抗精神病药物所致体重增加与多巴胺D2受体基因多态性和治疗效应的关联分析

目的　探讨抗精神病药物 (APS)所致体重增加与多巴胺D2 受体 (DRD2 )基因TaqIA多态性和治疗效应之间有无相关。方法　采用PCR RFLP方法分析 117例首发精神分裂症患者DRD2 基因TaqIA多态性 ,APS(氯丙嗪或利培酮 )单药治疗 10周 ,测定患者治疗前后体重和体重指数 (BMI) ,用阳性和阴性症状量表 (PANSS)评定患者治疗前后精神症状 ,并分析BMI变化值与基因型和PANSS减分率的相关性。结果　治疗后患者平均体重变化 (3 15± 3 47)kg或基础体重的(5 6 9± 6 15 ) % ,体重变化的范围为 - 7kg～ 12kg或 - 7 78%～ 32 43% ;患者年龄和基础BMI明显影响BMI变化值 ,差异有显著性 (P =0 0 3)和非常显著性 (P =0 0 0 0 1) ;A1等位基因和PANSS减分率对BMI变化值的影响差异均无显著性 (P >0 0 5 )。结论　DRD2 基因TaqIA多态性不可能是APS所致精神分裂症体重增加的主要遗传因素 ;体重增加不是APS临床治疗效果的指标。     

细胞色素P450酶1A2、2D6与多巴胺D2受体基因多态性对奥氮平治疗精神分裂症PANSS减分率的影响

目的 研究细胞色素P450酶(cytochromeSP450, CYP)1A2、2D6以及多巴胺D2(dopamine receptorSD2, DRD2)受体的基因多态性对奥氮平治疗精神分裂症阳性和阴性症状量表(positive and negative syndrome scale, PANSS)减分率的影响及其程度。方法 入组只用奥氮平治疗的精神分裂症住院患者178例,评定治疗前以及治疗4周后的PANSS量表得分,计算减分率。同时,收集血液,测定CYP1A2*1F、CYP2D6*10、DRD2 -141C Ins/Del、DRD2 -241 A>G、DRD2 Taq1A位点的基因多态性。通过方差分析,比较各基因型PANSS减分率的差异;通过多元线性回归分析,得出减分率的回归方程,并计算决定系数。结果 PANSS减分率在CYP1A2*1F(CC：65.68±11.22,CA：55.59±15.40,AA：43.75±15.20)、CYP2D6*10(CC：44.36±16.67,CT：51.78±17.81,TT：56.14±17.13)、DRD2 -141C Ins/Del(Ins/Ins：55.11±17.39,Ins/Del：39.16±14.28)和DRD2 -241 A>G(AA：45.47±17.52,GA：61.82±10.55,GG：75.43±17.71)不同基因型之间均有统计学显著差异(均P<0.01),而DRD2 Taq1A位点的基因型间PANSS减分率差异无统计学意义(P>0.05)。 PANSS减分率＝58.041-10.703╳CYP1A2*1F+4.272╳CYP2D6*10-11.921╳DRD2 -141C Ins/Del +13.443╳DRD2 -241 A>G(决定系数R_²＝0.517,P<0.05)。结论 CYP1A2*1F、CYP2D6*10、DRD2-141 C Ins/Del、DRD2-241A>G位点基因多态性影响奥氮平治疗精神分裂症疗效,但只解释了减分率的51.7%,有待纳入更多的影响因素进行分析。     

精神分裂症患者多巴胺D2受体和多巴胺转运体基因表达水平与临床症状的相关性分析

目的研究精神分裂症患者外周血淋巴细胞多巴胺D2受体(DRD2)、多巴胺转运体(DAT)基因表达与临床症状之间的关系。方法采用荧光定量PCR检测治疗前后不同时间段患者外周血淋巴细胞DRD2、DAT mRNA的表达量,并在不同治疗时间段对患者进行PANSS评分,分析两者之间的相关性。结果治疗组与对照组在治疗前、第1周、第3周、第5周后PANSS总分、DRD2 mRNA表达及DAT mRNA的表达总体存在差异。治疗组在接受治疗3、5周后PANSS总分、DRD2 mRNA表达及DAT mRNA表达低于治疗前(P<0.05);DRD2基因表达与PANSS总分和阳性症状呈正相关(r值分别为0.416与0.567,P<0.01),DAT基因表达与PANSS总分和精神病理症状呈负相关(r值分别为-0.447与-0.508,P<0.01)。结论 DRD2、DAT基因的表达水平与临床症状之间存在相关性。     

