In schizophrenia, psychomotor retardation is associated with executive and memory impairments, negative and psychotic symptoms, neurotoxic immune products and lower natural IgM to malondialdehyde

How to Construct a Bottom-Up Nomothetic Network Model and Disclose Novel Nosological Classes by Integrating Risk Resilience and Adverse Outcome Pathways with the Phenome of Schizophrenia

“…Furthermore, these impairments in the "cognitome" (the aggregate of cognitive dysfunctions) are strongly related with the symptomatome of schizophrenia and, based on the available knowledge, we concluded that these cognitome impairments may play a role in the development and maintenance of the symptomatome [1,5]. Lowered self-rated, health-related quality of life (HR-QoL) is another component of the phenome, namely the phenomenome, i.e., the description of the subjective experience from the patient [3,8].…”

“…Furthermore, we have shown that when OSOS increases, negative symptoms and PMR become more prominent and shape a distinct symptom profile, namely deficit schizophrenia [2]. The latter is delineated not only by negative symptoms and PMR, but also by PHEM symptoms [1][2][3][4][5].…”

“…Recently, we showed that the symptomatome of schizophrenia comprises psychosis, hostility, excitation, mannerism (PHEM), negative symptoms, formal thought disorders (FTD), and psychomotor retardation (PMR) and that these symptom domains are reflective manifestations of a single underlying trait, namely overall severity of schizophrenia (OSOS) [1,2]. Furthermore, we have shown that when OSOS increases, negative symptoms and PMR become more prominent and shape a distinct symptom profile, namely deficit schizophrenia [2].…”

“…Other key parts of the phenome of schizophrenia and deficit schizophrenia are neurocognitive impairments including executive functions, working memory, and semantic and episodic memory [2,3,5]. In addition, the impairments in these cognitive domains are reflective manifestations of an overall deficit in cognitive functioning, reflecting impairments in prefronto-temporal, prefronto-parietal, prefronto-striato-thalamic, and hippocampal and amygdalal neural circuits [1,3,[5][6][7].…”

“…Increases in multiple immune and oxidative toxicities (MITOTOX) predict the impairments in the cognitome, symptomatome, and phenomenome [9]. These MITOTOX biomarkers include increased levels of neurotoxic tryptophan catabolites (TRYCATs), tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine with neurotoxic effects; eotaxin (CCL11), an immune product with neurotoxic and anti-neurogenic effects; lipid hydroperoxides (LOOH) and malondialdehyde (MDA) indicating lipid peroxidation; advanced oxidation protein products (AOPPs), indicating increased chlorinative stress which exerts multiple toxic effects; increased IgM levels to zonulin, a toxic compound that leads to increased gut permeability; and increased bacterial translocation [1,[9][10][11]. Furthermore, indicants of breakdown of the paracellular gut and blood brain barriers may aggravate these neurotoxic responses [10,11].…”