Depression Cortisol Research Articles

Evaluation of dexamethasone suppression test in fibromyalgia patients with or without depression.

While in most healthy persons dexamethasone administration suppresses cortisol synthesis from the adrenal cortex, such suppression is not usually observed in patients with depression. We set out to investigate whether the dexamethasone suppression test (DST) reveals any neurobiological relationship between fibromyalgia (FM) and depression related to the hypothalamic-pituitary-adrenal (HPA) axis. To discover a relationship between depression and FM we performed the DST in 20 FM patients with depression, 26 FM patients without depression and 20 healthy subjects serving as a control group. Compared with the control group the cortisol level was found to be significantly higher in response to the DST in FM patients with depression (p = 0.03; z: -2.165), but not in those without depression (p = 0.153; z: -1.429). The cortisol level was not found to be statistically significant when patients with FM without depression were compared with the control group (p = 0.249; z: -1.152). In 7 FM patients with depression the DST failed to suppress cortisol; this was statistically significant compared with FM patients without depression (p = 0.014) and the control group(p = 0.008). Among FM patients without depression cortisol was not suppressed in one case. Cortisol was suppressed in all the controls. There was no statistically significant difference in cortisol suppression between FM patients without depression and the control group (p = 1.00). Our findings show that the DST reveals no neurobiological relationship between FM and depression related to the HPA axis.

11β-HSD and 17β-HSD as biological markers of depression: Sex differences and correlation with symptom severity

There is growing interest in the hydroxysteroid dehydrogenases (HSDs) as local modulators of hormone action. We have studied urinary steroid profiles from nine men and nine women with Major Depression to determine whether 11β-HSD and 17β-HSD activity are altered. Urinary steroid profiles were determined by high resolution gas chromatography. The ratio of 11-oxo over 11β-hydroxy metabolites of cortisol was used as the index of 11β-HSD activity and the ratio of dehydroepiandrosterone (DHA) over androstenediol-17β was used as the index of 17β-HSD activity. Symptom severity was assessed using the Hamilton Depression Rating Scale (HDRS). None of the measures of cortisol production, 9 AM plasma cortisol, 24 hour urinary free cortisol or 24 hour total urinary cortisol metabolites with HDRS in either men or women. 11β-HSD activity was altered and correlated with symptom severity in depressed women (r=0.688, p<0.05) but not men (r=0.132). In both depressed men and women, 17β-HSD activity was altered and correlated with HDRS scores (r=0.796, p<0.05 and r=0.688, p<0.05 respectively). However, although the ratio was changed in the same direction in depressed men and women, the correlation with symptom severity was positive in women but negative in men. We conclude that markers of subtle change such as these may prove more useful and informative than gross changes in plasma cortisol in depression.

Assessment of neuroendocrine dysfunction following traumatic brain injury

Posttraumatic neuroendocrine pathology may be a clinically significant complication following traumatic brain injury TBI. Metabolic abnormalities are described after TBI in two cases. A 21 year old male injured in a motor vehicle accident admitted in a minimally responsive condition presented with fluctuating high sodium levels, undetectable serum testosterone, and depressed cortisol and thyroid function. Imaging revealed near complete avulsion of the pituitary stalk leading to panhypopituitarism. A 38 year old male admitted for occipital skull fractures and brain contusions presented with hypona tremia and low serum testosterone. Both patients required hormonal replacement and correction of electrolyte abnormalities. A screening protocol adapted for selected patients at risk for endocrine problems is described. While neuroendocrine screening is not advocated in all TBI patients, physicians should be aware of the importance of neuroendocrine dysfunction following TBI.