多巴胺D_1受体-48 A/G基因多态性与脑出血的相关性研究

目的:探讨多巴胺D1受体基因-48 A/G[DRD1(-48 A/G)]多态性与中国湖南地区汉族人群脑出血发病的相关性。方法:筛选121例脑出血患者及115例年龄、性别相匹配的正常体检人群,应用聚合酶链式反应(PCR)-限制性片段长度多态性(RFLP)方法测定DRD1(-48 A/G)基因的多态性。结果:在中国湖南汉族人群中,DRD1(-48 A/G)基因型分布为AA 63.2%,AG 31.3%和GG 5.5%,等位基因A和G频率分别为78.9%和21.1%。DRD1(-48 A/G)三种基因型频率及两种等位基因频率在脑出血组和正常对照组分布差异无显著性(P>0.05)。脑出血组中高血压和非高血压两亚组间DRD1(-48 A/G)基因型频率分布差异无显著性(P>0.05),且它们分别和对照组比较DRD1(-48A/G)基因型频率分布差异无显著性(P>0.05)。Log istic回归调整了脑出血环境因素的影响后,DRD1(-48 A/G)基因多态性与脑出血的关系仍无统计学意义(P>0.05)。结论:DRD1(-48 A/G)基因多态性可能与中国湖南地区汉族人群脑出血无关。     

精神分裂症患者的多药耐药基因多态性与利培酮的疗效及不良反应的相关性

目的观察中国汉族精神分裂症患者多药耐药基因多态性与利培酮临床疗效和不良反应的相关性。方法入选192例符合DSM-IV精神分裂症诊断的患者,给予利培酮每天2～6 mg,治疗8周。在治疗基线、第4,8周,用阳性与阴性症状量表(PANSS)评估临床疗效。用聚合酶链式反应(PCR)和限制酶切法,检测患者rs1045642和rs2235048的基因多态性。不良反应观察指标为锥体外系不良反应(EPS)发生率、各实验室检查值的变化。结果 PANSS减分率在rs1045642和rs2235048不同基因型及等位基因间分布差异无统计学意义(P>0.05);药物不良反应和EPS的发生率在各基因型和等位基因间差异无统计学意义(P>0.05)。结论多药耐药基因rs1045642和rs2235048的基因多态性与利培酮的疗效和安全性可能无关联。     

二甲双胍减轻奥氮平治疗首发精神分裂症所致体重增加的疗效观察

目的探讨二甲双胍减轻奥氮平治疗首发精神分裂症所致体重增加的疗效与安全性。方法将64例首发的精神分裂症病人随机分为奥氮平合并二甲双胍组(研究组)和单用奥氮平组(对照组),分别在入组前和入组后的4、8、12周末各测定身高、体重、血压、空腹血糖(FBG)、血总胆固醇(TC)、血甘油三脂(TG),比较各时点的体重、体重指数(BMI)、空腹血糖、血总胆固醇、血甘油三脂减去入组前的体重、体质指数和空腹血糖血总胆固醇、血甘油三脂所得的差值。同时采用阳性与阴性症状量表(PANSS)、不良反应量表(TESS)分别评定疗效和不良反应。结果两组在治疗12周后的体重、体重指数、空腹血糖和血甘油三脂的变化有显著性差异,研究组明显低于对照组,差异有统计学意义(P<0.05),而PANSS评分、TESS评分两组差异无统计学意义(P>0.05)。结论二甲双胍能安全、有效地减轻长期服用奥氮平所致的体重增加。     

