Growth Hormone Responses to Administration of L-5-Hydroxytryptophan (L-5-HTP) in Manic-Depressive Psychoses

Fourteen hospitalized patients with manic-depressive psychoses received L-5-hydroxy-tryptophan (L-5-HTP), a serotonin precursor, which has been postulated as a potent antidepressive agent. Plasma human growth hormone (HGH) and glucose levels were measured at 30 minute intervals after oral administration of 200mg of L-5-HTP. Plasma cortisol levels prior to L-5-HTP administration were also measured. 1. In five manic-depressive (bipolar) patients, aged 17 to 60, each subject studied in manic state showed an adequate HGH response of more than 5.0ng/ml (maximum levels:17.7±7.1 ng/ml Mean± S.E.M., controls, aged 27 to 41:10.5±1.6 ng/ml), while those in depressive state failed to secrete HGH adequately (maximum levels ranged 1.4-4.8 ng/ml) (p>0.05). 2. Of five determinations from three endogenous depressive (unipolar) patients, aged 30 to 51, three showed adequate responses (maximum levels ranged 2.6–16.5 ng/ml). Nine out of 10 tests from six patients with protracted depressive symptoms prolonged for 2 to 6 years, aged 45 to 65, had deficient responses of HGH (maxi mum levels: 2.1±k0.5 ng/ml Mean±S.E.M., ranged 0.1–5.6 ng/ml) (p>0.01). 3. Deficiency of pituitary HGH secretion appeared to correlate neither with the score of Hamilton's Depression Scale nor with the global judgement on the severity of the illness. Increments in the blood glucose levels after L-5-HTP administration were only mild ones, to which HGH insensitivity may be irrelevant. Morning plasma cortisol levels in depressives, ob served as high as those in manics, also may be unrelated. 4. Treatment with 300 mg of L-5HTP daily for two weeks proved to have no favorable clinical effects on four depressive patients, who were categorized as non-responders of HGH. Because there is evidence suggesting pituitary hormone release related to brain bio-genic amines, the deficient HGH responses to L-5-HTP in depressed patients may be due to a neurochemical defect hypothesized in the manic-depressive psychoses. The HGH responses were most distinctly diminished in the protracted depressive patients, suggesting an endocrine hypofunction which may cause the fixation of the depressive symptoms.     

抑郁症晨重夕轻特征与生物学的关系

目的:探讨抑郁症患者临床症状晨重夕轻的特征与血浆皮质醇、细胞因子浓度的关系。方法:采用放射免疫法、酶联免疫吸附法对55例双相障碍(抑郁相)和抑郁发作诊断标准的抑郁症患者及38名正常对照组早7:00、晚7:00血浆皮质醇、IL-6、IL-2浓度进行测定,比较各指标早、晚浓度及早晚差值在抑郁症晨重夕轻组和无晨重夕轻组以及正常对照组的差异。结果:抑郁症晨重夕轻组和无晨重夕轻组早间的皮质醇浓度、早晚之间的皮质醇浓度差值均较正常对照组显著增高;晨重夕轻组晚间的血IL-6浓度较正常对照组显著增高,两组的IL-6早晚的差值与正常对照组相比有显著性差异;晨重夕轻组和无晨重夕轻组晚间IL-2水平均明显低于正常对照组。结论:抑郁症患者不管临床症状有无晨重夕轻的特征,均存在血浆皮质醇浓度早晨高于晚上和血浆IL-6浓度晚上高于早晨的异常改变。     

Reduction of Blood Platelet Serotonin Levels in Manic and Depressed Patients

Blood platelet serotonin levels were measured in unmedicated 12 manic and 74 depressive patients with 118 normal control subjects employed. Blood platelets were separated by multiple centrifugation in the medium of Naz-EDTA solution, and the loss of serotonin during collecting procedures was about 11%). The mean value of blood platelet serotonin levels in depressed patients was 594±288 ng/mg platelet protein (±S.D.), which was significantly lower than that for normal controls, 780±253 ng/mg protein (p<0.001). Age does not account for the reduction of serotonin levels both in depressed and in normal population. Unipolar and involutional depressed patients exhibited to have the most pronounced reduced levels of serotonin of various subtypes of depression, while bipolar depressed patients, neurotic and chronic characterological depressed patients as well as patients with first-episode depression had the values which were comparable with those in normal controls. Manic patients did not show enhancement but did reduction of serotonin levels, the mean being 5802±152 ng/mg protein, which made a contrast with their clinical manifestations of exhilaration and hyperactivity. Changes in blood platelet serotonin levels were determined before, during and after administration of L-5–HTP with a maintenance dose of 300 mg daily in nine depressed patients. Serotonin levels in all subjects were lifted to normal levels during the L-5–HTP treatment, while clinical symptoms were not improved with the treatment. Reduction of blood platelet serotonin levels in depressed patients may be due to their psychobiological distinction, which involves abnormal biogenic amine metabolism in the brain.     

