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。     

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。     

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     

精神疾病患者血小板5-羟色胺水平与自杀

目的：探讨精神分裂症和抑郁症患者血小板5-羟色胺（5-HT）水平与自杀的关系。方法：对66例精神分裂症患者、61例抑郁症患者和26名正常对照组，采用高效液相-电化学检测法测定血小板5-HT水平并作5年的随访。结果：精神分裂症自杀组血小板5-HT水平显著高于正常对照组，抑郁症患者血小板5-HT水平显著低于正常对照组。在入组后的5年间有26例再次发生自杀，再次自杀组的血小板5-HT水平显著低于未再自杀组。结论：低血小板5-HT水平可能对预测精神疾病患者未来的自杀有一定的参考价值。     

创伤后应激障碍与抑郁症患者对小剂量地塞米松抑制试验的反应

目的 通过小剂量的地塞米松抑制试验来比较抑郁症与创伤后应激障碍（PTSD）患者的垂体-肾上腺轴功能.方法 采用酶联免疫吸附法（ELISA）测定30例抑郁症和PTSD 患者的血浆中皮质醇、促肾上腺皮质激素基线水平,并行小剂量地塞米松（0.35 mg）抑制试验后再测定两组血浆的皮质醇、促肾上腺皮质激素水平.结果 抑郁症和PTSD 患者的的血浆皮质醇、促肾上腺皮质激素（ACTH）基线水平的差异无统计学意义（P＞0.05）;PTSD 患者对小剂量地塞米松抑制试验与抑郁症组比较,表现为皮质醇和ACTH的降低,即呈现超敏反应（P〈0.05）.结论 PTSD 患者对小剂量地塞米松抑制试验呈现超敏现象,这恰恰为该类PTSD 患者存在持久亢进的垂体-肾上腺轴功能的假说提供了证据.     

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。     

抑郁症的神经内分泌学初步研究

目的：研究抑郁症的血浆β-内啡肽及其他神经内分泌改变。方法：采用放射免疫法对抑郁症患者的血浆β-内啡肽及其他神经内分泌进行测定，并与正常人对照。结果：患者组的β-内啡肽（β-EP）,生长抑素（SS），肿瘤坏死因子（TNF），白细胞介素-8（IL-8），白细胞介素-10（IL-10）明显高于对照组，女性白细胞介素-6（IL-6）高于对照组，生长激素（GH）低于对照组，促肾上腺皮质激素（ACTH），促肾上腺皮质激素释放激素（CRH），催乳素（PRL），神经肽Y（NPY），白细胞介素-1（IL-1），白细胞介素-2（IL-2），白细胞介素-4（IL-4），两组无差异。结论：抑郁症存在血浆β-内啡肽及其他神经内分泌异常。     

抑郁障碍患者下丘脑—垂体—肾上腺轴的功能与自杀行为的关系(英文)

背景目前对抑郁障碍患者自杀行为的神经-内分泌研究仍较少,且结果多不一致。目的探讨国内抑郁障碍患者下丘脑-垂体-肾上腺(hypothalamus-pituitary-adrenal,HPA)轴释放功能与自杀行为的关系。方法比较14例2个月内有过自杀行为的抑郁障碍患者(抑郁研究组)和15例不伴自杀行为的抑郁障碍患者(抑郁对照组)的HPA轴功能。以地塞米松抑制试验(dexamethasone suppression test,DST)、一天中血浆皮质醇浓度的昼夜变化(在帕罗西汀治疗前及治疗6周后评估)以及治疗前和治疗后的24小时尿17-羟皮质醇和24小时尿游离皮质酮,评估HPA轴释放功能。同时以汉密顿抑郁量表(Hamilton Depression Rating Scale,HAMD)评定抑郁严重程度。另外测定15名无抑郁障碍的健康体检者的白天皮质醇浓度。结果抑郁研究组与抑郁对照组之间24h尿皮质醇浓度的差异无统计学意义,尿皮质醇浓度差异也无统计学意义。治疗前两组血浆皮质醇的午夜分泌低谷均不明显,而治疗后的分泌低谷变得明显。抑郁研究组DST阳性率显著高于对照组(57%对20%,χ2=4.24,p=0.039)。无论治疗前后,抑郁研究组患者血浆皮质醇水平与HAMD量表总分及绝望感和自杀观念的因子分呈显著正相关,但是抑郁对照组中这些相关系数无统计学意义。抑郁研究组早晨8点的血浆皮质醇浓度在治疗前后均显著高于健康对照组,而抑郁对照组的这一浓度并不比健康对照组高。结论本研究结果与先前关于抑郁症与HPA轴功能关系的研究结果大致相同。尽管如此,有自杀行为与无自杀行为的抑郁症患者之间还是存在某些差异。这些差异提示可能存在特定的自杀相关的HPA轴功能紊乱。有必要在大样本研究中进一步验证这些差异,以期能够在只报告有过自杀观念的人群中鉴别出实际有过自杀行为的个体。     

