Abstract
BackgroundCognitive impairment is considered a central feature of psychotic disorders, with an important impact on prognosis and functional outcome (Nuechterlein et al., 2011). Among the etiological explanations on psychosis, several hypotheses involving alterations in the immune / inflammatory system have been proposed and recent research links these inflammatory processes with cognitive function, suggesting that the presence of inflammation is associated with poorer cognitive performance (Ribeiro-Santos et al., 2014, Cabrera et al., 2016). The study of the influence of gender on the possible association between inflammatory biomarkers and cognitive performance may favor the implementation of personalized treatments.The aim of the study is to investigate the association between inflammatory biomarkers and gender-based cognition in a sample of first psychotic episode (FEP). A total of 92 patients with a FEP, 62 men and 30 women, recruited in five clinical centers were included. A neurocognitive assessment was performed and the expression of pro and anti-inflammatory mediators in peripheral blood mononuclear cells (PBMC) and plasma was measured.MethodsIn the neurocognitive evaluation the domains of attention, verbal and working memory and executive function were included. Other and clinical variables included the assessment of psychotic and affective symptoms, age, sex, educational level and socio-economic level. The expression of the proinflammatory mediators (NFκB, iNOS, COX-2, PGE2, NO-2 and TBARS) and anti-inflammatory (15d-PGJ2, PPARγ and IκBα) of the main intracellular inflammatory pathway was measured in PBMC and plasma.ResultsA correlation was made between inflammatory biomarkers and neurocognitive performance according to gender, and significant associations were selected to perform a subsequent hierarchical regression analysis. In the final model, only the expression of COX2 was associated with better performance in executive function in males (B = 0.504, p = <0.001) and the expression of NO2 to worse performance in working memory in women (B = -0.911; p = 0.010), after controlling the confounding factors. Men and women did not differ in any of the confusing variables.DiscussionThe expression of certain pro / anti-inflammatory components could have a differential effect according to the gender of patients with FEP. The expression of COX2 could be beneficial in the case of males, explaining part of the variability in executive function. On the contrary, the expression of NO2 could have a detrimental effect on working memory in women. The establishment of biomarkers linked to gender-based cognition could be useful for monitoring the course of cognitive decline and could guide treatment programs, providing tools to select a personalized approach.
Highlights
Genetic variants in miRNA genes and abnormalities in the concentration of microRNAs in tissues and biological fluids have recently been associated with a diagnosis of schizophrenia
Five miRNAs were upregulated in cerebrospinal fluid (CSF) samples and six were upregulated in plasma samples of spectrum disorder (SSD) patients compared to healthy volunteers
The aims of this work were 1) to evaluate the expression of Grin1, Grin2A and 2B genes by qPCR of patients with first episode of schizophrenia compared with the siblings and controls; 2) to quantify the NR1 and NR2 subunits plasma concentrations by ELISA; 3) to evaluate the Grin1, Grin2A and 2B gene expression by qPCR in peripheral blood and animals brain tissue
Summary
Abnormal mismatch negativity (MMN), thought to be a putative marker of glutamatergic function, has been reported in non-Asian, first episode schizophrenia and clinical high-risk for psychosis (CHR) individuals as indicative of impairments in pre-attentive processes. Reports of abnormal MMN in Asian populations are sparse, as well as its relationships to glutamate and γ–aminobutyric acid (GABA) levels in medial prefrontal cortex. The present longitudinal study explored MMN differences between CHR subjects who will and who will not remit, and its relationships with prefrontal glutamate and GABA levels. Duration MMN amplitude was measured at electrodes F1/2, Fz, FC1/2, FCz, C1/2 and Cz. Concentrations of glutamate+glutamine (Glx) and GABA in the medial prefrontal cortex (mPFC) were quantified using the LCModel software (version 6.3-0I). Correlations of the dMMN amplitude (averaged over the 9 electrodes) and Glx and GABA concentrations were assessed by Pearson correlation tests for each group. Results: There was a significant main effect of group (F(2,121)=3.14, p
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