阿立哌唑治疗奥氮平所致精神分裂症患者体质量增加的随机双盲对照研究

目的:探讨阿立哌唑干预奥氮平所致体质量增加的有效性及安全性。方法:将服用单一奥氮平治疗所致体质量增加≥7%的入组对象72例随机分为A组(加服阿立哌唑10 mg组,36例)及B安慰剂组(36例),入组时、治疗4周及8周分别测定体质量、体质量指数(BMI)、空腹血糖(FG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)及高密度脂蛋白(HDL),并用阳性和阴性症状量表(PANSS)评定精神症状。结果:两组治疗前体质量、BMI、FG、TC、TG、LDL、HDL,差异无统计学意义(P0.05)。与治疗前比较,治疗8周,A组体质量、BMI、FG均明显下降(P0.05或P0.01),而HDL有明显增高(P0.05);B组体质量、BMI、FG均明显增高(P0.05或P0.01)。治疗4周体质量、BMI的变化值、治疗第8周体质量、BMI、FG、HDL的变化值,两组均差异有统计学意义(P0.05或P0.01)。结论:阿立哌唑能有效减轻奥氮平所致体质量增加和糖脂代谢紊乱。     

齐拉西酮与奥氮平干预首发精神分裂症的临床疗效及安全性

目的观察齐拉西酮与奥氮平干预首发精神分裂症的临床疗效及不良反应。方法精神分裂症患者72例,随机分为试验组35例,对照组37例。试验组采用齐拉西酮治疗,对照组采用奥氮平干预,疗程为6周,治疗后观察阳性与阴性症状量表(PANSS)评分、临床总体印象量表(CGI-S)评分、体重指数(BMI)、血糖、胆固醇、甘油三酯情况及不良反应。结果 2组PANSS和CGI-S评分比较差异无统计学意义(P=0.117,P=0.425);术后奥氮平组BMI高于齐拉西酮组(P=0.018);齐拉西酮组的平均空腹血糖、胆固醇及甘油三酯均低于奥氮平组(P=0.000,P=0.001,P=0.001)。2组不良反应方面比较无显著差异。结论齐拉西酮与奥氮平干预首发精神分裂症疗效确切,不良反应少,齐拉西酮对体重指数和糖脂代谢的影响较小,而奥氮平更易导致显著的体质量增加和糖代谢异常。     

奥氮平合并不同剂量二甲双胍对精神分裂症患者体质量和糖脂代谢的影响

目的:探讨二甲双胍早期干预对精神分裂症患者体质量和糖脂代谢的有效性和安全性。方法:150例首发精神分裂症患者分为治疗组(奥氮平联合二甲双胍)和对照组30例(奥氮平单药),治疗组根据联合二甲双胍不同剂量(即奥氮平10～20 mg/d+二甲双胍250 mg/d、500 mg/d、750 mg/d)分为治疗1组(30例)、治疗2组(30例)及治疗3组(28例)。分别于治疗前和治疗4、8及12周测定体质量指数(BMI)及空腹血糖(FBG)、糖化血红蛋白(HbA 1c)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL);采用阳性和阴性症状量表(PANSS)治疗前后评定疗效,并记录不良事件评定安全性。结果:治疗12周,各组体质量及BMI均较治疗前显著增加,治疗3组与对照组比较差异有统计学意义(χ2=10.138,t=2.905;P0.01);各组TC、TG、LDL、对照组及治疗1组FBG、HbA 1c较治疗前增加(P均0.05)、HDL较治疗前降低(P0.05);各组间比较,治疗2组和治疗3组TC、TG、HDL、LDL与对照组比较差异有统计学意义(P均0.05);治疗3组胃肠道不适症状较多。结论:早期合并二甲双胍(500 mg/d)干预奥氮平所致的体质量增加和糖脂代谢紊乱的效果有限。     

氨磺必利替换奥氮平治疗对伴有代谢综合征精神分裂症患者的影响

目的:观察氨磺必利替换奥氮平治疗对伴有代谢综合征精神分裂症患者的影响。方法:92例奥氮平治疗伴代谢综合征的精神分裂症患者随机分为氨磺必利组(治疗组)及奥氮平组(对照组)各46例。治疗组在2周内将奥氮平换为氨磺必利,对照组维持奥氮平治疗,观察12周。入组时及第6、12周末测量腰围、血压、体质量指数(BMI)及空腹血糖(FBS)、高密度脂蛋白(HDL)、三酰甘油(TG)水平。应用阳性和阴性症状评定量表(PANSS)和治疗中出现的症状量表(TESS)进行疗效和安全性评定。结果:治疗12周末,治疗组腰围、收缩压、BMI、TG、FBS均显著低于对照组(P0.05或P0.01),两组PANSS评分差异无统计学意义(P0.05),而TESS评分治疗组低于对照组(P0.05)。结论:氨磺必利替换奥氮平治疗对精神分裂症患者体质量增加及代谢综合征有显著改善作用。     

