Monoamine oxidase and cortisol response in depression and schizophrenia.

The relationship between hypothalamic-pituitary-adrenal (HPA) axis function and platelet monoamine oxidase (MAO) activity was examined in drug-free depressed (n = 32) and schizophrenic (n = 36) inpatients. HPA function was measured by determining plasma cortisol levels at 8:30 a.m. and 11 p.m. before, and 8:30 a.m., 4 p.m., and 11 p.m. after administration of 1 mg of dexamethasone (DEX). There was a significant correlation between platelet MAO activity and all post-DEX cortisol levels (8:30 a.m., 4 a.m., and 11 p.m.) in depressed patients, and MAO activity and pre-DEX cortisol levels (11 p.m.) in schizophrenic patients. MAO activity was significantly higher in depressed DST nonsuppressors than in suppressors, and there were more DST nonsuppressors in high-MAO groups as compared with low-MAO groups. Our results thus suggest a strong relationship between platelet MAO activity and HPA function in depressed patients. These biochemical markers are potentially useful in the identification of biochemically and clinically homogeneous subgroups of depressed patients.     

Plasma ACTH levels in primary depression: relationship to the 24-hour dexamethasone suppression test

The failure of adequate cortisol suppression after 1 mg dexamethasone in 50% of patients with endogenous depression has been attributed to abnormal hypothalamic-pituitary-adrenal axis regulation, resulting in high levels of adrenocorticotropic hormone (ACTH). Because studies of plasma ACTH have been conflicting, we studied plasma ACTH levels during the 24-hour dexamethasone suppression test in a homogeneous group of 29 hospitalized patients with primary endogenous depression and 19 normal volunteers. No differences were found in ACTH levels among normal volunteers, depressed cortisol suppressors, and depressed cortisol nonsuppressors at either 4 p.m. or 11 p.m.     

Psychopathology and plasma cortisol responses to dexamethasone in prepubertal psychiatric inpatients

This study of 51 prepubertal psychiatric inpatients evaluates plasma cortisol measurements at 8 AM, 4 PM, and 11 PM before and after dexamethasone was administered in counterbalanced order at doses of 0.5 mg and 1.0 mg. Approximately 76.5% of the children had an affective disorder. Major depressive disorder was associated with higher plasma cortisol levels than other disorders. Pre- and postdexamethasone plasma cortisol levels using 0.5 mg dexamethasone exhibited a circadian variation. The optimal criterion for cortisol nonsuppression was 5 micrograms/dl measured at 8 AM after administration of 0.5 mg dexamethasone.     

Specificity of plasma HVA response to dexamethasone in psychotic depression

Earlier reports have suggested that dexamethasone significantly increases levels of plasma homovanillic acid (HVA) in normal subjects, but that this effect may be altered in some depressed patients. To investigate the specificity of such alterations, we administered dexamethasone (1 mg p.o. at 11 p.m.) to 33 normal subjects, 27 depressed patients (8 with psychotic features), and 16 schizophrenic patients. Plasma for assay of cortisol and HVA was obtained at 4 p.m. before and on the day following dexamethasone administration. Dexamethasone induced significant increases in plasma HVA in the normal subjects and in the schizophrenic patients, but not in the depressed patients. Indeed, psychotically depressed patients tended to show a dexamethasone-associated decrease in plasma levels of HVA. In contrast to cortisol "suppression" or "nonsuppression," dexamethasone-induced changes in plasma levels of HVA (i.e., increases or decreases) sensitively and specifically discriminated between patients with affective and nonaffective psychoses.     

Dexamethasone suppression test: use of two different dexamethasone doses

The endocrinologic methods used in the dexamethasone suppression test (DST) for depression were examined, by employing two different doses of dexamethasone (0.5 or 1.0 mg) at 11 p.m. Nonsuppression to the 1.0 mg DST (plasma cortisol criterion value of 5 micrograms/dl) was seen in 33% of major depressives and in 15% of schizophrenics. A similar result was obtained with the 0.5 mg DST when 12 micrograms/dl was employed as the plasma cortisol criterion value. Plasma cortisol levels 33 hours postdexamethasone did not distinguish between major depressives and schizophrenics.     