DST与精神病理及临床变化的关系

近来,情感性精神病的研究集中在神经内分泌上。DST敏感性强,特异性高,因而被广泛用于临床。尽管DST有些矛盾的结果,仍有50%以上的急性内源性抑郁病人,服地塞米松后抑制皮质醇分泌的能力降低。但关于内源性及神经症性抑郁的定义,仍存在争论。所以,神经内分泌研究结果的一致性,可能部分取决于各临床诊断标准中对抑郁症亚型的定义。     

抑郁症的唾液地塞米松抑制试验

研究抑郁性神经症ＨＰＡ轴功能及唾液皮质醇和血浆皮质醇的相关性。对２４例重型抑郁症，２０例抑郁性神经症、１８例健康对照组进行了血浆和唾液地塞米松抑制试验。结果 唾液皮质醇和血浆皮质醇有明显的相关性，抑郁性神经症和重型抑郁症的ＤＳＴ阳性率基本一致，没有明显差异。     

The endocrine abnormalities of depressive patients]

In the present study, the levels of the baseline cortisol, thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4) and growth hormone (GH) were determined in 64 depressive patients, 17 patients with other depressive disorders and 19 normal controls. Meanwhile, dexamethasone suppression test (DST) and insulin tolerance test (ITT) were conducted. The baseline cortisol level at 23:00 in the depressive group (8.12 +/- 5.55 micrograms/dl) was significantly higher than that in the normal control group (4.80 +/- 2.10 micrograms/dl), and DST nonsuppression ratio in the depressive group (14.5%) was significantly higher than those in the other two groups (0%). There were not significantly differences in the levels of the baseline TSH, T3 and T4 between the three groups. There were not significantly differences in the baseline GH level between the three groups, but GH level in the depressive group at 90 min. after infusing insulin was significantly lower than that in the normal control group. The results showed the HPA axis hyperactivity, normal thyroid function and blunted GH response to insulin-induced hypoglycemia at 90 min. in ITT in the depressive patients.     

The dexamethasone/corticotropin-releasing hormone test in depression in bipolar and unipolar affective illness.

The combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test was performed in forty patients with depression (12 male, 28 female), aged 20-68 years, in the course of affective illness (16 bipolar, 24 unipolar) both during acute depressive episode and in remission. The results were compared with those of 20 healthy control subjects (10 male, 10 female), aged 22-52 years. During acute depressive episode, cortisol concentration at 16 h after dexamethasone, 1.5 mg, and cortisol release after subsequent infusion of CRH, 100 microg, were significantly elevated in bipolar patients compared with unipolar ones and with control subjects. Patients with multiple episodes of unipolar depression exhibited greater cortisol levels after CRH than control subjects. In remission, significantly higher cortisol concentrations measured at 30 min(-1) h after CRH infusion were found in bipolar than in unipolar patients. Male bipolar patients had significantly higher cortisol level than bipolar females before and at 1.5 h after CRH. First episode unipolar patients during remission had lower levels of cortisol than control subjects before and at 1.5 h after CRH. Correlation between the magnitude of cortisol response and age was found within unipolar depressed patients but not in bipolar ones. On the other hand, correlation of test results with intensity of depression measured by Hamilton scale as well as with insomnia and anxiety subscales was more robust in bipolar subjects than in unipolar ones. It is concluded that the dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity, detected by DEX/CRH test is significantly more marked in patients with depression in the course of bipolar affective illness than in unipolar depression. Within unipolar depression, this dysregulation may increase with the time course of the illness.     

Serotonergic and dopaminergic neuroendocrine responses of male depressive patients before and after a therapeutic ECT course