奥氮平对体重、肝功能、血糖、血胆固醇水平的影响

目的:回顾性调查奥氮平对患者体重、肝功能、血糖、血胆固醇水平的影响。方法:87例奥氮平治疗至少6周的精神分裂症患者,比较治疗前后体重、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(T-Bil)、血糖(GLU)、血胆固醇(CHO)的变化。结果:治疗6周后患者体重明显增加,平均增加2.2kg,与基线相比具有显著性差异(P<0.001)。治疗后ALT,AST和CHO水平也明显高于基线值,具有显著性差异(P<0.01)。但治疗后T-Bil水平降低,与基线相比差异具有显著性(P=0.026)。治疗前后血糖无显著差异(P=0.882)。体重的变化与年龄和基线体重呈负相关,相关系数分别为-0.33和-0.32(P=0.003和0.004)。ALT及AST的变化与治疗6周后的体重变化呈正相关,相关系数分别为0.34和0.40(P=0.024和0.007)。结论:奥氮平引起患者体重增加、无症状性转氨酶升高和CHO升高。     

奥氮平致体质量增加与HTR2C受体基因-759C/T多态性的关联研究

目的探讨奥氮平在治疗精神分裂症患者过程中出现的体质量增加与5-羟色胺2C(HTR2C)受体基因启动子区-759C/T(rs3813929)单核苷酸多态性的关系。方法选择首发精神分裂症患者181例,测定其接受奥氮平单药治疗前及治疗12周后的体质量、血糖、三酰甘油、胆固醇指标,计算体质量指数(BMI),采用聚合酶链反应-限制性片段长度多态(PCR-RFLP)技术检测各患者HTR2C受体基因-759C/T位点的半合子型或基因型,分析BMI的变化与-759C/T的相关性。结果 181例患者经奥氮平治疗后平均体质量增加(4.33±4.15)kg或超过基础体质量的(7.1±6.3)%,体质量变化范围为0～22 kg或0%～38%,平均BMI变化值为(1.52±1.48)kg.(m2)-1。92例男患者突变型半合子(-759T)频率为13.0%,89例女患者突变型纯合子(-759T/T)频率为0%,杂合子频率(-759C/T)为29.2%。-759C/C野生型纯合子女患者和-759C半合子男患者经奥氮平治疗后体质量增加更明显。结论 HTR2C受体基因启动子-759C/T单核苷酸多态性与奥氮平治疗导致患者体质量增加相关联,携带-759T等位基因可能是限制体质量增加的保护因子。     

低碳水化合物饮食结合利拉鲁肽治疗2型糖尿病合并肥胖症的临床疗效

目的 探讨低碳水化合物饮食结合利拉鲁肽治疗2型糖尿病合并肥胖症的临床疗效.方法 将入组的60例2型糖尿病合并肥胖症患者随机分为2组,A组给予低碳水化合物饮食+利拉鲁肽干预治疗;B组给予低碳水化合物饮食,比较治疗后两组患者的体重、体重指数(BMI)、腰围、血脂(TC、TG、LDL、HDL)、脂肪率、内脏脂肪、空腹血糖(FBG)、餐后2小时血糖(2hPBG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)等指标的变化情况.结果 A组治疗后体重降至(79.00±11.95) kg,腰围降至(97.48±10.78) cm,BMI降至(27.72±3.10) kg/m2,TC、TG、LDL分别降至[(4.42±0.86)、(1.57±0.54)、(3.12±0.61)mmol/L],FBG、2hPBG分别为[(5.42±0.86)、(7.26±0.84)mmol/L],HbA1c降至(5.93±0.63)％,FINS为(13.72±4.20)μIU/nl;B组治疗后体重降至(81.04±8.78)kg,腰围降至(99.32±8.08) cm,BMI降至(28.84±2.35) kg/m2,TC、TG、LDL分别降至[(4.74±0.72)、(1.72±1.09)、(3.25±0.84) mmol/L],FBG、2hPBG分别为[(5.84±0.79)、(7.99±1.04) mmol/L],HbAIc降至(6.11±0.87)％,FINS为(15.71±3.27)μIU/ml,A、B组两组治疗后比较,体重、BMI、腰围、TC、TG、LDL、脂肪率、内脏脂肪FBC、2hPBG、HbA1c、FINS、HOMA-IR比较差异有统计学意义(P＜0.05),但HDL干预后改善不显著(P＞0.05).结论 低碳水化合物饮食结合利拉鲁肽可明显降低患者体重,改善肥胖相关指标、降低血糖、改善胰岛素抵抗,且效果优于单纯低碳水化合物饮食.     

