齐拉西酮与阿立哌唑对血清催乳素及体重的影响

目的 探讨精神分裂症患者应用齐拉西酮与阿立哌唑治疗前后对血清催乳素（PRL）及体重的影响.方法 对60例未曾治疗或停药3个月的精神分裂症患者随机给予齐拉西酮与阿立哌唑规范治疗,于治疗前及治疗第8周末用化学发光法测查患者PRL水平并监测体重,进行对比分析.结果 服用齐拉西酮、阿立哌唑患者治疗前后血清催乳素及体重无明显变化（P＞0.05）;同组间比较,治疗前后血清催乳素及体重亦无显著差异（P＞0.05）,性别对血清催乳素无明显影响（P＞0.05）.结论 齐拉西酮与阿立哌唑对患者血清催乳素及体重无升高作用,是较安全的新型抗精神病药物.     

Short- and long-term effects of antipsychotic drug treatment on weight gain and H1 receptor expression

The present study investigated body weight gain, food intake, open-field activity and brain histamine H1 receptor mRNA and protein expression in rats treated with three types of antipsychotics. Rats were divided into eight groups and treated with aripiprazole (2.25 mg/kg/day), olanzapine (1.5 mg/kg/day), haloperidol (0.3 mg/kg/day) or vehicle (as control) for 1 or 12 weeks. Administration of olanzapine for 1 week led to a threefold increase in body weight gain and a 35% increase in fat deposits compared to controls (p<0.05). In the 12-week olanzapine treatment group, accumulative food intake was significantly higher in the first 7 weeks of treatment compared to controls (p<0.018), while body weight gain was significantly greater in the first 8 weeks compared to controls (p<0.045). Using in situ hybridization, we found that olanzapine treatment, but not aripiprazole or haloperidol treatment, significantly reduced H1 receptor mRNA expression in the arcuate hypothalamic nucleus (Arc: −18%, p=0.006, 1 week; −20%, p=0.008, 12 weeks) and ventromedial hypothalamic nucleus (VMH: −22%, p=0.006, 1 week; −19%, p=0.042, 12 weeks) compared to controls. The quantitative autoradiography data showed a reduction in VMH H1 receptor binding density after 1 (−12%, p=0.040) and 12 (−10%, p=0.094) weeks of olanzapine treatment. There were significant negative correlations between the levels of H1 receptor mRNA expression, and body weight gain and energy efficiency in the Arc and VMH after 1- and 12-week antipsychotic treatments in all groups. In addition, H1 receptor mRNA expression in the Arc showed a significant negative correlation with food intake and fat mass in all groups. Furthermore, there were negative correlations between H1 receptor binding density in the VMH and total fat mass and body weight gain after 1 week of antipsychotic treatment. The present study suggests that downregulated VMH and Arc H1 receptor expression may be a key factor contributing to olanzapine-induced obesity.     

齐拉西酮对首发与慢性女性精神分裂症甲状腺激素水平的影响

目的探讨齐拉西酮对女性精神分裂症住院患者甲状腺激素的影响及首发与慢性患者（病程≥5年）的差异。方法随机抽取女性精神分裂症患者64例（首发组30例,慢性组34例）,均用齐拉西酮治疗,于治疗前和治疗8周末测定甲状腺激素。对照组为30例正常健康女性。结果治疗前慢性组T3、TSH低于对照组,有显著性差异（P〈0.05）。齐拉西酮治疗后慢性组T4水平明显下降,而TSH水平则明显升高,且有显著性差异（P〈0.05）;首发组治疗前后无显著性差异。结论慢性精神分裂症患者存在甲状腺功能异常。齐拉西酮治疗可降低慢性精神分裂症患者血清甲状腺素T4水平,升高促甲状腺素（TSH）水平;对三碘甲腺原氨酸T3、游离三碘甲腺原氨酸FT3、游离甲状腺素FT4无明显影响;首发与慢性患者无显著性差异。     