齐拉西酮与奥氮平对女性精神分裂症患者阴、阳性症状与内分泌代谢的影响

目的比较齐拉西酮与奥氮平对女性精神分裂症患者阴、阳性症状与内分泌代谢的影响。方法选取我院2015年6月～2017年6月收治的138例女性精神分裂症患者为研究对象,按随机数表法分为齐拉西酮组与奥氮平组,每组69例。齐拉西酮组给予齐拉西酮治疗,奥氮平组给予奥氮平治疗,均持续治疗6周。比较两组精神分裂严重程度,检测患者内分泌代谢指标,统计治疗期间不良反应发生率。结果齐拉西酮组治疗6周后阳性与阴性症状评分(PANSS)与奥氮平组比较差异无统计学意义。齐拉西酮组治疗6周后空腹血糖(FBG)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)显著低于奥氮平组(P0.05)。结论齐拉西酮与奥氮平对女性精神分裂症患者均具有良好疗效,但齐拉西酮对患者内分泌代谢影响小。     

第2代抗精神病药对代谢的影响

目的：探讨奥氮平、奎硫平和齐拉西酮对首发精神分裂症患者血脂和体质量的影响。方法：选择件院治疗的首发精神分裂症患者114例．随机分为奥氮平组35例、奎硫平组41例、齐拉西酮组38例治疗前、治疗4周和治疗8周检测血脂水平和体质量。结果：奥氮平组治疗4周、治疗8周总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL）和体质量均较治疗前显著升高（P〈0．05）;高密度脂蛋白胆固醇（HDL）水平垃著降低（P〈0．05）;奎硫平组至治疗8周时,TC、TG、低密度脂蛋白胆固醇（LDL）和体质量均较治疗前显著升高（P〈0．05）;而齐拉西酮组治疗4周和治疗8周与治疗前比较,TC、TG、HDL、LDL、体质量水平差异均无显著性。在治疗8周奥氮平组、奎硫平组TC、TG、HDL、LDL、体质餐变化与齐拉西酮组比较差异有显著性（P〈0．05）。结论：齐拉西酮对精神分裂症患者血脂和体质量的影响较奥氮平、奎硫平小,奥氮平和奎硫平在精神分裂症治疗过程中均可导致血脂异常和体质量增加。     

齐拉西酮与奥氮平在精神分裂症患者中的疗效对比观察及糖脂代谢安全性研究

目的观察齐拉西酮与奥氮平在精神分裂症患者中的临床治疗效果及糖脂代谢安全性情况。方法取精神分裂症患者90例,随机分为对照组(n=45)和观察组(n=45)。对照组采用奥氮平治疗,观察组采用齐拉西酮治疗,采用全自动生化分析仪测定2组患者治疗前、后血脂及血糖水平,比较2组临床疗效及对糖脂代谢的影响。结果 2组治疗前PANSS评分比较差异无统计学意义(P0.05);观察组治疗后3周、8周PANSS评分,低于对照组(P0.05);2组治疗前血脂水平中TG、TC、HDL及LDL水平比较差异无统计学意义(P0.05);观察组治疗后8周TC、TG、HDL及LDL水平,低于对照组(P0.05);2组治疗前FBS、INS及IRI水平比较差异无统计学意义(P0.05);观察组治疗后FBS、INS及IRI水平,低于对照组(P0.05);2组治疗后药物不良反应发生率比较差异无统计学意义(P0.05)。结论精神分裂症患者采用齐拉西酮治疗效果理想,对患者脂糖代谢的影响相对较小,值得推广应用。     

奥氮平联合金刚烷胺治疗精神分裂症首次发病患者的随机双盲对照研究

目的:探讨金刚烷胺添加对奥氮平治疗精神分裂症首次发病患者疗效及脂代谢的影响。方法:采用随机双盲法,将61例精神分裂症首次发病的患者随机分为研究组(31例)和对照组(30例),在奥氮平治疗的基础上,研究组及对照组分别添加金刚烷胺200 mg/d及安慰剂;疗程8周。治疗前及治疗4、8周进行阳性和阴性症状量表(PANSS)及治疗过程中出现的症状量表(TESS)评定,测量体质量,检测血三酰甘油(TG)、低密度脂蛋白(LDL)、总胆固醇(TC)水平。结果:治疗后研究组PANSS阴性症状减分值显著大于对照组(P0.05);TESS评分两组间差异无统计学意义;两组体质量和TG增加值差异无统计学意义;对照组LDL、TC增加值显著大于研究组(P均0.05)。结论:添加小剂量金刚烷胺短期内可明显增加奥氮平对精神分裂症患者阴性症状的改善作用,减少血LDL和TC水平升高;但不能改善奥氮平所致的体质量增加。     