A 24-hr monitoring of the integrated plasma concentration of aldosterone and cortisol in manic patients

(1) A 24-hr continuous monitoring of the fluctuations of plasma levels of cortisol and aldosterone was carried out in three manic-depressive patients during the manic phase. This study was done using a newly developed, portable, non-thrombogenic, constant blood-withdrawal system, that made possible the collection of blood samples for a 24-hr period, without interfering with the activity of the patient. The integrated concentration of aldosterone and cortisol in the plasma of the patient was determined every 20 min using radioimmunoassay, and competitive protein binding method respectively. The results of these studies were compared with those obtained in six normal subjects during a day of normal activity. (2) The 24-hr integrated concentration of aldosterone in patients was found to be 11.2, 13.6 and 14.2 ng/100 ml. These results were above the range found in healthy subjects (3.8–10.7 ng/100 ml). These findings are in agreement with the higher than normal levels of plasma aldosterone obtained from single blood samples in seven manic patients. (3) The 24-hr integrated concentration of cortisol of the three manic patients were 8.6, 8.2 and 11.4 μg/100 ml (normal range: 3.7–8.4 μg/100 ml). The previously described peaks of cortisol levels in normal subjects, which have been shown to be often related to emotional stress (De Lacerda, Kowarski & Migeon, 1973) were also present in manic patients. However, the underlying diurnal variation detected in all control individuals was not present in the manic patients. This could be related to the lack of regular sleeping pattern in patients during their manic phase.     

Monoamine Oxidase Activity in Blood Platelets From Manic and Depressed Patients

To evaluate the possible abnormality in MAO activity in affective disorders, blood platelet samples were obtained from 80 patients with mania and depression. Blood-platelet MAO activity was measured by a newly developed assay procedures using serotonin as substrate. MAO activities in 121 normal adult subjects were in a range of 2.49-12.05 nM/mg protein/hour, with the mean values of 4.91 ±1.72 (±S.D.) for men and 6.88±1.99 for women. (p<0.001) MAO activities in the manic and depressed patients were in a range of 0.65–13.40 nM/mg protein/hour, and both manic and depressed patients showed the mean value very similar to that in the normal subjects. Bipolar depressed patients did not exhibited lower MAO activity in the blood platelets than other clinical subtypes of depressive illness, including unipolar, involutional, neurotic and chronic characterological, and first-episode depressions. No significant differences were established between these five subcategories of depression, while significant higher values were evident in female than male patients (p<0.001). No correlation was found between the MAO activity and serotonin levels in the blood platelets either in the normal subjects or in the depressed patients.     

Reduction of blood platelet serotonin levels in manic and depressed patients.

Blood platelet serotonin levels were measured in unmedicated 12 manic and 74 depressive patients with 118 normal control subjects employed. Blood platelets were separated by multiple centrifugation in the medium of Na2-EDTA solution, and the loss of serotonin during collecting procedures was about 11%. The mean value of blood platelet serotonin levels in depressed patients was 594 +/- 288 ng/mg platelet protein (+/- S.D.), which was significantly lower than that for normal controls, 780 +/- 253 ng/mg protein (p less than 0.001). Age does not account for the reduction of serotonin levels both in depressed and in normal population. Unipolar and involutional depressed patients exhibited to have the most pronounced reduced levels of serotonin of various subtypes of depression, while bipolar depressed patients, neurotic and chronic characterological depressed patients as well as patients with first-episode depression had the values which were comparable with those in normal controls. Manic patients did not show enhancement but did reduction of serotonin levels, the mean being 580 +/- 152 ng/mg protein, which made a contrast with their clinical manifestations of exhilaration and hyperactivity. Changes in blood platelet serotonin levels were determined before, during and after administration of L-5-HTP with a maintenance dose of 300 mg daily in nine depressed patients. Serotonin levels in all subjects were lifted to normal levels during the L-5-HTP treatment, while clinical symptoms were not improved with the treatment. Reduction of blood platelet serotonin levels in depressed patients may be due to their psychobiological distinction, which involves abnormal biogenic amine metabolism in the brain.     

