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。     

广泛焦虑障碍的下丘脑-垂体-肾上腺轴及PRL研究

目的　研究广泛焦虑障碍 (GAD)的下丘脑 垂体 肾上腺轴 (HPA轴 )功能及催乳素 (PRL)改变。方法　研究组分别为 3 0例GAD患者 ,对照组为 2 5例抑郁性神经症 (DN)患者及 1 5例健康人。测基础状态时皮质醇及PRL浓度 ,行地塞米松抑制试验 (DST)后再检测皮质醇浓度。比较GAD与DN及正常对照组 (NC)的差别。结果　 3组基础皮质醇、PRL水平无显著差异。GAD组DST阳性率显著小于DN组而大于正常组。DST阳性率与基础皮质醇呈正相关。 3组PRL浓度均无差异。结论　GAD可能有HPA轴功能异常 ,PRL未见异常     

强迫症患者血小板5-羟色胺、血浆催乳素及地塞米松抑制试验的研究

目的　从神经递质与神经内分泌角度探讨强迫症的生化病理机制。方法　采用高效液相色谱法及放射免疫测定法 ,分别测定 2 9例强迫症患者和 2 8名正常对照者血小板 5 羟色胺 (5 HT)含量及血浆催乳素 (PRL)含量 ,并进行地塞米松抑制试验 (DST)。结果　强迫症组血小板 5 HT水平[(0 8± 1 0 )nmol/10 9个血小板 ]低于正常对照组 [(1 4± 1 2 )nmol/10 9个血小板 ],差异有显著性 (P <0 0 5 ) ;而血浆PRL水平 [(337± 192 )nmol/L]与对照组 [(2 87± 116 )nmol/L]相比 ,差异无显著性 (P >0 0 5 ) ;强迫症组于晨 8时的血浆基础皮质醇含量 [(375± 15 2 )nmol/L]高于正常对照组 [(2 6 2± 138)nmol/L],差异有非常显著性 (P <0 0 1) ,其DST阳性率为 2 4 %～ 17% ,与正常对照组 (14 %～ 11% )相比 ,差异无显著性 (P >0 0 5 )。结论　强迫症患者存在 5 HT能低下和神经内分泌功能的紊乱 ,强迫症的 5 HT能假说能解释其某些内分泌功能紊乱。     

焦虑和抑郁障碍共病血浆单胺类神经递质研究

目的：探讨血浆单胺类神经递质与焦虑和抑郁障碍共病的关系。方法：使用高效液相－电化学检测法检测25例焦虑和抑郁障碍共病、30例抑郁症、20例焦虑症患者和21例正常人的血浆去甲肾上腺素（NE）和5－羟色胺（5－HT）浓度。结果：3组患者的血浆NE浓度均显著高于正常对照组,但共病组与抑郁症组和焦虑症组无明显差异;抑郁症组的血浆5－HT浓度显著低于正常对照组,共病组和焦虑症组的血浆5－HT浓度与正常对照组无显著差异,3组患者之间血浆5－HT浓度也无显著差异。结论：血浆单胺类神经递质不能鉴别抑郁症和焦虑症,也不支持焦虑和抑郁障碍共病是第3种疾病的观点。     

抑郁症患者单胺类神经递质与血脂的相关性

目的：探讨抑郁症患者血浆单胺类神经递质与血脂的关系。方法：检测55例抑郁症患者和21例正常人的血浆去甲肾上腺素(NE)、5—羟色胺(5—HT)、血清总胆固醉(CH0)、甘油三酯(TG)、高密度脂蛋白—胆固醇(HDL-C)和低密度脂蛋白—胆固醇(LDL-C)。结果：抑郁症患者的血浆5—HT浓度和血清CH0浓度显著低于正常对照组，血浆NE浓度显著高于正常对照组；抑郁症患者的血浆5-HT浓度和血清CH0浓度呈显著正相关，血浆NE浓度与血清HDL-C浓度呈显著正相关。结论：抑郁症患者的血脂代谢异常与血浆单胺类神经递质有关。     

Tourette综合征患儿血浆催乳素含量的变化

为了从神经内分泌角度探讨Touretter综合征(TS)的发病机制,采用放射免疫方法对未应用药物治疗的22例TS患儿血浆催乳素(PRL)含量进行了测定,并与18例正常对照组儿童比较。结果表明TS患儿的血浆PRL含量显著高于对照组,提示PRL可能参与了TS的发病过程。     

