利培酮和齐拉西酮对精神分裂症患者糖脂代谢及血浆细胞因子的影响
|
摘要
目的:本研究采用临床病例-对照及病例自身对照研究,探讨非经典抗精神病药利培酮和齐拉西酮对精神分裂症患者血糖、胰岛素、瘦素、血脂及血浆细胞因子水平的影响,并对此进行比较分析。
方法:患者组50例,其中利培酮组和齐拉西酮组各25例,对照组50例。所有入组者于入组次日及治疗8周后晨6时抽取空腹静脉血,以自动化分析仪器测定空腹血糖(FBG)及血脂各指标;采用电化学发光分析仪测定胰岛素各指标;采用酶联免疫吸附法(ELISA)测定细胞因子水平。所有入组的研究对象及患者的监护人均对本研究知情同意。用SPSS11.0软件包进行分析处理,实验数据用均数±标准差(X±S)做统计描述,治疗前后组内比较采用配对t-检验,组间比较采用独立样本t-检验。P<0.05为差异有显著性。
结果:(1)治疗前利培酮组和齐拉西酮组两组间血糖、胰岛素、瘦素和血脂水平比较无显著性差异(P>0.05)。(2)精神分裂症患者经利培酮治疗8周后,FBG水平升高,FINS水平及IRI升高,ISI降低,各指标与治疗前比较均有显著差异(P<0.01);经齐拉西酮治疗8周后,FBG水平与治疗前比较无显著性差异(P>0.05),而Fins水平及IRI升高,ISI降低,与治疗前比较有显著性差异(P<0.01)。(3)精神分裂症患者经利培酮治疗8周后,TC、TG、LDL-C、Lep水平均有升高,与治疗前比较有显著差异(P<0.01),而HDL-C水平无显著性差异(P>0.05);经齐拉西酮治疗8周后,TG、LDL-C、Lep水平均明显升高,与治疗前比较有显著性差异(P<0.01),TC、HDL-C水平与治疗前比较无显著性差异(P>0.05)。(4)利培酮和齐拉西酮组治疗前后IL-2、IL-6和TNF-a均高于对照组,两组间比较均有显著性差异(P<0.01);治疗8周后,IL-2、IL-6、IL-12及TNF-a水平均有降低,与治疗前比较有显著差异(P<0.01)。
结论:(1)抗精神病药物能够不同程度的影响机体的糖脂代谢及部分激素水平的含量,增加了心脑血管疾病、高血压、糖尿病等的发病风险,产生的可能机制有待于进一步的研究证实。(2)精神分裂症存在细胞因子介导的免疫功能障碍,表现为血浆细胞各因子含量升高,提示细胞因子水平升高可能与精神分裂症的发病过程有关。(3)抗精神病药物利培酮和齐拉西酮均对细胞因子具有调节作用,可能通过抑制细胞因子的有关机制产生免疫抑制作用,表现为抗精神病药物治疗后,各细胞因子水平明显下降。提示这可能是该药物的药理作用机制之一。(4)精神分裂症在缓解期仍存在着免疫功能障碍,表现为随着精神症状的缓解,细胞因子水平虽有明显改善,但仍未恢复到正常水平。提示该免疫功能在疾病的缓解期可能反映了精神分裂症有遗传性背景。
Objective: The purpose of this study was to investigate glucose, serum lipid, insulin, leptin and plasma cytokines levels in schizophrenia patients, and further to understand the influence of antipsychotic on glucose, serum lipid, insulin, leptin and plasma cytokines.
Methods: The case-control and self-control study were used. The study recruited 50 schizophrenia patients and 50 healthy controls matched by age, educational level and sex. All those patients take fasting blood sample at 6 o’clock in the morning before and after 8 weeks’treatment, and the controls take fasting blood sample at 6 o’clock in the morning. Fasting blood glucose and blood lipid levels were measured with Automated analyzer, and fasting insulin levels were measured with electrochemilumine scence analyzer, and plasma cytokines levels were measured with enzyme linked immunosorbent assay (ELISA). All experimental data were analyzed with SPSS14.0 statistical software, and were expressed as means and standard deviations ( x±SD). All data were analyzed with independence sample t-test and matched-pairs t-test. All p values were two-tailed, and P<0.05 for the difference was significant.
Results: (1) There were no significant differences between risperidone groups and ziprasidone groups on the levels of blood glucose, insulin, leptin and blood lipids before treatment (P> 0.05). (2) After using risperidone, The FBG levels, Fins levels and IRI increased and ISI decreased significantly, there were significant differences (P <0.01). After using ziprasidone, the Fins level and IRI increased, and ISI decreased significantly (P <0.01), while the FBG levels were no significant changes (P>0.05). (3) After using risperidone, TC, TG, LDL-C and Lep levels increased significantly (P <0.01), while HDL-C levels were no significant differences (P> 0.05). After using ziprasidone, TG, LDL-C and Lep levels were significantly increased (P <0.01), and TC and HDL-C levels had no significant differences (P>0.05). (4) IL-2, IL-6 and TNF-a levels before and after risperidone and ziprasidone’s treatment were all higher than the control groups, there were significant differences (P <0.01). After using risperidone and ziprasidone, IL-2, IL-6 and TNF-a levels decreased significantly (P <0.01).