Partial 11 beta-hydroxylase activity suppression after dexamethasone in patients with major depression

Eleven beta-hydroxylase activity was assessed by measuring the cortisol to 11-deoxycortisol ratio in 20 control subjects, 38 patients with major depression, and five patients with Cushing's disease before and after 1 mg of dexamethasone. The mean levels of 11 beta-hydroxylase activity did not differ among groups before dexamethasone. After dexamethasone patients with Cushing's disease showed a nonsignificant increase in 11 beta-hydroxylase activity while patients with major depression and controls subjects both showed a decrease. Endogenous depressive patients were no more likely to show high 11 beta-hydroxylase activity than neurotic depressive patients; however, depressed patients with cortisol nonsuppression after dexamethasone were. Post-dexamethasone 11 beta-hydroxylase activity is positively correlated with age in both control subjects and patients with depression.     

A modified dexamethasone suppression test for endogenous depression

In order to simplify the dexamethasone suppression test (DST), we have administered a lower dosage of dexamethasone (DEX) and shortened the sampling time to a single morning blood sample. DEX (in dosage increments from 0.125 to 1.0 mg, p.o.) was administered at 2300 h to normal volunteers in a double-blind randomized fashion, and blood samples were taken at 0700 h the following morning. While significant cortisol suppression occurred after the 0.375 mg, 0.5 mg, and 1.0 mg doses of DEX, the 0.5 mg dose was the smallest that clearly suppressed cortisol in all eight subjects. This dose then was used to test the feedback sensitivity of the central nervous system (CNS)-pituitary-adrenal axis in endogenously depressed patients. Twenty endogenously depressed patients and 20 normal volunteers were given both the standard 1.0 mg DST, with post-DEX serum cortisol determined at 1500 h, and the simplified 0.5 mg DST, with post-DEX serum cortisol determined at 0700 h. Four patients (20%) and one control (5%) were nonsuppressors after the 1.0 mg DST, and nine patients (45%) and one control (5%) were nonsuppressors after the 0.5 mg DST. In addition, nine patients with major depression (nonendogenous subtype) and 15 patients with panic attacks also were studied using the 0.5 mg DST. Only 2 of these 24 patients (8%) were nonsuppressors. The results suggest that the single-sample 0.5 mg DST is more sensitive than the standard 1.0 mg DST, and the specificity of the modified test appears comparable to the standard form of the test.     

Plasma dexamethasone levels in children given the dexamethasone suppression test

To determine whether children who demonstrate dexamethasone suppression test (DST) nonsuppression have lower plasma dexamethasone levels than DST suppressors, we administered the DST to 73 patients ranging in age from 5-14 years. Plasma dexamethasone levels and postdexamethasone cortisol levels were measured at 4:00 PM on day 2. We found: (1) DST nonsuppressors had significantly lower plasma dexamethasone levels (p less than 0.03) than suppressors; similar trends were observed when the population was divided into depressed and nondepressed patients; (2) mg/m2 dose of dexamethasone was directly correlated with plasma dexamethasone (p less than 0.003) and inversely correlated with postdexamethasone plasma cortisol levels (p less than 0.04); and (3) a statistically significant inverse correlation between plasma dexamethasone levels and postdexamethasone cortisol levels (p less than 0.04). Our findings show that plasma dexamethasone levels are important in evaluating DST results in psychiatrically disturbed children and suggest that dexamethasone dosage for use in the DST in children might be better calculated in terms of body surface area.     