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。     

广泛性焦虑障碍的神经生物学机制

广泛性焦虑障碍 (GAD)的神经生物学机制尚不清楚 ,神经影像学和神经递质研究提示某些特定脑区的功能异常 ,GABA/苯二氮复合体、 5 HT、去甲肾上腺素　一氧化氮、胆囊收缩素和下丘脑—垂体—肾上腺轴等功能紊乱均可能与GAD的发病有关。     

焦虑症患者的COR、甲状腺激素及自主神经的功能特点及神经内分泌、自主神经功能影响因素分析

目的探讨焦虑症患者的OR、甲状腺激素和自主神经功能特点,以及患者神经内分泌、自主神经功能的影响因素。方法选取我院收治的焦虑症患者98例,同时选取健康志愿者60例作为对照,测定COR、TSH、T3、T4以及HRV检测。结果与对照组相比,PD患者和GAD患者COR、TSH较高,HRV各项指标较低(P0.05);与GAD患者相比,PD患者COR和TSH较高,HRV指标较低(P0.05);与女性焦虑症患者相比,男性COR和TSH较低,HRV指标较高(P0.05);与≥50岁患者相比,50岁患者COR和TSH较低,HRV指标较高(P0.05)。结论焦虑症患者的性别、年龄和焦虑症的临床亚型对焦虑症患者自主神经功能以及神经内分泌紊乱有影响。     

广泛性焦虑障碍首次发病患者6种神经化学物质浓度的初步观察

广泛性焦虑障碍(GAD)是焦虑障碍的常见类型之一.虽有不少学者对多种相关神经化学物质进行研究,试图探索GAD发病机制及神经生化改变,但目前尚有许多不明之处.我们测定GAD患者血清脑源性神经营养因子(BDNF)、褪黑素、促肾上腺皮质激素、皮质醇、肾上腺素、去甲肾上腺素等浓度,并与正常对照组比较,旨在探讨GAD的生化改变.     

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.     

Psychoimmunoendocrine aspects of panic disorder.

Immunological, neuroendocrine and psychological parameters were examined in 14 psychophysically healthy subjects and in 17 panic disorder patients before and after a 30-day course of alprazolam therapy. T lymphocyte proliferation in response to the mitogen phytohemagglutinin, lymphocyte beta-endorphin (beta-EP) concentrations, plasma ACTH, cortisol and beta-EP levels were examined in basal conditions and after corticotropin-releasing hormone (CRH) stimulation. Cortisol inhibition by dexamethasone (DST) and basal growth hormone (GH) and prolactin levels were also examined. Depression, state or trait anxiety, anticipatory anxiety, agoraphobia, simple and social phobias, severity and frequency of panic attacks were monitored by rating scales. The immune study did not reveal any significant difference between patients and controls, or any effect of alprazolam therapy. The hormonal data for the two groups were similar, except for higher than normal basal ACTH and GH plasma levels, lower than normal ratios between the ACTH and cortisol responses to CRH, and blunted DST in some patients. All the impairments improved after alprazolam therapy, in parallel with decreases in anxiety and in severity and frequency of panic attacks.     

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.     

Higher postdexamethasone serum cortisol levels in agoraphobic than in nonagoraphobic panic disorder patients

The dexamethasone suppression test (DST) was performed in panic disorder (PD) patients with (n = 32) or without (n = 31) agoraphobia and in normal controls (n = 49). Postdexamethasone serum cortisol levels were significantly higher in agoraphobic PD patients (105.3 +/- 19.3 nmol/L) both when compared to PD patients without agoraphobia (47.3 +/- 7.7 nmol/L; p less than 0.01) and when compared to healthy controls (51.7 +/- 8.3 nmol/L; p less than 0.01). The rate of nonsuppressors (i.e., subjects displaying postdexamethasone cortisol levels greater than 138 nmol/L) was 28% and 3% in agoraphobic and nonagoraphobic PD patients, respectively, and 12% in controls. In patients, the postdexamethasone cortisol levels did not correlate with the number of panic attacks per week, baseline anxiety as measured using the Hamilton Anxiety Scale, depressive symptoms as measured using the Montgomery-Asberg Depression scale, or duration of illness. Data from eight patients in whom a second DST was performed after treatment with imipramine or clomipramine for three months indicate that a marked reduction of the number of anxiety attacks is not necessarily accompanied by a normalization of a pathological DST. In conclusion, it is suggested that the elevated postdexamethasone cortisol levels sometimes observed in agoraphobic PD patients are more closely related to the agoraphobic behavior than to the panic attacks per se.     