Conclusion: (1) Antipsychotic drugs affected the glucose, lipid and some hormone levels, which could increase the risk of cardiovascular diseases, hypertension and diabetes. The possible mechanisms need to be confirmed by further studies. (2) Schizophrenia patients had cytokine-mediated immune dysfunction. It showed that the change of plasma cytokines levels maybe related to the pathogenesis of schizophrenia. (3) Risperidone and ziprasidone could regulate the plasma cytokines levels, and educed immunosuppression function, which might be one of the mechanisms of the pharmacological effects. (4) Schizophrenia patients still had immune function dysfunction in remission, which suggested that the dysfunction may be a genetic trait of schizophrenia.
方法:患者组50例,其中利培酮组和齐拉西酮组各25例,对照组50例。所有入组者于入组次日及治疗8周后晨6时抽取空腹静脉血,以自动化分析仪器测定空腹血糖(FBG)及血脂各指标;采用电化学发光分析仪测定胰岛素各指标;采用酶联免疫吸附法(ELISA)测定细胞因子水平。所有入组的研究对象及患者的监护人均对本研究知情同意。用SPSS11.0软件包进行分析处理,实验数据用均数±标准差(X±S)做统计描述,治疗前后组内比较采用配对t-检验,组间比较采用独立样本t-检验。P<0.05为差异有显著性。
结果:(1)治疗前利培酮组和齐拉西酮组两组间血糖、胰岛素、瘦素和血脂水平比较无显著性差异(P>0.05)。(2)精神分裂症患者经利培酮治疗8周后,FBG水平升高,FINS水平及IRI升高,ISI降低,各指标与治疗前比较均有显著差异(P<0.01);经齐拉西酮治疗8周后,FBG水平与治疗前比较无显著性差异(P>0.05),而Fins水平及IRI升高,ISI降低,与治疗前比较有显著性差异(P<0.01)。(3)精神分裂症患者经利培酮治疗8周后,TC、TG、LDL-C、Lep水平均有升高,与治疗前比较有显著差异(P<0.01),而HDL-C水平无显著性差异(P>0.05);经齐拉西酮治疗8周后,TG、LDL-C、Lep水平均明显升高,与治疗前比较有显著性差异(P<0.01),TC、HDL-C水平与治疗前比较无显著性差异(P>0.05)。(4)利培酮和齐拉西酮组治疗前后IL-2、IL-6和TNF-a均高于对照组,两组间比较均有显著性差异(P<0.01);治疗8周后,IL-2、IL-6、IL-12及TNF-a水平均有降低,与治疗前比较有显著差异(P<0.01)。
结论:(1)抗精神病药物能够不同程度的影响机体的糖脂代谢及部分激素水平的含量,增加了心脑血管疾病、高血压、糖尿病等的发病风险,产生的可能机制有待于进一步的研究证实。(2)精神分裂症存在细胞因子介导的免疫功能障碍,表现为血浆细胞各因子含量升高,提示细胞因子水平升高可能与精神分裂症的发病过程有关。(3)抗精神病药物利培酮和齐拉西酮均对细胞因子具有调节作用,可能通过抑制细胞因子的有关机制产生免疫抑制作用,表现为抗精神病药物治疗后,各细胞因子水平明显下降。提示这可能是该药物的药理作用机制之一。(4)精神分裂症在缓解期仍存在着免疫功能障碍,表现为随着精神症状的缓解,细胞因子水平虽有明显改善,但仍未恢复到正常水平。提示该免疫功能在疾病的缓解期可能反映了精神分裂症有遗传性背景。
Objective: The purpose of this study was to investigate glucose, serum lipid, insulin, leptin and plasma cytokines levels in schizophrenia patients, and further to understand the influence of antipsychotic on glucose, serum lipid, insulin, leptin and plasma cytokines.
Methods: The case-control and self-control study were used. The study recruited 50 schizophrenia patients and 50 healthy controls matched by age, educational level and sex. All those patients take fasting blood sample at 6 o’clock in the morning before and after 8 weeks’treatment, and the controls take fasting blood sample at 6 o’clock in the morning. Fasting blood glucose and blood lipid levels were measured with Automated analyzer, and fasting insulin levels were measured with electrochemilumine scence analyzer, and plasma cytokines levels were measured with enzyme linked immunosorbent assay (ELISA). All experimental data were analyzed with SPSS14.0 statistical software, and were expressed as means and standard deviations ( x±SD). All data were analyzed with independence sample t-test and matched-pairs t-test. All p values were two-tailed, and P<0.05 for the difference was significant.
Results: (1) There were no significant differences between risperidone groups and ziprasidone groups on the levels of blood glucose, insulin, leptin and blood lipids before treatment (P> 0.05). (2) After using risperidone, The FBG levels, Fins levels and IRI increased and ISI decreased significantly, there were significant differences (P <0.01). After using ziprasidone, the Fins level and IRI increased, and ISI decreased significantly (P <0.01), while the FBG levels were no significant changes (P>0.05). (3) After using risperidone, TC, TG, LDL-C and Lep levels increased significantly (P <0.01), while HDL-C levels were no significant differences (P> 0.05). After using ziprasidone, TG, LDL-C and Lep levels were significantly increased (P <0.01), and TC and HDL-C levels had no significant differences (P>0.05). (4) IL-2, IL-6 and TNF-a levels before and after risperidone and ziprasidone’s treatment were all higher than the control groups, there were significant differences (P <0.01). After using risperidone and ziprasidone, IL-2, IL-6 and TNF-a levels decreased significantly (P <0.01).
