抑郁症与生长激素轴功能的研究进展

本文综述了抑郁症与生长激素轴功能的研究进展情况。     

抑郁症患者治疗前后血浆皮质醇水平的变化

目的:探讨抑郁症患者治疗前后血浆皮质醇水平的变化。方法:对160例抑郁症患者给予抗抑郁药治疗6周,分别于治疗前及治疗后进行汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评估及血浆皮质醇水平检测。结果:本组治疗前后HAMD总分分别为(24.98±5.10)和(7.57±5.61);HAMA总分分别为(20.62±6.90)和(6.21±5.17);血浆皮质醇水平分别为(407.34±144.29)nmol/L和(354.64±137.13)nmol/L。治疗后HAMD总分、HAMA总分及血浆皮质醇水平较治疗前明显下降(P均<0.001);不同性别间血浆皮质醇水平差异无统计学意义(P>0.05);血浆皮质醇变化值与HAMD、HAMA减分率不相关(r=0.084,r=0.049;P均>0.05)。结论:抗抑郁药物治疗可显著降低抑郁症患者血浆皮质醇水平。     

抑郁症患者血浆一氧化氮浓度检测及其临床意义

目的探讨血浆一氧化氮(NO)浓度与抑郁症之间的关系.方法采用硝酸还原酶法对34例抑郁症患者血浆一氧化氮(NO)浓度进行检测,并与正常对照组比较.结果抑郁症患者血浆一氧化氮(NO)浓度为20.79±12.80μmol/L,低于正常对照组30.68±13.5μmol/L,存在显著性差异(t=3.393,P＜0.001);治疗前后比较,治疗前血浆一氧化氮(NO)浓度(20.77±14.80)μmol/L低于治疗后(28.33±22.52)μmol/L,但无显著性差异(t=-1.313,P=0.203).血浆一氧化氮(NO)浓度与年龄、病程和家族史等无相关性.结论一氧化氮(NO)可能在抑郁症的发病机制中起一定作用.     

抑郁症患者血浆内皮素水平的研究

目的探讨抑郁症患者血浆内皮素（ＥＴ）水平及其与下丘脑垂体肾上腺（ＨＰＡ）轴之间可能的联系。方法采用放射免疫法测定４２例抑郁症患者及３０名正常对照的晨８时血浆ＥＴ１及皮质醇浓度。结果单、双相抑郁血浆ＥＴ１与皮质醇浓度均显著高于正常对照（Ｐ＜００１）,但仅双相抑郁血浆ＥＴ１与皮质醇有直线相关关系（ｒ＝０５３,Ｐ＜００１）。结论抑郁症患者血浆ＥＴ１水平升高可能与部分（双相）抑郁患者ＨＰＡ轴功能亢进有关。     

抑郁症自杀未遂患者血浆中细胞因子水平的研究

目的探讨细胞因子在抑郁症自杀未遂患者发病中的作用。方法对44例抑郁症自杀未遂患者在抗抑郁治疗前后分别进行HAMD评分,采用酶联免疫吸附法检测IL-2、IL-6,并以30例健康者作对照。结果抑郁症自杀未遂患者组治疗前IL-2、IL-6水平明显高于对照组（P〈0.05）,经6周治疗后,IL-2水平明显下降,IL-6水平有增高趋势（P〉0.05）。结论IL-2可能在抑郁症自杀的发病中起一定作用。IL-6的水平可作为抑郁症自杀的一个特征性标志。     

抑郁症患者血浆同型半胱氨酸水平的测定

目的:测定抑郁症患者及正常人血浆同型半胱氨酸(Hcy)水平,评价其意义. 方法:收集46例抑郁症(抑郁症组)及38名健康者(对照组)血液标本,采用高效液相色谱法测定血浆Hcy水平,放射免疫法测定血浆维生素B12和叶酸水平,比较两组间差异. 结果:抑郁症组血浆Hcy水平(13.2±6.2)μmol/L,显著高于对照组(7.6±2.4)μmol/L.抑郁症组平均血浆维生素B12水平为(334.0±5.7)ng/L,血浆叶酸水平为(5.9±4.0)μg/L;而对照组分别为(344.0±7.5)ng/L和(7.8±3.0)μg/L,均以抑郁症组显著较低(P<0.05). 结论:血浆Hcy水平升高可能与抑郁症有关.     

