Hypercortisolemic depression is associated with the metabolic syndrome in late-life

INTRODUCTION: Depression has been hypothesized to be associated with metabolic abnormalities which increase the risk of cardiovascular disease (CVD) and diabetes. Such a link could be due to increased HPA-axis activity. This study investigates the cross-sectional relationship between depression, urinary cortisol and metabolic syndrome in an older population. METHODS: Data are from 867 participants of the InChianti Study, aged 65 years. Depressive symptoms were assessed using the CES-D scale; cortisol levels were determined in 24-h urine samples. Metabolic syndrome was defined as three or more of the following: abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure, and high fasting glucose. RESULTS: Clinically relevant depressed mood (CES-D20) was present in 20.6% of the sample, and 24.5% had the metabolic syndrome. After adjustment for sociodemographics and health indicators, depression score (per SD increase: OR=1.20, 95% CI=1.02-1.41) and urinary cortisol level (per SD increase: OR=1.23, 95% CI=1.01-1.51) were significantly associated with presence of metabolic syndrome. There was, however, a significant interaction (p=0.003) between depressed mood and urinary cortisol in the probability of having metabolic syndrome. The odds of metabolic syndrome in persons with both depressed mood and urinary cortisol excretion in the highest tertile was 1.84 (95% CI=1.02-3.34) compared to persons with neither condition. DISCUSSION: This study suggests a synergistic relationship between depression, cortisol and metabolic syndrome. Hypercortisolemic depression may constitute a specific risk group for the metabolic syndrome.     

Neuroendocrine response to meta-chlorophenylpiperazine and ipsapirone in relation to anxiety and aggression

The aim of this study was to establish the association of trait anxiety and anger with hormonal responses to acute challenges with two different 5-HT agonists in a mixed group of patients with depressed mood. Fifteen patients and 16 normal controls received single oral doses of 0.5 mg/kg meta-chlorophenylpiperazine (MCPP), a 5-HT(2C) agonist, and 10 mg of ipsapirone, a 5-HT(1A) agonist, according to a double-blind, placebo-controlled, cross-over design. Dutch-adapted versions of the Spielberger Trait-Anxiety Inventory and the Spielberger Trait-Anger Scale administered assessed at study entry. Hormonal responses, expressed as drug-placebo differences, to MCPP and ipsapirone (changes in cortisol, ACTH and prolactin) were measured. Blood levels of MCPP and ipsapirone were also measured. MCPP and ipsapirone elevated cortisol, ACTH and prolactin. In the patient group, there was a significant correlation between trait anxiety and the cortisol response to MCPP. No significant correlations between the ACTH and prolactin responses to MCPP and levels of anxiety/anger were observed in the patients. No significant correlations could be established between levels of anxiety/anger and hormonal responses to ipsapirone. This study provided evidence for an association between measures of anxiety/aggression and the hormonal response to MCPP. Thus, in subjects with depressed mood, high levels of anxiety suggest a higher probability of 5-HT(2C) disturbances.     

Corticotropin-releasing factor (CRF): stimulation in normal controls and in patients with Cushing's syndrome

Synthetic ovine and human CRF were given as an i.v. bolus to six healthy volunteers in four and two different dosages, respectively (oCRF: 25, 50, 100 and 200 micrograms; hCRF: 50 and 100 micrograms). There was a significant increase of ACTH and cortisol after the injection of all dosages though the dose-response relationship was only significant between the 50 and 100 micrograms dose of oCRF. No significant differences between ACTH and cortisol secretion after oCRF and hCRF were observed. Repetitive stimulation by hCRF led to repetitive release of identical amounts of ACTH. The CRF test with the 100 micrograms dosage was used in patients with proven Cushing's syndrome (n = 30). Results showed that the CRF test is useful in making the differential diagnosis of established Cushing's syndrome. In patients with ACTH-dependent Cushing's disease (n = 21), normal or elevated basal ACTH levels were significantly higher after stimulation by CRF compared to normal controls, with one exception. The pattern of cortisol secretion after CRF administration corresponded to the pattern of ACTH secretion in these patients. In two patients with ectopic ACTH syndrome, extremely elevated ACTH and cortisol levels did not change or showed only a small increase after CRF administration. In patients with unilateral adrenal adenoma or carcinoma (n = 7), suppressed ACTH levels did not rise after CRF administration. In addition, no significant change in cortisol secretion could be observed. After surgical removal of cortisol-producing adrenal tumors, the ACTH response to CRF can be demonstrated when cortisol levels are still undetectable. Pulsatile administration of CRF in one patient after unilateral adrenalectomy revealed that ACTH responses to CRF normalize rapidly but cannot be sustained if CRF administration is withdrawn, suggesting that the cause of adrenal failure after unilateral adrenalectomy for Cushing's syndrome or with long-term corticoid therapy is due to hypothalamic CRF deficiency. The suppression of ACTH responses to CRF in glucocorticoid-treated patients correlated with the daily corticoid dosage. Since the ACTH hyper-response to CRF in six patients with Cushing's disease was suppressed by short-term dexamethasone treatment, the pituitary as a target site for feedback inhibition also was demonstrated.     

