氯氮平对首发精神分裂症帕罗西汀激发试验的影响

目的　探讨首发精神分裂症的中枢 5 羟色胺 (5 HT)系统的功能 ,以及氯氮平对神经内分泌激发试验的影响。方法　无重大躯体疾病、既往未服过药物治疗的首发分裂症患者 2 4例 (患者组 ) ,另选择与患者组年龄、性别相匹配的 15名正常人为对照组。口服 4 0mg帕罗西汀作为激发剂 ,每隔 1 5h共 5次 (包括试验前 )连续抽取静脉血 ,使用酶联免疫吸附法测定血浆皮质醇 (COR)及催乳素 (PRL)浓度。患者组分别在氯氮平治疗前后各做 1次激发试验 ,对照组仅做 1次激发试验。氯氮平的平均日剂量为 (2 6 8± 75 )mg ,疗程为 12周。结果　治疗前患者组血浆基础PRL及COR浓度明显高于对照组 (P <0 0 5 ) ,PRL、COR对帕罗西汀的反应明显高于对照组 (P <0 0 5～ 0 0 1)。氯氮平治疗后 ,患者组PRL、COR对帕罗西汀反应明显迟缓 ,与对照组的反应的显差异无显著性 (P >0 0 5 ) ,氯氮平显著提高了外周血COR浓度 (P <0 0 5～ 0 0 1)。结论　首发精神分裂症患者中枢 5 HT功能可能存在亢进。     

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     

精神分裂症神经内分泌激发试验研究

目的：通过内分泌激发实验,探讨慢性精神分裂症中枢５－ＨＴ功能状态。方法：对７８例精神分裂症、１８例正常对照进行帕罗西汀激发实验研究,以皮质醇和催乳素作为激发实验的应答指标。同时,对病人进行阳性和阴性症状评定量表（ＰＡＮＳＳ）测查。结果：治疗前精神分裂症组催乳素基础值明显低于对照组,帕罗西汀激发实验后催乳素释放增高,曲线下面积（ＡＵＣ）与对照组无显著关异。病人治疗前皮质醇基础值明显高于对照组,帕罗西     

慢性精神分裂症神经内分泌功能与症状的关系

神经内分泌的研究一直是精神分裂症研究的一个重要方面，尤其是近年来中枢5-HT功能异常在精神分裂症病因和病理发展中的作用又引起重视，一些研究进行了中枢5-HT功能的神经内分泌激发试验，并得出一些有意义的结果。本研究以选择性5-HT重摄取抑制剂帕罗西汀为探针，通过激发实验，测定血浆泌乳素、皮质醇水平，以探讨慢性精神分裂症中枢5-HT功能状态。     

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     

抑郁症的生化病理机制探讨

目的：从神经递质与神经内分泌角度探讨抑郁症的生化病理机制。方法：采用高效液相色谱法及放射免疫测定法，分别测定15例抑郁症患者和27例正常对照者血小板5-羟色胺（5-HT）含量及血浆催乳素（PRL）含量，地塞米松抑制实验（DST）皮质醇含量。结果：抑郁症组血小板5-HT水平低于正常对照组，血浆基础皮质醇及服地塞米松后皮质醇均高于正常对照组，DST阳性率高于正常对照组。结论：抑郁症患者存在神经递质和神经内分泌功能的紊乱，抑制症的5-HT能假说能解释其某些内分泌功能紊乱。     

