Abstract
In schizophrenia, a single latent trait underlies psychosis, hostility, excitation, mannerism, negative (PHEMN) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR). Schizophrenia is accompanied by a breakdown of gut and blood-brain-barrier (BBB) pathways, increased tryptophan catabolite (TRYCAT) levels, bacterial translocation, and lowered natural IgM and paraoxonase (PON)1 activity. The aim of this study was to examine the factor structure of schizophrenia symptom domains and the biomarker correlates of these factors. We recruited 80 patients with schizophrenia and 40 healthy subjects and assessed the IgA/IgM responses to paracellular/transcellular (PARA/TRANS) ratios, IgA responses to TRYCATs, natural IgM to malondialdehyde and Gram-negative bacteria, and PON1 enzymatic activity. Direct Hierarchical Exploratory Factor Analysis showed a bifactorial oblique model with a) a general factor which loaded highly on all symptom domains, named overall severity of schizophrenia ("OSOS"); and b) a single-group factor (SGF) loading on negative symptoms and PMR. We found that 40% of the variance in OSOS score was explained by IgA/IgM to PARA/TRANS ratio, male sex and education while 36.9% of the variance in SGF score was explained by IgA to PARA/TRANS, IgM to Gram-negative bacteria, female sex (positively associated) and IgM to MDA, and PON1 activity (negatively associated). Schizophrenia phenomenology comprises two biologically-validated dimensions, namely a general OSOS dimension and a single-group negative symptom dimension, which are associated with a breakdown of gut/BBB barriers, increased bacterial translocation and lowered protection against oxidation, inflammation and bacterial infections through lowered PON1 and natural IgM.
Highlights
It is considered that schizophrenia consists of various symptoms domains including positive symptoms, negative symptoms, and neurocognitive deficits [1,2,3,4,5]
We found that 50.3% of the variance in the latent vector (LV) extracted from the 8 symptom indicators was explained by IgA and IgM PARA/TRANS ratios and the sum of noxious tryptophan catabolite (TRYCAT), and education and sex
The first major finding of this study is that the 8 key domains of schizophrenia phenomenology (SANS and PANSS negative, PHEM symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR)) are most appropriately modeled using a bi-dimensional oblique solution with a general factor (GF) that reflects overall severity of illness (OSOS GF) and a single-group factor (SGF) reflecting negative symptoms and PMR
Summary
It is considered that schizophrenia consists of various symptoms domains including positive symptoms (such as hallucination, delusions, hostility, excitation, and disorganized thinking), negative symptoms (such as flattening of affect, alogia, avolition, and anhedonia), and neurocognitive deficits (such as impairments in episodicThis work is licensed under the Creative Commons210 Michael Maes et al: Schizophrenia phenomenology comprises a bifactorial general severity...and semantic memory as well as in executive functions) [1,2,3,4,5]. It is considered that schizophrenia consists of various symptoms domains including positive symptoms (such as hallucination, delusions, hostility, excitation, and disorganized thinking), negative symptoms (such as flattening of affect, alogia, avolition, and anhedonia), and neurocognitive deficits The score of this reflective latent construct is a reliable and replicable index of overall severity of schizophrenia (OSOS), which modulates the various symptom manifestations of OSOS [12]. These findings await confirmation in other populations while no research has examined whether this latent trait exists in subjects with deficit and non-deficit schizophrenia combined
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