Cortisol, ACTH, and beta-endorphin after dexamethasone administration in Parkinson's dementia

The dexamethasone suppression test (DST) has been suggested as an effective tool for differentiating between depression and dementia. After administering 1 mg dexamethasone, we measured cortisol, ACTH, and beta-endorphin levels in 32 nondepressed patients with idiopathic Parkinson's disease (PD) (14 also with dementia) and 20 healthy, age-matched controls. Four of the 20 controls, 9 of the 18 with PD alone, and 8 of the 14 with PD and dementia were dexamethasone nonsuppressors (cortisol value greater than or equal to 5 micrograms/100 ml). PD patients without dementia (nonsuppressors) showed higher basal plasma values of cortisol (22.06 +/- 5.30 micrograms/100 ml) compared with the suppressors (13.38 +/- 3.30 micrograms/100 ml). Plasma ACTH and beta-endorphin responded in a coupled way to dexamethasone challenge. Higher basal levels of both peptides were found among PD patients (demented and nondemented), nonresponders to DST. Thus, the DST does not appear to be effective in differentiating between depression and dementia in PD. In addition, PD nonsuppressors showed higher basal values of plasma ACTH, beta-endorphin, and cortisol (similar to patients with major depression). This suggests that although the depression is clinically undetectable, both disorders may share some pathophysiological features at the hypothalamic hypophyseal adrenal level.     

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.     

Somatic symptoms and physiologic responses in generalized anxiety disorder and panic disorder: an ambulatory monitor study

BACKGROUND: Physiologic responses of patients with anxiety disorders to everyday events are poorly understood. OBJECTIVE: To compare self-reports and physiologic recordings in patients with panic disorder (PD), patients with generalized anxiety disorder (GAD), and nonanxious controls during daily activities. DESIGN: Participants underwent four 6-hour recording sessions during daily activities while wearing an ambulatory monitor. Physiologic and subjective data were recorded every 30 minutes and during subject-signaled periods of increased anxiety or tension or panic attack. SETTING: Participants' everyday environment. PARTICIPANTS: Twenty-six patients with PD and 40 with GAD, both without substantial comorbidity, and 24 controls. INTERVENTIONS: Recordings obtained during everyday activities. MAIN OUTCOME MEASURES: Recordings of heart interbeat intervals, skin conductance levels, respirations, motion, and ratings of subjective somatic symptoms and tension or anxiety. RESULTS: Patients with anxiety disorders rated higher on psychic and somatic anxiety symptoms than did controls. Common to both anxiety disorders was diminished autonomic flexibility that manifested itself throughout the day, accompanied by less precise perception of bodily states. The main differences between patients with PD and GAD were a heightened sensitivity to body sensations and more frequent button presses. There also was a trend toward heightened basal arousal in patients with PD, manifesting itself in a faster heart rate throughout the day. CONCLUSIONS: Patients with PD or GAD are more sensitive to bodily changes than nonanxious individuals, and patients with PD are more sensitive than those with GAD. Patients with PD experience more frequent distress than those with GAD and controls, but their physiologic responses are comparable in intensity. The findings suggest that the perception of panic attacks reflects central rather than peripheral responses. The diminished autonomic flexibility observed in both anxiety conditions may result from dysfunctional information processing during heightened anxiety that fails to discriminate between anxiety-related and neutral inputs.     

Platelet serotonin, plasma cortisol, and dexamethasone suppression test in schizophrenic patients.

BACKGROUND: Serotonin (5-HT) regulates hypothalamic-pituitary-adrenal (HPA) axis activity. Abnormal response to the dexamethasone suppression test (DST) and altered platelet 5-HT concentration have been shown in some schizophrenic patients. METHODS: Platelet 5-HT and plasma cortisol concentrations were determined simultaneously in 86 male schizophrenic patients before and after DST. Basal plasma cortisol and platelet 5-HT levels were also determined in 69 healthy male persons. RESULTS: Schizophrenic patients had higher plasma cortisol and platelet 5-HT concentrations than healthy persons. An abnormal escape from dexamethasone suppression was observed in 50% of patients. In these patients predexamethasone cortisol and platelet 5-HT concentrations were higher than in patients with normal DST. CONCLUSIONS: This study demonstrates that schizophrenic patients have the HPA axis dysregulation that could be connected with a disturbance in the 5-HT system.