A comparison of salivary cortisol in chronic fatigue syndrome, community depression and healthy controls

Background: Previous studies reporting cortisol hyposecretion in chronic fatigue syndrome may have been confounded by venepuncture, fasting and hospitalisation. Methods: Morning and evening salivary cortisol were obtained on consecutive days in the first 3 days of the menstrual cycle and compared in three samples of women taking no medication and matched for age: 14 patients with chronic fatigue syndrome, 26 community cases of ICD-10 current depressive episodes and 131 healthy community controls. Results: The mean evening cortisol was significantly lower in the chronic fatigue syndrome patients compared to controls with depression ( P=0.02) and healthy controls ( P=0.005). Chronic fatigue syndrome patients without psychiatric disorder had significantly lower morning salivary cortisols compared to controls ( P=0.009). Conclusion: Chronic fatigue syndrome patients display cortisol hyposecretion in saliva as well as plasma compared to patients with depression and healthy controls. Limitations: Small samples of female patients with cortisol estimated at only two time points in the day. Cortisol secretion may be secondary to other neurotransmitter abnormalities or other physiological or lifestyle factors in chronic fatigue syndrome patients. Clinical relevance: Chronic fatigue syndrome is biochemically distinct from community depression.

Evaluation of Hypothalamic-Pituitary-Adrenocortical Hormones and Inflammatory Cytokines in Patients with Persistent Vegetative State

Hypothalamic-pituitary-adrenocortical hormones, i.e. prolactin (PRL), human growth hormone (hGH), thyroid stimulating hormone (TSH), and Cortisol and plasma levels of cytokines, i.e. tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and interleukin-6 (IL-6), were assessed in 27 patients with persistent vegetative state (PVS) and in 16 outcome patients. In comparison with normal parameters, plasma levels of TSH were not significantly altered, while elevated basal hGH concentrations in 48.1% of PVS subjects and depressed cortisol levels in all PVS individuals and in patients who emerged from coma (outcome patients), respectively, were observed. In addition, higher TNF-α plasma levels in PVS subjects than in outcome patients and in healthy donors were found, while IL-1β plasma levels were elevated in both groups of patients in comparison with healthy controls. Of interest, in 55 % PVS male patients hyperprolactinemia was observed, whereas in outcome patients more than six months these values were within normal range. In four patients, who emerged from coma in the course of this study, prolactin plasma levels were followed-up and increased basal values progressively fell to normal range within six months.

Electroencephalographic sleep and urinary free cortisol in adolescent depression: A preliminary report of changes from episode to recovery

Electroencephalographic (EEG) sleep and hypothalamic-pituitary-adrenal (HPA) axis changes associated with adult major depressive disorder (MDD) are among the best replicated findings in biological psychiatry (Holsboer 1995; Reynolds and Kupfer 1987). More recently, attention has shifted to the question as to whether or not sleep and HPA axis changes observed in depression are exclusively present during the depressive episode (state related) or may persist after clinical remission (traitlike). The delineation of state-dependent and state-independent correlates of depression would be relevant for models of biologic vulnerability, course of illness, and prediction of treatment response. Longitudinal studies of adult depressed patients have shown that most EEG sleep measures are relatively stable from episode to clinical remission (Buysse et al 1992; Giles et al 1993; Lee et al 1993; Riemann and Berger 1989; Rush et al 1986; Schultz et al 1979; Steiger et al 1989; Thase et al 1994). In contrast, changes in the HPA axis appear to be state-related (Gerken et al 1985; Greden et al 1983; Holsboer et al 1982; Steiger et al 1989; Targum 1983). In contrast to adults, the question of whether EEG sleep and HPA axis changes are associated with adolescent depression

Dexamethasone suppression test by measuring spot urinary free cortisol in depression

Dexamethasone suppression test by measuring spot urinary free cortisol in depression

Effects of ipsapirone on plasma cortisol and body temperature in major depression

Major depressed patients have been reported to exhibit significantly attenuated hypothermic responses to ipsapirone, a serotonin (5-HT)-1A partial agonist, compared to normal controls. This study further investigated the cortisol and temperature responses to ipsapirone (0.5 mg/kg orally) and placebo in 20 normal volunteers and 12 major depressed patients. Both plasma cortisol and temperature were measured every 30 min before ipsapirone or placebo administration until 180 min post administration. Ipsapirone administration produced a significant increase in plasma cortisol levels as well as hypothermia. Major depressed patients showed significantly blunted ipsapirone-induced cortisol responses compared to normal controls. No significant differences in ipsapirone-induced hypothermic responses were found between major depressed patients and normal controls.

