Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the ha...Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the hallmarks of psychiatric disorders(PDs).In addition to insulin,de novo lipogenesis(DNL)also plays an essential role in NSC proliferation and function as it supplies fatty acids for membrane phospholipid synthesis and cell signaling.However,enhanced DNL is associated with lipid/fatty acid accumulation,IR,and impaired NSC proliferation.Intriguingly,data from lipidomic studies suggest that DNL could be enhanced before the onset of classical symptoms in patients with PDs.Further,evidence suggests that patients with PDs may develop IR during childhood or before adolescence;therefore,DNL could be enhanced preceding the development of IR.Regarding treatment,while most antidepressants and antipsychotic drugs have been shown to further deteriorate IR and stimulate DNL,various adjunctive drugs/therapies,including chemical,physical,and stem cell therapy,which have shown promising success in treating PDs,reduce DNL while enhancing insulin sensitivity,NSC proliferation,and cognitive function in laboratory animals.Preliminary clinical outcomes and future prospects of these adjunctive drugs/therapies,especially stem cell therapy in treating PDs including schizophrenia and depression,are discussed.展开更多
BACKGROUND Nervonic acid(NA,C24:1,w9)is a monounsaturated fatty acid that plays a crucial role in myelination and motor function.It also regulates cognitive and metabolic functions,suggesting that impaired NA metaboli...BACKGROUND Nervonic acid(NA,C24:1,w9)is a monounsaturated fatty acid that plays a crucial role in myelination and motor function.It also regulates cognitive and metabolic functions,suggesting that impaired NA metabolism may contribute to the pathophysiology of schizophrenia.Although several studies have measured erythrocyte membrane NA in first-episode psychosis(FEP),findings are conflicting,and the fate of NA in patients with chronic schizophrenia(CSZ)or under long-term antipsychotic treatment schedules remains unknown.AIM To measure erythrocyte membrane NA and determine its association with psychopathology and metabolic parameters in drug-naive patients with FEP and antipsychotic-treated patients with CSZ.METHODS In this study,twenty-one drug-naive patients with FEP,twenty patients with CSZ treated with atypical antipsychotics,and fourteen healthy male subjects were analyzed.Erythrocyte membrane NA was measured using ultrathin capillary gas chromatography,plasma leptin was measured using enzyme-linked immunosorbent assay,and body mass index(BMI)was calculated by using the formula:Weight(kg)/height(m^(2)).Psychiatric symptoms were evaluated using the brief psychiatry rating scale and the positive and negative syndrome scale(PANSS).Pearson correlation coefficient(r)was computed to find the association between erythrocyte membrane NA,PANSS scores,plasma leptin,and BMI.RESULTS In patients with FEP,erythrocyte NA was non-significantly increased(about 12%)and negatively correlated with negative symptoms(PANSS-negative symptom scores,r=-0.4323,P=0.023)but not with positive symptoms(PANSS-positive symptom scores,r=-0.2915,P=0.09).In patients with CSZ,erythrocyte NA was reduced considerably(about 40%,P<0.001 vs FEP and about 30%vs control(CNT)subjects,P=0.037)and negatively correlated with both PANSS-negative symptom scores(r=-0.4562,P=0.013)and PANSS-positive symptom scores(r=-0.3911,P=0.041).Additionally,in patients with FEP,erythrocyte NA was not significantly correlated either with BMI(r=-0.2532,P=0.231)or plasma leptin(r=-0.3001,P=0.102).However,in patients with CSZ,it did negatively correlate with both BMI(r=-0.4721,P=0.029)and plasma leptin(r=-0.4701,P=0.031).CONCLUSION Erythrocyte membrane NA level could be used for predicting the development of metabolic abnormalities,treatment resistance,and prognosis in schizophrenia.展开更多
