强迫症、抑郁症及焦虑症患者血小板5-羟色胺浓度的对照研究

目的　研究 5 羟色胺 ( 5 HT)在强迫症发病中的作用及强迫思维与强迫动作亚组、抑郁症及焦虑症患者间血小板 5 HT含量的差异。方法　采用高效液相色谱法 ,分别测定 2 9例强迫症患者 [(强迫症组 ,根据Y BOCS强迫量表因子得分将其分为强迫思维 ( 16例 )、强迫动作 ( 7例 )和混合性( 6例 ) 3组 ]、2 0例抑郁障碍患者 (抑郁症组 )、17例焦虑障碍患者 (焦虑症组 )和 2 8名正常人 (正常人组 )的血小板 5 HT含量。结果　强迫症组血小板 5 HT水平 [( 139± 172 ) μg/L]低于正常人组 [( 2 4 8±2 15 ) μg/L]及焦虑症组 [( 397± 4 0 1) μg/L],差异具有显著性 (P =0 0 39;P =0 0 2 0 ) ;与抑郁症组 [( 2 0 2± 16 2 ) μg/L]的差异无显著性 ( P >0 0 5 ) ;强迫思维 [( 85± 6 6 ) μg/L]与强迫动作组 [( 16 9± 10 0 ) μg/L]间血小板 5 HT含量的差异有显著性 (P =0 0 2 5 )。结论　强迫症患者 5 HT浓度变化与抑郁障碍患者趋同 ,与焦虑障碍患者的差异有显著性 ;单纯强迫思维者的 5 HT浓度与单纯强迫动作患者的差异有显著性     

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。     

帕金森病患者基础PRL水平与并发痴呆及抑郁关系的研究

目的探讨帕金森病(PD)患者基础血浆泌乳素(prolactin,PRL)水平及与PD伴随的痴呆及抑郁的关系。方法测定167名在我院体检的正常老人(正常对照组)及113例PD患者(PD组)基础血浆PRL水平,并采用汉密顿抑郁量表(HAMD)、简明智能状况评价量表(MMSE)把PD患者分别划为痴呆组和非痴呆组及伴发抑郁组和非抑郁组,同时筛选同期我科收治的阿尔茨海默病(AD)患者20例及心理门诊治疗的功能性抑郁症患者50例(功能性抑郁组)。分别比较各组的PRL水平。结果PD组者的基础血浆PRL平均水平为(9.44±4.07)μg/L,与正常对照组[(9.76±3.97)μg/L]比较无统计学差异;PD伴发抑郁组平均PRL水平为(8.75±4.12)μg/L,与PD非抑郁组[(10.52±3.97)μg/L]、功能性抑郁组[(9.52±5.17)μg/L]比较均无统计学差异;PD伴发痴呆组平均PRL水平为[(5.26±4.90)μg/L],明显低于PD非痴呆组[(10.19±5.19)μg/L]及AD组[(7.85±4.25)μg/L]。结论PD患者出现痴呆时其基础血浆PRL水平降低。PD患者可能有DA、Ach、5HT能神经递质平衡的紊乱。     

性激素受体蛋白表达异常与多发性硬化

目的　探讨多发性硬化 (MS)患者性激素及性激素受体的改变 ,阐明其在多发性硬化发生发展中的作用。方法　应用放射免疫法和放射配体结合法测定了 15例多发性硬化患者血浆E2 、T和外周血白细胞ER、AR等指标。结果　女性患者E2 和T分别为 ( 194 0 9± 97 85)pmol L、( 0 85± 0 54)nmol L ,明显低于对照组[( 4 2 6 2 0± 160 4 8)pmol L、( 2 4 5± 0 4 7)nmol L ,P <0 0 1];男性患者E2 与对照组无差异 [( 10 2 0 1± 79 39)、( 58 74± 2 6 60 )pmol L ,P >0 0 5],T明显低于对照组 [( 9 30± 5 4 3)、( 2 4 0 8± 3 73)nmol L ,P <0 0 1]。男女性患者的ER分别为 ( 2 33± 138)和 ( 392± 81)位点 细胞 ,明显低于对照组 [( 511± 75)、( 888± 88)位点 细胞 ,P <0 0 1];AR分别为 ( 52 2± 12 3)和 ( 166± 57)位点 细胞 ,明显低于对照组 [( 853± 54)、( 52 0± 75)位点 细胞 ,P <0 0 1]。结论　多发性硬化患者存在性激素及性激素受体的异常 ,在MS发生发展中可能起一定作用     