综合干预对抗精神病药所致精神分裂症患者体质量增加及糖脂代谢的影响

目的:探讨综合干预对精神分裂症患者因抗精神病药所致体质量增加及糖脂代谢的影响。方法:将120例因抗精神病药导致体质量增加的患者随机分为两组,研究组给予综合干预36周,依次进行心理行为干预、合并二甲双胍750 mg/d及更换抗精神病药3个阶段,每个阶段12周;对照组不干预直接随访;分别于入组前及入组后每12周测量体质量、体质量指数(BMI)、腰围、空腹血糖(FBG)、血脂及进行阳性与阴性症状量表(PANSS)评分。结果:110例完成观察(研究组52例,对照组58例)。经36周干预后,研究组29例(48.3%)BMI恢复正常,体质量、BMI、腰围、FBG、胆固醇(TC)水平较干预前明显下降(P0.05或P0.01);而对照组三酰甘油较观察前显著增加(P0.05)。研究组干预前后体质量、BMI、腰围、FBG、TC差值显著高于对照组(P0.05或P0.01);两组干预前后PANSS评分差异无统计学意义。结论:综合干预措施能降低抗精神病药所致体质量增加,改善糖脂代谢。     

奥氮平、辛伐他汀联合用药对精神分裂症患者脂质代谢的影响

目的探讨奥氮平联合辛伐他汀治疗对患者的临床效果及脂质代谢的影响。方法选取2012年1月~2015年6月在本院精神科治疗的48例精神分裂症患者采用抽签法进行随机分组,其中观察组(奥氮平+辛伐他汀)和对照组(奥氮平)各24例,疗程8周。结果治疗前、治疗2周、4周、8周,两组患者的PANSS评分差异无统计学意义(P0.05),治疗2周、4周、8周,两组患者的PANSS评分均呈逐渐降低的趋势(P0.05);治疗前,两组患者的TG、TC、HDL-C、LDL-C、FPG、Fins、BMI差异无统计学意义(P0.05),治疗8周后,观察组患者的TG、TC、LDL-C、FPG、Fins均显著低于对照组(P0.05);治疗后,对照组患者的TG、TC、LDL-C、FPG、Fins较治疗前显著提高(P0.05)。结论奥氮平联合辛伐他汀治疗精神分裂症患者不会影响治疗效果,同时能够有效减轻奥氮平治疗过程中引起的血脂、血糖代谢紊乱。     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

Opiate and digitalis receptor assays distinguish between neuroexcitant and inactive organochlorines and between anesthetics and convulsants

Specific binding of [3H]naloxone to rat brain tissue in vitro was inhibited by the excitant organochlorinated insecticides (OCI), by ether (E) and octanol (OCT), and by the convulsant indoklon (IND) and its anesthetic isomer, isoindoklon (ISO). In the presence of 100 mM NaCl the inhibition of naloxone binding by E, OCT and ISO was greatly potentiated, whereas that by OCI and IND was attenuated. KCl (100 mM) was equally effective as NaCl on the action of anesthetics, but the effect of the excitant drugs was, in contrast to NaCl, unaffected by KCl. Specific binding of [3H]ouabain in the absence of Na, was depressed by anesthetics and enhanced by neuroexcitants. In the presence of NaCl, which by itself inhibits ouabain binding to brain, both anesthetics and excitants enhanced ouabain binding. DDE, a non-insecticidal analog of DDT, and the dimethyl derivative of the OCI, lindane, were inactive in the receptor assays. These observations point to a unique isolated system which responds consistently to anesthetic agents as a class and, in a different way, to neuroexcitant compounds.     

Learning and forgetting new names and objects in MCI and AD

We studied how subjects with mild cognitive impairment (MCI), early Alzheimer's disease (AD) and age-matched controls learned and maintained the names of unfamiliar objects that were trained with or without semantic support (object definitions). Naming performance, phonological cueing, incidental learning of the definitions and recognition of the objects were tested during follow-up. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, suggesting that the MCI patients’ preserved semantic memory can compensate for impaired episodic memory. The MCI group performed equally well as the controls in the tasks measuring incidental learning and recognition memory, whereas the AD group showed impairment in this respect. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that word learning is compromised in both MCI and AD, whereas long-term retention of newly learned words is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI.     