Measurement of ACTH and prolactin in the dexamethasone suppression test

Plasma concentrations of ACTH and prolactin were measured in psychiatric inpatients at 8 a.m. and 4 p.m. before and after the standard 1 mg overnight Dexamethasone Suppression Test (DST). Plasma concentrations of cortisol were measured at 8 a.m. and 4 p.m., and 11 p.m. before and after 1 mg dexamethasone. Dexamethasone suppressed plasma concentrations of ACTH, prolactin and cortisol in the subject group as a whole. "Cut Points" obtained using Fisher's Exact Test identified plasma ACTH values at 8 a.m. baseline, 4 p.m. baseline and 8 a.m. post-dexamethasone and plasma prolactin values at all four times that significantly differentiated patients with bipolar depressive disorder and major depressive disorder from other psychiatric patients. There were no cut points found at any of the six times for plasma levels of cortisol that significantly differentiated between these two diagnostic groups. Of interest in this subject population, basal (pre-dexamethasone) plasma concentrations were of more diagnostic information than post-dexamethasone values. These pilot findings suggest that monitoring plasma prolactin and ACTH concentrations before and after dexamethasone might increase the sensitivity and specificity of this laboratory test for depression.     

Lack of effects of hospitalization and oral contraceptives on DST results in control subjects

The effect of oral contraceptive use and hospitalization stress on the results of the dexamethasone suppression test (DST) were assessed. This test, in which 1 mg dexamethasone is given at 11:00 p.m., and blood cortisol is analyzed the following day, is used as an indicator or major or endogenous depression, as opposed to situational depression, but specificity of the test remains in dispute. The test subjects were 15 normal volunteers, mostly staff, and 27 surgical patients, who were planning orthopedic surgery the following day. Of the 20 women, 7 took oral contraceptives, (Sequilar, Microgynon 50, Trigynon, Microgynon 30 and Diane). Cortisol was radioimmunoassayed at 4:00 p.m. in volunteers and at 8:00, 4:00 and 11:00 p.m. in hospital patients. Only 1 subject had a positive test (non-suppressor), a non oral contraceptive user, with a cut-off point of 50 mcg/L. The hospital patients' cortisol levels were slightly higher (n.s.). Pill users' cortisol levels were unchanged.     

Cortisol, 11-deoxycortisol, and ACTH concentrations after dexamethasone in depressed patients and healthy volunteers

The 1 mg dexamethasone suppression test was used to assess pituitary-adrenal activity in 23 depressed patients and 8 healthy volunteers. At 1600h, after administration of the test dose of dexamethasone at 2300h, levels of cortisol, 11-deoxycortisol, and corticotropin were determined following a chromatographic extraction step applying highly specific radioimmunoassay techniques. Cortisol nonsuppressors had significantly increased adrenocorticotropic hormone (ACTH) values and cortisol/11-deoxycortisol ratios. The cortisol/11-deoxycortisol ratio was regarded as a measure of biologically active ACTH. The present results, which indicate a concordance of corticotropin and corticosteroid response, suggest that the parent abnormality of dexamethasone-resistant cortisol concentrations is elevation of biologically active corticotropin.     

Plasma ACTH and cortisol concentrations before and after dexamethasone

Alteration in the hypothalamic-pituitary-adrenal (HPA) axis occurs in up to 50% of depressed patients and is demonstrated by the failure to suppress cortisol concentrations after dexamethasone administration. Evidence suggesting that these cortisol abnormalities reflect hypothalamic-pituitary dysfunction has been inconsistent. We administered the dexamethasone suppression test to 28 psychiatric inpatients, including 17 cortisol suppressors and 11 nonsuppressors. Adrenocorticotropic hormone (ACTH) concentrations at 8 a.m. pre- and postdexamethasone were significantly greater in cortisol nonsuppressors than in suppressors. Our data support the hypothesis that pituitary ACTH secretion is altered in depressed patients who have HPA axis abnormalities demonstrated by plasma cortisol measurements.     

Major Depressive Episode and Low Dose Dexamethasone Suppression Test

Abstract: The authors studied the validity of a low dose (0.5 mg) dexamethasone suppression test (DST) in identifying depression. Nine patients who met the criteria of major depressive episode (MDE) in the Diagnostic and Statistical Manual of Mental Disorders, another nine psychiatric patients and one normal subject underwent the DST. At least one of the two blood samples obtained either at 8 a.m. or at 2 p.m. from each of the nine patients with MDE showed a Cortisol concentration of over 5.0 μg/dl, while the Cortisol concentration in the other 10 subjects was uniformly suppressed under this level. All the patients with MDE could be identified by nonsuppression of the Cortisol secretion at 8 a.m. or at 2 p.m. An "early escape" phenomenon in depressed patients reported by Carroll et al. (1976) was absent in a 0.5 mg DST, and the blood samples at 8 p.m. were less useful for identifying the depressive patient. The reason why the one point sampling method used by previous investigators was insufficient to identify the depressed patient was discussed.     

