Cortisol suppression index: a further evaluation

The cortisol suppression index (CSI) is the ratio of pre- to postdexamethasone plasma cortisol concentrations. The 8 a.m. CSI was previously found to identify 66% of a sample of psychiatric inpatients with major depression. In the present study, a 4 p.m. CSI identified 71% of psychiatric inpatients with major depression, in contrast to 53% when using DST criteria alone. This finding adds further validation to the CSI. Further studies of the utility of the CSI are suggested to help improve the detection of major depression.     

A comparison of the cortisol suppression index and the dexamethasone suppression test

The cortisol suppression index (CSI) (the ratio of pre- to postdexamethasone serum cortisol concentrations) was compared to the dexamethasone suppression test (DST) in endogenously depressed DST suppressors (N = 20) and nonsuppressors (N = 21) and in normal controls (N = 23). The 8 a.m. CSI detected 17.1% and 31.7% of endogenous depressives at the 4.0 and 6.0 thresholds; for the 4 p.m. CSI, rates were 48.8% and 65.9%. The 4 p.m. CSI produced 17.4% and 39.1% false positives in normal controls at the two thresholds, whereas the false positive rate for the DST was 4.3%. These data suggest that the CSI is not as specific as the standard DST for the detection of endogenous depression.     

A comparison of the cortisol suppression index and the dexamethasone suppression test in prepubertal children

Results of the dexamethasone suppression test (DST) and the cortisol suppression index (CSI) were compared in 50 depressed prepubertal children and 36 control subjects. The 4:00 p.m. DST, the two-point DST, and the 8:00 a.m. revised criterion CSI yielded the best results and had similar clinical utility and diagnostic confidence values.     

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.     

Three tests of cortisol secretion in adult endogenous depressives

Seventy-nine drug-free adult patients fitting RDC criteria for major depressive disorder endogenous subtype (EMDD), and 64 normal adult volunteers, were studied at pretreatment with at least one of three tests of cortisol secretion. The tests were: 1) Mean half-hourly cortisol concentrations from 1 p.m. to 4 p.m. (1-4 PM CORT); 2) plasma cortisol response to 0.15 mg/kg of dextroamphetamine hydrochloride (DACT) in the afternoon; 3) dexamethasone suppression test (DST) using 1 or 2 mg. Thirty-six depressive and 27 volunteers underwent all three tests. Analysis of the data was performed for each test singly, for all pairs of tests and for all three tests in same subjects. Results show that the single most sensitive cortisol test for depressions is the DACT (72%), with a specificity of 88%. These tests may measure different underlying pathophysiologies associated with 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.     

Comparison of the dexamethasone suppression test and the cortisol suppression index

Among 50 inpatients, the sensitivity and specificity of the dexamethasone suppression test (DST) were 51.7% and 85.7%, respectively. For the cortisol suppression index they were 10.3% and 91% at 8:00 a.m. and 51.7% and 57.1% at 4:00 p.m. Thus, the cortisol suppression index does not appear to be an adequate substitute for the DST.     

HPA-axis hyperactivity and mortality in psychotic depressive disorder: preliminary findings

BACKGROUND: The excess mortality associated with depressive disorders has been most often attributed to risks for suicide but diverse findings indicate that depressive disorders also increase risks for cardiovascular (CV) mortality. Among the possible mediators is the hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity that characterizes many cases of relatively severe depressive disorder and severity is characteristic of psychotic depressive disorder. METHODS: The following describes a 17-year mortality follow-up of 54 patients with Research Diagnostic Criteria (RDC) psychotic major depression or schizoaffective, mainly affective, depression. All had baseline assessments that included a 1mg dexamethasone suppression test with post-dexamethasone samples at 8 a.m., 4 p.m. and 11 p.m. RESULTS: Regression analyses showed that both greater age and higher maximum post-dexamethasone cortisol concentrations predicted deaths due to CV causes (t=4.01, p<0.001 and t=3.03, p=0.004, respectively). The 4 who died from CV disease had a mean (SD) post-dexamethasone cortisol concentration of 18.0 (6.0)microg/dl while the mean (SD) value for the remaining 50 patients was 7.6 (6.6)microg/dl (t=3.03, df=53, p=0.004). Regression analyses showed the 11 p.m. post-dexamethasone value to be predictive of suicide (t=2.05, p=0.048). CONCLUSIONS: Conclusions should be tentative because an earlier follow-up of a more heterogeneous, but larger, sample did not find a relationship between DST results and CV mortality, and because only 4 CV deaths occurred in the present study. HPA-axis hyperactivity is probably only one of a number of factors that link depressive disorder to CV mortality.     

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.     