齐拉西酮对首发精神分裂症患者认知功能的影响

目的探讨齐拉西酮和氯丙嗪对首发精神分裂症患者认知功能的影响。方法将符合入组标准的首发精神分裂症86例随机分为齐拉西酮组与氯丙嗪组,分别进行8周的系统治疗,使用阳性与阴性症状量表(PANSS)评定疗效,治疗时出现的症状量表(TESS)评定不良反应,韦氏成人智力量表(WAISR)、韦氏记忆量表(WMS)和威斯康星卡片分类测验(WCST)评定治疗前后患者认知功能的改变。结果治疗后86例PAN-SS总分明显下降,两组之间差异无显著性(均P>0.05);齐拉西酮不良反应较氯丙嗪少,治疗前两组患者均有认知功能损害,治疗8周后,齐拉西酮组患者的认知功能有明显提高,而氯丙嗪组则无明显改善。结论齐拉西酮治疗精神分裂症疗效与氯丙嗪相当,且不良反应小,在改善认知功能方面优于氯丙嗪。     

Behavioural actions of prolactin locally applied into the hippocampus of adult female rats

Summary The probable behavioural effects of rat prolactin (rPRL) locally applied into the ventral hippocampus (HPC) were studied in cycling female rats. Three experiments were performed examining the behavioural responses of rats subjected to three different situations: (i) Exploratory activity in an enriched holeboard (ii) exploratory activity under conflicting situation and (iii) escape behaviours in a forced swimming test. Behavioural parameters studied were: underground and object-directed exploration and locomotion (Experiment 1); latency time and exploration behaviours (Experiment 2); swimming time and escape behaviours (Experiment 3). In Experiment 1 results showed that rPRL decreased the underground exploration and also locomotion but increased the object-directed exploration and had no effect on non-ambulatory activity. In Experiment 2 results showed that treatment of rPRL increased the latency time but did not modify the exploratory activity. In Experiment 3 results showed that rPRL augmented the swimming time and one of two parameters (frequency of immersions intents) of the escape behaviour. Results are interpreted as local actions of PRL on hippocampal neuron affecting expression of behaviours of rats depending on the stressful conditions of the environment.     

利培酮、氯丙嗪致腹部脂肪沉积及其与血瘦素相关性的研究

目的　探讨首次治疗精神分裂症患者经抗精神病药 (APS)治疗致腹部脂肪沉积及其与血瘦素和胰岛素水平的关系。方法　于利培酮 [平均 (4 8± 0 9)mg/d]、氯丙嗪 [平均 (480± 12 2 )mg/d]单药治疗 10周前后 ,采用放射免疫法测定 4 5例精神分裂症患者 (患者组 )血浆瘦素和胰岛素水平 ,测量身高、体重 ,计算体重指数 (BMI)和腰围 /臀围比值 ,采用核磁共振测定其中 39例患者腹部脂肪分布 ,并与 38名健康对照者 (对照组 )比较 (其中 2 2名测定腹部脂肪分布 )。结果　 (1)治疗前 ,患者组各项体重指标和血浆瘦素、胰岛素水平与对照组比较 ,差异均无显著性 (P >0 0 5 )。 (2 )治疗后 ,患者组的各项体重指标均较治疗前显著增加 (P <0 0 0 1) ;血瘦素亦明显增加 [治疗前为 (7 6± 7 8) μg/L ,治疗后为 (2 1 9± 17 2 ) μg/L];(3)腹部皮下脂肪变化率与治疗前后血瘦素呈显著负相关 (r =- 0 4 97和 - 0 5 0 0 ,均P =0 0 0 3)。结论　氯丙嗪和利培酮治疗精神分裂症患者可引起腹部脂肪沉积伴瘦素增高 ;提示瘦素系统对APS所致腹部脂肪增加虽有一定控制能力 ,但已处于失代偿状态。     

Massage-like stroking influences plasma levels of gastrointestinal hormones, including insulin, and increases weight gain in male rats

