In (deficit) schizophrenia, a general cognitive decline (G-CoDe) partly mediates the effects of neuro-immune and neuro-oxidative toxicity on the symptomatome and quality of life

Abstract

Objective: Schizophrenia and deficit schizophrenia are accompanied by neurocognitive impairments. The aim of this study was to examine whether a general factor underpins impairments in key Cambridge Neuropsychological Test Automated Battery (CANTAB) probes, verbal fluency (VFT), world list memory (WLM), true recall, and Mini Mental State Examination (MMSE). Methods: We recruited 80 patients with schizophrenia and 40 healthy controls. All patients were assessed using CANTAB tests, namely paired-association learning (PAL), rapid visual information (RVP), spatial working memory (SWM), one touch stocking (OTS), intra/extradimensional set shifting (IED), and emotional recognition test (ERT). Results: We found that a general factor, which is essentially unidimensional, underlies those CANTAB, VFT, WLM, True Recall, and MMSE scores. This common factor shows excellent psychometric properties and fits a reflective model and, therefore, reflects a general cognitive decline (G-CoDe) comprising deficits in semantic and episodic memory, recall, executive functions, strategy use, rule acquisition, visual sustained attention, attention set-shifting, and emotional recognition. Partial least Square analysis showed that 40.5% of the variance in G-Code is explained by CCL11, IgA to tryptophan catabolites, and increased oxidative toxicity; and that G-CoDe explains 44.8% of the variance in a general factor extracted from psychosis, hostility, excitation, mannerism, negative symptoms, formal thought disorders, and psychomotor retardation; and 40.9% in quality of life scores. The G-CoDe is significantly greater in deficit than in nondeficit schizophrenia. Conclusions: A common core shared by a multitude of neurocognitive impairments (G-CoDe) mediates the effects of neurotoxic pathways on the phenome of (deficit) schizophrenia