Dexamethasone suppression test and familial subtypes of unipolar depression

We have studied the suppression of plasma cortisol after dexamethasone (1 mg) and the peak post-dexamethasone cortisol values in 84 hospitalized patients with a diagnosis of primary unipolar depression. The non-suppressor responses in the three familial subgroups (Winokur) were: 11/22 in familial pure depressive disorder (FPDD), 21/49 in sporadic depressive disease (SDD) and 1/13 in depression spectrum disease (DSD) (FPDD vs. SDD, p less than 0.05; SDD vs. DSD, p less than 0.05). When considering the peak post-dexamethasone cortisol value, or the 8.30-9.00-hour values, the results in the DSD group were lower than in the other two groups (p less than 0.05). These results suggest a different behaviour of DSD as compared with FPDD and SDD.     

Neuroendocrine aspects of primary endogenous depression: VI. Receiver operating characteristic analysis of the cortisol suppression index versus the dexamethasone suppression test in patients and matched controls

The cortisol suppression index (CSI), which is the ratio of the predexamethasone (DEX) serum cortisol concentration to the post-DEX cortisol concentration, has been investigated as an alternative means of analyzing the response of the hypothalamo-pituitary-adrenal axis to DEX. We used receiver operating characteristic (ROC) analysis to examine the CSI versus the corresponding standard post-DEX cortisol values in a sample of 40 primary endogenous major depressives versus 40 matched normal control subjects who underwent a DEX suppression test (DST). The CSI was highly correlated with post-DEX cortisol values and showed no advantage in test performance over the standard DST across a wide range of criterion values. ROC analysis is a useful technique for determining the utility of the DST and other biological markers in psychiatry.     

Simple laboratory test of neuroendocrine disturbance in depression: 11 p.m. saliva cortisol

Saliva cortisol was measured at 11 p.m. in a sample of 74 psychiatric inpatients composed of 24 primary endogenous depressives, 40 secondary depressives and 20 nondepressives (DSM III and Saint-Louis criteria). Primary depressives had significantly higher 11 p.m. saliva cortisol levels than nondepressives (p less than 0.02) and secondary depressives (p less than 0.05). In contrast, there were no significant differences between secondary depressive and nondepressive saliva cortisol levels. A saliva cortisol cutoff limit of 3.45 nmol/l identified primary depressives with a sensitivity of 62.5% and with a specificity of 75% in the depressive group, and 90% in the nondepressive group. The measurement of saliva cortisol at 11 p.m. could be used alone as a reliable and practical index of hypothalamic-pituitary-adrenal axis activity in depression, especially in outpatients.     

4 p.m. baseline cortisol level as a predictor of DST results in depression

To assess the relationship of baseline cortisol to the 1 mg dexamethasone suppression test (DST), 4 p.m. baseline and 4 p.m. postdexamethasone blood samples were drawn on 52 consecutive depressed outpatients. Baseline cortisol correlated significantly with post-DST values, and baseline levels above 15 micrograms/dl predicted DST nonsuppression with 90.4% accuracy. These data lend some support to the usefulness of baseline cortisol determination in depressed outpatients in whom a full DST may be difficult.     

Adrenocortical hyperactivity in depression: effects of agitation, delusions, melancholia, and other illness variables

In an attempt to determine the relative contributions to adrenocortical hyperactivity in depression of agitation, delusions, and melancholic subtype, we measured cortisol levels before and after dexamethasone in 93 unipolar major depressed inpatients. Stepwise multiple regression showed that agitation predicted 22% of the variance in a.m. cortisol level after dexamethasone. Addition of the variables melancholia and delusionality to the regression model accounted for 27% and 34%, respectively, of the variance in the same cortisol variable. Age, illness severity, and weight loss added no further significant predictive value. Age, weight loss, and illness severity did affect cortisol levels when examined separately from the other variables. Rate of nonsuppression on the dexamethasone suppression test (DST) differed between the nonmelancholic major depressive group and any other group with melancholia. These results suggest why some discrepancies may exist between studies of the DST in delusional depression and indicate that agitation merits careful assessment in future studies of DST response.     

Dexamethasone suppression test and the levels of serum growth hormone, plasma vasopressin and plasma homovanillic acid in depressed in- and outpatients

A total of 206 depressive patients (176 outpatients and 30 inpatients) underwent a dexamethasone suppression test (DST). Resting levels of serum growth hormone (GH), plasma vasopressin (AVP) and plasma homovanillic acid (HVA) were also measured in a proportion of the patients. Fifty-seven per cent of the endogenous patients showed nonsuppression of cortisol in the DST, while 92% in the nonendogenous group showed normal suppression. The diagnostic confidence of a positive test was 83%. The sensitivity and specificity of the test was slightly higher among inpatients than out-patients, and serum cortisol value at 4 p.m. was more useful than the morning value. No significant correlation was found between severity of the depression as measured by the Hamilton Rating Scale for Depression and serum cortisol. In single subjects there was, however, an obvious correlation. The levels of serum GH, plasma AVP and plasma HVA did not differ in the endogenous and nonendogenous groups, and there was no correlation between serum cortisol in the DST and the concentrations of the other hormones or HVA in plasma.     

Dexamethasone suppression test findings in subjects with personality disorders: associations with posttraumatic stress disorder and major depression

OBJECTIVE: Previous studies using the 1.0-mg dexamethasone suppression test (DST) in subjects with personality disorders have produced mixed results. However, these studies focused on major depression and did not consider the possible effects of the comorbidity of posttraumatic stress disorder (PTSD). PTSD has been shown to be associated with increased cortisol suppression. To investigate the effect of PTSD, the authors conducted a 0.5-mg DST, which is more sensitive than the 1.0-mg DST for detection of increased cortisol suppression, in a group of subjects with personality disorders. METHOD: Subjects with personality disorders (N=52) ingested 0.5 mg of dexamethasone. Pre- and postfasting blood samples were drawn for measurement of cortisol levels. A three-way analysis of covariance was used to test for the main effects of major depression, PTSD, and gender on percent cortisol suppression, with plasma dexamethasone concentration as a covariate. Secondary analyses assessed for main and interaction effects of age at which trauma(s) occurred and a diagnosis of borderline personality disorder. RESULTS: Neither major depression nor gender had a significant effect on percent cortisol suppression. Subjects with PTSD had significantly higher percent cortisol suppression than subjects with major depression. Age at which trauma(s) occurred and a borderline personality disorder diagnosis had no significant main or interaction effects on cortisol suppression. CONCLUSIONS: A high level of cortisol suppression was associated with PTSD in subjects with personality disorder. This finding is similar to published findings for PTSD subjects without personality disorders. Major depression, gender, age when trauma(s) occurred, and a diagnosis of borderline personality disorder did not have significant main or interaction effects on cortisol suppression.     

The dexamethasone suppression test: identification of subtypes of depression

In this study mean 4 p.m. cortisol levels were significantly higher in patients with major depression than in control subjects or in patients with bipolar depression or dysthymic-related disorders. Moreover, the distribution of values differed significantly among groups. Eighteen of 45 patients with major depression had cortisol levels of 10 micrograms/dl or more, compared with 2 of 20 bipolar depressed patients and 0 of 31 controls. Patients with very high cortisol levels (15 micrograms/dl or more) tended to fulfill criteria for major depression with mood-congruent psychosis. The distribution of values in the major depression group also suggested the existence of three major subgroups. The authors discuss the implications of these data.     

Results of the 8 a.m. dexamethasone suppression test constitute a suitable tool for confirming the diagnosis of melancholia. A test unaffected by the variations in the bioavailability of dexamethasone

This prospective study was conducted in order (1) to examine which postdexamethasone cortisol value i.e., 8 a.m., 4 p.m. or peak cortisol - is most suitable as a laboratory test to help confirm the diagnosis of melancholia and (2) to investigate the influence of the dexamethasone levels in the results of the dexamethasone suppression test (DST). To this end we administered the DST to 48 controls and 115 depressed inpatients categorized according to DSM-III. The 8 a.m. and 4 p.m. dexamethasone levels were determined in 100 subjects. We found that an 8 a.m. postdexamethasone cortisol value greater than or equal to 3.5 micrograms/dl was of the most significant diagnostic value in order to separate melancholia from normal controls and/or minor depressives. The 8 a.m. and 4 p.m. dexamethasone values did not differ between healthy controls, minor and severely depressed patients. Although cortisol nonsuppressors exhibited significantly lower dexamethasone values, the predictive value of the DST for melancholia was not affected by the large variation in the bioavailability of dexamethasone.     

CSF corticotropin-releasing hormone in depressed patients and normal control subjects

The authors studied CSF corticotropin-releasing hormone (CRH) and plasma cortisol in 22 depressed patients and 18 normal control subjects. CRH levels were similar in the two groups. Depressed patients who were nonsuppressors on the dexamethasone suppression test had significantly higher levels of CRH than suppressors did. The depressed patients' CRH levels were significantly correlated with 4:00 p.m. postdexamethasone plasma cortisol levels. While the inclusion of a depressed patient with an outlier CRH value resulted in the loss of statistical significance for both of these findings, the authors suggest that these results support the hypothesis that hypercortisolism in depressed patients in part reflects a defect at or above the hypothalamus, resulting in hypersecretion of CRH.     

Occurrence of high concentrations of postdexamethasone cortisol in elderly psychiatric inpatients

The authors retrospectively studied 161 psychiatric inpatients who had received a dexamethasone suppression test (DST). The majority of the patients were over 60 years old, female, and had concurrent chronic medical illnesses. Age was significantly correlated with log-transformed postdexamethasone cortisol concentrations in the 118 nondemented patients with major depression. Four p.m. cortisol concentrations greater than 15 micrograms/dl occurred in 15 patients. All were over 60 years old; all but one had major depressive disorder (MDD); and five had dementia plus MDD. In the same population, a 5 micrograms/dl criterion did not distinguish MDD from non-MDD patients. The results support the existence of a clinically relevant age effect on the DST in patients with MDD. Elderly depressed patients with markedly elevated cortisol concentrations occur frequently, and warrant further clinical and pathophysiological study.