Satellite cells and myonuclei in young and elderly women and men

The overall aim of this study was to assess the effects of aging on the satellite cell population. Muscle biopsies were taken from the tibialis anterior muscle of healthy, moderately active young (age range, 20-32 years; n = 31) and elderly (age range, 70-83 years; n = 27) women and men with comparable physical activity pattern. Satellite cells and myonuclei were visualized using a monoclonal antibody against neural cell adhesion molecule and counterstained with Mayer's hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for each individual. Compared with the young women and men, the elderly subjects had a significantly lower (P < 0.011) number of satellite cells per muscle fiber but a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The number of satellite cells relative to the total number of nuclei [satellite cells/(myonuclei + satellite cells)] was significantly lower in the elderly than in the young women and men. These results imply that a reduction in the satellite cell population occurs as a result of increasing age in healthy men and women.     

Necdin蛋白与神经元的生长分化

在神经系统 ,Necdin只在成熟神经元的细胞核中表达 ,可能与成熟神经元分裂静止状态的保持有关。近年的研究表明 ,Necdin是一种生长抑制蛋白 ,能与多种因子如SV4 0大T抗原 ,腺病毒E1A ,转录因子E2F1以及肿瘤抑制蛋白p5 3等结合 ,在功能上类似于成视网膜瘤蛋白Rb。necdin基因缺陷时 ,会引起脑内 ,特别是下丘脑神经元分化障碍。人类necdin基因位于PWS综合征的基因缺失区 ,可能与PWS的一些症状有关。本文从Necdin蛋白的基本概况 ,生物功能以及Necdin与疾病三个方面进行了综述     

Necdin蛋白与神经元的生长分化

在神经系统,Necdin只在成熟神经元的细胞核中表达,可能与成熟神经元分裂静止状态的保持有关.近年的研究表明,Necdin是一种生长抑制蛋白,能与多种因子如SV40大T抗原,腺病毒E1A,转录因子E2F1以及肿瘤抑制蛋白p53等结合,在功能上类似于成视网膜瘤蛋白Rb.necdin基因缺陷时,会引起脑内,特别是下丘脑神经元分化障碍.人类necdin基因位于PWS综合征的基因缺失区,可能与PWS的一些症状有关.本文从Necdin蛋白的基本概况,生物功能以及Necdin与疾病三个方面进行了综述.     

Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics

We recently reviewed the status of peptide and nonpeptide agonists and antagonists for the V(1a), V(1b) and V(2) receptors for arginine vasopressin (AVP) and the oxytocin receptor for oxytocin (OT). In the present review, we update the status of peptides and nonpeptides as: (i) research tools and (ii) therapeutic agents. We also present our recent findings on the design of fluorescent ligands for V(1b) receptor localisation and for OT receptor dimerisation. We note the exciting discoveries regarding two novel naturally occurring analogues of OT. Recent reports of a selective VP V(1a) agonist and a selective OT agonist point to the continued therapeutic potential of peptides in this field. To date, only two nonpeptides, the V(2) /V(1a) antagonist, conivaptan and the V(2) antagonist tolvaptan have received Food and Drug Administration approval for clinical use. The development of nonpeptide AVP V(1a), V(1b) and V(2) antagonists and OT agonists and antagonists has recently been abandoned by Merck, Sanofi and Pfizer. A promising OT antagonist, Retosiban, developed at Glaxo SmithKline is currently in a Phase II clinical trial for the prevention of premature labour. A number of the nonpeptide ligands that were not successful in clinical trials are proving to be valuable as research tools. Peptide agonists and antagonists continue to be very widely used as research tools in this field. In this regard, we present receptor data on some of the most widely used peptide and nonpeptide ligands, as a guide for their use, especially with regard to receptor selectivity and species differences.     

Retrospective and prospective design and data

The study of the presentation, symptomatology and family characteristics of an exclusively adolescent sample of patients with borderline personality disorder (BPD) was undertaken. Twenty-four cases of borderline personality disorder, 20 females, 4 males, identified using chart review and meeting the criteria of the Diagnostic Interview for Borderlines (DIB) and DSM III-R, were matched with psychiatric controls. Adolescents with borderline personality disorder were found to have high rates of affective symptomatology with Axis I diagnosis of major depressive disorder - MDD (DSM-III-R), and high rates of interpersonal psychopathology, i.e., manipulation, devaluation, and a pervasive sense of boredom. The latter seem to be characteristic as for adults with borderline personality disorder. The families were particularly angry and volatile.     

Cortisol levels and depression in men and women using heroin and cocaine

Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender.