Relationship Between Serum Uric Acid And Cognitive Function In Patients With Schizophrenia

BackgroundPrevious studies on uric acid(UA)in the general population and people with certain diseases have found that high UA is associated with enhanced function.The mechanism to explain this association may be that UA acts as an important antioxidant with neuroprotective effects.Schizophrenia patients have severe oxidative stress abnormalities,and cognitive impairment is the main obstacle to their rehabilitation.At present,there are few studies on UA and cognitive impairment in schizophrenia.This study aims to clarify the relationship between UA and cognitive impairment in the maintenance phase of schizophrenia,and to explore and validate a simple diagnostic model of cognitive impairment in schizophrenia that includes UA.MethodsA total of 755 patients with schizophrenia in the maintenance period of Baiyun Jingkang Hospital were enrolled.Cognitive function was assessed by Mini-mental State Examination(MMSE).Higher scores represent better cognitive status.UA was determined using the Plus method.Participants were grouped according to UA levels to assess lownormal(3.50-5.07 mg/dL for men and 2.50-4.19 mg/dL for women),moderate-normal(5.07-6.39 mg/dL for men,and 2.50-4.19 mg/dL for women).4.19-5.18 mg/dL for women),high-normal(6.39-7.00 mg/dL for men,5.18-6.00 mg/dL for women)and higher-normal(7.00 mg/dL for men,6.00 mg/dL for women)UA levels were associated with cognitive function.Multiple Logistic regression and linear regression models and restricted cubic spline(RCS)were used to evaluate the relationship between the two.Stratified analyses were conducted according to anticholinergic negative cognitive burden(ACB),hypertension,diabetes,dyslipidemia,age,gender,and body mass index(BMI),and additive or multiplicative interactions were evaluated.Logistic regression and Lasso regression were used for variable screening,nomogram was used for model demonstration,and K-cross validation was used for model verification.The calibration curve,receiver operating characteristic curve(ROC),area under the curve(AUC),clinical decision curve(DCA),and net reclassification index(NRI)were used to evaluate the model.ResultsSerum UA level is positively correlated with multiple cognitive dimensions in patients with schizophrenia.The β values(95%CI)of overall cognition,orientation,memory,attention and calculation,recall,and language were 0.531(0.168,0.895),0.290(0.126,0.455),0.118(0.045,P<0.05),respectively.0.191),0.122(0.012,0.231),0.139(0.073,0.206)and 0.350(0.216,0.484).Stratified analysis showed that age≥45 and high ACB had a negative multiplication interaction with UA in the association with cognitive function(P<0.05).In addition,a 10-factor model with good diagnostic ability for cognitive impairment in schizophrenia was established(low UA,age,female,negative symptoms,positive symptoms,low activation,high ACB,dyslipidemia,low APOB,and high TP were related to cognitive impairment),and the C-index was 0.7679(0.7316,0.8041).The internal cross validation C-index was 0.7503.ConclusionFirst,high UA is associated with better cognitive function in patients with schizophrenia,and the underlying mechanism of this association may be related to the powerful antioxidant properties of UA.Second,reducing the use of high-ACB antipsychotics may strengthen the association between UA and cognitive function in schizophrenia;Aging may weaken the association between UA and cognitive function.This suggests that when exploring the relationship between UA and cognitive function in schizophrenia in the future,we should pay attention to high-risk populations such as high ACB and middle-aged and elderly people.Third,UA is a potential diagnostic factor for constructing a diagnostic model of cognitive impairment in schizophrenia.