Conclusion: (1) Antipsychotic drugs affected the glucose, lipid and some hormone levels, which could increase the risk of cardiovascular diseases, hypertension and diabetes. The possible mechanisms need to be confirmed by further studies. (2) Schizophrenia patients had cytokine-mediated immune dysfunction. It showed that the change of plasma cytokines levels maybe related to the pathogenesis of schizophrenia. (3) Risperidone and ziprasidone could regulate the plasma cytokines levels, and educed immunosuppression function, which might be one of the mechanisms of the pharmacological effects. (4) Schizophrenia patients still had immune function dysfunction in remission, which suggested that the dysfunction may be a genetic trait of schizophrenia.
引文
[1]中国精神卫生工作规划(2002-2010年)[J].上海精神医学,2003,15(2):125-128.
[2] Henderson DC, Cagllero E, Gray C, et al. Clozapine diabetes mellitus, weight gain and lipid abnormalities:a five-year naturalistic study [J]. Am J Psychiatry, 2000, 157(6):975-981.
[3] Melksson K, Hulting AL. Antipsychotic drugs can affect hormone balance. Weight gain, blood lipid disturbances and diabetes are important [J]. Lakartidninger, 2001,98(48):5462-5464.
[4] Hagg S, Joelsson L, Mjorndal T. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. Clin Psy,1998,59:294
[5] Spivak B, Lamschtein C, Talmon Y, et al. The impact of clozapine treatment on serum lipids in chronic schizophrenic patients [J]. Clin Neuropharmacol, 1999,22(2):98-101.
[6] Melkersson K, Hulting AL. Insulin and leptin levels in patients with schizophrenia or related psychoses - a comparison between different antipsychotic agents. Psychopharmacology, 2001,154:205-212
[7]王从杰,张志,孙静,等.血清瘦素与抗精神病药源性肥胖及糖尿病的相关性研究[J].上海精神医学,2004,16(6):336-339.
[8] Allison DB,Casey DE. Antipsyehotic-induced weight gain: areview of the literature[J]. Am J Psyehiatry 2001:62[supp17]:22-23
[9]敢秋明,谢良平.精神疾病与糖尿病共病分析.临床精神医学杂志,2000,l0(5):272
[10]徐韬园主编.现代精神医学.上海:上海医科大学出版社,2000,274
[11]谢启文主编.现代神经内分泌学.上海:上海医科大学出版社,1999,75
[12] Leadbelter R. Clozpine-induced weight gain. Am J Psychiatry, 1992,149(l):68
[13]石夏明,成秀芳,姚尚武等.氯氮平与抗精神病药物对精神分裂症血塘影响的比较.四川精神卫生,2000,13(3):174
[14] Gaulin BD. Clozapine associated elevation in serum triglycerides. Am J Psychiatry. 1999,156(8):1270
[15]陈振华,黄永兰,赵厚裕.氯氮平所致体重增加与精神症状相关性研究.中国神经精神病杂志,1997,23(2):80
[16] Newcomer JW, Haupt DW, Fucetola R, et al. Abnormalities in glucose regulations during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry, 2002, 59: 337-345.
[17] Sirota P,Schild K,Elizur A,et al. Increased interleukin-1 and interleukin-3 like activity in schizophrenic patients[J]. Prog neuro-psychopharmacol Biol Psychiatry,1995,19(1):75-83
[18] Rapaport MH,Mcallister CG,Pickar D,et al. CSF IL-1andIL-2 inmedicated schizophrenic patients and normal voluneers[J]. Sehizophr-Res, 1997 ,25(2):123-129
[19] Barak V,Barak Y,Levine J,et al. Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of Schizophrenic patients[J]. J Basic Clin physiol Pharmacol,1995,6(l):61-69
[20] Katila H,Hanninen K,Hurme Mganguli R,et al.Polymorphisms of the interleukin-1 gene complex in Schizophrenia[J]. Md psychiatry , 1999 ,4(2):179-181
[21]Song C,Lin Ah,ect.Immunosupporessive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist.Schizophrenia-Res.2000. Apr 7;42(2):157-64.
[22] Maes M. In vivo immunomodulatory effects of clozapine in schizophrenia, schizo-Res.1997.Aug 29;26(2-3):221-5.
[23] Plata Salaman CR. Immunoregulators in the nervous system. Neurosci-Biobehav-Res 1991, 15:185-215.
[24] Muller N. Role of the cytokine network in the CNS and psychiatric disorders.Nerbenarzt.1997.Jan:68(1):11-20.
[25] Licinio J, Seibyl JP,Altemu M,et al. Elevated CSF levels Of interleukin-2 in neuroleptic一free schizophrenic patients[J]. Am J Psyehiatry,1993,150(9),1408.
[26] Muller N, Empl M. Neuroleptic treatment increase soluble IL-2 receptors and decreases soluble IL-6 receptors in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 1997,247(6)308-13.
[27] Rothermunt M, Arolt V.Immunological dysfunction in schizophrenia:a systematic approach.Neuropsychobiology.1998.37(4):186-193.
[28] Zalcman-s. Interleukin-2 and IL-6 induce behavioral-acting effects in mice Brain Res. 1998.Nov 16; 811(1-2):111-121.