The aim of the present study was to investigate the effects of repeated massage-like stroking on plasma levels of some gastrointestinal hormones, insulin included, glucose and weight gain. For this purpose, male rats were exposed to stroking on the ventral side of the abdomen for 3 or 14 times. The treatments were given every second day. Control rats were picked up at the same time but received no stroking. Body weight was measured regularly. Rats were decapitated 10 min after the last treatment. Hormone levels were radioimmunoassayed and glucose was measured by spectrophotometry. In rats exposed to 3 sessions of massage-like stroking plasma levels of insulin (p<0.05) and somatostatin (p<0.01) were significantly decreased 10 min after the last treatment. After 14 treatments of massage-like stroking, decreased plasma levels of insulin (p<0.01) and gastrin (p<0.01) as well as increased glucose levels (p<0.01) were observed 10 min after the last treatment. In addition, weight gain was significantly increased (ANOVA p<0.0001) in rats exposed to 14 treatments. In conclusion, repeated massage-like stroking decreased plasma levels of gastrin, insulin and somatostatin, increased plasma levels of glucose and promoted weight gain. The effects were influenced by the number of treatments.     

齐拉西酮与利培酮治疗精神分裂症对照研究的Meta分析

目的评价齐拉西酮与利培酮治疗精神分裂症的疗效和安全性以及与对照组之间的差异。方法应用循证医学方法对符合标准的15项研究进行分析，评价齐拉西酮与与利培酮治疗精神分裂症的有效率、痊愈率以及副作用的差异。结果齐拉西酮组与利培酮治疗精神分裂症的有效率以及痊愈率均没有显著性差异（P〉0．05），但是利培酮的副作用，特别是EPS显著高于齐拉西酮（P〈0．01）。结论齐拉西酮和利培酮都是治疗精神分裂症良好的药物，但是它们的副作用存在差异。     

Differential effects of ziprasidone and haloperidol on immobilization stress-induced mRNA BDNF expression in the hippocampus and neocortex of rats

Recent in vivo and in vitro experiments have demonstrated that second-generation antipsychotic drugs (SGAs) might have neuroprotective effects. Ziprasidone is a SGA that is efficacious in the treatment of schizophrenia. In this study, we sought to analyze the effects of ziprasidone on the expression of the neuroprotective protein brain-derived neurotrophic factor (BDNF) in the rat hippocampus and neocortex, with or without immobilization stress. The effect of ziprasidone (2.5 mg/kg) on the expression of BDNF mRNA was determined by in situ hybridization in tissue sections from the rat hippocampus and neocortex. Haloperidol (1.0 mg/kg) was used for comparison. Haloperidol strongly decreased the expression of BDNF mRNA in both the hippocampal and cortical regions, with or without immobilization stress (p < 0.01). In contrast, the administration of ziprasidone significantly attenuated the immobilization stress-induced decrease in BDNF mRNA expression in the rat hippocampus and neocortex (p < 0.01). Ziprasidone exhibited differential effects on BDNF mRNA expression in the rat hippocampus and neocortex. These results suggest that ziprasidone might have a neuroprotective effect by recovering stress-induced decreases in BDNF mRNA expression.     

Serum BDNF levels and weight gain in schizophrenic patients on long-term treatment with antipsychotics

Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates food intake, metabolism, and increases in body weight. Reports have also shown that serum BDNF is altered in schizophrenic patients treated with antipsychotics. This study aimed to determine if there was a relationship between BDNF and antipsychotic-induced weight gain in patients with chronic schizophrenia. Serum BDNF was measured in 124 schizophrenia patients chronically treated with clozapine (n = 57), risperidone (n = 23) or typical antipsychotics (n = 44) and 50 healthy control subjects. To further assess group differences in serum BDNF, additional analyses were performed in a subset of patients and controls individually matched for body mass index (BMI). BDNF levels were lower in patients with schizophrenia than normal controls. However, this difference was not present when controlling for current BMI. In the individually BMI-matched sample, no differences in serum BDNF levels were observed in schizophrenic patients compared to BMI-matched healthy controls. BDNF levels negatively correlated with BMI gain in female but not in male patients when gender was considered. Antipsychotic class exerted differential effects over BDNF levels and BMI gain. Our findings suggest that decreased BDNF levels may be associated with weight gain in female schizophrenic patients on long-term antipsychotic treatment.     