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。     

抑郁症患者血浆瘦素水平与童年受虐及下丘脑-垂体-肾上腺轴相关研究

目的:探讨儿童期受虐与抑郁症患者血浆瘦素水平及下丘脑-垂体-肾上腺轴功能之间的相关性。方法:选取首发抑郁症患者152例,使用儿童受虐问卷(CTQ)、汉密顿抑郁量表-24(HAMD-24)、汉密顿焦虑量表(HAMA)评定儿童期受虐状况及抑郁与焦虑严重程度;根据儿童受虐问卷评分将受试者分为受虐组(55例),无受虐组(97例)。采用酶联免疫吸附法测定血浆瘦素水平。各组行地塞米松抑制试验(DST),测量各组血浆皮质醇浓度,并计算各组脱抑制率。结果:152例入组患者中55例(36.18%)有儿童期受虐史。儿童期有无受虐组在首次发病年龄、性别比、HAMD-24总分、HAMA总分等方面差异均有统计学意义。儿童期受虐组的血浆瘦素水平[(5.164±2.754) ug/L]低于无受虐组[(7.234±4.892) ug/L;P0.05]和正常对照组[(9.791±7.433) ug/L;P0.000],无受虐组的血浆瘦素水平低于正常对照组(P0.01)。儿童期受虐组和无受虐组DST前后皮质醇水平[(578±126,374±139)ng/L和562±131,333±135)ng/L)]和脱抑制率(71%和68%)高于对照组[(416±104,225±86)ng/L;43%],差异均有统计学意义(均P0.05)。结论:抑郁症患者血浆瘦素及HPA轴均存在明显异常,有儿童期虐待者表现更严重,儿童期受虐导致血浆瘦素水平下降及HPA轴异常可能是成年后罹患抑郁症的可能机制。     

头发、血浆皮质醇水平变化与抑郁症的相关性研究

目的探讨头发、血浆皮质醇水平在抑郁症发病过程中的特点及抗抑郁治疗前后的变化。方法纳入抑郁症患者47例和正常对照47名。抑郁症组给予选择性5-羟色胺再摄取抑制剂治疗4周,分别于治疗前、治疗4周后检测头发、血浆皮质醇水平,分别采用汉密尔顿抑郁量表17项(Hamilton Depression Rating Scale-17,HAMD-17)和汉密尔顿焦虑量表(Hamilton anxiety scale,HAMA)评估抑郁症状和焦虑症状的严重程度及疗效。对照组不予干预,于入组时检测头发、血浆皮质醇水平。结果抑郁症组治疗前头发皮质醇水平高于对照组[(17.42±12.40)nmol/L vs.(10.22±8.00)nmol/L,P0.01],血浆皮质醇水平两组间无统计学差异(P0.05)。抑郁症组治疗后HAMD-17总分[(10.60±4.57)vs.(24.00±4.86)]和HAMA总分[(6.30±4.86)vs.(15.78±5.45)]较治疗前均降低(P0.01),治疗后头发皮质醇水平较治疗前增高[(30.53±25.75)nmol/L vs.(16.02±11.77)nmol/L,P0.05],血浆皮质醇水平治疗前后差异无统计学意义(P0.05)。治疗后达到临床痊愈的患者治疗前血浆皮质醇水平高于非临床痊愈的患者[(27.47±14.48)nmol/L vs.(18.30±7.11)nmol/L,P0.05]。抑郁症组治疗前血浆皮质醇水平与HAMD-17中的胃肠道症状因子分呈正相关(r=0.335,P=0.023),与HAMD-17总分及其他因子的相关性均无统计学意义(P0.05)。结论抑郁症患者头发皮质醇水平高于正常对照,经抗抑郁药治疗后头发皮质醇水平较治疗前升高。治疗前血浆皮质醇水平高的患者可能对抗抑郁药治疗更敏感,可获得更好的临床疗效。     