Neurobiological effects of lumbar puncture stress in psychiatric patients and healthy volunteers

Several existing laboratory-based stress paradigms have significant shortcomings for assessing neurobiological correlates of stress in healthy volunteers and severely ill psychiatric patients. We have examined neuroendocrine effects of stress associated with the lumbar puncture (LP) procedure in drug-free depressed and schizophrenic patients and healthy volunteers. Healthy volunteers and depressed patients had significant stress-induced elevations in plasma levels of adrenocorticotropic hormone (ACTH), cortisol, and growth hormone associated with LP. In contrast, schizophrenic patients had no significant elevations in any of the neuroendocrine parameters. Depressed patients' cerebrospinal fluid norepinephrine levels were negatively correlated with stress-induced activation of the hypothalamic-pituitary-adrenal axis. In addition, depressed patients' basal plasma cortisol levels were strongly predictive of stress-related elevations in ACTH, cortisol, and growth hormone. Furthermore, stress-induced changes in schizophrenic patients' cortisol and ACTH levels were not correlated.     

Diurnal variation of mood and the cortisol rhythm in depression and normal states of mind

Summary A large scale chronobiological investigation was undertaken in 20 drug-free psychiatric inpatients displaying RDC major depression (endogenous subtype) in comparison to 10 healthy control subjects and 10 of the patients after clinical recovery. A series of measurements was taken 6 times a day and, in 8 of a total of 14 variables, also once a night over a period of 10 to 14 days. The following variables were assessed: mood (three different scales), performance (two tests), motor activity (three measures), salivary flow, urinary excretion of water, sodium, potassium, and free cortisol (UFC), and rectal temperature. A phase chart of the acrophases of the 8 variables with measurements taken during day and night revealed two clusters in the depressives and three in the non-depressed subjects. In the depressives, the acrophases of the mood scales clustered around the time of awakening in the morning, together with the acrophase of UFC, whereas all other acrophases clustered in the afternoon. In the non-depressed subjects, however, the mood scales reached their circadian maxima in the middle of the night around the time when sleep was interrupted to take measurements. All other acrophases corresponded roughly with those found in the depressives. The coincidence of the time course of depressed mood and cortisol excretion in the patients was interpreted as reflecting a temporal relationship between diurnal mood swings in depression and the cortisol rhythm. This interpretation was supported by the significant correlation between the acrophases of the two respective rhythms in patients showing a significant diurnal variation in mood. The mood curves of non-depressed subjects seemed unrelated to the cortisol rhythm. Probably, they mirror diurnal fluctuations of vigilance rather than fluctuations of mood. According to the literature, this rhythm is temporally related to the rhythm of melatonin secretion.     

Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment.