BACKGROUND Insulin resistance(IR)and impaired energy expenditure(IEE)are irreparable metabolic comorbidities in schizophrenia.Although mechanism(s)underlying IR and IEE remains unclear,leptin and fatty acid signaling,...BACKGROUND Insulin resistance(IR)and impaired energy expenditure(IEE)are irreparable metabolic comorbidities in schizophrenia.Although mechanism(s)underlying IR and IEE remains unclear,leptin and fatty acid signaling,which has profound influence on insulin secretion/sensitivity,glucose metabolism and energy expenditure,could be disrupted.However,no association of plasma leptin with erythrocyte membrane fatty acids,body mass index(BMI),and psychotic symptoms in the same cohort of untreated patients with first-episode psychosis(FEP)or medicated patients with chronic schizophrenia(CSZ)is presented before.These studies are crucial for deciphering the role of leptin and fatty acids in the development of IR and IEE in schizophrenia.AIM To determine the association between plasma leptin,erythrocyte membrane fatty acids,particularly,saturated fatty acids(SFAs),BMI and psychotic symptoms in patients with FEP and CSZ.METHODS In this study,twenty-two drug naive patients with FEP,twenty-one CSZ patients treated with atypical antipsychotic drugs,and fourteen healthy control(CNT)subjects were analyzed.Plasma leptin was measured using sandwich mode enzyme-linked immunosorbent assay.Erythrocyte membrane SFAs were measured using ultrathin capillary gas chromatography.BMI was calculated by using the formula:weight(kg)/height(m^(2)).Psychiatric symptoms were evaluated at baseline using brief psychiatric rating scale(BPRS),and positive and negative syndrome scale(PANSS).The total BPRS scores,positive and negative symptom scores(PANSS-PSS and PANSS-NSS,respectively)were recorded.Pearson correlation coefficient(r)analyses were performed to find the nature and strength of association between plasma leptin,PANSS scores,BMI and SFAs,particularly,palmitic acid(PA).RESULTS In patients with FEP,plasma leptin not BMI was significantly lower(P=0.034),whereas,erythrocyte membrane SFAs were significantly higher(P<0.005)compared to the CNT subjects.Further,plasma leptin showed negative correlation with erythrocyte membrane SFAs-PA(r=-0.4972,P=0.001),PANSS-PSS(r=-0.4034,P=0.028),and PANSS-NSS(r=-0.3487,P=0.048).However,erythrocyte membrane SFAs-PA showed positive correlation with PANSS-PSS(r=0.5844,P=0.0034)and PANSS-NSS(r=0.5380,P=0.008).In CSZ patients,plasma leptin,BMI,and erythrocyte membrane SFAs,all were significantly higher(P<0.05)compared to the CNT subjects.Plasma leptin showed positive correlation with BMI(r=0.312,P=0.032)but not with PANSS scores or erythrocyte membrane SFAs-PA.However,erythrocyte membrane SFAs-PA showed positive correlation with PANSS-NSS only(r=0.4729,P=0.031).Similar changes in the plasma leptin and erythrocyte membrane SFAs have also been reported in individuals at ultrahigh risk of developing psychosis;therefore,the above findings suggest that leptin-fatty acid biosynthesis could be disrupted before the onset of psychosis in schizophrenia.CONCLUSION Disrupted leptin-fatty acid biosynthesis/signaling could be an early manifestation of metabolic comorbidities in schizophrenia.Large-scale studies are warranted to validate the above findings.展开更多
Although significant advances have been made in understanding the pathophysiology of psychiatric disorders(PDs),therapeutic advances have not been very convincing.While psychotropic medications can reduce classical sy...Although significant advances have been made in understanding the pathophysiology of psychiatric disorders(PDs),therapeutic advances have not been very convincing.While psychotropic medications can reduce classical symptoms in patients with PDs,their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes,obesity and non-alcoholic fatty liver disease(NAFLD).The mechanism(s)underlying these metabolic abnormalities is not clear;however,lipid/fatty acid accumulation due to enhanced de novo lipogenesis(DNL)has been shown to reduce membrane fluidity,increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities.Intriguingly,emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity,diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs.In support of this,several adjunctive drugs comprising of anti-oxidants and antiinflammatory agents,that are used in treating PDs in combination with psychotropic medications,have been shown to reduce insulin resistance and development of NAFLD.In conclusion,the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities,and a new avenue for translational research and therapeutic drug designing in PDs.展开更多