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。     

利培酮和氟哌啶醇对精神分裂症患者超氧化物歧化酶及催乳素影响的临床对照研究

目的 探讨经第一、二代抗精神病药治疗的精神分裂症患者体内超氧化物歧化酶(SOD)、催乳素(PRL)与精神症状间的关系.方法 符合美国精神障碍诊断与统计手册第4版诊断标准的78例精神分裂症患者,随机分为利培酮组(41例),剂量为6 mg/d;氟哌啶醇组(37例),剂量为20mg/d;观察疗程均为12周.使用阳性和阴性症状量表(PANSS)评定临床疗效.采用放射免疫法在治疗前后分别测定患者血浆SOD及PRL浓度.以30名正常人为正常对照组.结果 利培酮组(40例)、氟哌啶醇组(33例)患者的基线SOD浓度[(794±126)ng/mg Hb,(750±101)ng/mg Hb]均明显高于正常对照组[(483±110)ng/mg Hb],而PRL浓度[(6±7)μg/L,(6±8)μg/L]均明显低于正常对照组[(18±12)μg/L],差异均有统计学意义(P均＜0.05).利培酮组和氟哌啶醇组患者的治疗前SOD与PRL间存在显著负相关(n=70,P＜0.05).治疗第12周末,利培酮组和氟哌啶醇组的SOD浓度[(499±98)ng/mg Hb,(482±76)ng/mg Hb]明显降低,而PRL浓度[(33±19)μg/L,(25±16)μg/L]则明显升高.利培酮组与氟哌啶醇组间治疗前后的SOD、PRL的差异均无统计学意义(P均＞0.05).治疗前后,阴性症状改善与SOD浓度差值(P＜0.05)、阳性症状改善与PRL浓度差值(n=70,P＜0.01)有相关性.结论 精神分裂症患者SOD及PRL浓度异常,两者间存在着相互作用,且对抗精神病药的临床疗效有影响.     

以阳性或阴性症状为主的精神分裂症患者脑脊液催乳素水平测定

目的　探讨以阳性症状为主 (以下简称阳性 )和以阴性症状为主 (以下简称阴性 )的精神分裂症患者脑脊液催乳素 {PRL)水平及氯氮平治疗前后的变化。方法　对 2 6例阳性精神分裂症患者 (阳性组 )和 2 2例阴性精神分裂症患者 (阴性组 )用氯氮平治疗 6周 ,用简明精神病量表 (BPRS)、阳性症状量表 (SAPS)或阴性症状量表 (SANS)评定疗效。治疗前及治疗 6周末用放射免疫测定法测定患者脑脊液PRL水平。结果　治疗前阳性组PRL水平 [(1.0 8± 0 .39) μg/L]低于阴性组 [(1.34± 0 .4 1) μg/L],P <0 .0 5 ;治疗后阳性组PRL水平 [(1.16± 0 .35 ) μg/L]较治疗前升高 ,阴性组 [(1.2 4± 0 .4 6 ) μg/L]较治疗前降低 ,差异均无显著性 (P >0 .0 5 )。两组治疗后BPRS、SAPS或SANS总分较同组治疗前下降均有极显著性差异 (P <0 .0 1)。结论　阳性和阴性精神分裂症患者脑脊液PRL基础水平有差异 ,氯氮平对精神分裂症患者脑脊液PRL水平影响较小。     

Prolactin and cortisol responses to MK-212, a serotonin agonist, in obsessive-compulsive disorder

To examine further the serotoninergic system in obsessive-compulsive disorder (OCD), the plasma concentrations of cortisol and prolactin and the behavioral responses after oral administration of MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine), a serotonin agonist, and placebo were studied in 17 patients with OCD and nine normal controls. The two groups did not differ significantly in basal plasma prolactin or cortisol levels. Nevertheless, both the prolactin and cortisol response to oral administration of MK-212 (20 mg) were significantly blunted in the patients with OCD compared with those of the normal controls. MK-212 did not affect the intensity of OCD symptoms. However, MK-212, as compared with placebo, produced slight but statistically significant increases in self-ratings of nausea, dizziness, anxiety, feeling strange, and mixed feelings of calmness and restlessness, as well as depression and feeling high. These behavioral ratings were not significantly different in patients and normal controls. These findings are consistent with previous reports of diminished serotoninergic responsivity in OCD and raise the possibility of subsensitivity of at least some serotonin receptors in this disorder.     