BACKGROUND: Depression has been linked to stress, memory deficits, and hypercortisolemia. However, the relationships between depression, hippocampal structure and function, and cortisol levels are unclear and the effects of antidepressant treatment on the measures are not well studied. METHODS: Whole hippocampal volume, performance on verbal and visual declarative memory function and cortisol status was evaluated in 38 subjects with major depressive disorder (MDD) and 33 healthy subjects. All measures were repeated in a subgroup (n = 22) of depressed patients after successful selective serotonin reuptake inhibitor (SSRI) treatment. RESULTS: Hippocampal volume was not significantly different between patients with untreated MMD and healthy subjects, after controlling for whole brain volume, age and gender. However, depressed subjects had significantly greater deficits in delayed memory and percent retention on the verbal portion of the Wechsler Memory Scale-Revised (WMS-R) compared with healthy subjects, without significant differences in visual memory, attention, vigilance, or distractibility. Baseline plasma or urinary free cortisol (UFC) was not related to either hippocampal volume or memory deficits. Successful treatment with antidepressants did not change hippocampal volume but did result in a significant improvement in memory function and a reduction in UFC excretion. CONCLUSIONS: Medication-free nonelderly depressed outpatients without alcohol dependence or adverse experiences in childhood had normal hippocampal volume. Focal declarative memory deficits in depression supported localized hippocampal dysfunction in depressed patients. Treatment with antidepressants significantly improved memory and depression but did not alter hippocampal volume, suggesting that antidepressants may improve hippocampal function in the absence of detectable structural changes.     

Effects of total sleep deprivation on urinary cortisol, self-rated arousal, and mood in depressed patients

The possibility that the clinical response to total sleep deprivation (TSD) is mediated by dimensions of arousal was investigated in a group of 16 depressed patients. Self-reports of activation, stress, and mood were assessed 3 days before, during, and 2 days after TSD. Urinary cortisol excretion and responses to the dexamethasone suppression test (DST) were also measured. TSD increased cortisol excretion in depressed patients and advanced the time of the maximal excretion of cortisol. No such changes have been reported for normal subjects. Neither the increased excretion nor the time shift was related to the mood response to TSD. The DST results were also unrelated to this response. Indications that the mood response to TSD may be mediated by dimensions of arousal are the significant relationships between this response and the responses of subjective stress and activation to TSD. The TSD-induced cortisol increase was not related to the subjective arousal response to TSD. The increased cortisol excretion itself could be predicted by the averaged baseline levels of subjective stress: the lower the stress levels before TSD, the larger the cortisol response to TSD.     

Stable adrenocorticotropin-stimulated 11-beta-hydroxylase activity but loss of age-related changes in patients with hypercortisolemia

Eleven-beta-hydroxylase activity was measured before and after acute adrenocorticotrophic hormone (ACTH) stimulation in 28 controls, 25 depressed Dexamethasone Suppression Test (DST) suppressors, 13 DST nonsuppressor patients, and 8 patients with Cushing's syndrome to investigate changes in states of cortisol hypersecretion. Eleven-beta-hydroxylase activity was equivalent among groups both before and after stimulation. Such 11-beta-hydroxylase stability, however, resulted in higher cortisol and 11-deoxycortisol poststimulation levels in both depressed DST nonsuppressors and Cushing's patients than in controls. Basal 11-beta-hydroxylase activity is positively correlated and 11-deoxycortisol is negatively correlated with age in controls and DST suppressors, but not in the patients tested with evidence of cortisol hypersecretion. These findings suggest that in vivo basal 11-beta-hydroxylase activity rises gradually with age, but does not rise after acute administration of exogenous ACTH. The age relationship is lost in states of cortisol hypersecretion, but the lack of response to acute exogenous ACTH is not affected.     

Discordant changes in plasma ACTH and β-lipotropin/β-endorphin levels in Clshing''s disease patients with depression

Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and β-lipotropin/β-endorphin (β-LPH/β-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean[±SD] depressed ood SCORE=0.17±0.4; modified Hamilton Depression scale SCORE=7.6±4.5) and five as severly and five as severely depressed (mean depressed mood SCORE=2.4±0.5; modified Hamilton Depession scale SCORE=15±5.6) (p<0.05). ACTH and β-LPH/β-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and β-LPH/β-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly DEPRESSED=90.0±16.7; severely DEPRESSED=34.6±8.7 (p<0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0mmg dexamethasone administration. These initial findings, taken together with data in related areas, suggest that greater diversity in regulation and consecretion of ACTH and β-LPH/β-E may occur than is currently suspected. Such diversity may play a role in the relationship between HPA axis dysregulation and mood disorders.     

