精神分裂症帕罗西汀激发试验及其与疗效的关系

目的探讨精神分裂症中枢5-羟色胺（5－HT）、多巴胺（DA）功能,以及非典型、典型抗精神病药对它们的影响。方法采用随机、双盲法应用固定剂量利培酮6mg/d、氟哌啶醇20mg／d治疗78例精神分裂症患者,共12周。治疗前后测定皮质醇、催乳素对帕罗西汀激发试验的反应,并以18名正常人为对照组。结果治疗前患者组基础皮质醇[（106±41）μg/L]、皮质醇对帕罗西汀激发试验的反应（曲线下面积AUC为717±229）高于对照组[（73±25）μg／L及AUC585±163],而基础催乳素[（5±7）μg/L]低于对照组[（9±5）μg／L]、催乳素对帕罗西汀激发试验的应答比对照组呈降低趋势（AUC49±41对68±43,P＞0．05）。治疗后,两组患者的催乳素基础值比治疗前均增高（P均＜0.05）;两组之间帕罗西汀介导的催乳素反应差异无显著性。治疗后,两组皮质醇的基础值[（74±32）μg/L及（82±27）μg/L]均较治疗前降低,其中利培酮治疗后降低更为明显。利培酮治疗后皮质醇对帕罗西汀激发试验的反应（AUC518±213）降低,并与对照组差异无显著性,而氟哌啶醇组皮质醇反应与治疗前差异光显著性（P＞0．05）。结论精神分裂症患者治疗前可能有中枢DA功能亢进和5－HT功能增高。利培酮治疗使患者原来过高的中枢5－HT功能接近正常,而氟哌啶醇     

精神分裂症d－芬氟拉明激发的神经内分泌反应与临床症状的关系

目的探讨ｄ－芬氟拉明（ｄ－ＦＦ）激发的神经内分泌反应与精神分裂症临床症状的关系。方法把１５例精神分裂症患者在氯氮平治疗前、后行ｄ－ＦＦ激发试验，同时以简明精神病评定量表（ＢＰＲＳ）、阳性症状量表（ＳＡＰＳ）、阴性症状量表（ＳＡＮＳ）评定精神症状。结果混合型患者治疗前基础皮质醇（ＣＯＲ）值、治疗后ｄ－ＦＦ激发的ＣＯＲ值及治疗前、后ｄ－ＦＦ激发的催乳素（ＰＲＬ）值均显著高于阳性型。症状评分与激素反应有一定的相关关系。结论提示精神分裂症的发生可能与中枢５－羟色胺／多巴胺（５－ＨＴ／ＤＡ）功能失平衡有关。     

精神分裂症患者神经内分泌激发试验对照研究

目的：以帕罗西汀为探针探讨首发精神分裂症的中枢5-羟色胺(5-HT)系统的功能。方法：患者组为首发精神分裂症患者24例；另选择年龄、性别相匹配的15名正常人为对照组。口服40mg帕罗西汀作为激发剂，每隔1．5h连续抽取静脉血，共5次。使用酶联免疫吸附法测定血浆皮质醇及催乳素浓度。结果：试验前患者组血浆基础催乳素及皮质醇浓度显著高于对照组，激发试验后患者组2种激素浓度显著高于基础值及对照组；而帕罗西汀对正常人催乳素、皮质醇的释放增加不明显。结论：首发精神分裂症患者中枢5-HT功能可能亢进。     

急性精神分裂症中枢5-HT功能状态的研究

目的：探讨急性精神分裂症中枢5-HT的功能状态，并了解与临床症状间的关系。方法：通过帕罗西汀激发实验，以催乳素（PRL）作为应答指标；精神症状采用阳性和阴性综合征量表（PANSS）进行评定。结果：（1）急性组PRL基础水平符合正态分布，且明显低于慢性对照组，与健康对照组比较无显差异。（2）急性组激发后的PRL含量虽有增高趋势，但缺乏显意义；与慢性和健康两个对照组比较，均有显差异。（3）急性组PRL水平、AUC（曲线下面积）以及激发反应值与PANSS多介无明显相关关系。结论：与慢性精神分裂症相比，急性精神分裂症中枢5-HT的功能可能更加亢进；但与精神症状之间尚缺乏明显的相关关系。     