UGT和FMOs基因多态性对奥氮平临床疗效的关联分析

目的 探讨尿苷二磷酸葡糖醛酸基转移酶1A4(UGT1A4)、尿苷二磷酸葡糖醛酸基转移酶2B10(UGT2B10)、黄素单氧化酶1(FMO1)、黄素单氧化酶3(FMO3)基因多态性与奥氮平临床疗效之间的关系。方法 104例精神分裂症患者均给予奥氮平5～20 mg·d^-1治疗6周。通过阳性和阴性症状量表(PANSS)来评估奥氮平治疗精神分裂症的疗效,按照PANSS减分率≥50%和<50%分为有效组和无效组。用Sequenom MassArray系统基因分型方法对患者检测UGT1A4(rs2011425)、UGT2B10(rs61750900)、FMO1(rs12720462)、FMO1(rs7877)、FMO3(rs2266780)基因多态性,用秩和检验分析基因多态性与临床疗效的关系;比较治疗前后患者体质量、尿素(Urea)、尿酸(UA)、谷丙转氨酶(GPT)、谷草转氨酶(GOT)、三酰甘油(TG)、血糖(GLU)、泌乳素(PRL)的变化。结果 治疗后,有效组81例,无效组23例。治疗前和治疗后第6周PANSS总分分别为80.25±7.01、42.18±2.92...     

The effect of long-term antipsychotic treatment on the body weight of patients suffering from chronic schizophrenia: clozapine versus classical antipsychotic agents.

The aim of this study was to evaluate the effect of long-term clozapine treatment on body weight changes in neuroleptic-resistant chronic schizophrenic patients and to compare it with that of classical antipsychotic agents. The body mass index (BMI) of 96 neuroleptic-resistant chronic schizophrenic patients was calculated before the beginning and after long-term (mean +/- SD 1.7 +/- 1.3 years) clozapine treatment. These data were compared to the BMI of 98 chronic schizophrenic patients maintained on classical antipsychotic agents for a similar duration (mean +/- SD 1.9 +/- 1.6 years). A significant elevation in BMI was detected in both groups during these periods (P < 0.0001 versus baseline, for both groups). The change in BMI (delta BMI) was similar in both groups (P < 0.9). We conclude that the increase in body weight caused by long-term (> 6 months) clozapine treatment is comparable to that obtained following long-term classical antipsychotic agents treatment.     

Effects of quetiapine and haloperidol on body mass index and glycaemic control: a long-term, randomized, controlled trial

The topic of antipsychotic-induced weight-gain and its relationship to glucose metabolism is under-studied. We evaluated the long-term effects of a new-generation antipsychotic, quetiapine and a conventional antipsychotic, haloperidol on body mass index (BMI) and glycaemic control in patients with schizophrenia previously treated with conventional antipsychotics. Forty-five clinically stable patients with schizophrenia participated in this randomized, investigator-blinded, parallel-group comparison of flexible doses of quetiapine and haloperidol treatment over 52 wk. Primary outcome measures were change from baseline in BMI and glycosylated haemoglobin (HBA1c) levels. There were no between-group differences at any of the time-points for BMI (F = 1.90, p = 0.1) and HBA1c (F = 1.17, p = 0.3) values, and there were no significant changes in BMI from baseline for either group. HBA1c levels decreased significantly at end-point for the haloperidol group (-1.5%, p = 0.04), but not for the quetiapine group (-0.3%, p = 0.5). Although the sample was not generally obese (mean baseline BMI 25.5 +/- 6.3 kg/m2), a large proportion exhibited evidence of abnormal glycaemic control prior to randomization (mean HBA1c 6.7 +/- 1.9%), with 48% having values that were at least mildly elevated (HBA1c > 6.1%) and 19% markedly elevated (HBA1c > 7%). The number of subjects with elevated HBA1c values decreased from baseline in both the haloperidol and quetiapine treatment groups. These findings suggest that switching treatment from a conventional antipsychotic to quetiapine is not associated with weight gain or worsening of glycaemic control, even in the long term. The study also highlights the high incidence of unrecognized glucose dysregulation in patients with schizophrenia receiving conventional antipsychotic treatment.     

Predictors of antipsychotic-induced weight gain in first-episode psychosis: conclusions from a randomized, double-blind, controlled prospective study of olanzapine, risperidone, and haloperidol

BACKGROUND: Antipsychotic-induced weight gain is one of the most distressing adverse effects being observed in recent times. Most studies have been limited by several confounders. AIM: To evaluate the predictors of antipsychotic-induced weight gain in drug-naive patients with first-episode psychosis treated with olanzapine, risperidone, or haloperidol and compare them with a healthy matched control group. METHODS: Newly diagnosed patients with first-episode schizophrenia treated with antipsychotic medication-olanzapine, risperidone, or haloperidol-and matched healthy controls were followed for 6 weeks. Body mass index (BMI), waist circumference, and weight changes and proportions of subjects with more than 7% weight gain were calculated. The predictors of weight gain were explored. RESULTS: Ninety-nine patients with first-episode schizophrenia and 51 healthy controls were examined. Waist circumference (r = -0.25; P < 0.01) and weight (r = -0.24; P < 0.01) at baseline in addition to the disease process (P < 0.001) as well as antipsychotic use (P < 0.001) were associated with greater increases in weight and BMI. Olanzapine (77%) had greater clinically significant weight gain as compared with risperidone (63%) and haloperidol (22%). Lower BMI at baseline and a diagnosis of undifferentiated schizophrenia were associated with antipsychotic-induced weight gain. CONCLUSIONS: The results confirm clinically significant and substantial weight gain induced by antipsychotic treatment in drug-naive patients with first-episode schizophrenia and identify several risk factors for weight gain such as lower BMI scores, use of olanzapine, and a diagnosis of undifferentiated schizophrenia.     

Long-term changes in weight and plasma lipids during maintenance treatment with ziprasidone.

To measure the long-term changes in weight and plasma lipids after switching antipsychotic treatment to ziprasidone, three 52-week, open-label extension studies of ziprasidone in outpatients (N=185) with schizophrenia or schizoaffective disorder successfully completing one of three, 6-week switch studies were carried out. Pre-switch treatment consisted of risperidone (n=43), olanzapine (n=71), or conventional antipsychotic agents (n=71). The maximum length of exposure to ziprasidone was 58 weeks. Nonfasting total cholesterol and triglyceride levels were obtained at baseline and at weeks 6, 19, 32, 45, and 58. Weight was measured at baseline and during each follow-up visit; height was recorded at baseline for the purpose of body mass index (BMI) calculation. Efficacy measures included the Positive and Negative Syndrome Scale and Clinical Global Impression-Severity scale which were obtained at baseline and major follow-up points. Clinically significant sustained improvements in weight, BMI, total cholesterol, and triglyceride levels were observed among patients switched to ziprasidone from risperidone or olanzapine. Switching from conventional antipsychotics was not associated with significant changes in weight and lipid parameters. Mean reductions in weight from baseline to study endpoint were 9.8 kg (p<0.001) and 6.9 kg (p<0.005) for patients previously treated with olanzapine and risperidone, respectively. These findings demonstrate that switching from risperidone or olanzapine to ziprasidone is associated with sustained, clinically significant improvements in weight and plasma lipids.     