[29] C.G.McCallister,D.P.Van Kammen,ect. Increases in CSF levels of interleukin-2: effects of recurrence of psychosis snd medication status,Am.J.Psychiatry 1995. 152:129-1297.
[30] Akiyama K. Serum levels of soluble IL-2 recepter alpha,IL-6 and IL-1 recepter antagonist in schizophrenia before and during neuroleptic administration[J]. Schizophr Res. 1999,37(1):97-106
[31] Naudin J, Mege L, etc. Elevated circulating levels of IL-6 in schizophrenia. Schizophr-Res.1996.20:269-273.
[32] Steve Zalcman,interleukin-6 increases sensitivity to the locomotor- stimulating effects of amphetamine in rats.Brain-Res.1999.847:276-283.
[33] Monteleone P,Fabrazzo M,Tortorella A,et al. Plasma levels of interleukin-6 and tumor necrosis factor alpha in chronic schizophrenia: effects of clozapine treatment[J]. psychiatry Res. 1997,71(1):11-17
[34] Maes M,Bosmans E,et al. Interleukin-2 and interleukin-6 in schizophrenia and mania,effect of neuroleptics and mood stabilizers[J]. Psychiatry Res,1995,29:141-152
[35] Parrillo Jp.Pathogenetic mechanisms of septic shock.N Engl J Med.1993.328:1471-7.
[36] Rothwell,N.J,Hopkins,S.J.Cytokines and the nervous system 2: Activation andmechanisms of action.Trends Neurosci.1995.18:130-135.
[37] Merrill,J.E.Tumor necrosis factor alpha,interleukin-1 and related cytokines in brain development:normal and pathological,Neurosci.1992.14:1-10.
[38]Weinberger,D.R,Lipska,B.K,1995.cortical maldevelopment, antipsychotic drugs and schizophrenia: a search for common ground. Schizophre-Res.16:87-110.
[39] Naudin J. A differential role of interleukin-6 and tumor necrosis factor alpha in schizophrenia. Schizophre-Res. 1997.26(2-3):227-33.
[40] Haack M, Hinze Selch D. Plasma levels of cytokines and soluble cytokin receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res. 1999, 33(5)407-18.
[41] C1trome L,Jaffe A,Levine J,et al. Relationship between antipsychotic medication treatment and new cases of diabetes among Psychiatric impatients[J]. Psychiatr Sery, 2004, 55:1006-1013.
[42] Jin H.,Meyer J. M., Jeste D.V. Phenomenology of and risk factors for new-onset diabetes mellitus and diabetic ketoacidosis associated with atypical antipsychotics: An analysis of 45 published cases[J]. Ann Clin Psychiatry, 2002, 14:59-64.
[43] Koller E. Doraiswamy PM. Cross, JT. Risperidone-associated diabetes. Presented at the 85th Annual Meeting of the Endocrine Society[R]. Philadelphia, PA,2002:19-22.
[44] Smith H, Kenney-Herbert J, Knowles L. Clozapine-induced diabetic ketoaeidesis [J]. Aust New Zialand J Psychiatry, 1999,33(1):120-122.
[45] Templeman LA, Reynolds GP, Arranz B, et al. Polymorphism of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis[J]. Pharmacogenet Genomies, 2005, 15(4):195-200.
[46] Atmaca M, Kuloglu M, Tezean E, et al. Serum leptin and triglyceride levels in patients on treatment with antipsychotics [J]. J Clin Psychiatry, 2003, 64(5):598-603.
[1] World Health Organization. WHO health report 2001-Mental health: new understanding,new hope. World Health OrganiZation,2001:33-34.
[2]中国精神卫生工作规划(2002一2010年)[J].上海精神医学,2003,15(2):125-128
[3] Allison DB , Casey DE. Antipsyehotic-induced weight gain: areview of the literature[J]. Am J Psyehiatry 2001:62[supp17]:22-23
[4] Melksson K, Hulting AL. Antipsychotic drugs can affect hormone balance. Weight gain, blood lipid disturbances and diabetes are important [J]. Lakartidninger, 2001,98(48):5462-5464.
[5] Spivak B, Lamschtein C, Talmon Y, et al. The impact of clozapine treatment on serum lipids in chronic schizophrenic patients [J]. Clin Neuropharmacol, 1999,22(2):98-101.
[6] Henderson DC, Cagllero E, Gray C, et al. Clozapine diabetes mellitus, weight gain and lipid abnormalities:a five-year naturalistic study [J]. Am J Psychiatry, 2000,157(6):975-981.
[7] Hagg S, Joelsson L, Mjorndal T. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. Clin Psy,1998,59:294
[8]敢秋明,谢良平.精神疾病与糖尿病共病分析.临床精神医学杂志,2000,l0(5):272
[9]徐韬园主编.现代精神医学.上海:上海医科大学出版社,2000,274
[10]谢启文主编.现代神经内分泌学.上海:上海医科大学出版社,1999,75
[11] Leadbelter R. Clozpine-induced weight gain. Am J Psychiatry, 1992,149(l):68
[12]石夏明,成秀芳,姚尚武等.氯氮平与抗精神病药物对精神分裂症血塘影响的比较.四川精神卫生,2000,13(3):174
[13] Gaulin BD. Clozapine associated elevation in serum triglycerides. Am J Psychiatry. 1999,156(8):1270
[14]陈振华,黄永兰,赵厚裕.氯氮平所致体重增加与精神症状相关性研究.中国神经精神病杂志,1997,23(2):80
[15] Melkersson K, Hulting AL. Insulin and leptin levels in patients with schizophrenia or related psychoses - a comparison between different antipsychotic agents. Psychopharmacology, 2001,154:205-212
[16] Newcomer JW, Haupt DW, Fucetola R, et al. Abnormalities in glucose regulations during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry, 2002, 59: 337-345.