焦虑症的生化病理机制探讨

目的：从神经递质与神经内分泌角度探讨焦虑症的生化病理机制。方法：采用高效液相色谱法及放射免疫测定法，分别测定25例焦虑症患者和28例正常对照者血小板5—羟色胺(5—HT)含量及血浆催乳素(PRL)含量、地塞米松抑制实验(DST)皮质醇含量。结果：广泛性焦虑(GAD)组血小板5—HT水平高于正常对照组，惊恐障碍(PD)组与正常对照组无显著差异；GAD组与对照组血浆PRL均极显著低于PD组；GAD组与PD组血浆基础皮质醇含量均显著高于正常对照组，两组DST阳性率均为20％，正常对照组为14．3％，3组阳性率无显著性差异；汉密尔顿焦虑量表(HAMA)评分与血浆皮质醇浓度呈显著正相关。结论：焦虑症患者存在神经递质和神经内分泌功能的紊乱，但不同亚型间可能存在不同的病理机制，皮质醇浓度可能是焦虑水平的标志因子。     

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。     

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     

精神分裂症患者某些化学物质改变的研究

目的：探讨精神分裂症与一氧化氮(No)、一氧化氮合酶(NOS)及金属蛋白超氧化物歧化酶(SOD)的关系。方法：分别测定59例男性精神分裂症患者和50例正常人血浆N0、NOS及SOD浓度。结果：患者组血浆CuZnSOD浓度显著高于对照组；患者组NOS浓度显著低于对照组，NOS与大体评定量表(GAS)呈负相关；两组N0浓度无显著差异。结论：N0可能与精神分裂症发病有关。而NOS和SOD可间接反映两者关系。     

Hormone responses to fenfluramine and placebo challenge in endogenous depression.

Plasma prolactin and cortisol levels after oral administration of d-l fenfluramine hydrochloride (60 mg) and placebo were examined in 24 endogenously depressed patients and 21 age- and sex-matched normal control subjects in a randomized, double-blind study. Prolactin levels were significantly increased by fenfluramine in both groups, but the response was significantly blunted in the depressed patients compared with the controls. This effect was partially dependent upon elevated baseline cortisol levels in the depressed group and was also influenced by a history of weight loss. Plasma cortisol levels were not increased by fenfluramine in either group. These findings confirm previous reports and suggest that patients with endogenous major depression are characterized by central serotonergic hyporesponsivity. The need to account for baseline effects on hormonal responses to putative serotonergic agents is supported by the findings; however, these effects appear to be less striking when endogenicity is a prominent clinical feature of the depressive syndrome. The apparently complex influence of weight loss on prolactin response to serotonergic challenge remains to be clarified as well as the role played by the bioavailability of the challenge drug and its metabolite.     

Neuroendocrine and behavioral responses to challenge with the indirect serotonin agonist dl-fenfluramine in adults with obsessive-compulsive disorder.

Neuroendocrine and behavioral responses to a single 60-mg oral dose of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated adults with obsessive-compulsive disorder (OCD) and neuroendocrine results contrasted with those in normal control subjects. Net fenfluramine-induced prolactin release did not differ significantly between OCD patients and normal controls. Prolactin responses in the OCD group were not significantly correlated with baseline Yale-Brown Obsessive Compulsive Scale scores for either obsessions or compulsions, but were positively correlated with the baseline Hamilton Depression Scale score and Hamilton Anxiety Scale score. No clear difference in the severity of patients' obsessions or compulsions was found following challenge with fenfluramine versus placebo. Although the present study does not demonstrate a serotonergic abnormality in OCD, this may be more a reflection of limitations of the test procedures than evidence that central nervous system (CNS) serotonergic function is normal in the disorder.     

Serotonin dysregulation in adolescents with major depression: hormone response to meta-chlorophenylpiperazine (mCPP) infusion