Reduction of cortisol levels after single intra-articular and intramuscular steroid injection

This study was undertaken to determine the influence of single intra-articular or intra muscular injections of methylprednisolone acetate on the hypothalamic-pituitary-adrenal axis. Twenty-one patients with rheumatic disease who had never been treated with systemic glucocorticoids and had not received local injections of these agents for the preceding 2 months, were given 40 mg of methylprednisolone acetate. Group I (11 patients) received one intra-articular injection into the knee, and Group II (10 patients) received the same dose intramuscularly. In Group I, serum cortisol levels were significantly decreased 24 hours after injection (228.2 +/- 8.7 nmol/L versus 193 +/- 16.3 nmol/L; P < 0.05). Serum cortisol levels were decreased in 9 of the 11 patients, by an average of 21.5%. Two patients' levels were below 138 nmol/L, which is considered to be the lower limit of normal range. Serum cortisol levels were below normal range in 3 patients 72 hours after intra-articular steroid injection. In Group II, serum cortisol levels were significantly decreased at 72 hours after injection (239.6 +/- 10.3 nmol/L versus 175.6 +/- 21.4 nmol/L; P < 0.01). Three patients' levels were below normal. By 72 hours postinjection, serum cortisol concentrations in 9 of 10 patients were decreased by an average of 31% compared to preinjection values. The present study suggests that decreased adrenocortical secretion, as reflected in depressed cortisol levels, can result from a single, low-dose, intra-articular or intramuscular injection of depot corticosteroids.

Plasma cytokines, acute phase proteins and cortisol in major depression

Plasma cytokines, acute phase proteins and cortisol in major depression

Stimulation of gastric proteases in the neonatal pig by a rise in adrenocortical secretion at parturition

In many species adrenocortical activity and glucocorticoid secretion increase in late gestation and reach a peak at birth. In this study, we investigated the hypothesis that glucocorticoids stimulate the synthesis of gastric protease zymogens in the perinatal period of pigs. Pigs were delivered by Caesarean section 3-4 days prior to term (to circumvent the natural cortisol surge) and treated daily with either saline (n = 11), metyrapone (an inhibitor of cortisol synthesis, n = 12), adrenocorticotropic hormone (ACTH, n = 14) or cortisol-acetate (n = 6). The pigs were killed at 3 or 6-7 days of age and concentrations of protease zymogens in gastric mucosal extracts determined by electroimmunoassay. Zymogen contents were also determined in control (untreated) pigs from one week before birth to four weeks after birth. In control pigs, concentration of prochymosin increased rapidly before term, peaked at birth, and decreased in the postnatal period; concentrations of pepsinogen A, pepsinogen B and progastricsin were low in newborn pigs and increased in the weeks after birth. Caesarean-delivered pigs injected with saline had lower concentrations of prochymosin and pepsinogen A at 6-7 days than vaginally delivered pigs of the same postnatal age. The concentrations of these zymogens were further reduced after metyrapone treatment (depressed cortisol secretion) but were increased after treatment with ACTH (stimulated cortisol secretion) or cortisol-acetate (exogenous glucocorticoid). No consistent effects were observed for the two minor gastric protease zymogens in the pig, pepsinogen B and progastricsin. The results suggest that the normal pre-partum surge in circulating cortisol stimulates the development of the major gastric protease zymogens in the pig, prochymosin and pepsinogen A.

The cortisol response to clonidine in acute and remitted depressed men

To assess the relationship between the hypothalamo-pituitary-adrenal (HPA) axis and the noradrenergic system in patients with major depression, 26 normal controls, 32 acutely depressed patients, and 21 patients with remitted depression, all men, were administered intravenous clonidine (2 μg/kg) or placebo. Acute, but not remitted, depressed patients had a greater plasma cortisol baseline than did normal controls ( t = 2.0, p < 0.03). Only acutely depressed patients had a greater decrease in plasma cortisol in response to clonidine than to placebo ( t = 2.5, p < 0.02). Statistically controlling for both diurnal variation and baseline cortisol, acute, but not remitted, depressed patients had a greater decrease in plasma cortisol in response to clonidine than did the controls (analysis of covariance: F[1,35] = 4.26, p < 0.05). These results support a state-dependent noradrenergic-HPA axis regulatory disturbance in depressed patients, suggesting that clonidine inhibits the elevated plasma cortisol in acute depression but not the normal concentrations observed in remitted depression or healthy controls.

Adrenal androgens and cortisol in major depression.

Nine depressed subjects and nine comparison subjects completed a study of abnormalities in adrenal androgen and cortisol metabolism. Serum levels of cortisol and dehydroepiandrosterone (DHA) at 8:00 a.m. and 4:00 p.m. revealed hypercortisolemia and loss of diurnal DHA variation but not cortisol variation in the depressed group. These findings suggest that in depression, adrenal androgens, in contrast to cortisol, are partially regulated by mechanisms independent of ACTH.

Clinical correlates of response to DST: The Dexamethasone Suppression Test in depression: A World Health Organisation collaborative study

From 9 centres 293 patients took part in the WHO-collaborative study on Dexamethasone-Suppression-Test (DST) in depression to examine the relationship of psychopathological and psychiatric history information to cortisol-levels and suppression/non-suppression status. Differences between the centres were large and significant on nearly all of the measures. The predictor analyses generally suffered from numerically weak correlations with many variables correlating to sex and age. Therefore analyses of the data were adjusted for centre-, sex-, and age-influences. The best predicting features of cortisol were ‘fitful, restless sleep’, ‘change of bodyweight’ and ‘affective disorders in blood relatives’. The last 2 items together with ‘hypersomnia’ and ‘ideas of insufficiency’ were the best predictors of suppression/nonsuppression status. However, statistical evidence did not seem to be strong enough to describe a typical symptom profile of a depressive cortisol suppressor or nonsuppressor.

Cortisol, thyroid hormone, and mood in atypical depression: A longitudinal case study

It has been hypothesized that major depression may be divisible into subtypes based, in part, on divergent alterations in the activity of stress-responsive neurohormonal systems (Gold et al 1988; Kling et al 1989; Smith et al 1989). Thus, although the classic farm of major depression, melancholia, is associated with symptoms of dysphoric hyperarousal, including psychomotor agitation, insomnia, loss of appetite, and weight loss; atypical depressive syndromes are characterized by symptoms of hypoarousal, with fatigue, lethargy, anergia, weight gain, and hypersomnia. Whereas hypercortisolemia is consistently observed in melancholic depression (Sachar et ,'tl 1970; Carroll et al 1976, 1981), perhaps re, suiting from central nervous system hypersecretion of fiae adrenocorticotropic hormone (ACTH) secretagoguc corticotropin-releasing hormont:~ (Gold et a! 1984; Nemeroff et al 1984; Gold et al 1986), fewer data are available conc~xning the activity of the hypothalamic-pituitary-adrenal axis in atypical depressions. In the present study, we sought to determ;,ae the relate,reship between mood and adrenocortical activity over a 6-month period in a patient with a depressive syndrome characterized by the atypical features of lethargy, hyperphagia, weight gain, and hypersomnia. We also evaluated pituitary-thyroid function in our patient because abnormalities therein are not uncommon in patients with depressive syndromes (Gold et al 1981; Loosen and Prange 1982) and because controlled longitudinal c~tudies regarding the behavioral effects of thyroid hormone alone are lacking (Prange et al 1984).

Hormonal Responses to Fenfluramine in Depressive Subtypes

In order to study putative differences in central neurotransmitter function in depressive subtypes, serum cortisol and prolactin responses to the putative serotonin agonist fenfluramine were examined in 30 subjects with major depression. Patients with endogenous depression (melancholia) as defined by each of ICD-9, DSM-III, RDC and Newcastle scale demonstrated a reduced prolactin response to 60 mg oral fenfluramine when compared with non-endogenous subjects. This was independent of either prolactin or cortisol baseline levels, and indicates that there are differences in brain neurotransmitter function in the endogenous and non-endogenous subtypes of depression. Basal prolactin levels were reduced in bipolar compared with unipolar subjects, and delusional compared with non-delusional patients, although there were no differences in the prolactin responses to fenfluramine between these subgroups. Basal cortisol levels and cortisol response to fenfluramine did not distinguish between any of the subtypes.