[17] Atmaca M, Kuloglu M, Tezcan E,et al. Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics [J]. J Clin Psychiatry, 2003,64(5):598-604.
[18]杨斌,王有德,张兰.氯氮平、利司培酮和氟哌啶醇对首发精神分裂症患者血浆瘦素的影响[J].第四军医大学学报,2004,25(14):1323-1325.
[19] Baptista T,Lacruz A,Angeles F,et al. Endocrine and metabolic abnormalities involved in obesity associated with typical antipsychotic drug administration. harmacopschiatry, 2001, 34(6): 223-231
[20] Sirota P,Schild K,Elizur A,et al. Increased interleukin-1 and interleukin-3 like activity in schizophrenic patients[J]. Prog neuro-psychopharmacol Biol Psychiatry,1995,19(1):75-83
[21] Rapaport MH,Mcallister CG,Pickar D,et al. CSF IL-1andIL-2 inmedicated schizophrenic patients and normal voluneers[J]. Sehizophr-Res, 1997 ,25(2):123-129
[22] Barak V,Barak Y,Levine J,et al. Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of Schizophrenic patients[J]. J Basic Clin physiol Pharmacol,1995,6(l):61-69
[23] Katila H,Hanninen K,Hurme Mganguli R,et al.Polymorphisms of the interleukin-1 gene complex in Schizophrenia[J]. Md psychiatry,1999,4(2):179-181
[24] Song C,Lin Ah,ect.Immunosupporessive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist.Schizophrenia-Res 2000.Apr 7;42(2):157-64.
[25] Maes M.In vivo immunomodulatory effects of clozapine in schizophrenia,schizo-Res.1997.Aug 29;26(2-3):221-5.
[26] Plata Salaman CR,Immunoregulators in the nervous system.Neurosci-Biobehav-Res 1991;15:185-215.
[27] Muller N,Role of the cytokine network in the CNS and psychiatric disorders. Nerbenarzt.1997.Jan:68(1):11-20.
[28] Katila H. polymorphisms of the IL-1 gene complex in schizophrenia. Mol-Psychiatry. 1999.Mar;4(2):179-81.
[29] Licinio J, Seibyl JP,Altemu M,et al. Elevated CSF levels Of interleukin-2 in neuroleptic一free schizophrenic patients[J]. Am J Psyehiatry,1993,150(9),1408
[30] Muller N, Empl M. Neuroleptic treatment increase soluble IL-2 receptors and decreases soluble IL-6 receptors in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 1997,247(6)308-13.
[31] Rothermunt M, Arolt V.Immunological dysfunction in schizophrenia:a systematic approach.Neuropsychobiology.1998.37(4):186-93.
[32] Zalcman-s,interleukin-2 and IL-6 induce behavioral-acting effects in mice Brain Res. 1998.Nov 16;811(1-2):111-21.
[33] C.G.McCallister,D.P.Van Kammen,ect.Increases in CSF levels of interleukin-2: effects of recurrence of psychosis snd medication status,Am.J.Psychiatry 1995. 152:129-1297.
[34] Akiyama K. Serum levels of soluble IL-2 recepter alpha,IL-6 and IL-1 recepter antagonist in schizophrenia before and during neuroleptic administration[J]. Schizophr Res. 1999,37(1):97-106
[35] J.Naudin,J.L.Mege,etc.Elevated circulating levels of IL-6 in schizophrenia. Schizophr-Res.1996.20:269-273.
[36] Steve Zalcman. Interleukin-6 increases sensitivity to the locomotor- stimulating effects of amphetamine in rats.Brain-Res.1999.847:276-283.
[37] Monteleone P,Fabrazzo M,Tortorella A,et al. Plasma levels of interleukin-6 and tumor necrosis factor alpha in chronic schizophrenia: effects of clozapine treatment[J]. psychiatry Res. 1997,71(1):11-17
[38] Maes M,Bosmans E,et al. Interleukin-2 and interleukin-6 in schizophrenia and mania,effect of neuroleptics and mood stabilizers[J]. Psychiatry Res,1995,29:141-152
[39] Parrillo Jp. Pathogenetic mechanisms of septic shock.N Engl J Med.1993.328: 1471-1477.
[40] Rothwell,N.J, Hopkins,S.J. Cytokines and the nervous system 2: Activation and mechanisms of action.Trends Neurosci.1995.18:130-135.
[41] Merrill,J.E.Tumor necrosis factor alpha,interleukin-1 and related cytokines in brain development:normal and pathological,Neurosci.1992.14:1-10.
[42] Weinberger,D.R,Lipska,B.K,1995.cortical maldevelopment,antipsychotic drugs and schizophrenia:a search for common ground.Schizophre-Res.16:87-110.