氯丙嗪和氯氮平对血清催乳素和生长素的影响

目的：探讨精神分裂症患者用氯丙嗪和氯氮平治疗前后血清催乳素（ＰＲＬ）、生长素（ＧＨ）的变化及其与临床疗效的关系。方法：采用固定剂量的氯丙嗪和氯氮平治疗首发精神分裂症患者５６例,疗程８周;在治疗前后评定简明精神病评定量表（ＢＰＲＳ）,并用放射免疫法测定治疗前后血清中ＰＲＬ和ＧＨ浓度,以２０例健康者为对照。结果：氯丙嗪组及氯氮平组基础ＰＲＬ水平皆较正常对照组显著为高。用氯丙嗪治疗后ＰＲＬ水平显著升高,且与ＢＰＲＳ减分值显著相关;用氯氮平治疗后ＰＲＬ水平变化不明显,且与ＢＰＲＳ减分值无显著相关。两组ＧＨ基础水平相仿;治疗后两组ＧＨ水平皆显著下降,但与ＢＰＲＳ减分值无显著相关。结论：支持精神分裂症多巴胺（ＤＡ）功能亢进假说,精神分裂症患者可能有中枢５－羟色胺（５－ＨＴ）功能障碍。     

强迫症的神经内分泌研究

对探讨强迫症患者的下丘脑－垂体－肾上腺皮质系统的功能状态及强迫症与抑郁症的生物联系，作者对３０例未服药的强迫症患者的基础血浆皮质醇、地塞米松抑制试验（ＤＳＴ）及氯丙咪嗪治疗前后的血催乳素含量进行测定，并以２０例健康志愿者的血浆皮质醇、ＤＳＴ和血催乳素测定值作对照。结果显示：强迫症患者基础血浆皮质醇和基础血催乳素含量高于对照组，但ＤＳＴ无一例呈脱抑制反庆；患者经氯丙咪嗪治疗后，血浆催乳素含量明显升高     

氯氮平对精神分裂症d—芬氟拉明激发试验的影响

以选择性５－羟色胺（５－ＨＴ）释放／再摄取抑制剂ｄ－芬氟拉明（ｄ－ＦＦ）为探针，研究精神分裂症患者的中枢５－ＨＴ活动情况，探讨氯氮平的抗精神病作用机制，以放射免疫法测定１６例正常人和１５例精神分裂症患者氯氮平治疗前后血浆催乳素（ＰＲＬ）、皮质醇（ＣＯＲ）、生长激素（ＧＨ）对ｄ－ＦＦ激发试验的反应。结果发现；精神分裂症组治疗前血浆ＰＲＬ、ＧＨ对ｄ－ＦＦ的反应显著高于正常对照组；氯氮平不影响其基础ＰＲ     

精神分裂症患者血清催乳素和生长激素水平的观察

为研究精神分裂症患者血清中催乳素（ＰＲＬ）、生长激素（ＧＨ）的基础水平与正常人的差异，及精神分裂症患者治疗前后ＰＲＬ、ＧＨ水平的变化，以及与临床疗效的关系，采用放射免疫法，测定２０例精神分裂症患者治疗前和治疗后第２，４，６，８周末的ＰＲＬ、ＧＨ水平，并与１０名正常人对照，同时进行治疗前和治疗后第２，４，８周末简明精神病评定量表（ＢＰＲＳ）的评定。结果显示：精神分裂症患者的基础ＰＲＬ水平较正常对照组低，而ＧＨ水平较高，但无统计学意义；用抗精神病药治疗后ＰＲＬ升高，ＧＨ下降，ＰＲＬ水平的升高与ＢＰＲＳ减分值明显相关，支持精神分裂症的多巴胺功能亢进的假说。提示ＰＲＬ对治疗的反应可能是预测临床疗效的一个指标。     

氟哌啶醇对精神分裂症超氧化物歧化酶的作用

目的：探讨精神分裂症自由基代谢酶超氧化物歧化酶（ＳＯＤ）在氟哌啶醇治疗前后的变化。方法：用固定剂量氟哌啶醇治疗４６例慢性精神分裂症患者１２周，在治疗前后应用放射免疫法测定血ＳＯＤ含量，并评定ＢＰＲＳ、ＳＡＰＳ和ＳＡＮＳ量表。结果：治疗前ＳＯＤ值与ＳＡＰＳ总分正相关（Ｐ〈０．０５）。治疗后，治疗前高ＳＯＤ组明显降低，而低ＳＯＤ组明显增高（Ｐ均〈０．０５）。阴性型亚组中，治疗前ＳＯＤ值与治疗前后ＳＡＮ     

阴性和阳性精神分裂症地塞米松抑制试验比较

目的：了解了 和阳性精神分裂症ＨＰＡ轴调节功能的差异。方法：应用放射免疫法（ＲＩＡ）测试精神分裂症患者服用地塞米松前后的皮质醇水平,评价方法依Ｃａｒｏｌｌ方法进行,并引入新的地塞米松抑制试验（ＤＳＴ）统计方法,即血浆皮质醇绝对变化９ＡＣＰＣ０和血浆皮质醇相对变化（ＲＣＰＣ）。结果阳生精神分裂症ＤＳＴ前晨８时基础血浆皮质醇水平显著高于阴性精神分裂症,阳性精神分裂症ＤＳＴ后下竿４时和１１时两个时点血浆     

The MCPP challenge test in schizophrenia: hormonal and behavioral responses.

