In Schizophrenia, Increased Plasma IgM/IgA Responses to Gut Commensal Bacteria Are Associated with Negative Symptoms, Neurocognitive Impairments, and the Deficit Phenotype

Upregulation of the Nitrosylome in Bipolar Disorder Type 1 (BP1), but not BP2, and Major Depression: Increased IgM Antibodies to Nitrosylated Conjugates are Associated with Indicants of Leaky Gut

“…It is probably that such disorders indicate a response of innate like B cells, namely marginal zone B and B1 cells, producing increased natural IgM, directed to self antigens (including oxidative-specific epitopes), which in turn have strong anti-inflammatory and immune-regulatory effects and constitute a first-line defense of innate immunity against pathogens including Gram-negative bacteria. 22,46 Moreover, increased bacterial translocation may drive nitrosylation and thus the production of IgM responses to NO neoepitopes. Induction of the nitrosylome may play a key role in the impairments in neuro-glial interactions, synaptic plasticity, neuroprotection, neurogenesis and antioxidant defenses, the activation of immune-inflammatory and oxidative pathways in mood disorders as well as in comorbid CAD.…”

High Mobility Group Protein 1 and Dickkopf-Related Protein 1 in Schizophrenia and Treatment-Resistant Schizophrenia: Associations with Interleukin-6, Symptom Domains, and Neurocognitive Impairments

“…29 We computed scores reflecting PHEM (psychosis, hostility, excitation, and mannerism) symptoms, FTD (formal thought disorders) and PMR (psycho-motor retardation) as explained previously. 16,19 Towards this end we also assessed the Brief Psychiatric Rating Scale (BPRS), 30 the Hamilton Depression Rating Scale 31 and the positive and negative syndrome scale (PANSS) for schizophrenia. 32 On the same day, a well-trained research psychologist, blinded to the clinical diagnosis, completed the Brief Assessment of Cognition in SCZ (BACS) 33 was measured on the same day as the clinical interview and was scored as body weight (kg) / length (m 2 ).…”

“…14 Importantly, products of M1, Th-1 and Th-2 have multiple neurotoxic effects and as such may cause deficits in executive functions, and episodic and semantic memory and as a consequence also SCZ symptom domains including negative and PHEM (psychosis, hostility, excitation, and mannerism) symptoms. [15][16][17] Neurotoxic compounds that are upregulated in SCZ or SCZ phenotypes comprise IL-1β, TNF-α, IL-6, IFN-γ, CCL11, IL-4, IL-13, TRYCATs, and LPS. 11, [15][16][17][18][19] Severe IRS responses, as in sepsis, are mediated by high mobility group protein (HMGB)1, a damage-associated molecular pattern (DAMP) released by injured or necrotic cells, which acts as a pro-inflammatory cytokine promoting the release of IL-6, TNF-α and IFN-γ.…”

“…[15][16][17] Neurotoxic compounds that are upregulated in SCZ or SCZ phenotypes comprise IL-1β, TNF-α, IL-6, IFN-γ, CCL11, IL-4, IL-13, TRYCATs, and LPS. 11, [15][16][17][18][19] Severe IRS responses, as in sepsis, are mediated by high mobility group protein (HMGB)1, a damage-associated molecular pattern (DAMP) released by injured or necrotic cells, which acts as a pro-inflammatory cytokine promoting the release of IL-6, TNF-α and IFN-γ. 20,21 In neurological disorders, HMGB1 is a biomarker of neuroinflammation and neurodegeneration, which may cause blood-brain barrier (BBB) dysfunctions.…”

Breakdown of the Paracellular Tight and Adherens Junctions in the Gut and Blood Brain Barrier and Damage to the Vascular Barrier in Patients with Deficit Schizophrenia<strong></strong>

“…Recently we reported that deficit schizophrenia, PHEMN (indicating psychosis, hostility, excitation, mannerism and negative) symptoms and impairments in semantic and episodic memory are significantly associated with an upregulated intestinal paracellular pathway with breakdown of the tight (TJ) and adherens (AJ) junctions and increased bacterial translocation (Maes et al, 2018a;. These conclusions were derived from findings that deficit schizophrenia and its phenomenological characteristics are accompanied by increased IgM responses to occludin and Ecadherin, which are both core transmembrane components of the TJs and AJs in the gut, and increased IgA/IgM responses to sonicated Gram-negative gut commensal bacteria (Maes et al, 2018a;. Occludin contributes to the stability and integrity of the TJs thereby regulating the permeability of the transcellular pathway (Yu et al, 2005;Suzuki et al, 2009;Elias et al, 2009;Furuse et al, 1993;Balda and Matter, 2000;Cummings 2012).…”