[43] Monteleone.P.Fsbrazzo.M.Plasma levels of interleukin-6 and tumor necrosis factor alpha in chronic schizophrenia:effects of Clozapine treatment. Psychiatry Res. 1997.71:11-17.
[44].Naudin J. A differential role of interleukin-6 and tumor necrosis factor alpha in schizophrenia.Schizophre-Res.1997.26(2-3):227-33.
[45] Haack M, Hinze Selch D. Plasma levels of cytokines and soluble cytokin receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res. 1999. Sep-Oct:33(5)407-18.
[2] Henderson DC, Cagllero E, Gray C, et al. Clozapine diabetes mellitus, weight gain and lipid abnormalities:a five-year naturalistic study [J]. Am J Psychiatry, 2000, 157(6):975-981.
[3] Melksson K, Hulting AL. Antipsychotic drugs can affect hormone balance. Weight gain, blood lipid disturbances and diabetes are important [J]. Lakartidninger, 2001,98(48):5462-5464.
[4] Hagg S, Joelsson L, Mjorndal T. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. Clin Psy,1998,59:294
[5] Spivak B, Lamschtein C, Talmon Y, et al. The impact of clozapine treatment on serum lipids in chronic schizophrenic patients [J]. Clin Neuropharmacol, 1999,22(2):98-101.
[6] Melkersson K, Hulting AL. Insulin and leptin levels in patients with schizophrenia or related psychoses - a comparison between different antipsychotic agents. Psychopharmacology, 2001,154:205-212
[7]王从杰,张志,孙静,等.血清瘦素与抗精神病药源性肥胖及糖尿病的相关性研究[J].上海精神医学,2004,16(6):336-339.
[8] Allison DB,Casey DE. Antipsyehotic-induced weight gain: areview of the literature[J]. Am J Psyehiatry 2001:62[supp17]:22-23
[9]敢秋明,谢良平.精神疾病与糖尿病共病分析.临床精神医学杂志,2000,l0(5):272
[10]徐韬园主编.现代精神医学.上海:上海医科大学出版社,2000,274
[11]谢启文主编.现代神经内分泌学.上海:上海医科大学出版社,1999,75
[12] Leadbelter R. Clozpine-induced weight gain. Am J Psychiatry, 1992,149(l):68
[13]石夏明,成秀芳,姚尚武等.氯氮平与抗精神病药物对精神分裂症血塘影响的比较.四川精神卫生,2000,13(3):174
[14] Gaulin BD. Clozapine associated elevation in serum triglycerides. Am J Psychiatry. 1999,156(8):1270
[15]陈振华,黄永兰,赵厚裕.氯氮平所致体重增加与精神症状相关性研究.中国神经精神病杂志,1997,23(2):80
[16] Newcomer JW, Haupt DW, Fucetola R, et al. Abnormalities in glucose regulations during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry, 2002, 59: 337-345.
[17] Sirota P,Schild K,Elizur A,et al. Increased interleukin-1 and interleukin-3 like activity in schizophrenic patients[J]. Prog neuro-psychopharmacol Biol Psychiatry,1995,19(1):75-83
[18] Rapaport MH,Mcallister CG,Pickar D,et al. CSF IL-1andIL-2 inmedicated schizophrenic patients and normal voluneers[J]. Sehizophr-Res, 1997 ,25(2):123-129
[19] Barak V,Barak Y,Levine J,et al. Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of Schizophrenic patients[J]. J Basic Clin physiol Pharmacol,1995,6(l):61-69
[20] Katila H,Hanninen K,Hurme Mganguli R,et al.Polymorphisms of the interleukin-1 gene complex in Schizophrenia[J]. Md psychiatry , 1999 ,4(2):179-181
[21]Song C,Lin Ah,ect.Immunosupporessive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist.Schizophrenia-Res.2000. Apr 7;42(2):157-64.
[22] Maes M. In vivo immunomodulatory effects of clozapine in schizophrenia, schizo-Res.1997.Aug 29;26(2-3):221-5.
[23] Plata Salaman CR. Immunoregulators in the nervous system. Neurosci-Biobehav-Res 1991, 15:185-215.
[24] Muller N. Role of the cytokine network in the CNS and psychiatric disorders.Nerbenarzt.1997.Jan:68(1):11-20.
[25] Licinio J, Seibyl JP,Altemu M,et al. Elevated CSF levels Of interleukin-2 in neuroleptic一free schizophrenic patients[J]. Am J Psyehiatry,1993,150(9),1408.
[26] Muller N, Empl M. Neuroleptic treatment increase soluble IL-2 receptors and decreases soluble IL-6 receptors in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 1997,247(6)308-13.
[27] Rothermunt M, Arolt V.Immunological dysfunction in schizophrenia:a systematic approach.Neuropsychobiology.1998.37(4):186-193.
[28] Zalcman-s. Interleukin-2 and IL-6 induce behavioral-acting effects in mice Brain Res. 1998.Nov 16; 811(1-2):111-121.
[29] C.G.McCallister,D.P.Van Kammen,ect. Increases in CSF levels of interleukin-2: effects of recurrence of psychosis snd medication status,Am.J.Psychiatry 1995. 152:129-1297.
[30] Akiyama K. Serum levels of soluble IL-2 recepter alpha,IL-6 and IL-1 recepter antagonist in schizophrenia before and during neuroleptic administration[J]. Schizophr Res. 1999,37(1):97-106
[31] Naudin J, Mege L, etc. Elevated circulating levels of IL-6 in schizophrenia. Schizophr-Res.1996.20:269-273.