In a neuroendocrine challenge paradigm, the present study investigated responses of schizophrenic patients to m-chlorophenylpiperazine (MCPP), a serotonin (5-hydroxytryptamine, 5HT) agonist. In an oral dose of 0.25 mg/kg, MCPP was administered in a placebo-controlled double-blind design to male schizophrenic patients (n = 7) and normal male controls (n = 8). Behavioral (Positive and Negative Syndrome Scale; PANSS) and hormonal (cortisol, prolactin) variables were measured over the subsequent 210 min. The schizophrenic patients experienced an overall exacerbation of psychopathology on MCPP as compared with placebo (p less than 0.05), with specific worsening of PANSS-positive symptoms (p less than 0.025) and PANSS activation (p less than 0.001). In addition, the schizophrenic patients showed significantly lower cortisol (p less than 0.05) and prolactin (p less than 0.05) responses than the normal subjects. The schizophrenic patients had lower peak MCPP blood levels than the normal subjects, although this difference was not statistically significant. The findings are discussed in terms of 5HT receptor(s) sensitivity and the pharmacokinetics of MCPP in schizophrenia.     

Prolactin hyperresponsiveness to D-fenfluramine in drug-free schizophrenic patients: a placebo-controlled study.

BACKGROUND: Functional alterations in the central serotonergic system have been reported in schizophrenia but no conclusive data have been provided. In the present study, we investigated the prolactin (PRL) response to the selective serotonin (5-HT) releasing agent D-fenfluramine in both patients with schizophrenia and matched healthy subjects. METHODS: Sixteen drug-free schizophrenics and 16 healthy subjects were randomized in a double-blind neuroendocrine test to D-fenfluramine (30 mg p.o.) or placebo. Blood PRL and cortisol concentrations were determined by radioimmunoassay, while plasma levels of D-fenfluramine were measured by mass spectrometry. RESULTS: In schizophrenic patients, baseline plasma PRL levels were not different from controls, whereas plasma cortisol concentrations were significantly increased (p < .03). The PRL response to D-fenfluramine was significantly enhanced in patients as compared to matched control subjects (p < .005). Schizophrenics meeting Kane's criteria for previous nonresponse to typical neuroleptics exhibited a PRL response to D-fenfluramine significantly higher than non-drug-resistant patients (p < .04). No significant difference in plasma D-fenfluramine concentrations was observed between schizophrenic and healthy subjects. CONCLUSIONS: These findings suggest a serotonergic hypersensitivity in chronic schizophrenia. This alteration seems to be peculiar to those patients refractory to typical neuroleptics.     

Changes in central serotonergic function as a correlate of duration of illness in paranoid schizophrenia

There is evidence that the duration of untreated psychosis may affect both the course and outcome of treatment in schizophrenic patients. In the present study, we used neuroendocrine probes to test the hypothesis that untreated psychosis may induce time-dependent changes in central serotonergic and dopaminergic neurotransmission. Prolactin responses to the administration of clomipramine (i.v.) and haloperidol (i.m.) were measured in healthy control subjects and in 16 never-treated male patients with DSM-IV diagnoses of schizophreniform or schizophrenic disorders of paranoid subtype, both before and after 5 weeks of treatment with haloperidol. In the drug-free state, schizophrenic patients exhibited significantly increased prolactin responses to clomipramine administration compared with both the healthy control subjects and the schizophreniform patients. Maximum prolactin responses to clomipramine in the total group of patients were positively correlated with the duration of psychotic illness and negatively correlated with changes in Positive and Negative Syndrome Scale (PANSS) total, negative symptoms and general psychopathology scores after 5 weeks of treatment with haloperidol. Prolactin responses to haloperidol challenge in the drug-free state were lower in the schizophreniform group than in the control and the schizophrenic groups, but the differences did not reach statistical significance. The results provide evidence that the persistence of psychotic psychopathology induces secondary neuroadaptive effects, which seem to involve changes in central serotonergic function.     