文摘Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the hallmarks of psychiatric disorders(PDs).In addition to insulin,de novo lipogenesis(DNL)also plays an essential role in NSC proliferation and function as it supplies fatty acids for membrane phospholipid synthesis and cell signaling.However,enhanced DNL is associated with lipid/fatty acid accumulation,IR,and impaired NSC proliferation.Intriguingly,data from lipidomic studies suggest that DNL could be enhanced before the onset of classical symptoms in patients with PDs.Further,evidence suggests that patients with PDs may develop IR during childhood or before adolescence;therefore,DNL could be enhanced preceding the development of IR.Regarding treatment,while most antidepressants and antipsychotic drugs have been shown to further deteriorate IR and stimulate DNL,various adjunctive drugs/therapies,including chemical,physical,and stem cell therapy,which have shown promising success in treating PDs,reduce DNL while enhancing insulin sensitivity,NSC proliferation,and cognitive function in laboratory animals.Preliminary clinical outcomes and future prospects of these adjunctive drugs/therapies,especially stem cell therapy in treating PDs including schizophrenia and depression,are discussed.
文摘BACKGROUND Nervonic acid(NA,C24:1,w9)is a monounsaturated fatty acid that plays a crucial role in myelination and motor function.It also regulates cognitive and metabolic functions,suggesting that impaired NA metabolism may contribute to the pathophysiology of schizophrenia.Although several studies have measured erythrocyte membrane NA in first-episode psychosis(FEP),findings are conflicting,and the fate of NA in patients with chronic schizophrenia(CSZ)or under long-term antipsychotic treatment schedules remains unknown.AIM To measure erythrocyte membrane NA and determine its association with psychopathology and metabolic parameters in drug-naive patients with FEP and antipsychotic-treated patients with CSZ.METHODS In this study,twenty-one drug-naive patients with FEP,twenty patients with CSZ treated with atypical antipsychotics,and fourteen healthy male subjects were analyzed.Erythrocyte membrane NA was measured using ultrathin capillary gas chromatography,plasma leptin was measured using enzyme-linked immunosorbent assay,and body mass index(BMI)was calculated by using the formula:Weight(kg)/height(m^(2)).Psychiatric symptoms were evaluated using the brief psychiatry rating scale and the positive and negative syndrome scale(PANSS).Pearson correlation coefficient(r)was computed to find the association between erythrocyte membrane NA,PANSS scores,plasma leptin,and BMI.RESULTS In patients with FEP,erythrocyte NA was non-significantly increased(about 12%)and negatively correlated with negative symptoms(PANSS-negative symptom scores,r=-0.4323,P=0.023)but not with positive symptoms(PANSS-positive symptom scores,r=-0.2915,P=0.09).In patients with CSZ,erythrocyte NA was reduced considerably(about 40%,P<0.001 vs FEP and about 30%vs control(CNT)subjects,P=0.037)and negatively correlated with both PANSS-negative symptom scores(r=-0.4562,P=0.013)and PANSS-positive symptom scores(r=-0.3911,P=0.041).Additionally,in patients with FEP,erythrocyte NA was not significantly correlated either with BMI(r=-0.2532,P=0.231)or plasma leptin(r=-0.3001,P=0.102).However,in patients with CSZ,it did negatively correlate with both BMI(r=-0.4721,P=0.029)and plasma leptin(r=-0.4701,P=0.031).CONCLUSION Erythrocyte membrane NA level could be used for predicting the development of metabolic abnormalities,treatment resistance,and prognosis in schizophrenia.