[32] Steve Zalcman,interleukin-6 increases sensitivity to the locomotor- stimulating effects of amphetamine in rats.Brain-Res.1999.847:276-283.
[33] Monteleone P,Fabrazzo M,Tortorella A,et al. Plasma levels of interleukin-6 and tumor necrosis factor alpha in chronic schizophrenia: effects of clozapine treatment[J]. psychiatry Res. 1997,71(1):11-17
[34] Maes M,Bosmans E,et al. Interleukin-2 and interleukin-6 in schizophrenia and mania,effect of neuroleptics and mood stabilizers[J]. Psychiatry Res,1995,29:141-152
[35] Parrillo Jp.Pathogenetic mechanisms of septic shock.N Engl J Med.1993.328:1471-7.
[36] Rothwell,N.J,Hopkins,S.J.Cytokines and the nervous system 2: Activation andmechanisms of action.Trends Neurosci.1995.18:130-135.
[37] Merrill,J.E.Tumor necrosis factor alpha,interleukin-1 and related cytokines in brain development:normal and pathological,Neurosci.1992.14:1-10.
[38]Weinberger,D.R,Lipska,B.K,1995.cortical maldevelopment, antipsychotic drugs and schizophrenia: a search for common ground. Schizophre-Res.16:87-110.
[39] Naudin J. A differential role of interleukin-6 and tumor necrosis factor alpha in schizophrenia. Schizophre-Res. 1997.26(2-3):227-33.
[40] Haack M, Hinze Selch D. Plasma levels of cytokines and soluble cytokin receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res. 1999, 33(5)407-18.
[41] C1trome L,Jaffe A,Levine J,et al. Relationship between antipsychotic medication treatment and new cases of diabetes among Psychiatric impatients[J]. Psychiatr Sery, 2004, 55:1006-1013.
[42] Jin H.,Meyer J. M., Jeste D.V. Phenomenology of and risk factors for new-onset diabetes mellitus and diabetic ketoacidosis associated with atypical antipsychotics: An analysis of 45 published cases[J]. Ann Clin Psychiatry, 2002, 14:59-64.
[43] Koller E. Doraiswamy PM. Cross, JT. Risperidone-associated diabetes. Presented at the 85th Annual Meeting of the Endocrine Society[R]. Philadelphia, PA,2002:19-22.
[44] Smith H, Kenney-Herbert J, Knowles L. Clozapine-induced diabetic ketoaeidesis [J]. Aust New Zialand J Psychiatry, 1999,33(1):120-122.
[45] Templeman LA, Reynolds GP, Arranz B, et al. Polymorphism of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis[J]. Pharmacogenet Genomies, 2005, 15(4):195-200.
[46] Atmaca M, Kuloglu M, Tezean E, et al. Serum leptin and triglyceride levels in patients on treatment with antipsychotics [J]. J Clin Psychiatry, 2003, 64(5):598-603.
[1] World Health Organization. WHO health report 2001-Mental health: new understanding,new hope. World Health OrganiZation,2001:33-34.
[2]中国精神卫生工作规划(2002一2010年)[J].上海精神医学,2003,15(2):125-128
[3] Allison DB , Casey DE. Antipsyehotic-induced weight gain: areview of the literature[J]. Am J Psyehiatry 2001:62[supp17]:22-23
[4] Melksson K, Hulting AL. Antipsychotic drugs can affect hormone balance. Weight gain, blood lipid disturbances and diabetes are important [J]. Lakartidninger, 2001,98(48):5462-5464.
[5] Spivak B, Lamschtein C, Talmon Y, et al. The impact of clozapine treatment on serum lipids in chronic schizophrenic patients [J]. Clin Neuropharmacol, 1999,22(2):98-101.
[6] Henderson DC, Cagllero E, Gray C, et al. Clozapine diabetes mellitus, weight gain and lipid abnormalities:a five-year naturalistic study [J]. Am J Psychiatry, 2000,157(6):975-981.
[7] Hagg S, Joelsson L, Mjorndal T. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. Clin Psy,1998,59:294
[8]敢秋明,谢良平.精神疾病与糖尿病共病分析.临床精神医学杂志,2000,l0(5):272
[9]徐韬园主编.现代精神医学.上海:上海医科大学出版社,2000,274
[10]谢启文主编.现代神经内分泌学.上海:上海医科大学出版社,1999,75
[11] Leadbelter R. Clozpine-induced weight gain. Am J Psychiatry, 1992,149(l):68
[12]石夏明,成秀芳,姚尚武等.氯氮平与抗精神病药物对精神分裂症血塘影响的比较.四川精神卫生,2000,13(3):174
[13] Gaulin BD. Clozapine associated elevation in serum triglycerides. Am J Psychiatry. 1999,156(8):1270
[14]陈振华,黄永兰,赵厚裕.氯氮平所致体重增加与精神症状相关性研究.中国神经精神病杂志,1997,23(2):80
[15] Melkersson K, Hulting AL. Insulin and leptin levels in patients with schizophrenia or related psychoses - a comparison between different antipsychotic agents. Psychopharmacology, 2001,154:205-212
[16] Newcomer JW, Haupt DW, Fucetola R, et al. Abnormalities in glucose regulations during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry, 2002, 59: 337-345.