This study examined central serotonin disturbance, as reflected by neuroendocrine hormones, among adolescents with major depression. Prolactin, cortisol, and growth hormone were measured following the infusion of a serotonin agonist, meta-chlorophenylpiperazine (mCPP). Twelve (M=6, F=6) medication-free adolescents with major depression (MDD) were compared with 12 (M=6, F=6) matched normal control subjects, ranging in age from 13 to 17 years. Baseline evaluations and a battery of laboratory tests were completed. mCPP, 0.1 mg/kg i. v., was administered in a placebo-controlled design. Analyses of the neuroendocrine hormones revealed that the depressed group had a higher baseline prolactin level and an augmented prolactin response to mCPP challenge than did the control group. The depressed group experienced a sharper baseline-cortisol decline between 08.00 and 11.00 h, and compared to control subjects they displayed an augmented response to the challenge. The depressed group reported more side effects than the control group during saline infusion, but not during mCPP infusion. Findings suggest that depressed adolescents have an elevated baseline prolactin level, and also experience enhanced prolactin and cortisol responses to the serotonergic challenge. These preliminary findings will be confirmed during our ongoing study.     

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.     

Fenfluramine stimulation of prolactin in obsessive-compulsive disorder.

The success of serotonergic reuptake inhibitors in the treatment of obsessive-compulsive disorder (OCD) has suggested that serotonergic neurotransmission may play a role in the pathogenisis of this disorder. Prolactin responses to a 60-mg oral dose of fenfluramine in 26 medication-free patients with a DSM-III-R diagnosis of OCD were compared with those of 20 controls subjects. Fenfluramine produced a significant elevation of prolactin levels in both OCD patients and controls. Prolactin responses were significantly blunted in OCD patients compared with responses in control subjects. Female subjects in both groups showed greater prolactin responses to fenfluramine than did their male counterparts. There was a significant interaction between sex and the presence of OCD such that female patients had lower prolactin responses than their controls, while the difference between male patients and controls was not significant. Prolactin responses were not correlated with age, weight, drug level, depression, anxiety, or degree of OCD symptoms. The results are consistent with a relative reduction in serotonergic efficacy in the setting of OCD.     

Serotonergic studies in patients with affective and personality disorders. Correlates with suicidal and impulsive aggressive behavior

Dysfunction of the central serotonergic system has been variously associated with depression and with suicidal and/or impulsive aggressive behavior. To evaluate central serotonergic function in relation to these variables, prolactin responses to a single-dose challenge with fenfluramine hydrochloride (60 mg orally), a serotonin releasing/uptake-inhibiting agent, were examined in 45 male patients with clearly defined major affective (n = 25) and/or personality disorder (n = 20) and in 18 normal male control patients. Prolactin responses to fenfluramine among all patients were reduced compared with responses of controls. Reduced prolactin responses to fenfluramine were correlated with history of suicide attempt in all patients but with clinician and self-reported ratings of impulsive aggression in patients with personality disorder only; there was no correlation with depression. These results suggest that reduced central serotonergic function is present in a subgroup of patients with major affective and/or personality disorder and is associated with history of suicide attempt in patients with either disorder, but with impulsive aggression in patients with personality disorder only.     

Abnormal neuroendocrine response to clomipramine in hereditary affective psychosis

Background: Blunting of prolactin response after serotonergic stimulation during a major depressive episode has been described by several investigators. In this study, the neuroendocrine responses to clomipramine were assessed in remitted patients suffering from hereditary depression. Methods: Twenty remitted patients from 11 large families with multigenerational, multiple cases of major affective disorder (bipolar disorder n=15, recurrent depression n=5, according DSM‐IV) and 12 healthy relatives were investigated. After intravenous application of 12.5 mg of the serotonin re‐uptake inhibitor clomipramine, serum prolactin and cortisol levels were analysed. Results: Patients and comparison group did not differ significantly with respect to age, baseline prolactin and cortisol concentrations. A gender effect was found in an exploratory analysis for prolactin but not for cortisol and therefore the data for prolactin were analysed seperately. After clomipramine infusion, the increase of cortisol was significantly lower in patients than in the comparison group (P=.046). For prolactin, this effect could be found in the male (P=.012) as well as in the female (P=.007) subsample. Conclusions: These results suggest that blunted prolactin and cortisol responses to serotonergic stimulation are characteristic for remitted depressive patients with previous episodes of major affective disorders. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.     

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.