The Association Of Second-Generation Antipsychotic Drugs And Blood Lipids With Cognitive Function In Schizophrenia

BackgroundCognitive dysfunction is one of the core symptoms of schizophrenia and an important factor affecting the prognosis of patients.Second-generation antipsychotics(SGAs)are the first-line drugs used in the treatment of schizophrenia.According to previous studies,the effect of SGAs on cognitive function remains unclear and can be affected by a variety of factors.As one of the main side effects of SGAs,dyslipidemia may not only directly affect cognitive function,but also affect the influence of SGAs on cognitive function.However,the majority of published studies have focused on pairwise associations between the SGAs,blood lipids and cognitive function.More complex interactions between three factors have been largely unexplored.Therefore,this study employed hospitalized schizophrenia patients as the research subject to investigate whether blood lipid level might be the intermediary variable of the association between SGAs and cognitive function and whether there was interaction between SGAs and blood lipid level.This study offered insights on how SGAs affect cognitive function and guidance to psychiatrists on how to treat patients’ blood lipid levels and cognitive performance in order to enhance their prognosis.MethodsThis cross-sectional study recruited patients with schizophrenia who were admitted to a psychiatric hospital from 2020 to 2022.The use of antipsychotic drug,blood lipid levels,cognitive function status,and related cofounders were all collected.Antipsychotics included first generation antipsychotics and SGAs(Olanzapine,clozapine,quetiapine,risperidone).Blood lipid parameters included total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),non-high density lipoprotein cholesterol(NHDL-C),triglyceride(TG),apolipoprotein Al(ApoA1),apolipoprotein B(ApoB).The connection between SGAs and cognitive impairment,lipid level and cognitive dysfunction,and SGAs and lipid level,respectively,was estimated using a logistic regression model.The total effect of SGAs and lipid levels on cognitive impairment was decomposed into direct effect,reference interaction,simple mediation effect and mediation interaction by four-way decomposition,in order to explore whether blood lipid level might be the mediating variable of the association between SGAs and cognitive function and whether there was an interaction between SGAs and blood lipid level.ResultsIn the present study,515 hospitalized patients with schizophrenia were recruited,of whom approximately 70%had cognitive impairment(361/515).The main results of logistic regression analysis were:(1)Olanzapine(OR:2.26,95%confidence interval(CI):1.12-4.55)was associated with worse cognitive function,while clozapine(OR:0.48,95%CI:0.23-0.98)and risperidone(OR:0.45,95%CI:0.26-0.77)was associated with better cognitive function.(2)Increased ApoA1(OR:0.54,95%CI:0.31-0.94)or increased ApoB(OR:0.42,95%CI:0.26-0.67)were associated with better cognitive function.(3)Clozapine was associated with elevated TG levels(OR:2.08,95%CI:1.10-3.95),while olanzapine was negatively associated with increased ApoB(OR:0.52,95%CI:0.28-0.97).According to the results of the four-way decomposition,no mediating effect between SGAs and cognitive function mediated by lipid level was found,while clozapine and ApoB level,and risperidone and ApoB level had antagonistic effects on cognitive impairment.The specific results were as follows:The interaction coefficient of clozapine and ApoB on cognitive impairment was 0.2289(P=0.012).The interaction coefficient of risperidone and ApoB on cognitive impairment was 0.1528(P=0.025).ConclusionIn this study,we found that:(1)Olanzapine was associated with worse cognitive function in patients with schizophrenia,while clozapine and risperidone were associated with better cognitive function in patients with schizophrenia;(2)Increased ApoA1 or ApoB in patients with schizophrenia was associated with better cognitive function;(3)Clozapine,risperidone and increased ApoB had antagonistic interactions on cognitive function,suggesting that ApoB levels in patients receiving clozapine and risperidone might need to be monitored and controlled to improve cognitive function.The findings of this study provided hints about the mechanism of SGAs on cognitive function in schizophrenia patients,and offered psychiatrists guidance on how to administer medication and monitor blood lipid levels to improve patients’ cognitive function and prognosis.