RAPID ESCAPE OF CORTISOL FROM SUPPRESSION IN RESPONSE TO I. V. DEXAMETHASONE IN ANOREXIA NERVOSA*

The suppressive effect of dexamethasone (Dex) on plasma cortisol and beta-lipotrophin (beta LPH) was investigated in patients with anorexia nervosa. Dex was given either orally, 1 mg at 2400 h, with blood sampling at 0800 h on the days before and after Dex, or by i.v. infusion starting at 1100 h (1 mg/h) for 4 h with sampling at 0800, 1100, 1500, 2000 and 2400 h and at 0800 h the following day. The plasma cortisol and beta LPH levels during oral or i.v. Dex administration were compared between patients and normally menstruating women of normal weight. The results showed that Dex administration depressed cortisol significantly (P less than 0.0001) during oral or i.v. infusion in most patients, without, however, suppressing it entirely as is the case in normal women. Moreover, during i.v. Dex infusion, the concentrations of cortisol escaped suppression and were higher than in normal women (less than 50 nmol/l) by 0800 h on the day following infusion. In the patients who were reinvestigated after re-feeding and weight gain (n = 9), a normal suppression of cortisol in response to i.v. Dex infusion was observed in only five cases and a slight failure to suppress, although concentrations were lower than before refeeding, was still evident in four. We concluded that, in anorexia nervosa, cortisol concentration rapidly escapes suppression by Dex administration, and that this escape is not related to the degree of starvation.

Cortisol in major depression

Cortisol in major depression

The dexamethasone suppression test: an overview of its current status in psychiatry. The APA Task Force on Laboratory Tests in Psychiatry.

The dexamethasone suppression test (DST) has had unprecedented evaluation among biological tests proposed for clinical use in psychiatry. It is hypothesized to reflect pathophysiologic changes at the CNS level. The sensitivity of the DST (rate of a positive outcome, or nonsuppression of cortisol) in major depression is modest (about 40%-50%) but is higher (about 60%-70%) in very severe, especially psychotic, affective disorders, including major depression with psychotic as well as melancholic features, mania, and schizoaffective disorder. The specificity (true negative outcome) of the DST in normal control subjects is above 90%, but it varies from less than 70% to more than 90% in psychiatric conditions that often need to be separated from major affective disorders. In dementia the specificity is even lower. In addition, a number of medical conditions, including severe weight loss and use of alcohol and certain other drugs (barbiturates, anticonvulsants, and others), can produce false positive results. Positive initial DST status in major depression does not add significantly to the likelihood of antidepressant response, and a negative test is not an indication for withholding antidepressant treatment. Some recent data suggest that DST-positive depressions (cortisol nonsuppression) are less likely than DST-negative cases (cortisol suppression) to respond to a placebo. If this is confirmed, it would increase the real magnitude of the difference in treatment response between DST-positive and DST-negative depressed patients. Failure to convert to normal suppression of cortisol with apparent recovery from depression suggests an increased risk for relapse into depression or suicidal behavior. Although the clinical utility of the DST as currently understood is limited, in certain specific situations its thoughtful use may aid clinical decision making. The association of an abnormal test result with major affective disorders encourages continued research on the DST.

A combined study of cortisol, ACTH and dexamethasone concentrations in major depression. Multiple time-point sampling.

The pathophysiology of hypercortisolaemia in major depression was examined. ACTH was measured using a novel immunoradiometric assay of high specificity and sensitivity. Twenty-eight patients with major depression and 18 control subjects were studied. Blood samples for basal hormone concentration were taken at 09:00, 16:00 and 23:00 on day 1, followed by administration of 1 mg dexamethasone at 23:00. Further samples were taken at 09:00 and 16:00 on day 2. Dexamethasone concentration was measured in day 2 samples and no significant difference was found between the depressed group and control subjects. In the depressed group cortisol concentration was elevated at 23:00 on day 1, and ACTH concentrations were elevated in post-dexamethasone samples. ACTH and cortisol concentrations were not directly correlated in individual patients. The elevated plasma cortisol associated with major depression is not solely mediated by changes in ACTH.