| Background:Cognitive impairment is a core symptom domain of schizophrenia,seriously affecting social function and prognosis of patients.The pathological mechanism of cognitive impairment is currently unknown.We investigated the demography and clinical characteristics of cognitive impairment in patients with schizophrenia,and examined whether there was a correlation between cognitive function and kynurenine metabolites and brain gray matter volume.We hypothesized that the brain gray matter volume in schizophrenic patients might have a mediating effect between kynurenine metabolites and cognitive function using a mediating model.Objectives:(1)To investigate the cognitive function of patients with schizophrenia and its correlation with clinical characteristics.(2)To explore the correlation between cognitive function and plasma kynurenine levels in patients with schizophrenia.(3)To explore the correlation between cognitive function and brain gray matter volume in patients with schizophrenia.(4)To investigate the correlation between cognitive function and kynurenine metabolites and brain gray matter volume in patients with schizophrenia,and whether there is a mediating effect between kynurenine metabolites and cognition function in brain gray matter volume.Methods:(1)A total of 41 patients with schizophrenia and 60 healthy controls were included.Psychotic symptoms were assessed with the Positive and Negative Symptom Scale(PANSS),and cognitive function of schizophrenia patients and healthy controls were evaluated with MATRICS Consensus Cognitive Battery(MCCB).For categorical variables,the Chi-square test was used.For continuous variables,two independent sample T tests were used,such as age,education,and MCCB scores which were normally distributed.The independent sample t test was also used to examine the differences of gender(male versus female)and illness duration(first episodes versus relapses)in cognitive functions.Pearson correlation was applied to analyze the correlation between MCCB scores and age,age of onset,duration of disease,and scores in each dimension of PANSS,respectively.Finally,the linear regression model was utilized to analyze the relationship between clinical characteristics and MCCB scores in each dimension.(2)Based on the samples of study 1,a total of 41 patients and 60 healthy controls were included in this study.Blood samples of participants were collected in the morning,and complete the examination of tryptophan(TRP),kynurenine(KYN),and kynurenic acid(KYNA).The comparison of plasma kynurenine metabolite levels between schizophrenia patients and healthy controls were conducted by using covariance analysis.The correlation between MCCB scores and plasma kynurenine metabolites levels was further analyzed by partial correlation analysis.(3)Based on the samples of study 1,a total of 41 patients with schizophrenia and 60 healthy controls were included,completing the data collection of structural magnetic resonance.Covariance analysis was used to compare the differences in gray matter volume between schizophrenia patients.The correlation between brain gray matter-volume and cognitive function was further analyzed by partial correlation analysis.(4)Based on the Study above,we came up with the research hypothesis:the brain gray matter volume of schizophrenia may have a mediating effect between kynurenine metabolites and cognitive function.This study validates this hypothesis through an intermediary model.The independent variable of the mediation hypothesis model was kynurenine metabolite levels,the dependent variable was cognitive function,and the intermediate variable was brain gray matter volume.Results:(1)Among the seven dimensions of MCCB,the scores of processing speed,attention/alertness,working memory,speech learning and memory,visual learning and memory,reasoning and problem solving,social cognition and total scores were significantly lower in schizophrenia patients than in healthy controls(all P<0.001).Linear regression analysis showed that negative symptoms were negatively associated with processing speed(B=-0.912,P=0.028).Relapse was negatively associated with word learning(B=-7.230,P=0.045),but male was positively associated with working memory(B=-8.749,P=0.018).(2)Covariance analysis showed that patients with schizophrenia were associated with higher KYNA concentration and rate of KYNA/KYN than those of healthy controls.The partial correlation analysis showed that KYNA concentration of schizophrenia was negatively associated with the attention and alertness and social cognition.(3)The comparison of the GMV brain area between schizophrenia patients and healthy controls was conducted by using covariance analysis.The volumes of brain gray matter of GMV39(left anterior cingulate gyrus),GMV40(left island lobes),GMV53(right island leaves),GMV59(right cingulate gyrus),GMV71(Right spindle nucleus),GMV88(left inferior temporal gyrus)were significant lower in schizophrenia patients than in healthy controls(P<0.001),passing the correction of FDR(False Discovery rate).Partial correlation analysis showed that the left island leaf GMV of schizophrenia patients was positively correlated with processing speed(r=0.354,P=0.029)and visual learning(r=0.337,P=0.039),as well as the right island leaf GMV of schizophrenia patients was positively related to processing speed(r=0.401,P=0.013),reasoning and problem solving ability(r=0.341,P=0.036)and MCCB total scores(r=0.366,p=0.033).(4)Partial correlation analysis showed that KYN concentration of schizophrenia was negatively associated with left anterior cingulate gyrus GMV(r=-0.325,p=0.046),and KYN/TRP was negatively associated with the left island leaf GMV(r=-0.396,p=0.014)and the right island leaf GMV(r=-0.385,p=0.017).After intermediary test,there was no intermediary effect between the brain gray matter volume and kynurenine metabolites and cognitive function.Conclusions:(1)patients with schizophrenia were associated with comprehensive cognitive impairment including processing speed,attention/alertness,working memory,speech learning and memory,visual learning and memory,reasoning and problem solving,social cognition and total scores when compared to healthy age and gender matched controls.Negative symptoms of schizophrenia were negatively associated with processing speed.Relapse was negatively associated with word learning,but male was positively associated with working memory.(2)Plasma kynurenine metabolites levels of schizophrenia are abnormal.Elevated plasma KYNA levels may serve as a biomarker of cognitive impairment in SCZ patients(3)Schizophrenia was associated with the atrophy of gray matter volume,including left anterior cingulate gyrus,left islet lobes,right islet lobes,right middle cingulate gyrus,right spindle nucleus,and left inferior temporal gyrus.The volume of brain gray matter in schizophrenia patients was positively associated with cognitive function.The volume of gray matter on the left island and on the left island leaf may serve as a Morphological markers of cognitive impairment in SCZ patients.(4)KYN concentration of schizophrenia was negatively associated with left anterior cingulate gyrus GMV(r=-0.325,p=0.046),and KYN/TRP was negatively associated with the left island leaf GMV(r=-0.396,p=0.014)and the right island leaf GMV(r=-0.385,p=0.017).There is no mediating effect of brain gray matter volume between kynurenine metabolites and cognitive function. |
PDF Full Text Request