抑郁症患者血小板蛋白激酶C水平的变化

目的：探讨抑郁症患者血小板细胞浆和细胞膜蛋白激酶C(PKC)的变化及其意义。方法：采用[^3H]12,13-二丁酰佛波醇酯(PDBu)结合法,测定23例抑郁症患者和10名正常对照者的血小板细胞浆和细胞膜PKC水平。结果：与正常对照组比较,抑郁症组血小板胞膜PKC水平显著降低,血小板胞浆PKC水平差异无显著性。结论：蛋白激酶C的改变在抑郁症发病机制中可能起一定作用。     

抑郁症患者血浆孤啡肽含量研究

目的为探讨抑郁症的可能病因,对抑郁症患者血浆孤啡肽(OFQ)含量进行了对照研究。方法抽取29例抑郁症患者和24例正常人的静脉血,用放射免疫(RIA)的方法分别测其血浆中OFQ含量,比较抑郁症患者和正常人血浆OFQ含量有无差异,抑郁症患者OFQ含量与汉密顿抑郁量表(HAMD)评分的相关性,及抑郁症患者血浆OFQ含量的影响因素。结果与正常人比较,抑郁症组OFQ含量明显升高(t=8．70,P＜0．0001)；OFQ含量与HAMD评分呈正相关(r=0．63,P＜0．01)；OFQ含量主要与抑郁情绪、夸大、失眠、自卑感、自杀、强迫症状、教育水平、关注身体健康等因素相关,而年龄、性别、职业、病程、曾用药等其他因素与OFQ含量无明显相关。结论通过测量血浆OFQ含量可作为抑郁症诊断的参考指标。     

抑郁症患者血浆P物质含量变化及其相关性研究

目的探讨抑郁症患者血浆P物质水平的变化及其与抑郁症的关系。方法对32例抑郁症患者(抑郁症组)应用帕罗西汀治疗6周,分别于治疗前和治疗后第6周末采用放射免疫法测定患者血浆P物质含量;同时以汉密尔顿抑郁量表(24项,HAMD)、汉密尔顿焦虑量表(18项,HAMA)评定症状严重程度,以HAMD减分率评定疗效。以32名健康志愿者为对照组。结果抑郁症组患者治疗前血浆P物质水平[(51±13)ng/L]明显高于对照组[(43±11)ng/L],差异有统计学意义(P=0.010);治疗后血浆P物质水平[(44±10)ng/L]较治疗前明显下降,差异有统计学意义(P=0.001);治疗前后血浆P物质的变化与HAMD总分值的减分率呈显著正相关(rs=0.826,P=0.000)。结论抑郁症患者的血浆P物质存在异常,动态观察血浆P物质水平变化可能有助于判断疗效。     

Plasma levels of beta-endorphin, cortisol, prolactin and growth hormone in depressed patients

Basal serum cortisol, growth hormone, prolactin and immunoreactive (IR) plasma beta-endorphin levels were measured in 31 depressed patients (14 endogenous, 17 nonendogenous) undergoing the dexamethasone suppression test. The endogenously depressed patients had significantly higher (22.55 +/- 1.34 micrograms/dl) predexamethasone cortisol levels than the nonendogenous patients (16.34 +/- 1.93 micrograms/dl). The mean serum prolactin and growth hormone values of these two groups were not significantly different, while plasma IR-beta-endorphin levels of the endogenous group (40.11 +/- 3.57 pg/ml) were significantly lower than those of the nonendogenous group (120.33 +/- 27.98 pg/ml). Neither group showed a significant correlation between plasma IR-beta-endorphin and serum cortisol values. These results indicate that measurement of predexamethasone serum cortisol values and plasma IR-beta-endorphin could be valuable laboratory tests in the diagnosis of depression.     

难治性抑郁症的临床特征以及甲状腺激素水平的对照研究

目的探讨难治性抑郁症的临床特征以及甲状腺激素水平。方法采用汉密尔顿抑郁量表17项版(HRSD-17)和汉密尔顿焦虑量表(HAMA)对符合《国际疾病分类(第10版)》(ICD-10)诊断标准的48例难治性抑郁症患者和54例非难治性抑郁症患者进行测评,采用放射免疫法测定两组患者血清促甲状腺激素(TSH)、总三碘甲状腺原氨酸(TT3)、总甲状腺素(TT4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)水平。结果难治性抑郁症组(TRD组)与非难治性抑郁症组(非TRD组)比较,起病年龄更早[(16.4±3.8)岁vs.(23.6±4.3)岁],受教育年限更短[(8.7±2.1)年vs.(10.6±2.3)年],本次发病病程更长[(65.1±18.3)月vs.(4.9±2.5)月],HRSD-17中行为阻滞因子评分更高[(8.37±2.43)分vs.(6.51±2.55)分],血清FT3水平更低[(3.93±0.52)pmol/L vs.(4.21±0.49)pmol/L],差异均有统计学意义(P0.05)。结论难治性抑郁症患者单次病程长,起病早,文化水平低,阻滞症状重,血清FT3水平低。     