Disturbances in the hypothalamo-pituitary-adrenal and other neuroendocrine axes in bulimia

Disturbances in the hypothalamo-pituitary-adrenal (HPA) and other endocrine axes were assessed in 24 women with bulimia and healthy controls. Overnight blood samples for measuring nocturnal plasma cortisol, prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) were obtained at 30-min intervals. A 1.5 mg dexamethasone suppression test (DST) and a TRH-test were performed. Patients were monitored closely while their nutritional intake was recorded over 21 days. Compared with healthy controls, nocturnal cortisol plasma levels were not elevated in the bulimics. There was a trend toward insufficient cortisol suppression in the DST in patients with bulimia, which was most pronounced in patients with signs of restricted caloric intake. Plasma dexamethasone levels were significantly reduced in bulimics compared with healthy controls. There was a trend for blunted thyrotropin stimulating hormone (TSH) responses to thyrotropin releasing hormone (TRH) in bulimia. The prolactin response to TRH was significantly reduced in bulimics with a history of anorexia nervosa. Plasma LH and plasma FSH were significantly reduced in bulimics with signs of reduced caloric intake [low T3, high levels of beta-hydroxy-butyric acid (BHBA), reduced daily caloric intake, high number of fasting days] as compared with healthy controls. Bulimics with high BHBA levels had significantly reduced nocturnal prolactin plasma levels. Results show that multiple neuroendocrine disturbances exist in bulimia in a milder form than in anorexia nervosa. Evidence for the impact of caloric intake on endocrine functions is presented. Endocrine dysfunctions in our bulimic sample did not show a positive association with the presence of depressive symptoms.     

Platelet serotonin and plasma prolactin and cortisol in healthy, depressed and schizophrenic women

Serotonin (5-hydroxytryptamine, 5-HT) is involved in the regulation of hypothalamic-pituitary-adrenal axis (HPA) activity and prolactin (PRL) secretion. The present study examined the relationship between platelet 5-HT and plasma cortisol and PRL concentrations in 20 schizophrenic, 25 depressed, and 25 healthy women. At the time of blood sampling, the schizophrenic and depressed patients had been drug-free for at least 7 days. Platelet 5-HT, plasma cortisol and PRL concentrations were determined by spectrofluorimetric, radioimmunoassay and immunoradiometric methods, respectively. Platelet 5-HT concentration was significantly higher in schizophrenic patients than in depressed patients or in healthy controls, while it was significantly lower in depressed patients than in healthy controls or in schizophrenic patients. Plasma cortisol levels were significantly increased both in schizophrenic and in depressed patients compared with values in healthy controls. Values of plasma PRL were similar across groups. A significant correlation was found between platelet 5-HT and plasma cortisol, and platelet 5-HT and plasma PRL concentrations in healthy controls, but not in schizophrenic or depressed patients. There was no significant relationship between plasma PRL and cortisol levels in any of the groups. Our data, although obtained on peripheral biochemical markers, indicate that depression and schizophrenia are characterized by disturbed 5-HT transmission and dysregulated HPA axis activity.     