二甲双胍联合行为干预治疗抗精神病药所致体质量增加及糖代谢紊乱的研究

目的验证二甲双胍与行为干预单一或联合治疗抗精神病药所致的体质量增加及糖代谢紊乱的疗效。方法将抗精神病药所致体质量增加≥10％的128例精神分裂症患者随机分为四组：二甲双胍（750mg／d）联合行为于预组（以下简称A组，32例）；二甲双胍（750mg／d）组（以下简称B组，32例）；行为干预联合安慰剂组（以下简称C组，32例）；安慰剂对照组（以下简称D组，32例）；治疗观察期均为12周。四组患者于治疗前及治疗后第4，8，12周末测定空腹血糖、胰岛素、身高、体质量、腰围，计算体质量指数（BMI）及胰岛素抵抗指数（IRI）并进行比较。结果（1）A、B、C组患者治疗后的体质量、BMI、空腹血糖、空腹胰岛素及IRI均明显低于治疗前（P〈0．05）；D组患者的体质量、BMI、腰围、空腹胰岛素、IRI治疗后均明显高于治疗前（P〈0，05）。（2）治疗4周末，A组与B组体质量、BMI的下降程度相同，但均明显高于C组。治疗12周末，体质量、BMI的下降程度以A组最高，其次为B组和C组。治疗后各时点，A组与B组的空腹胰岛素、IRI的下降程度相同，均明显高于C组。结论二甲双胍与行为干预单一或联合治疗均能有效减轻抗精神病药所致的体质量增加及胰岛素抵抗，二甲双胍联合行为干预的疗效最好。单用二甲双胍与二甲双胍联合行为干预治疗缓解抗精神病药引起的胰岛素抵抗的疗效相同。     

Comparative effects of the antipsychotics sulpiride or risperidone in rats. I: bodyweight,food intake,body composition,hormones and glucose tolerance

Obesity and related metabolic disorders are important side effects of some antipsychotic drugs (APs). The currently available animal model of AP-induced bodyweight gain (BWG) in rats is based on administration of sulpiride (SUL). However, this model has important limitations. For example, SUL is a pure dopamine antagonist, whereas most APs in current clinical use interact with multiple neurotransmitter receptors involved in food intake (FI) and metabolism regulation. Therefore, we evaluated the effects of risperidone (RIS, 0.125, 0.25 or 0.5 mg/kg during 16 days) on BWG and FI in male and female rats. Comparison between RIS (0.5 mg/kg), SUL (20 mg/kg) and vehicle (VEH) during 12 days was also conducted in females. In male rats, RIS did not significantly affect BWG, FI, glucose tolerance or leptin levels, even though prolactin and corticosterone were significantly elevated. In females, both APs significantly increased BWG and FI, but the effect was stronger with SUL. The BWG was significantly associated with an increase in body fat. Serum leptin levels were increased only in SUL-treated rats. The area under the curve for glucose (AUGC) was significantly lower in the SUL group, but it was similar for insulin in all treatment groups. The area under the curve for insulin (AUIC) and BWG positively correlated only in the RIS group. Prolactin and corticosterone were significantly increased by both APs. Serum estradiol levels were significantly increased by RIS but not by SUL, but progesterone levels were similar in both groups. The observed positive correlation between BWG and the AUIC during RIS administration suggests that this agent may represent a better model of AP administration in humans. The animal model of RIS-induced obesity in rats might be improved by testing other doses, route of administration and type of diet.     

Reversible effects of antiepileptic drugs on reproductive endocrine function in men and women with epilepsy--a prospective randomized double-blind withdrawal study

PURPOSE: Epilepsy, antiepileptic drugs (AEDs), and reproductive endocrine function have complex interactions. In this study, we wanted to investigate the effects of AEDs on reproductive endocrine function after withdrawal of AEDs and look for reversible endocrine effects. METHODS: The study was prospective, randomized, and double-blinded. A total of 160 patients were included and randomized to withdrawal or not and 150 (80 females, 53%) patients went through the intervention and was included in the study for 12 months. Complete serum samples from before and 4 months after completed withdrawal/no withdrawal were obtained from 130 patients (63 females, 48%). RESULTS: The main finding was that reversible endocrine changes in sex steroid hormone levels could be observed in both sexes after withdrawal of AEDs. For CBZ, which was the drug used by the majority of the patients, withdrawal led to significant increases in serum testosterone concentrations and free androgen index (FAI) in both men (n = 19) and women (n = 19). Mean differences in change in FAI between the withdrawal group and nonwithdrawal group were in men 17.49 (CI 10.16-24.81, p 相似文献   