Corticotropin-releasing factor test in melancholic patients in depressed state versus recovery: a comparative study

PURPOSE: Basal adrenocorticotropin hormone (ACTH) and cortisol levels and their response to corticotropin-releasing factor (CRF) test were studied in melancholic depressive patients in depressed state and recovery, and compared with healthy controls. METHODS: Fifty-four outpatients diagnosed with unipolar depressive disorder with melancholic features according to DSM-IV and 23 healthy controls were included in the study. The Structured Clinical Interview for DSM-IV (SCID-IV) was used for diagnosis. Twenty-nine patients were in recovery, while 25 were in depressed state at the moment of the administration of the CRF test. FINDINGS: No differences were found between the recovered and depressed groups with respect to CRF test. Lower ACTH and higher cortisol levels with significant differences were shown in the neuroendocrine variables at 15, 30, and 60 min, and in peak response and increase, in the ACTH and cortisol response curves to CRF challenge between the groups of melancholic patients, both recovered and depressed, compared with the healthy control subjects. Moreover, recovered and depressed melancholic patients had a higher whole cortisol area under the curve with significant differences than the healthy control subjects. CONCLUSIONS: The crossover clinical status at the moment of the CRF test doesn't differentiate changes in the HPA axis in melancholic patients, while we did find significant differences in the group of healthy controls in comparison with the groups of melancholic patients both in depressive state and recovery. This supports the hypothesis that hypothalamic pituitary adrenal (HPA) axis shows alterations that remain in depressive patients even after recovery.     

Melatonin, cortisol and ACTH in patients with major depressive disorder and healthy humans with special reference to the outcome of the dexamethasone suppression test

The 24 hr profiles of melatonin and cortisol in serum, morning levels of ACTH in plasma, and the dexamethasone suppression test (DST) were investigated in 32 acutely ill patients with a RDC diagnosis of major depressive disorder, 24 patients with a history of longlasting unipolar or bipolar major depressive disorder studied in remission, and 33 healthy subjects. A significant decrease in maximum nocturnal melatonin level (MTmax) was found in the acutely ill depressed patients with abnormal DST compared to both those with normal DSTs and the healthy subjects. The MTmax levels were unaltered when these patients were reinvestigated in remission. A decrease of MTmax was also seen in the group of unipolar and bipolar patients studied in remission. Low nocturnal melatonin is proposed to be a trait marker for major depressive disorder and depressive states with abnormalities in the hypothalamic--pituitary--adrenal (HPA) axis. A significant decrease of ACTH levels at 0800 hr after dexamethasone administration the preceding evening was found in the healthy subjects, the unipolar--bipolar patients in remission, and the acutely ill depressed patients with normal DSTs, but was not found in the acutely ill depressed patients with abnormal DSTs. These findings support the hypothesis that pituitary ACTH regulation is altered in depressed patients with abnormal DST. Morning plasma ACTH before the administration of dexamethasone did not significantly differ between the acutely ill depressed patients with abnormal DSTs, normal DSTs, the patients with unipolar--bipolar disease in remission, or the healthy subjects. Thus, the abnormalities in the HPA axis in depresséd patients are proposed to be due to a hypersecretion of corticotrophin releasing factor (CRF) with a subsequent stimulus-induced pituitary desensitization. A significant decrease of melatonin after dexamethasone was seen at 0800 hr in the unipolar--bipolar patients in remission as well as in the healthy subjects, at 1600 hr and 2200 hr in the acutely ill depressed patients in remission, but not at 0800 hr in the acutely ill depressed patients in relapse. A significant regression was found between MTmax levels and the degree of non-suppression of cortisol at 0800 hr in the DST in the acutely ill depressed patients both in relapse and in remission. Melatonin thus is proposed to be an inhibiting factor for CRF during depression. A trend to a phase-advance of cortisol nadir and melatonin peak was seen in the acutely ill depressed patients with abnormal DST, possibly indicating an involvement of the suprachiasmatic nuclei in the hypothalamus.     