Early predictors of substantial weight gain in bipolar patients treated with olanzapine

To determine predictors of substantial weight gain (SWG) during treatment of bipolar disorder with olanzapine, data were pooled from 4 long-term randomized, multicenter studies in patients with bipolar mania or mixed mania (N = 948 at initiation of olanzapine). SWG was defined as gaining 5 kg or 7% of initial weight in 30 +/- 2 weeks. Logistic regression estimated odds ratios associated with early weight gain and baseline risk factors for predicting SWG. A classification system to identify patients at risk for SWG was constructed by recursive data partitioning. Baseline characteristics significantly associated with SWG included younger age, nonwhite ethnicity, lower body mass index (BMI), nonrapid cycling, and psychotic features. Weight gain of 2 or more kg in the first 3 weeks of therapy predicted SWG by 30 weeks (sensitivity = 57%; specificity = 71%). A classification system with thresholds for early weight gain, baseline BMI, and ethnicity further improved SWG predictability (sensitivity = 79%; specificity = 70%). In conclusion, patients with bipolar disorder who gained 2 to 3 kg during the first 3 weeks of treatment with olanzapine, SWG was predicted after 30 weeks of treatment. Patients with less pronounced early weight gain might still be at risk for later SWG if they have close to normal BMI (< or =27 kg/m) at treatment initiation.     

Some dopaminergic genes polymorphisms are not associated with response to antipsychotic drugs in schizophrenic patients

BackgroundTherapeutic effects of all clinically used antipsychotics are related to the reduction of dopaminergic transmission in the limbic system. The aim of present study was two-fold. First, efficacy of atypical drugs (ziprasidone and olanzapine) against schizophrenia symptoms was compared to that offered by a typical antipsychotic medication, perazine. Second, associations between some dopaminergic genes polymorphisms and therapeutic response to antipsychotics were assessed in the same group of schizophrenia patients.MethodsOne hundred ninety one Caucasian patients admitted with exacerbation of paranoid schizophrenia were genotyped for polymorphisms of the DRD2 [the ins/del -141C (rs1799732) and exon 8 (rs 71653615)], DRD2/ANKK1 Taq IA (rs 1800497), DAT1 (the 40 bp VNTR), COMT (rs 4680), and MAOA gene (the 30 bp VNTR in promoter). The patients were randomly assigned to the treatment with perazine, olanzapine or ziprasidone givenasmonotherapy for 3 months. Treatment efficacy was measured from baseline (T0) to T1 (14 days) and T2 (3 months). A retention rate was also assessed at T1 and T2.ResultsThe three antipsychotics did not differ in terms of reduction of the PANSS score or retention rate at the follow-up. There was no interaction between the investigated polymorphisms and response to the antipsychotic treatment.ConclusionsThe present results suggest that: i) there are no major differences in short-term efficacy or effectiveness of atypical (olanzapine, ziprasidone) and typical (perazine) antipsychotic drugs; ii) the studied polymorphisms are not primarily involved in treatment response to antipsychotics in schizophrenia patients.     

A retrospective analysis of the short-term effects of olanzapine and quetiapine on weight and body mass index in children and adolescents

STUDY OBJECTIVE: To evaluate changes in short-term weight and body mass index (BMI) in children and adolescents receiving olanzapine or quetiapine. DESIGN: Retrospective study Setting. Austin State Hospital, Austin, Texas. PATIENTS: One hundred three patients younger than 18 years who were admitted to the hospital and treated with olanzapine (50 patients) or quetiapine (53) for at least 2 weeks between October 1, 1997, and October 31, 2001. INTERVENTION: Treatment with at least 2 weeks of olanzapine or quetiapine. MEASUREMENTS AND MAIN RESULTS: Mean+/-SD daily doses of olandzapine and quetiapine were 13.9+/-7.3 and 510.9+/-250.3 mg, respectively Weight and height were measured at baseline and 14 or more days after baseline. Body mass index (in kg/m2) was calculated using serial measurements of weight and height, and change in BMI was determined. The olanzapine group gained an average of 3.8 kg, the quetiapine group 0.03 kg. In the olanzapine group, BMI increased by an average of 1.3 kg/m2; in the quetiapine group, BMI decreased by 0.2 kg/m2. After controlling for baseline differences, significant between-group differences in weight and BMI change were noted. Change in BMI correlated significantly with baseline BMI in quetiapine-treated girls. CONCLUSION: Patients taking olanzapine had greater increases in weight and BMI than those taking quetiapine. Further studies are necessary to determine the relative risk, magnitude, and time course of antipsychotic-induced weight gain in this patient population.     