Predictors of rapid high weight gain in schizophrenia: Longitudinal analysis of the French FACE-SZ cohort

Metabolic syndrome (MetS) is highly prevalent in schizophrenia. However very little is known about the time course of MetS and its components. The few longitudinal studies that have been carried out had small sample sizes and a short follow-up. The aim of our study was to evaluate the prevalence of MetS and its components, at baseline and one year later, and to investigate predictors of weight gain (WG) in a cohort of individuals with schizophrenia. We followed 167 schizophrenia patients from the FACE-SZ cohort for one year. The Structured Clinical Interview for DSM-IV (SCID) was used to confirm the diagnosis of schizophrenia. Data on socio-demographic and clinical characteristics, antipsychotic treatment, and comorbidities were collected, and a blood sample was drawn.We found that the prevalence of MetS increased from 21.0% to 26.6% after one year. Patients with baseline depressive symptoms had a 4.5-fold higher risk of WG at the one-year follow-up (p = 0.02) than those without depressive symptoms, after adjusting for confounding variables. WG also correlated with high levels of metabolic parameters and peripheral inflammation. These findings highlight the need to systematically diagnose depression in Schizophrenia. Future studies should determine whether specific pharmacological and non-pharmacological interventions for depression in SZ subjects are effective in preventing rapid high weight gain.     

氯丙嗪与齐拉西酮对精神分裂症患者生活质量影响的对照研究

目的探讨药物对精神分裂症患者生活质量的长期影响。方法采用生活满意度量袁（LSR）、社会功能缺陷筛选量表（SDSS）、阳性症状和阴性症状评定量表（PANSS）、副反应量表（TESS）对山东省临沂市精神卫生中心符合中国精神障碍分类与诊断标准的使用氯丙嗪或齐拉西酮治疗获临床治愈或显著进步的门诊、住院精神分裂症患者128例进行评定。结果齐拉西酮组两次TESS评分低于氯丙嗪组,差异有显著性（P〈0．01）,齐拉西酮组患者LSR量表各因子分愿望与已实现、热情与冷漠、自我评价、心境差异有显著性（t=2．455～3．341,P〈0．05）高于氯丙嗪组;氯丙嗪治疗组患者家庭外社会活动、家庭内活动过少、婚姻职能、社会退缩、对外界兴趣缺陷程度显著高于齐拉西酮治疗组患者（t=2．869～3．181,P均〈0．01）,个人生活自理、责任心和计划性的缺陷程度高于齐拉西酮治疗组（t=2．153,2．30,P均〈0．05）。多元逐步回归分析显示生活满意度与药物副反应、阴性症状得分成负相关（r=-0．238,-0．211）。结论与氯丙嗪相比服齐拉西酮的精神分裂症患者的生活质量较好,患者主客观生活满意度与药物副反应呈负相关。     

Role of dietary fat in calorie intake and weight gain

This paper reviews the literature on the role of dietary fat in calorie intake and body weight gain in humans and laboratory animals. An overview of 40 animal studies which compared growth on high-fat (HF) and high-carbohydrate (HC) solid/powdered diets indicated that the HF diet elicited greater weight gain in 33 out of 40 studies. Enhanced growth on the HF diet was often, but not exclusively, attributable to greater caloric intake. Additional evidence for the growth-enhancing effect of HF diets emerges from "diet option" and "supermarket" feeding studies in rats, and experimental and epidemiological studies in humans. Three principal factors that contribute to the different responses to HF and HC diets are (a) caloric density, (b) sensory properties and palatability, and (c) postabsorptive processing. It is concluded that both calorie intake and metabolic energy expenditure are biased towards weight gain when a HF diet is consumed, and that the high caloric density of high-fat diets plays a primary role in weight gain. Humans may be biologically predisposed to gain weight when a HF diet is consumed.     