Influence of mirtazapine on urinary free cortisol excretion in depressed patients

Mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on urinary free cortisol (UFC) excretion was investigated in depression. Twenty patients (six men, 14 women) suffering from major depression according to DSM-IV criteria were treated with mirtazapine for 3 weeks. The patients received 15 mg mirtazapine on day 0; 30 mg mirtazapine on day 1; and 45 mg mirtazapine per day from day 2 to the end of the study (day 21). UFC excretion was measured before treatment (day 1), at the beginning (day 0), after 1 week (day 7) and after 3 weeks (day 21) of treatment with mirtazapine. Urine samples were collected from 08:00 to 08:00 h the following day. On the days of urine sampling, the severity of depressive symptoms was assessed using the 21-item version of the Hamilton Rating Scale for Depression (21-HAMD). There was a significant reduction of UFC excretion during 3-week mirtazapine therapy, which was already obvious after the first day of treatment (day 0). However, there were no significant across-subjects correlations between UFC reduction and decrease in 21-HAMD sum scores. Apparently, the mirtazapine-induced rapid reduction of cortisol secretion in depressed patients is not necessarily correlated with a favorable therapeutic response.     

Salivary cortisol levels and their correlation with plasma ACTH levels in depressed patients before and after the DST.

OBJECTIVE: The aim of this work was to study the clinical utility of salivary cortisol concentrations in a group of depressed patients undergoing the dexamethasone suppression test (DST) and the correlation of these concentrations with plasma ACTH levels. METHOD: Twenty outpatients from the psychiatric department of a Barcelona hospital who were diagnosed as having nonendogenous (N = 9) or endogenous (N = 11) depression according to DSM-III criteria and the Newcastle scale participated in the study. The comparison group consisted of 12 healthy volunteers. Blood and saliva samples were taken before and after administration of 1 mg of dexamethasone Salivary cortisol and plasma ACTH concentrations were determined by direct iodine-125 radioimmunoassay with commercial kit reagents. RESULTS: Predexamethasone salivary cortisol concentrations were significantly higher in the group with endogenous depression than in the comparison group. A significant correlation was obtained between plasma ACTH and predexamethasone salivary cortisol levels in the group with nonendogenous depression and in the comparison subjects. CONCLUSIONS: These preliminary findings indicate that salivary cortisol could substitute for plasma cortisol in clinical studies in which the DST and hypercortisolemia are evaluated. The lack of correlation between ACTH and cortisol levels in saliva in the group of endogenously depressed patients could indicate a disturbance in the regulation of cortisol secretion in major depression.     

Diurnal rhythms of plasma cortisol, beta-endorphin and prolactin, and cerebrospinal fluid amine metabolite levels before suicide. Case report

There are indications to suggest a relationship between low levels of 5-hydroxy-indoleacetic acid (5HIAA) in the cerebrospinal fluid and suicidal behavior. Many depressed patients show an elevated cortisol secretion. As beta-endorphin is derived from the same precursor as ACTH, it is expected that plasma beta-endorphin levels will also rise in depressed patients. We report here a case of severe depression with diurnal variation who showed low CSF 5HIAA prior to his suicide. In contrast, his catecholamine metabolites were 50% above the mean values of other depressed patients. Hormonal measurements, however, showed low cortisol, prolactin and beta-endorphin levels.     

Multiple steroid hormone levels in depressed patients and normal controls before and after exogenous ACTH

Forty depressed patients and 36 age- and sex-matched controls were given 250 μg ACTH_1–24 by bolus. Plasma steroid hormone levels were measured prior to and 60 min after ACTH administration. The depressed patients had significantly greater cortisol (F), 11-deoxycortisol (S), androstenedione (AD), and 17-hydroxyprogesterone (17-OHP) responses (delta; p<0.05) and a marginally greater 11β-hydroxyandrostenedione (11β-OHAD) response (delta; p=0.091) than the controls. There was no significant difference in the corticosterone (B) response between the two groups.

With the exception of 11β-OHAD, all the steroid hormones were significantly negatively correlated with age in the controls, but only S and AD marginally demonstrated this relationship in the depressed patients. F, S, AD, 17-OHP, and B, but not 11β-OHAD, were significantly positively correlated with each other in the controls, but only F was significantly correlated with AD in the depressed patients. These data suggest that the hypercortisolemia found in some depressed patients involves increased precursor and metabolite levels both at baseline and in response to exogenous ACTH, compared to controls. Furthermore, variability in these precursors is greater in depressed patients, and their relationship to age is lost. These findings are consistent with the hypothesis that adrenal products other than cortisol also could be related to affective symptoms.     