Effect of clonidine on growth hormone release in psychiatric patients and controls

The stimulation of human growth hormone (HGH) release by clonidine (0.15 mg i.v.) was studied as a test of the postsynaptic α-receptor sensitivity of psychiatric patients. In this test, endogenous depressives showed a significantly reduced HGH response to clonidine as compared to normal controls, neurotic-reactive depressives, and schizophrenics. However, no differences were found between the endogenous depressives and a group of schizoaffective patients. HGH response to clonidine was not correlated with plasma levels of noradrenaline, serum cortisol, free fatty acids, or blood glucose. Within the group of normal control subjects, a reduced HGH response was found in most postmenopausal women and in some regular users of alcohol. Our findings suggest that patients with endogenous depression are characterized by a subsensitivity of postsynaptic α-receptors or of structures related to them. The clonidine test shows promise as an indicator of vulnerability to endogenous depression.     

Anatomically specific changes in the expression of somatostatin, growth hormone-releasing hormone and growth hormone receptor mRNA in diabetic rats

Growth hormone (GH) secretion is altered in poorly controlled diabetic animals. However, modifications in the hypothalamic neuropeptides that control GH secretion, somatostatin and GH-releasing hormone (GHRH), as well as changes in the sensitivity of the hypothalamus and pituitary to the feedback effects of GH, are less clear. We have used RNase protection assays and in-situ hybridization to address whether the mRNA expression of GH, somatostatin and GHRH, as well as of the GH receptor (GHR) in the hypothalamus and anterior pituitary, are altered in streptozotocin-induced diabetic rats. After induction of diabetes, rats were treated with insulin twice daily for 3 weeks to obtain either poorly controlled (mean plasma glucose >300 mg/dl) or well-controlled diabetic rats. Although no significant change in pituitary GH mRNA expression was found, the hypothalamic expression of GHRH and somatostatin mRNA was reduced in poorly-controlled diabetic rats and returned to control values with normalisation of plasma glucose concentrations (P<0.0001 and P<0.002, respectively). Somatostatin mRNA expression was reduced only in the central portion of the periventricular nucleus, with no change being seen in the other areas of the periventricular nucleus or in the arcuate, suprachiasmatic or paraventricular nuclei. A significant decline in GHRH mRNA expression was observed in both the arcuate nucleus and ventromedial hypothalamus. Anterior pituitary GHR mRNA expression was significantly reduced in both well and poorly-controlled diabetic rats, while there was no change in the hypothalamus. To examine whether the evolution time of the diabetes influences these parameters, in a subsequent experiment, diabetic rats received no insulin for 2 months. A significant decline in GHRH and somatostatin mRNA expression was also observed in these rats. In addition, pituitary GH mRNA expression declined significantly in long-term diabetic rats. These results demonstrate that: (1) the expression of both GHRH and somatostatin declines specifically in anatomical areas involved in anterior pituitary hormone control; (2) GHR mRNA expression is decreased in the pituitary of diabetic rats, but not in the hypothalamus, and does not return to control values with normalisation of mean blood glucose concentrations; and (3) the evolution time of the diabetes is important for detecting some changes, including the decrease in pituitary GH mRNA expression.     

Dextro- and L-amphetamine are equipotent in releasing human growth hormone

(1) Peak plasma human growth hormone (HGH) response to a single intravenous administration of d- and l-amphetamine sulfate 0.1 mg/kg was evaluated in ten healthy subjects each being his own control. (2) No statistical difference was found between the mean HGH responses of the subjects to either amphetamine isomer. Also, the number of deficient HGH responses to d- and l-amphetamine was equal. (3) By analogy with similar data from studies in monkeys, the involvement of noradrenergic rather than dopaminergic mechanisms in mediating amphetamine-induced HGH release in man is tentatively suggested and possible implications for recent neuroendocrinological findings in endogenous depressives are discussed.     