反复发作抑郁症患者甲状腺素水平观察

目的：了解反复发作抑郁症患者的甲状腺激素水平。方法：按性别,年龄１：１匹配选取序贯就诊的患者和健康者各２８例,采用放射免疫法测定患者组治疗前,后和对照组血清Ｔ３、Ｔ４、Ｔ３和ＴＳＨ浓度。     

Dexamethasone suppression test and weight loss

The mean maximum prolactin response following administration of morphine sulfate, 5 mg, i.v., was significantly lower in 15 unmedicated inpatients with major depressive disorder than in 8 normal controls and 11 unmedicated inpatients with other psychiatric diagnoses. The maximum prolactin response of 8/15 depressed patients was less than the lowest response of any of the normal controls. Six of 15 depressed patients had blunted prolactin responses (less than 2 ng/ml) in the 60-minute sample. The diminished increase in serum prolactin after morphine in depressed patients may reflect anterior pituitary dysfunction or abnormalities in central endogenous opioid, dopamine, serotonin, or other neuroregulatory systems.     

Diurnal patterns of serotonin, 5-hydroxyindoleacetic acid, tryptophan and fibrinolytic activity in blood of depressive patients and healthy volunteers.

Diurnal changes of serotonin-related factors in whole blood and fibrinolytic activity were determined in depressed patients and healthy controls. Whole blood serotonin concentration of depressed patients showed marked changes throughout daytime, with maximum values in the evening and lowest values in the morning, whereas its metabolite 5-HIAA followed a contrary pattern. The circadian rhythm of 5-HT and 5-HIAA in the control group was quite different from depressed patients. Plasma levels of tPA decreased from 12:30 to 16:30. Concentrations of free plasminogen activator inhibitor (PAI-1) and complex of tPA-PAI-1 decreased from 8:30 to 16:30. Plasma levels of total PAI-1 decreased from 8:30 to 16:30. Plasma levels of the fibrinolytic parameters may be lower in depressive patients than in normal controls. These results support the changes in the circadian rhythm of serotonin and its related substances in the blood of depressive patients.     

Soluble lectin-like oxidized low-density lipoprotein receptor-1 as a novel biomarker for large-artery atherosclerotic stroke

Background: Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been shown associated with the progression of atherosclerosis in endothelial cells. We sought to assess whether the baseline serum sLOX-1 levels are correlated with the presence and short-term functional outcome of large-artery atherosclerotic (LAA) stroke. Methods: The study recruited 241 subjects, including 148 consecutive patients with acute ischemic stroke with the subtype of LAA and 93 non-stroke controls. Clinical and laboratory data, including serum concentration of sLOX-1, were collected within 24 h of admission, and the severity of LAA stroke patients was evaluated by National Institutes of Health Stroke Scale score. And functional outcome was assessed by modified Rankin Scale three months after stroke. The association between sLOX-1 level and the functional outcome at three months was analyzed by multiple logistic regression models. Results: Serum levels of sLOX-1 in the LAA stroke patients were significantly higher as compared to normal controls (2.48 ± 0.93 ng/ml vs. 2.22 ± 0.79 ng/ml in the controls, t = 2.301, p = 0.022). The levels of serum sLOX-1 in patients with good outcome were significantly lower than those with poor outcome (2.39 ± 0.94 ng/ml vs. 2.77 ± 0.84 ng/ml, p = 0.032). After adjusting for potential confounders, sLOX-1 was still an independent predictor for the function outcome with an adjusted OR of 3.39 (95% CI, 1.61–7.11, p = 0.001). Conclusions: The serum sLOX-1 level was higher in patients with LAA stroke, and it was an independent predictor of functional outcome in patients with LAA ischemic stroke.     

Cerebrospinal fluid levels of selenium in patients with Alzheimer's disease

Summary. We compared CSF and serum selenium levels, measured by atomic absorption spectrophotometry, in 27 patients with Alzheimer's disease (AD) (13 females, 14 males, mean ± SD age 73.6 ± 7.4 years) without major clinical signs of undernutrition, and 34 matched controls (18 females, 16 males, mean ± SD age 70.7 ± 7.8 years). CSF and serum selenium levels did not differ significantly between AD-patient (11.4 ± 7.8 ng/ml and 28.5 ± 13.0 ng/ml, respectively) and control groups (13.3 ± 7.0 ng/ml and 22.5 ± 17.5 ng/ml). These values were not correlated with age, age at onset, duration of the disease, and scores of the MiniMental State Examination in the AD group. Weight and body mass index were significantly lower in AD patients than in controls. These results suggest that CSF selenium concentrations are apparently unrelated with the reported oxidative stress processes in patients with AD. Received May 5, 1998; accepted September 9, 1998     

Low serum folate levels as a risk factor for depressive mood in patients with chronic epilepsy

