Objective To explore the correlation of serum glutamate(Glu)and gamma-aminobutyric acid(GABA)levels with clinical symptoms in chronic schizophrenia patients,and to assess their diagnostic value for cognitive impairment.Methods A total of 92 patients with chronic schizophrenia and another 80 healthy individuals in Wuhan Mental Health Center/Wuhan Hospital for Psychotherapy from January 2021 to July 2022 were enrolled as study group and control group,respectively.The patients in the study group were divid-ed into the cognitive impairment group(44 cases)and the cognitive normal group(48 cases)according to Montreal Cognitive Assessment Scale(MoCA).Clinical symptoms were assessed by using Positive and Nega-tive Syndrome Scale(PANSS).MoCA was used to evaluate the cognitive function.The levels of Glu and GA-BA in plasma were determined by high-performance liquid chromatography/electrospray tandem mass spec-trometry.The scores of PANSS and MoCA as well as serum levels of Glu and GABA were compared between two groups.Then the correlation of serum Glu and GABA levels with clinical symptoms and the diagnostic value for cognitive impairment in the patients in the study group were investigated.Results The Glu level in the study group was higher than that in the control group,and the GABA level was lower than that in the con-trol group(P＜0.05).The serum Glu levels in both the cognitive impairment group and the cognitive normal group were higher than the normal range,and the Glu level in the cognitive impairment group was higher than that in the cognitive normal group(P＜0.05).The serum GABA levels in both the cognitive impairment group and the cognitively normal group were lower than the normal range,and the GABA level in the cogni-tive impairment group was lower than that in the cognitive normal group(P＜0.05).In the study group,ser-um Glu level was positively correlated with negative,positive,general psychopathological symptom scores,and overall score in PANSS(P＜0.05),while GABA level was negatively correlated with negative,positive,gener-al psychopathological symptom scores,and overall score in PANSS(P＜0.05).The sensitivity of the single and combined detection of serum Glu and GABA for the diagnosis of cognitive impairment in patients with chronic schizo-phrenia was 77.3％,72.7％and 93.2％,respectively,and the specificity was 72.9％,72.9％,and 75.0％,respec-tively,and the area under the curve was 0.778,0.769,and 0.868,respectively.Conclusion Serum Glu level in patients with chronic schizophrenia is higher than that in healthy individuals,while GABA level is lower than that in healthy individuals,and the above two indicators are correlated with PANSS score,which have high value in diagnosing cognitive impairment and could be used as effective biological indicators to help clinical doctors judge patients'cognitive function.