The thyrotropin-releasing hormone test in the diagnosis of unipolar depression

The establishment of criteria for a blunted thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) may prove useful in distinguishing patients with major unipolar depression from patients with nonmajor depressions and controls. To this end, we administered the TRH test to a group of depressed, euthyroid inpatients diagnosed by Research Diagnostic Criteria and 20 normal volunteer controls. The mean maximal TSH response (delta TSH) to infusion of 500 micrograms of TRH of 7.3 +/- SD 4.6 microIU/ml in the 105 patients with major depressive disorder, primary unipolar subtype was significantly lower than that of 13.4 +/- SD 4.4 in the 20 controls and 10.9 +/- SD 4.4 in the 40 patients with nonmajor depressions. The differences were not explainable by differences in baseline thyroid function, age, or sex. When a delta TSH less than or equal to 7.0 microIU/ml was used as a diagnostic test for unipolar depression, the sensitivity of the TRH test was 56%, the specificity 93%, and the predictive value 91%. These results suggest that the TRH test may be useful in confirming the diagnosis of major unipolar depression and hence identifying patients likely to respond to antidepressant medications or electroconvulsive therapy.     

Acute cortisol administration increases sleep depth and growth hormone release in patients with major depression

Acute administration of cortisol increases non-rapid-eye movement (non-REM) sleep, suppresses rapid-eye movement (REM) sleep and stimulates growth hormone (GH) release in healthy subjects. This study investigates whether cortisol has similar endocrine and electrophysiological effects in patients with depression who typically show a pathological overactivity of the hypothalamus-pituitary-adrenal (HPA) system. Fifteen depressed inpatients underwent the combined dexamethasone/corticotropin-releasing hormone test followed by three consecutive sleep EEG recordings in which the patients received placebo (saline) and hourly injections of cortisol (1mg/KG BW). Cortisol increased duration and intensity of non-REM sleep in particular in male patients and stimulated GH release. The activity of the HPA axis appeared to influence the cortisol-induced effects on non-REM sleep and GH levels. Stimulation of delta sleep was less pronounced in patients with dexamethasone nonsuppression. In contrast, REM sleep parameters were not affected by the treatment. These data demonstrate that the non-REM sleep-promoting effects of acute cortisol injections observed in healthy controls could be replicated in patients with depression. Our results suggest that non-REM and REM sleep abnormalities during the acute state of the disease are differentially linked to the activity of the HPA axis.     

Longitudinal neuroendocrine changes assessed by dexamethasone/CRH and growth hormone releasing hormone tests in psychotic depression

Although psychotic depression has been reported to exhibit a greater degree of dysregulation of hypothalamic-pituitary-adrenocortical (HPA) function than non-psychotic depression, little is known concerning hypothalamic-pituitary-somatotropic (HPS) function in psychotic depression and how neuroendocrine function changes after treatment. To investigate the longitudinal changes in HPA and HPS system function in psychotic depression, we performed repeated dexamethasone/corticotropin releasing hormone (DEX/CRH) tests and growth hormone (GH) releasing hormone (GHRH) tests in inpatients with major depressive disorder. The psychotic depression group exhibited greater elevation of ACTH responses to the DEX/CRH test and stronger decreases in GH responses to the GHRH test than the non-psychotic depression group at admission. At discharge, the neuroendocrine responses to the DEX/CRH test of the psychotic depression group were still stronger than those of the non-psychotic depression group, though there were no significant differences in severity of depression between the groups. There were significant longitudinal changes in neuroendocrine responses to the DEX/CRH test between admission and discharge. The psychotic depression group exhibited increased GH responses to GHRH at discharge compared with those at admission, whereas no significant longitudinal change in GH response was found in the non-psychotic depression group. Consequently, there were no significant differences in GH responses to GHRH between the psychotic and non-psychotic depression groups at discharge. The results of GHRH test showed no significant relationships with severity of depression except psychotic features and the results of the DEX/CRH test. Our findings suggest that the HPS axis may be associated with psychotic features rather than general severity of depression. Further longitudinal studies are needed to clarify the role of HPS function in psychotic depression and whether sustained dysregulation of HPA function in psychotic depression is associated with a poor outcome after discharge.     

Electroconvulsive therapy (ECT) increases plasma growth hormone, prolactin, luteinising hormone and follicle-stimulating hormone but not thyrotropin or substance P

(1) Using radioimmunoassay, plasma levels of pituitary hormones and substance P were measured during the first 30 min after ECT in 28 sets of peripheral blood samples obtained from 21 patients (14 males and seven females) treated with ECT for endogenous depression. (2) The earliest increase was in plasma growth hormone and follicle-stimulating hormone occurring 5–14 min after ECT, followed by increases in plasma prolactin and luteinising hormone, 15–24 min after ECT. At 25–35 min after ECT only the increase in plasma growth hormone was still significant. (3) ECT had no effect on plasma levels of thyrotrophin or substance P. (4) It is suggested that the observed changes in peripheral levels of pituitary hormones are compatible with non-specific stimulation of the hypothalamo-pituitary system due to the acute stress of ECT or anesthesia.