Effect of comorbid anxiety disorders on the hypothalamic-pituitary-adrenal axis response to a social stressor in major depression.

BACKGROUND: Major depressive disorder (MDD) is often complicated by anxiety symptoms, and anxiety disorders occur in approximately 30% of mood cases. This study examined the influence of anxiety comorbidity on the hypothalamic-pituitary-adrenal (HPA) axis response to stress in patients with MDD. METHODS: Untreated subjects with pure MDD (n = 15), MDD with comorbid anxiety disorders (n = 18), and pure anxiety disorders (n = 15) were recruited by advertising. Age- and gender-matched control subjects were recruited for each subject with a psychiatric diagnosis (n = 48). All subjects underwent a social stressor, the Trier Social Stress Test (TSST), and blood was collected for adrenocorticotropic hormone (ACTH) and cortisol assay. RESULTS: When all depressed patients (n = 33) were compared with their matched control subjects (n = 33), they showed a significantly greater ACTH response to the stressor; however, this exaggerated ACTH response was exclusively due to the depressed group with comorbid anxiety disorders. A similar but nonsignificant effect was observed in the cortisol response. Subjects with pure mood or pure anxiety disorders showed normal ACTH and cortisol responses to the TSST. All patient groups showed similar levels of TSST-induced anxiety. CONCLUSIONS: Comorbid anxiety disorders might play a role in the increased activation of the HPA axis observed in patients with major depression.     

The corticotropin-releasing hormone stimulation test in patients with panic disorder

Eight patients with panic disorder had significantly lower ACTH and cortisol responses to corticotropin-releasing hormone and a significantly lower ratio of ACTH to cortisol response than 30 normal control subjects. These responses resemble those previously reported for depressed patients except that they occurred in the face of significantly elevated basal cortisol and ACTH levels. These results suggest that patients with panic disorder have an element of chronic hypercortisolemia, like depressed patients, but also a more acute perturbation in ACTH secretion, not previously seen in depressed patients.     

Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders. II. Relation to suicide, psychosis, and depressive symptoms

Serum cortisol levels were significantly higher after administration of 5-hydroxytryptophan (5-HTP), 200 mg orally, in unmedicated patients with affective disorders than in controls. The magnitude of the serum cortisol increase correlated positively with the Schedule for Affective Disorders and Schizophrenia-Change (SADS-C) depression syndrome ratings and correlated negatively with psychotic symptoms in 26 patients with major depression. The serum cortisol response was greater in four depressed and three manic patients who made suicide attempts than in 33 patients who were not suicidal or only had suicidal thoughts. The cortisol response was also greater in patients with bipolar depression than in those with unipolar depression and those with a first-degree relative with an affective disorder. Absence of psychotic symptoms and commission of suicidal acts were associated with an increased cortisol response to 5-HTP in the depressed patients. The cortisol response to 5-HTP in the manic patients also tended to correlate with the SADS-C manic syndrome score.     

ACTH, cortisol and growth hormone 24-hour profiles in major depressive illness

Circadian rhythms of ACTH, cortisol and growth hormone have been studied in eighteen major depressives (eight unipolar and ten bipolar) as well as in eight normal controls. Both unipolar and bipolar depressed patients secreted more growth hormone than normal men. This hypersecretion occurred during waking hours rather than during sleep. An early sleep GH increase was found in all but one of the normal men, but was absent in seven of the eight unipolar depressed patients, who had instead a presleep increase. No consistent disturbance of the temporal association between sleep onset and GH secretion was found in bipolar depressed patients. Both unipolar and bipolar depressed patients had higher 24 h mean cortisol levels than normal men, but no significant difference was found for 24 h ACTH levels. An early timing of the nadir of ACTH-cortisol secretion which was observed in our depressed patients also suggest that disorders of circadian time keeping may characterize major endogenous depression.     

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。