenine (3HK), picolinic (PA), xanthurenic (XA) and kynurenic acid (KA) and anthranilic acid (AA). More than 50% of the patients studied had elevated levels of physio-somatic (PS) symptoms, significantly co-occurring with depression and anxiety, but not with negative or positive symptoms. PS symptoms were significantly associated with IgA/IgM responses to TRYCATs, including increased IgA responses to 3 HK, PA and XA, and lowered IgA to QA and AA. Fatigue, muscle pain and tension, autonomic and cognitive symptoms and a flu-like malaise were strongly associated with cognitive impairments in spatial plan-
ning and working memory, paired associative learning, visual sustained attention and attention set shifting. PS symptoms in schizophrenia aggregate with depression and anxiety symptoms and may be driven by TRYCAT patterning of IgA/IgM- responses, with IgA indicating mucosal-mediated changes and IgM indicating regulatory functions. As such, the patterning of IgA/IgM responses to TRYCATs may indicate differential TRYCATs regulation of neuronal and glia activity that act to regulate PS signalling in schizophrenia."

Full article on Sci Hub: https://sci-hub.se/10.1007/s11011-017-9982-7

 

According to the preprint version, this Fibromyalgia and Chronic Fatigue Syndrome Rating scale (FF) is just a mixture of symptoms from both FM and CFS conditions, without PEM. Here is how this test was used to obtain the FF physiosomatic score (the authors kept only the "somatic" items, but excluding sleep disturbances):

Although I only skimmed the paper, the authors do not seem to refer particularly to the "psychological" side.

For those interested, here is a link to the preprint version:
https://www.medrxiv.org/content/10.1101/2021.05.09.21256897v1.full-text

 

The scale used is also discussed in this thread, including listing the questions asked

 

Aren't tryptophan catabolites too small for meaningful Ig responses?

The only people talking about this is M Maes and colleagues - I can't find any attempted replications by other groups in the 6 years they've been publishing this stuff.

 

Or to look at it another way, are patients with primary ME CFS being diagnosed as schizophrenic?

My experiences with diagnosed ME CFIDS would lead me to believe this was very possible due to the way apparent neurological inflammation from immune activity against viruses can affect sensitivity to stimuli, cognition and autonomic balance in a way which can can cause significant psychological dysfunction including profound referential problems if inappropriately managed i.e. a kind of chronic delirium akin to the delirium which is sometimes attributed to fever inducing infections.

The question is how many? What proportion of schizophrenia diagnoses are of this kind, where an immune disease is being treated as a mental illness, thus perpetuating it and obstructing appropriate management which might improve it?

 

I looked at this video* - for like 2 minutes and haven't looked at the abstract - but that doesn't stop me having opinions!

Comments re "tight junctions" or whatever remind me of James Baraniuk's** work - he's taken out a patent ---

I also recall folks like Chris Armstrong talking about intestinal permeability --- pathogens (or stuff they produce - there a LPPS ---) being translocated across the gut and leading to ME/CFS ---

If any of this is relevant then would it turn up in GWAS [Chris Ponting's study] & if so what would you expect to see? Markers related to the genes coding for proteins linked to junctions or whatever?


*

https://www.youtube.com/watch?v=9OPSJmqpSCM

**https://faculty.georgetown.edu/baraniuj/Site/Welcome.html

 

As far as I can make out this is complete gobbledygook. Not just psychobabble but behavioral-cognitive-physical-psychosociobabble. Antibodies to tryptophan metabolites sound highly dubious.

Whatever that might mean.


This is just a word salad.

 

The complement system was something I thought may link both
Schizophrenia’s strongest known genetic risk deconstructed
https://www.nih.gov/news-events/new...as-strongest-known-genetic-risk-deconstructed

https://pubmed.ncbi.nlm.nih.gov/3875548/
Complement factor C4 in schizophrenia