文摘BACKGROUND Insulin resistance(IR)and impaired energy expenditure(IEE)are irreparable metabolic comorbidities in schizophrenia.Although mechanism(s)underlying IR and IEE remains unclear,leptin and fatty acid signaling,which has profound influence on insulin secretion/sensitivity,glucose metabolism and energy expenditure,could be disrupted.However,no association of plasma leptin with erythrocyte membrane fatty acids,body mass index(BMI),and psychotic symptoms in the same cohort of untreated patients with first-episode psychosis(FEP)or medicated patients with chronic schizophrenia(CSZ)is presented before.These studies are crucial for deciphering the role of leptin and fatty acids in the development of IR and IEE in schizophrenia.AIM To determine the association between plasma leptin,erythrocyte membrane fatty acids,particularly,saturated fatty acids(SFAs),BMI and psychotic symptoms in patients with FEP and CSZ.METHODS In this study,twenty-two drug naive patients with FEP,twenty-one CSZ patients treated with atypical antipsychotic drugs,and fourteen healthy control(CNT)subjects were analyzed.Plasma leptin was measured using sandwich mode enzyme-linked immunosorbent assay.Erythrocyte membrane SFAs were measured using ultrathin capillary gas chromatography.BMI was calculated by using the formula:weight(kg)/height(m^(2)).Psychiatric symptoms were evaluated at baseline using brief psychiatric rating scale(BPRS),and positive and negative syndrome scale(PANSS).The total BPRS scores,positive and negative symptom scores(PANSS-PSS and PANSS-NSS,respectively)were recorded.Pearson correlation coefficient(r)analyses were performed to find the nature and strength of association between plasma leptin,PANSS scores,BMI and SFAs,particularly,palmitic acid(PA).RESULTS In patients with FEP,plasma leptin not BMI was significantly lower(P=0.034),whereas,erythrocyte membrane SFAs were significantly higher(P<0.005)compared to the CNT subjects.Further,plasma leptin showed negative correlation with erythrocyte membrane SFAs-PA(r=-0.4972,P=0.001),PANSS-PSS(r=-0.4034,P=0.028),and PANSS-NSS(r=-0.3487,P=0.048).However,erythrocyte membrane SFAs-PA showed positive correlation with PANSS-PSS(r=0.5844,P=0.0034)and PANSS-NSS(r=0.5380,P=0.008).In CSZ patients,plasma leptin,BMI,and erythrocyte membrane SFAs,all were significantly higher(P<0.05)compared to the CNT subjects.Plasma leptin showed positive correlation with BMI(r=0.312,P=0.032)but not with PANSS scores or erythrocyte membrane SFAs-PA.However,erythrocyte membrane SFAs-PA showed positive correlation with PANSS-NSS only(r=0.4729,P=0.031).Similar changes in the plasma leptin and erythrocyte membrane SFAs have also been reported in individuals at ultrahigh risk of developing psychosis;therefore,the above findings suggest that leptin-fatty acid biosynthesis could be disrupted before the onset of psychosis in schizophrenia.CONCLUSION Disrupted leptin-fatty acid biosynthesis/signaling could be an early manifestation of metabolic comorbidities in schizophrenia.Large-scale studies are warranted to validate the above findings.
文摘Although significant advances have been made in understanding the pathophysiology of psychiatric disorders(PDs),therapeutic advances have not been very convincing.While psychotropic medications can reduce classical symptoms in patients with PDs,their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes,obesity and non-alcoholic fatty liver disease(NAFLD).The mechanism(s)underlying these metabolic abnormalities is not clear;however,lipid/fatty acid accumulation due to enhanced de novo lipogenesis(DNL)has been shown to reduce membrane fluidity,increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities.Intriguingly,emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity,diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs.In support of this,several adjunctive drugs comprising of anti-oxidants and antiinflammatory agents,that are used in treating PDs in combination with psychotropic medications,have been shown to reduce insulin resistance and development of NAFLD.In conclusion,the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities,and a new avenue for translational research and therapeutic drug designing in PDs.