This study takes into consideration whether low serum folate levels may contribute to depressive mood in patients with chronic epilepsy. The serum folate levels and the score on the Self-Rating Depression Scale (SDS) were examined in 46 patients with chronic epilepsy. Patients with a score indicating at least minor depression on the SDS had a significantly lower serum folate level than patients with a normal score on SDS. There was a significant negative correlation between the serum folate levels and the SDS score. A serum folate level below 7.5 ng/ml was significantly associated with a pathological score on SDS. Because a serum folate level of 7.5 ng/ml is in the normal range for many laboratories, further studies using total plasma homocysteine as a sensitive measure of functional folate deficiency are required to elucidate the impact of folate metabolism on depressive mood in patients with chronic epilepsy.     

cTnI测定在急性脑心综合征中的意义

目的:探讨心肌肌钙蛋白I(cTnI)测定在急性脑心综合征中的意义。方法:对37例血清相关酶谱增高的急性脑梗死患者并设对照组进行cTnI测定,对各组结果进行对照分析。结果:急性脑梗死合并急性心肌梗死患者13例,cTnI水平测定为2.631±1.235ng/ml,与正常对照组(cTnI测定为0.022±0.014ng/ml)有非常显著差异P<0.001)。脑心综合征(脑心反应组)24例,cTnI水平测定为0.033±0.021ng/ml,与正常对照组无显著差异(P>0.05)。脑梗死合并心肌梗死组cTnI与脑心综合征组比较有显著差异(P<0.05)。结论:cTnI测定可以对急性脑梗死患者血清相关酶谱增高的原因(有无心肌梗死)进行鉴别。     

Electrooculographic (EOG) findings in manic-depressive illness

An electrooculographic (EOG) study was carried out in 20 depressed (12 with retarded and eight with agitated depression) and in 12 manic patients. Compared with controls, EOG ratios obtained from our patient's groups differed significantly and were low in depressive and high in manic patients. Appropriate treatment (tricyclics to depressives and haloperidol to manics) restored EOG ratio values to control levels. The observed EOG changes in manic-depressive illness are discussed in terms of their origin and the involvement of a neuroendocrine, dopamine-controlled, mechanism is postulated.     

Clinical response and plasma levels: effect of dose, dosage schedules, and drug interactions on plasma chlorpromazine levels.

Plasma chlorpromazine (CPZ) levels of 50 psychotic inpatients were measured by gas liquid chromatography; the clinical progress of 29 of these patients with acute psychoses was also assessed. CPZ levels of 50-300 ng/ml were usually associated with clinical improvement; there was also a relationship between CPZ levels and increases in certain symptoms. The 50-300 ng/ml level was best attained by doses of 400-800 mg/day. Trihexyphenidyl decreased plasma CPZ by a mean of 44.7% in 12 of 15 patients. A single 400-800-mg dose of CPZ at bedtime produced steady states equal to or better than those achieved with multiple doses. Those patients who failed to attain CPZ levels of more than 70 ng/ml despite doses of 400-1000 mg/day were receiving lithium throughout the study and had discharge diagnoses of manic-depressive psychosis, manic type, and schizo-affective schizophrenia--a finding with implications for future research.     

情感性精神障碍治疗前后血清甲状腺激素水平的对照观察

目的了解血清甲状腺激素水平与情感性精神障碍的关系。方法对２６例住院的情感性精神障碍患者做了治疗前后血清三碘甲状腺原氨酸（Ｔ３）、甲状腺素（Ｔ４）、Ｔ３树脂摄取比值（ＲＵＲ）和游离甲状腺素指数（ＦＴ４Ｉ）的对照观察，其中躁狂发作１９例，抑郁发作７例。同时以３０名健康人作为对照组。治疗前后应用Ｂｅｃｈ－Ｒａｆａｅｌｓｅｎ躁狂量表（ＢＲＭＳ）和汉密尔顿抑郁量表（ＨＡＭＤ）评定躁狂和抑郁症状的严重程度。结果患者组治疗前后的Ｔ４（１４２±４０和１３１±３７ｍｍｏｌ／Ｌ）、ＦＴ４Ｉ（１０．６±３．４和１０．５±３．７ｍｍｏｌ／Ｌ）明显高于对照组（１１１±２２，８．３±２．４ｍｍｏｌ／Ｌ）。治疗前７例躁狂发作患者的Ｔ３（１．０９±０．１６ｍｍｏｌ／Ｌ）低于正常组（２．０±０．５ｍｍｏｌ／Ｌ）；抑郁发作的Ｔ４（１７９±３１ｍｍｏｌ／Ｌ）、ＦＴ４Ｉ（１２．５±４．５ｍｍｏｌ／Ｌ）治疗前高于正常水平，治疗后均恢复到正常范围，ＢＲＭＳ和ＨＡＭＤ评分也随之明显下降。结论提示某些情感性精神障碍患者的甲状腺激素改变与症状的消长有关，甲状腺素异常是继发于情绪障碍，这种类型可能是情感性精神障碍的具有某种生物学异常的一个亚型。     

Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders. I. Enhanced response in depression and mania

The serum cortisol concentration following administration of 5-hydroxytryptophan (5-HTP), 200 mg orally, a precursor of serotonin (5-HT), was significantly greater in unmedicated depressed and manic patients than in normal controls. Increases in serum cortisol levels greater than 5 micrograms/dL were significantly more frequent in both unmedicated depressed and manic patients than in the normal controls. There was significant test-retest reliability. Baseline serum cortisol concentration correlated negatively with the cortisol response to 5-HTP in normal controls. These results suggest increased 5-HT receptor sensitivity may be present, possibly in the hypothalamus or pituitary, in some patients with affective disorders. These results are consistent with the hypothesis that decreased serotonergic activity, which would be expected to produce increased 5-HT receptor sensitivity, may be present in both depression and mania.     

Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination

In a double-blind, long-term follow-up study, 117 bipolar patients received lithium carbonate, imipramine hydrochloride, or both and 150 unipolar patients received lithium carbonate, imipramine, both lithium carbonate and imipramine, or placebo. With bipolar patients, lithium carbonate and the combination treatment were superior to imipramine in preventing manic recurrences and were as effective as imipramine in preventing manic recurrences and were as effective as imipramine in preventing depressive episodes. The combination treatment provided no advantage over lithium carbonate alone. With unipolar patients, imipramine and the combination treatment were more effective than lithium carbonate and placebo in preventing depressive recurrences. The combination treatment provided no advantage over imipramine alone. The lithium carbonate-treated group had fewer manic episodes than the other groups. Treatment outcome, which was evaluated primarily in terms of the occurrence of major depression or manic episodes, was significantly related to characteristics of the index episode, ie, the episode that brought the patient into the study.     

Effect of nomifensine on cortisol, prolactin and biogenic amines in neurotic depressed patients

The effect of nomifensine on plasma levels of cortisol, prolactin, dopamine, noradrenaline, adrenaline and serotonin were studied in neurotic depressive patients. Cortisol levels were elevated in the morning and were significantly decreased by nomifensine treatment. Prolactin levels were within the normal range and nomifensine did not modify them. A significative increase in catecholamine plasma levels was observed at the 6th week of treatment in depressed patients (dopamine: 106%; noradrenaline: 14%; adrenaline: 10%) whose nomifensine plasma levels ranged between 84 and 105 ng/ml. No statistical differences were found between pre- and post-treatment serotonin concentration. Reduction of plasma cortisol and clinical improvement may be related to increased catecholamine levels.     

Overexpression of Hepatocyte growth factor and its soluble receptor (s-cMet) in the serum of patients with different grades of meningioma

ObjectivesMeningiomas are the most common primary intracranial tumor. Hepatocyte growth factor (HGF) and its receptor, cMet, were shown to be involved in meningioma. This study was aimed to determine the concentration of HGF and soluble cMet (s-cMet) in the serum of patients with different grades of meningioma.MethodsNinety serum samples from different grades of meningioma patients (42 cases of grade I, 28 grade II, 20 grade III) and 51 controls were included in this study. The serum total protein concentration (TPC) was measured by a Bio-Rad protein assay and serum concentration of HGF and s-cMet by enzyme linked immunosorbent assay (ELISA).ResultsNo significant change in the serum TPC of patients was seen as compared to controls. We also showed that serum HGF and s-cMet concentration in meningioma patients was higher than in controls. The results showed that starting from grades I to III meningioma, a significant increase in HGF and s-cMet serum concentration was observed (HGF; 380 ± 57.69, 430.27 ± 48.72, 596.36 ± 104.49 pg/ml, respectively, as compared to controls which was 327.72 ± 49.68 pg/ml and for s-cMet was 274.45 ± 45.05, 314.81 ± 38.71, 433.54 ± 51.81 ng/ml, respectively, as compared to controls which was 213.72 ± 29.13 ng/ml). The results showed that a high concentration of HGF and s-cMet is associated with advanced grades of meningioma.ConclusionIt is concluded that HGF and s-cMet serum levels increased in meningioma patients and their concentration was significantly higher in more advanced grades of the disease. It is also suggested that HGF/s-cMet might be involved in the progression of meningioma.