Background: Electroconvulsive therapy (ECT) is an effective treatment for major depressive illness, even for patients who do not respond to antidepressant drugs. According to the prevailing neurophysiological hypotheses for depression, it can be expected that an ECT therapeutic course modulates the responsivity of central neurotransmitter systems, but the results up to now have been inconclusive. To test such hypotheses, we studied possible changes in the serotonergic and in dopaminergic systems' responsivity in 11 male patients with major depression by performing neuroendocrine challenge tests before and after a therapeutic ECT course. Methods: Serotonergic responsivity was assessed by measuring the prolactin and cortisol responses to i. v. administration of the serotonin uptake inhibitor clomipramine (CMI test), and dopaminergic responsivity by measuring the prolactin responses to the dopamine receptor blocker haloperidol (HAL test), administered intramuscularly. The prolactin and cortisol responses during the first and the last ECT of the course (8 to 13 sessions) were also assessed. The CMI and HAL tests were also performed in 13 male healthy subjects. Results: The prolactin responses to CMI were significantly blunted in the patient group compared to the control group, and remained unaltered at the end of the ECT course, although the depressive symptomatology was substantially reduced from 27.8 ± 7.1 to 4.8 ± 2.3 points in the Hamilton Depression Rating Scale. The cortisol responses to CMI were blunted before the ECT course compared to controls, but not after the course: there was a moderate increase of cortisol at + 30 min in the CMI test after the ECT course compared to that before ECT (p = 0.05). The prolactin and cortisol responses to the electrical stimulus during the first and the last ECT were identical. Conclusions: The strong therapeutic effect of ECT in depression, observed already at the end of the course, is not a result of considerable modifications in central serotonergic or dopaminergic responsivity, as revealed by the neuroendocrine challenge tests and the hormone responses to the electrical stimulus. The enhancement of the cortisol responses to CMI after the course may indicate a moderate increase in 5-HT1A receptor responsivity. Received: 5 March 2002 / Accepted: 15 July 2002     

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.     

抑郁症患者脑脊液生长抑素及单胺代谢产物的测定

目的 探讨抑郁症可能的生化病理机制,方法 采用放射免疫测定法及高效液相色谱法,分别测定２７例抑郁症患者和２７例对照者脑脊液（ＣＳＦ）生长抑素（ＳＳ）及单胺代谢产物水平。结果抑郁症组ＧＳＦ中ＳＳ水平和３－甲氧－４羟苯乙二醇（ＭＨＰＧ）水平（Ｐ〈０．０５）和５－羟吲哚乙酸水平（Ｐ〈０．０１）,均低于对照组,而抑制症组ＣＳＦ中高香草酸含量与对照组间的差异无显著性（Ｐ〉０．０５）;抑郁症组ＣＳＦ中ＳＳ与Ｍ     

Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome

Maximum nocturnal serum melatonin level (MTmax) in relation to some clinical variables was studied in 32 patients with a major depressive episode and in 33 healthy subjects with reference to the outcome of the dexamethasone suppression test (DST). Significant regressions were found between MTmax levels and clinical rating scores in CPRS, interpreted as retardation symptoms. Four healthy subjects with disposition for dysthymic reactions had subnormal MTmax levels, which differed from MTmax levels in subjects without such disposition. Patients but not the healthy subjects, who reported parental loss before 17 years of age, had subnormal MTmax levels and differed from patients with no reported parental loss. Patients with no reported suicidal behaviour in clinical history had significantly lower MTmax levels than patients with reported suicide attempts. No relations were found between low MTmax levels and diagnoses, duration of illness, reported inheritance for depressive illness or sleep disturbances. A hypothetical low melatonin syndrome in depression is proposed: low nocturnal melatonin, abnormal dexamethasone suppression test, disturbed 24-h rhythm of cortisol, less pronounced daily and annual cyclic variation in depressive symptomatology.     

Platelet MAO activity and the dexamethasone suppression test in bipolar depression

The correlation between postdexamethasone cortisol levels after the dexamethasone suppression test (DST) and platelet monoamine oxidase (MAO) activity was studied in 31 depressed female inpatients with Research Diagnostic Criteria primary, endogenous, bipolar depression (12 bipolar 1 and 19 bipolar 11). Out of the 31 patients, 25 showed abnormal DST results. Platelet MAO activity did not differ significantly from the matched control group. There was a trend that patients with higher MAO activity had lower postdexamethasone cortisol levels, but it was significant only for the 0800 hr cortisol levels.     

Release of corticotropin after administration of corticotropin-releasing hormone in depressed patients in relation to the dexamethasone suppression test

The possible hypersecretion involvement of corticotropin-releasing hormone (CRH) in the pathophysiology of hypothalamic-pituitary-adrenocortical axis disturbances in patients with major depressive episode and with an abnormal dexamethasone suppression test (DST) was investigated. The corticotropin (ACTH) and cortisol response to the injection of 45 μg of synthetic human CRH at 1630 were analyzed in 24 inpatients with normal (suppressors) or abnormal (nonsuppressors) DST. The outcome of the DST was analyzed using 3 cut-off points for the cortisol levels. The clinical assessments included two rating scales. The results showed that nonsuppressors had a significantly lower ACTH response to CRH stimulation than suppressors at all cut-off points (calculated as net area under the curve and as the difference between the peak and the baseline level) despite no significant differences in the severity of depression.