联用帕罗西汀治疗精神分裂症阴性症状研究

目的:探讨抗精神病药联用帕罗西汀治疗精神分裂症阴性症状的疗效.方法:以阴性症状为主的住院慢性精神分裂症33例,在原用抗精神病药基础上,联用帕罗西汀,疗程12周.使用阳性 与阴性症状量表(PANSS)和副反应量表(TESS)评定,在治疗前和治疗4、8、12周末各评定1次.结果:联用帕罗西汀12周后,PANSS总分、阴性症状因子分及情感迟钝、情感退缩、情感交流障碍、被动/淡漠及社交退缩因子分均比治疗前显著降低.结论:以阴性症状为主的慢性精神分裂症,在使用抗精神病药物的同时联用帕罗西汀,对改善阴性症状有明显作用.     

精神分裂症儿茶酚氧位甲基转移酶功能基因多态性研究

目的 :分析儿茶酚氧位甲基转移酶 (COMT)功能基因多态性与精神分裂症患者精神症状严重程度和抗精神病药急性期治疗疗效的相关性。　方法 :采用多聚酶链反应 限制性内切酶片断长度多态性技术 (PCR RFLP)方法分析 138例首次治疗的精神分裂症患者COMT基因缬氨酸 (Val) 15 8蛋氨酸(Met)功能多态性 ;采用阳性症状和阴性症状量表 (PANSS)评定患者治疗前后精神症状 ,并分析等位基因和基因型与临床指标、治疗前PANSS分值及治疗 10周后PANSS减分率的相关性。　结果 :COMTVal15 8Met基因型在患者组和男女亚组的分布频率均符合Hardy Weinberg定律 ;等位基因和基因型在治疗显效组和未显著进步组分布频率差异均无显著性 ;各基因型亚组及是否携带Met等位基因亚组的临床指标差异均无显著性 ;基因型与治疗前PANSS总分和阴性症状分显著相关 ,而与PANSS总减分率和各分值减分率无显著相关。　结论 :COMTVal/Val基因型主要与首次治疗精神分裂症患者阴性症状相关 ,支持COMTVal等位基因是精神分裂症脑前额皮质多巴胺功能低下的遗传影响因子的研究发现。     

利培酮联合帕罗西汀治疗慢性精神分裂症阴性症状

目的:探讨利培酮联合帕罗西汀治疗慢性精神分裂症阴性症状的临床疗效以及安全性.方法:将126例以阴性症状为主的慢性精神分裂症住院患者随机分为研究组(利培酮联合帕罗西汀治疗)和对照组(单用利培酮治疗),疗程12周,采用阳性和阴性症状量表(PANSS)和治疗中出现的症状量表(TESS)评定疗效和安全性. 结果:治疗后两组PANSS评分均较治疗前有显著降低(P＜0.05).治疗后4、8、12周末,研究组阴性因子分及情感迟钝、情感退缩、情感交流障碍及社会退缩因子分均显著低于对照组,差异具有统计学意义(P＜0.05或P＜0.01).两组不良反应均为轻至中度. 结论:利培酮联合帕罗西汀较单用利培酮治疗慢性精神分裂症阴性症状具有起效更快、疗效更好、依从性好的特点.     

Pindolol does not augment cortisol and prolactin responses to paroxetine in healthy subjects

OBJECTIVE: Animal studies have shown that pindolol augmentation of selective serotonin re-uptake inhibitors (SSRIs) may act through inhibition of 5-HT(1A) autoreceptors in the raphe. The combination of pindolol plus a SSRI produces increased synaptic 5-HT levels that are greater than those achieved with a SSRI alone. However, it is unclear whether this actually occurs in humans, and clinical studies of pindolol augmentation have produced inconsistent results. Since the release of cortisol and prolactin is under serotonergic control, we hypothesized that pindolol augmentation of synaptic 5-HT concentrations produced by an SSRI in humans should lead to enhanced SSRI-induced cortisol and prolactin responses. METHODS: Cortisol and prolactin responses were measured after challenge tests with paroxetine (20-40 mg) plus pindolol (5 mg) and after paroxetine plus placebo in six non-depressed, healthy control subjects. RESULTS: No differences were observed in the cortisol or prolactin responses between either neuroendocrine challenge test. CONCLUSIONS: These results suggest that SSRI augmentation with usual clinical doses of pindolol does not increase central synaptic 5-HT neurotransmission sufficient to induce an enhanced neuroendocrine response.