Afternoon plasma cortisol in relation to depression. A replication study

In 37 consecutive depressed inpatients afternoon plasma cortisol (1500-1520 h) was measured in 3 ways: 1) spontaneously; 2) 2 h after oral administration of 60 mg oxazepam; and 3) 16 h after oral administration of 2 mg dexamethasone. Both oxazepam and dexamethasone caused a significant suppression of cortisol secretion. Spontaneous and suppressed cortisol levels correlated significantly to stress/distress items on the Hamilton Rating Scale for Depression (sum of items 8, 9, 10 and 12), whereas no correlations to age, or type of depression were found. In an earlier similar study of 35 patients both spontaneous and suppressed cortisol levels correlated significantly with age, type and severity of depression as well as with the stress/distress items. Those patients were older, more depressed (HRSD-17) and had higher stress/distress scores compared with the present sample of 37 patients. The consistent finding of a correlation with the stress/distress items suggest that this factor is important in relation to the hypersecretion of cortisol during depression and this may explain the limited diagnostic power of spontaneous and suppressed cortisol levels.     

The Dexamethasone Suppression Test for Japanese with Eating Disorders

Abstract: A one-mg oral overnight dexamethasone suppression test (DST) was conducted on 22 inpatients with eating disorders. To confirm that the dexamethasone tablets had been ingested, we measumd the plasma concentrations of dexamethasone the next morning (at 0900 hr after DST). The diagnosis of anorexia nervosa and bulimia was made according to the criteria for DSM-III, respectively. Of the 22 patients with eating disorders, 16 satisfied the criteria for anorexia nervosa and 6 for bulimia. The DST was carried out within 2 weeks of hospitalization on each patient. The subjects were given 1 mg of dexamethasone in the evening (at 2300 hr) and blood samples were collected the following day (at 0900, 1600 and 2100 hr, respectively). The plasma cortisol and dexamethasone levels were concurrently determined by RIA. The criterion for non-suppression was a failure to suppress the plasma cortisol levels below 5.0 μg/dl in any one of the three samples. All but one patient with bulimia had ingested the dexamethasone. Thirteen (62%) of 21 patients with eating disorders were nonsuppressors. We found a significant positive correlation between the plasma cortisol levels at 1600 hr or 2100 hr and a decrease in ideal body weight (n = 16, r = 0.613, p < 0.05; r = 0.75, p < 0.01, respectively) and a significant inverse relationship between the plasma dexamethasone levels at 0900 hr and the plasma cortisol levels at 1600 hr was recognized (n = 21, r - 0.631, p < 0.01). These results suggest that the blood dexamethasone levels as well as body weight might contribute to the abnormalities of DST seen in patients with eating disorders.     

The dexamethasone suppression test and unipolar/bipolar distinctions

In an attempt to validate several subtypes of affective disorders, 52 consecutive patients hospitalized at a clinical research center were comprehensively classified along several diagnostic and phenomenologic axes. Cortisol levels of each patient were evaluated at baseline and after the administration of 0.5 and 1.0 mg dexamethasone. None of the depressive subtypes responded significantly differently to the 1.0 mg dose. However, the bipolar subtype was associated with significantly different DST responses to the 0.5 mg dose. Patients with bipolar affective disorder, both manic and depressed, had higher postdexamethasone mean cortisol levels than all other groups. The results support the distinctiveness of the bipolar diagnosis.     