Plasma dexamethasone concentrations and the dexamethasone suppression test

Altered bioavailability or altered pharmacokinetics of dexamethasone (dex) may contribute to a positive Dexamethasone Suppression Test (DST) in psychiatric patients. We measured plasma dex and plasma cortisol concentrations in 32 patients with primary major depressive disorder (MDD), 14 patients with other psychiatric disorders, and 16 normal controls. Cortisol was measured by the competitive protein binding (CPB) assay and dex by RIA (IgG Corp.). Additionally, cortisol was measured by a fluorescent polarization immunoassay (FPIA) available on the Abbott TDx analyzer in an attempt to validate this method for use in the DST. The agreement between FPIA and CPB cortisol results was excellent. Depressed nonsuppressors, by definition, had significantly higher mean plasma cortisol concentrations than depressed suppressors, psychiatric controls, and normal volunteers at 8:00 AM, 3:00 PM, and 10:00 PM postdex. When DST nonsuppressors and suppressors were compared regardless of diagnostic group, plasma dex concentrations were significantly lower (p less than 0.01) in the DST nonsuppressors. There was a significant negative correlation between plasma cortisol levels and plasma dex levels across all subjects at 8:00 AM (r = -0.365, n = 44, p less than 0.05). When the subjects were sorted by diagnostic category, there was a strong, but not statistically significant, trend toward lower plasma dex concentrations in the melancholic nonsuppressors versus the melancholic suppressors and between the psychiatric control non-suppressors and the corresponding suppressor group. These relationships disappeared when we restricted our analyses to an empirically derived middle range of plasma dex concentrations within which the DST results were considered to be valid. We conclude that bioavailability or pharmacokinetics of dex may significantly contribute to DST results. Further investigation is needed to determine whether or not the quantification of dex and its metabolites and their determination at which specific timepoints during the DST will enhance the predictive or interpretive value of the DST in psychiatric patients.     

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.     

Hypersensitivity of 5-HT2 receptors in OCD patients. An increased prolactin response after a challenge with meta-chlorophenylpiperazine and pre-treatment with ritanserin and placebo

INTRODUCTION: Several studies in obsessive compulsive disorder (OCD) have provided circumstantial evidence that the 5-HT-system is involved in the pathophysiology of OCD. To further examine the role of 5-HT receptors we studied the behavioural and neuroendocrine effects of different doses of meta-chlorophenylpiperazine (mCPP) in OCD patients and healthy controls, after pre-treatment with ritanserin, a 5-HT2 receptor antagonist, and placebo. DESIGN: Twenty patients and 20 healthy controls received 0.1, 0.3 or 0.5 mg/kg mCPP or placebo orally. Each subject was tested two times, receiving both times the same dosage of mCPP or placebo with ritanserin or placebo pre-treatment. All was done under double-blind conditions. OC-symptoms and hormone levels were measured. RESULTS: The increase in prolactin level after mCPP administration was more robust in patients than in controls. The prolactin response following 0.5 mg/kg of mCPP was partially blocked by ritanserin in patients, but totally blocked in healthy controls. The cortisol responses in both groups did not differ statistically significant from each other and were entirely blocked by ritanserin. None of the subjects experienced an exacerbation of obsessive compulsive symptoms. CONCLUSION: The neuroendocrine results show an enhanced susceptibility of OCD patients for the mCPP-induced prolactin response, which effect seems to be due to an increased sensitivity of 5-HT2 receptors.     

Dexamethasone suppression test and plasma dexamethasone levels in bulimia

A 1-mg dexamethasone suppression test (DST) was carried out in 66 women with bulimia and in 26 age- and sex-matched controls. Blood samples were obtained at 4 PM on the day following dexamethasone ingestion, and levels of cortisol and of dexamethasone in the plasma were measured. Thirty-two percent of the patients vs only 7% of the controls had plasma cortisol levels of 140 nmol/L (5 micrograms/dL) or greater following the DST (a positive DST). The plasma levels of dexamethasone varied substantially, and there was a significant inverse relationship between the plasma level of cortisol and that of dexamethasone. Patients with positive DST results had lower levels of plasma dexamethasone than did those with negative DST results, and the mean plasma level of dexamethasone was lower in the bulimic group than in the control group. These results suggest that factors other than a disturbance of hypothalamic-pituitary-adrenal activity may contribute to positive DST results in bulimia.     

The effect of stress on the dexamethasone suppression test

The dexamethasone suppression test (DST) was studied in 40 presurgical subjects and 20 controls. Cortisol plasma concentrations were measured before and after a nocturnal dose of 1 mg dexamethasone. Nineteen of the 40 patients (47.5%) failed to show a suppression of plasma cortisol after dexamethasone. Nonsuppression on the DST was associated with a significantly higher baseline plasma cortisol concentration. Another putative indicator of emotional stress, the level of acute anxiety, was also studied. There was a significant difference in the level of acute anxiety among suppressors, nonsuppressors, and controls--the level of anxiety in nonsuppressors being significantly higher than in controls. It is concluded that stress associated with a physical danger can be a cause of nonsuppression on the DST.