Fluoxetine treatment for weight reduction in steroid-induced obesity: a pilot study in myasthenia gravis patients.

To evaluate the weight reducing effect of fluoxetine on steroid-induced obesity, we conducted an open, clinical intervention study of 20-40 mg/day fluoxetine, 24 weeks duration. Thirteen myasthenia gravis, overweight, long-term steroid-treated patients [age: 31-59, body mass index (BMI): 29-54 kg/m2] were included. Measurements of weight, BMI, and routine laboratory tests, were undertaken at baseline, 12 and 24 weeks. Muscle strength and fatigue parameters were assessed at 4 week intervals. Fluoxetine induced mean weight loss of 7.7+/-2.6 kg and 10.3+/-2.9 kg over a period of 12 and 24 weeks respectively, (P<0.05). Mean BMI decreased from 35.8 to 32.2 kg/m2 over the study period. No significant side effects were noted. We conclude that patients suffering from steroid-induced obesity respond to fluoxetine treatment of overweight by significant weight loss.     

Association of clozapine-induced weight gain with a polymorphism in the leptin promoter region in patients with chronic schizophrenia in a Chinese population

Weight gain is a problem commonly encountered with antipsychotic treatment and has become more apparent with increasing use of the newer atypical antipsychotics. The adipocyte-derived hormone, leptin, has been associated with body weight and energy homeostasis, and abnormal regulation of leptin could play a role in weight gain induced by antipsychotics. We investigated whether a leptin gene promoter variant affected weight gain after long-term treatment with clozapine in chronic schizophrenia. Leptin G2548A polymorphism was genotyped in 102 Chinese Han inpatients with chronic schizophrenia treated with clozapine. Weight gains, expressed as change in body mass index (BMI), were monitored after long-term clozapine treatment. We found a significant relationship between the 3 leptin G/A genotypes and mean BMI gain (F(2,99) = 3.35, P = 0.039, r(2) = 0.09). Moreover, genotype had a strong effect on BMI gain in male (P = 0.004, r(2) = 0.16), but not in female patients (P > 0.05). Thus, variation in the leptin gene may be a risk factor for weight gain in male patients with schizophrenia on long-term clozapine treatment.     

Addition of memantine to antipsychotic treatment in schizophrenia inpatients with residual symptoms: A preliminary study.

BACKGROUND: Schizophrenia is comprised of several debilitating symptoms. Antipsychotics offer an effective treatment for positive symptoms, while the negative signs and cognitive deficits are usually treatment-resistant. It was suggested that glutamate dysregulation may be involved in the neuropathology of schizophrenia, mainly through NMDA dysfunction. We hypothesized that addition of memantine, a weak non-selective NMDA receptor antagonist approved for dementia, to antipsychotics would improve the clinical status of un-remitted schizophrenia patients, notably the negative signs and cognitive deficits. METHODS: Seven schizophrenia patients, were included in a six-week open-label study, with weekly increasing dosage (5, 10, 15, 20 mg) of memantine added to their on-going antipsychotic treatment. RESULTS: We found a significant improvement of the PANSS score (baseline 116.28+/-21.9 vs. 97.86+/-24.48 after six weeks, t=5.98, p<0.001) with the most prominent improvement (21%) in negative signs sub-scale (baseline 40+/-6.38 vs. 31.71+/-7.76 after six weeks, t=5.87, p<0.001). Cognitive status, measured with the Neurobehavioral Cognitive Examination (NCSE) and Clock Drawing Test (CDT) showed no improvement. CONCLUSION: Memantine addition to antipsychotic treatment, in schizophrenia patients might improve their clinical status, primarily the negative signs, but not their cognitive deficits. Further research is needed to replicate these observations.