The Glucolipid Metabolic Dysregulation And The Effects Of Antipsychotics On Glucolipid Metabolism In Patients With First-episode Schizophrenia

Objective:To elaborate the relationship between abnormal glucolipid metabolism and schizophrenia itself as well as early antipsychotics treatment,so as to provide ideas and clues for early clinical intervention.The objectives include the following aspects:1.To study whether abnormal glucolipid metabolism had existed prior to antipsychotics treatment in patients with first-episode schizophrenia.2.To study the correlation between glucolipid metabolic indexes and cognition function and grey matter volume in patients with first-episode schizophrenia.To explore the relationship among glucolipid metabolism,cognitive performance and grey matter volume in patients with first-episode schizophrenia.3.To study the effect of glucolipid metabolism and gender differences in early antipsychotics treatment in patients with first-episode schizophrenia.Objects and Methods:1.63 patients with first-episode schizophrenia and 31 healthy controls were included in this study.Fasting levels of glucolipid metabolic indexes including fasting glucose(FG),triglycerides(TG),cholesterol(CHOL),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)were measured after a 10-12 h overnight fast.We evaluated insulin resistance index based on the ratio of TG to HDL-C(TG/HDL-C).Positive and Negative Syndrome Scale(PANSS)was performed by a psychiatrist to assess the severity of symptoms in patients with firstepisode schizophrenia.Three tests of Cambridge Neuropsychological Test Automated Battery(CANTAB),which were Rapid Visual Information Processing(RVP),Intra/Extradimensional Set Shift(IED)and Delayed Matching To Sample(DMS),were selected to assess the cognition function of all subjects.Three dimensional(3D)structural magnetic resonance imaging was used to collect raw data of all subjects.Compare the difference of glucolipid metabolism,cognitive performance and grey matter volume between two groups.To explore the relationship between glucolipid metabolism and cognition function and grey matter volume using partial correlation analysis.To explore the associations of glucolipid metabolism,cognitive performance and grey matter volume using mediation analysis.2.853 first-episode,drug-na?ve schizophrenia patients and 472 first-episode medicated schizophrenia patients(no more than 8 weeks of cumulative(lifetime)antipsychotics exposure before hospitalization)were retrospectively analyzed.Basic information,the antipsychotics and daily dose after admission,and the levels of FG,TG,CHOL,HDL-C and LDL-C and the time of measurement were collected from the patients’ medical records.We evaluated insulin resistance index based on the ratio of TG to HDL-C(TG/HDL-C).Compare the changes of glucolipid metabolism before and after early antipsychotics treatment.Results:1)First-episode schizophrenia patients had higher levels of FG,TG and insulin resistance index(p<0.05),and had lower levels of CHOL and HDL-C(p<0.05),compared to controls.No significant difference of LDL-C between the two groups was found(p>0.05).2)Compared to healthy subjects,the first-episode schizophrenia patients did worse in some/all of the tests of RVP,IED,and DMS that reflected attention,executive function,and visual memory(p<0.05).In the first-episode schizophrenia patients,the RVP mean latency was negatively correlated with TG,insulin resistance index and BMI,respectively,and was positively corrected with HDL-C.3)Compared to healthy subjects,the first-episode schizophrenia patients showed the decreased grey matter volume in bilateral insula,left middle occipital gyrus and left postcentral.In the first-episode schizophrenia patients,TG and insulin resistance index were positively corrected with grey matter volume in right insula,respectively.CHOL and LDL-C were negatively correlated with grey matter volume in left postcentral gyrus,respectively.BMI was negatively correlated with grey matter volume in left insula,left middle occipital gyrus,and left postcentral gyrus,respectively.4)In the first-episode schizophrenia patients,the mediation model confirmed a negative direct effect of TG and insulin resistance index on RVP mean latency,respectively.The mediation model furthermore yielded a significant positive mediated effect of TG and insulin resistance index on RVP mean latency through the grey matter volume in right insula,respectively.5)Compared to the baseline values,there was a significant increase in insulin resistance index,and the levels of TG,CHOL and LDL-C after 2 weeks of antipsychotics treatment(p<0.05);there was a significant decrease in the levels of FG after 2 weeks of antipsychotics treatment(p<0.05);there was a significant decrease in the levels of HDL-C after 4 weeks of antipsychotics treatment(p<0.05).6)At baseline,the male patients with first-episode schizophrenia had higher levels of TG and insulin resistance index(p<0.05),and lower levels of HDL-C(p<0.05),compared to female patients.No significant difference in the levels of FG,CHOL and LDL-C between male and female patients was found(p>0.05).After 2weeks of antipsychotics treatment,the male patients with first-episode schizophrenia had higher levels of TG and insulin resistance index(p<0.05),and lower levels of HDL-C(p<0.05),compared to female patients.No significant difference in the levels of FG,CHOL and LDL-C between male and female patients was found(p>0.05).Conclusions:1.Abnormal glucolipid metabolism may be occurred prior to antipsychotics exposure,including the significant increased levels of fasting glucose,triglycerides,and insulin resistance,and the significant decreased levels of cholesterol and highdensity lipoprotein cholesterol.2.In the first-episode schizophrenia patients,grey matter volume is a mediator of glucolipid metabolism affecting cognitive performance.Although in the early stage of schizophrenia,glucolipid metabolism does not directly lead to cognition impairment,but could indirectly lead to cognition deficits through the mediator of grey matter volume.3.In the first-episode schizophrenia patients,insulin resistance and dyslipidemia have occurred in the early stage of antipsychotics treatment.4.In the first-episode schizophrenia patients,male may be more predisposed to glucolipid metabolic abnormalities than female and the effects of antipsychotics on glucolipid metabolism in male is greater than that in female.