Effect of endogenous cortisol levels on natural killer cell activity in healthy humans

The aim of this study was to examine the effects of increasing and decreasing endogenous cortisol levels on natural killer (NK) cell activity in vivo. Normal healthy volunteers participated in the following studies: baseline (n = 27), metyrapone challenge test (n = 10), dexamethasone suppression test (n = 10), and adrenocorticotropic hormone (ACTH) stimulation test (n = 8). Each subject served as his own control for each study. Each subject was tested for NK activity and plasma cortisol levels at 9 a.m., just before the challenge drug administration, and at 10 a.m., except for the dexamethasone study, in which only the 9 a.m. blood was drawn, 10 h after the dexamethasone administration. On the baseline study day, a significant decrease in plasma cortisol levels was found from 9 to 10 a.m. (p <.02) along with a significant increase in NK activity (p <.001). On the metyrapone test day, plasma cortisol levels at 10 a.m. were significantly reduced (p <.005) as expected, while NK activity at the same time point was not affected and was increased to an extent equivalent to the baseline study day. On the dexamethasone test day, plasma cortisol concentrations were significantly decreased (p <.0001) as compared to the same time point on the baseline day, without any significant change in the NK activity. On the ACTH test day, plasma cortisol rose significantly at 10 a.m. (p <.02), with no change in NK activity. We conclude that plasma cortisol alone has no significant effect on NK activity in vivo.     

Dexamethasone increases plasma free dopamine in man

In man, unconjugated plasma DA is normally undetectable or present in minute amounts. Twelve medication-free volunteers received a 1 mg dose of dexamethasone which produced pronounced increases of plasma free DA but not of other catecholamines. Mean plasma free dopamine levels after dexamethasone at 8 a.m. (155 ± 102 pg/ml) and 4 p.m. (163 ± 70 pg/ml) were significantly higher (p< 0.001) than those at 8 a.m. (50 ±18 pg/ml) and 4 p.m. (42 ± 7 pg/ml) before dexamethasone. Although the mechanism of increased dopaminergic activity after a dose of dexamethasone remains for future research, the data presented in this paper may explain the observations that corticosteroids lower prolactin levels and may induce psychiatric disturbances, as well as the finding that depressed patients with high postdexamethasone cortisol levels are frequently psychotic.     

Baseline plasma cortisol and dexamethasone test in unselected psychiatric inpatients

The plasma cortisol (PC) level at 08.00 a.m. was assessed in 250 unselected psychiatric inpatients suffering from various disorders, assorted in 8 diagnostic groups. Endogenously depressive patients showed a significantly higher rate of cortisol hypersecretion (PC greater than 560 nmol/l = 20 micrograms/dl) than the neurotically or reactively depressed patients and than schizophrenics or paranoid psychotics. The PC level after the midnight dose of 1 mg dexamethasone was examined in 125 patients at 08.00 a.m. (group I) and in 125 patients at 04.00 p.m. (group II). There was no statistical difference in the rate of dexamethasone test (DST) nonsuppressors (PC greater than 140 nmol/l = 5 micrograms/dl) in the separate diagnostic groups between group I and II, but in the postdexamethasone blood samples at 04.00 p.m., significantly more DST nonsuppressors were detected than in the samples at 08.00 a.m. in the total number of all patients, regardless of their diagnosis. DST nonsuppressors were found in all of our diagnostic groups with the exception of manic syndrome, and their various rates will be discussed and compared with the results of previous studies. The DST shows a high sensitivity in endogenous depression, but its diagnostic value is limited as a result of its relative lack of specificity.     

The dexamethasone suppression test in prepubertal depressed children

The dexamethasone suppression test (DST) was performed in 50 hospitalized prepubertal children who met DSM-III criteria for major depressive episode, 18 hospitalized controls with a psychiatric disorder, and 18 nonhospitalized normal controls. Baseline and post-DST cortisol levels were measured at 8 a.m. and 4 p.m. The depressed children had consistently higher cortisol levels than the controls at baseline and post-DST. The DST was positive in 82% of depressed children, 28% of psychiatric controls, and 11% of normal controls. The results indicate that prepubertal depressed children may have abnormalities in the hypothalamic-pituitary-adrenal axis similar to those in adults with a major depressive illness.