The effect of therapeutically induced weight gain on plasma leptin levels in patients with anorexia nervosa

Previously it was shown that hyperleptinemia ensues from the therapeutically induced weight gain in patients with anorexia nervosa (AN). However, not all studies have been able to confirm this finding. To further investigate leptin secretion during weight gain in AN and potential functional implications serum leptin levels, body mass index (BMI),% body fat, fT3, fT4 and TSH of 18 adolescent AN patients (BMI at admission: 14.4+/-1.2) were examined four times during 11 weeks of re-feeding and compared to 18 weight stable controls. Additionally, serum leptin levels, BMI and % body fat were determined in patients reaching target weight after 11-20 weeks (mean 14.3+/-3) of inpatient re-feeding. At admission patients showed lower lg10 leptin levels (P=0.000) and BMI (P=0.000) than controls. At target weight patients still had significantly lower BMI (P=0.000) and% body fat (P=0.000) than controls but lg10 leptin levels of patients were higher than those of controls when adjusted for BMI and% body fat (ANCOVA, group P=0.038). In patients, correlation coefficients between lg10 leptin levels and BMI increments increased during the 11 weeks of re-feeding. BMI,% body fat and fT3 levels were not significantly correlated to lg10 leptin levels in week 11, however, 53% of the variance of leptin levels (corrected R(2)=0.53, P=0.001) was explained by BMI increments between weeks 7 and 11 (P=0.001) and lg10 leptin level at admission (P=0.002). In conclusion, we confirmed weight gain induced hyperleptinemia in AN. Further research is required to assess if this phenomenon contributes to renewed weight loss.     

Comparing weight gain in the year prior to treatment for overweight and obese patients with and without binge eating disorder in primary care

Objective

To examine weight change trajectories among overweight and obese patients with binge eating disorder (BED) versus without (NBO) during the year prior to seeking treatment.

Methods

Participants were 97 (75 women, 22 men) overweight and obese patients recruited for the same weight-loss treatment in primary care; 26 (27%) met DSM-5 BED criteria. Participants were assessed with the Eating Disorder Examination and completed self-report questionnaires about their weight histories and the Beck Depression Inventory-II.

Results

Participants' self-reported current weight and measured current weight were significantly correlated and did not statistically differ. Reported weight changes during the year prior to seeking treatment differed significantly by group: BED patients gained an average of 18.3 lb (8.2 kg) whereas NBO patients gained an average of 1.5 lb (0.7 kg). Among BED patients, but not NBO, weight change during the prior year was positively correlated with greater eating-disorder psychopathology, binge-eating frequency, frequency of overeating at lunch and dinner, and depression scores. For the overall group, BED status and binge-eating frequency each made independent significant contributions to predicting weight change in the past year.

Conclusion

Findings suggest BED patients are gaining considerably more weight during the year prior to treatment than NBO patients. BED treatment may interrupt a steep weight gain trajectory and prevent further weight gain for BED patients suggesting need for early intervention. Primary care physicians should screen for BED when overweight and obese patients present with rapid weight gain.     

齐拉西酮对精神分裂症患者体质量、血糖和泌乳素的影响

目的探讨齐拉西酮对精神分裂症患者体质量、血糖和泌乳素的影响。方法用随机方法将100例符合中国精神障碍分类与诊断标准第3版（CCMD--3）的精神分裂症患者分成齐拉西酮组和氯氮平组,治疗12周。用全自动生化分析仪测定血糖,放射免疫法测定泌乳素。测定方法：于疗前和疗后4,8,12周测量体质量、血糖和泌乳素。结果治疗前后齐拉西酮组体质量、血糖和泌乳素水平无明显变化,而氯氮平组有显著性差异;且同期比较,氯氮平组与齐拉西酮组的体质量、血糖和泌乳素水平也有显著性差异（P〈0．01或P〈0．05）。结论齐拉西酮对精神分裂症患者的体质量、血糖和泌乳素影响较小。