[17] Atmaca M, Kuloglu M, Tezcan E,et al. Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics [J]. J Clin Psychiatry, 2003,64(5):598-604.
[18]杨斌,王有德,张兰.氯氮平、利司培酮和氟哌啶醇对首发精神分裂症患者血浆瘦素的影响[J].第四军医大学学报,2004,25(14):1323-1325.
[19] Baptista T,Lacruz A,Angeles F,et al. Endocrine and metabolic abnormalities involved in obesity associated with typical antipsychotic drug administration. harmacopschiatry, 2001, 34(6): 223-231
[20] Sirota P,Schild K,Elizur A,et al. Increased interleukin-1 and interleukin-3 like activity in schizophrenic patients[J]. Prog neuro-psychopharmacol Biol Psychiatry,1995,19(1):75-83
[21] Rapaport MH,Mcallister CG,Pickar D,et al. CSF IL-1andIL-2 inmedicated schizophrenic patients and normal voluneers[J]. Sehizophr-Res, 1997 ,25(2):123-129
[22] Barak V,Barak Y,Levine J,et al. Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of Schizophrenic patients[J]. J Basic Clin physiol Pharmacol,1995,6(l):61-69
[23] Katila H,Hanninen K,Hurme Mganguli R,et al.Polymorphisms of the interleukin-1 gene complex in Schizophrenia[J]. Md psychiatry,1999,4(2):179-181
[24] Song C,Lin Ah,ect.Immunosupporessive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist.Schizophrenia-Res 2000.Apr 7;42(2):157-64.
[25] Maes M.In vivo immunomodulatory effects of clozapine in schizophrenia,schizo-Res.1997.Aug 29;26(2-3):221-5.
[26] Plata Salaman CR,Immunoregulators in the nervous system.Neurosci-Biobehav-Res 1991;15:185-215.
[27] Muller N,Role of the cytokine network in the CNS and psychiatric disorders. Nerbenarzt.1997.Jan:68(1):11-20.
[28] Katila H. polymorphisms of the IL-1 gene complex in schizophrenia. Mol-Psychiatry. 1999.Mar;4(2):179-81.
[29] Licinio J, Seibyl JP,Altemu M,et al. Elevated CSF levels Of interleukin-2 in neuroleptic一free schizophrenic patients[J]. Am J Psyehiatry,1993,150(9),1408
[30] Muller N, Empl M. Neuroleptic treatment increase soluble IL-2 receptors and decreases soluble IL-6 receptors in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 1997,247(6)308-13.
[31] Rothermunt M, Arolt V.Immunological dysfunction in schizophrenia:a systematic approach.Neuropsychobiology.1998.37(4):186-93.
[32] Zalcman-s,interleukin-2 and IL-6 induce behavioral-acting effects in mice Brain Res. 1998.Nov 16;811(1-2):111-21.
[33] C.G.McCallister,D.P.Van Kammen,ect.Increases in CSF levels of interleukin-2: effects of recurrence of psychosis snd medication status,Am.J.Psychiatry 1995. 152:129-1297.
[34] Akiyama K. Serum levels of soluble IL-2 recepter alpha,IL-6 and IL-1 recepter antagonist in schizophrenia before and during neuroleptic administration[J]. Schizophr Res. 1999,37(1):97-106
[35] J.Naudin,J.L.Mege,etc.Elevated circulating levels of IL-6 in schizophrenia. Schizophr-Res.1996.20:269-273.
[36] Steve Zalcman. Interleukin-6 increases sensitivity to the locomotor- stimulating effects of amphetamine in rats.Brain-Res.1999.847:276-283.
[37] Monteleone P,Fabrazzo M,Tortorella A,et al. Plasma levels of interleukin-6 and tumor necrosis factor alpha in chronic schizophrenia: effects of clozapine treatment[J]. psychiatry Res. 1997,71(1):11-17
[38] Maes M,Bosmans E,et al. Interleukin-2 and interleukin-6 in schizophrenia and mania,effect of neuroleptics and mood stabilizers[J]. Psychiatry Res,1995,29:141-152
[39] Parrillo Jp. Pathogenetic mechanisms of septic shock.N Engl J Med.1993.328: 1471-1477.
[40] Rothwell,N.J, Hopkins,S.J. Cytokines and the nervous system 2: Activation and mechanisms of action.Trends Neurosci.1995.18:130-135.
[41] Merrill,J.E.Tumor necrosis factor alpha,interleukin-1 and related cytokines in brain development:normal and pathological,Neurosci.1992.14:1-10.
[42] Weinberger,D.R,Lipska,B.K,1995.cortical maldevelopment,antipsychotic drugs and schizophrenia:a search for common ground.Schizophre-Res.16:87-110.
[43] Monteleone.P.Fsbrazzo.M.Plasma levels of interleukin-6 and tumor necrosis factor alpha in chronic schizophrenia:effects of Clozapine treatment. Psychiatry Res. 1997.71:11-17.
[44].Naudin J. A differential role of interleukin-6 and tumor necrosis factor alpha in schizophrenia.Schizophre-Res.1997.26(2-3):227-33.
[45] Haack M, Hinze Selch D. Plasma levels of cytokines and soluble cytokin receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res. 1999. Sep-Oct:33(5)407-18.