Comparison of solid-phase radioimmunoassay and competitive protein binding method for postdexamethasone cortisol levels in psychiatric patients

Results obtained by competitive protein binding assay (PBA) and a solid-phase radioimmunoassay (RIA) for cortisol were compared in 157 samples from 100 psychiatric patients given a dexamethasone suppression test (DST). Cortisol levels in plasma samples obtained at 8:00 a.m. or 4:00 p.m. the day following 1.0 mg dexamethasone orally at bedtime ranged from 0 to 30 micrograms/dl and correlated closely (r = 0.96). However, RIA gave values that were consistently and significantly lower (average = 8.9%) than those obtained by PBA. When samples were further assayed by a specific RIA for corticosterone, there was a strong correlation between cortisol and corticosterone RIA values (r = 0.79), and corticosterone (7.8% of cortisol levels) accounted for most of the difference between PBA and RIA for cortisol. The relationship between results of the two cortisol assay methods can be expressed (in micrograms/dl) by the equation: RIA = 0.92(PBA) - 0.10, based on findings obtained in a separate analysis of 127 samples with cortisol values in the 0-10 micrograms/dl range, critical to the valid interpretation of the DST in melancholia. A reported criterion of a "positive" DST in psychiatry, of plasma cortisol of greater than or equal to 5.0 micrograms/dl has been suggested by use of a PBA. Use of the present RIA required that this value be adjusted downward, at least to 4.5 micrograms/dl; application of this criterion increased the clinical sensitivity of the DST by 10%. We urge local, independent verification of criteria to define the DST as "positive" in each laboratory and with each method of assay.     

Dexamethasone suppression in major depression

Overnight 1 mg dexamethasone suppression tests were performed on 37 hospitalized patients with unipolar major depression and 13 psychiatric controls: 62% of the depressives and 38% of controls failed to suppress below 6 micrograms/dl of plasma cortisol at least once on the day after dexamethasone. Specificity for depressive diagnosis was only 62% but rose to 100% when a plasma cortisol value of 10 micrograms/dl was used as the criterion for normal suppression. Depressed patients were significantly more likely to show normal suppression if they were under age 65 (56% vs. 24% in the geriatric sample). Other demographic and clinical variables examined in the depressed sample did not assort by suppressor status.     

Use of the dexamethasone suppression test in an inpatient setting: a replication and new findings

The dexamethasone suppression test (DST) was administered to 131 depressed and 109 nondepressed psychiatric inpatients. The depressed patients were categorized according to DSM-III as minor depression, major depression without melancholia, and major depression with melancholia and/or with psychotic features. The nondepressed patients were stratified over several DSM-III subcategories. DST nonsuppression was nonspecific for major depression: the mean post-dexamethasone cortisol value and the number of nonsuppressors were not significantly different between the major depressives and the nondepressed psychiatric controls. Within the depressive sample the DST was a significant (p less than 0.01) discriminator between major and minor depression. Postdexamethasone plasma greater than or equal to 3.5 micrograms/dl at 0800h was the most sensitive (39%) and specific (94%) criterion; cortisol values at 1600h and 2300h showed no significant discriminating power for major vs. minor depression. The diagnostic utility of the DST thus appears to be limited to confirming the diagnosis of major depression, once the clinical diagnosis of depression is made. There was no significant influence of age or gender on postdexamethasone cortisol values.     

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.     

Evaluation of depression in a general hospital: utility and limitations of the dexamethasone suppression test

Use of the DST was studied in medically hospitalized, depressed patients. Although complicating medical factors necessarily excluded nearly 60% of referrals, post-dexamethasone plasma cortisol values were significantly higher in 14 major depressives appropriate for the DST as compared to 12 patients with milder, subsyndromal depressive conditions. Using a plasma cortisol criterion of greater than 7 micrograms/dl, the DST identified major depression with 57% sensitivity and 92% specificity in this subsample (p less than 0.005). While limited by a high exclusion rate, the DST may be useful for confirmation of major depression in carefully screened general hospital patients. Implications for research and practice are discussed.     

L-5-hydroxytryptophan stimulated cortisol escape from dexamethasone suppression in melancholic patients

The dexamethasone suppression test (DST) was carried out in 62 depressed patients. At 0800 the postdexamethasone cortisol values were determined and 125 mg L-5-hydroxytryptophan (L-5-HTP) was administered. The second cortisol sample at 0930 revealed a significant enhancing effect for L-5-HTP on the postdexamethasone cortisol values in melancholic patients, whereas no effects were detected in minor depressives. Our results show that L-5-HTP converts some DST suppressors into nonsuppressors, whereas the escape from dexamethasone in some nonsuppressors is markedly stimulated. The L-5-HTP-stimulated 0930 postdexamethasone cortisol values performed markedly better than the 0800 DST results: at a cut-off value of greater than or equal to 5 micrograms/dl the sensitivity for melancholia increased from 46% to 68%, and the specificity remained unchanged (96%).     

Plasma cortisol and 11-deoxycortisol activity in depressed patients and normal volunteers.

Plasma cortisol and 11-deoxycortisol were measured in 30 depressed patients and 110 normal volunteers before and after a 1.0 mg dexamethasone suppression test (DST). Post-dexamethasone plasma cortisol, 11-deoxycortisol and the cortisol/11-deoxycortisol ratio were significantly higher in the depressives compared to the controls, even when age and sex were taken into account. Pre-dexamethasone plasma cortisol, post-dexamethasone cortisol, 11-deoxycortisol and their ratio were significantly higher in the cortisol nonsuppressors than in the suppressors. The measurement of post-dexamethasone 11-deoxycortisol and the ratio did not differentiate between endogenous and reactive depression. Using the normative data, we explored several methods for determining a criterion value to define abnormal post-dexamethasone plasma 11-deoxycortisol and the cortisol/11-deoxycortisol ratio in depressed patients. All showed poor sensitivity and a low positive predictive value for depression. The measurement of 11-deoxycortisol thus does not enhance the clinical utility of the DST.     

The dexamethasone suppression test in a group of research diagnostic criteria schizoaffective depressed men

A dexamethasone suppression test (DST) was performed on 8 schizoaffective depressed men. Cross-sectional comparisons were made with three groups: schizophrenics (n = 10), unipolar major depressives (n = 23) and healthy controls (n = 43). All were drug-free and similar in age and body weight. Evaluations utilized the Research Diagnostic Criteria (RDC) for diagnosis, and the Hamilton Rating Scale for Depression for depressive symptom rating. DST nonsuppression, defined as a blood cortisol level of greater than or equal to 5.0 micrograms/dl at 16.00 h postdexamethasone, was observed in 43.5% of the major depressive disorder patients. This was different from the other three groups: 12.5% in schizoaffective depressed, 10.0% in schizophrenics and 9.3% in healthy controls (p less than 0.01, p less than 0.01, and p less than 0.001 respectively). Although schizoaffective depressed patients were significantly different from major depressive disorder patients in their DST responses, both groups were similar in their total HRSD scores and different from the schizophrenics (p less than 0.01 for each). These results, together with others previously reported by us on the thyrotropin-releasing hormone challenge in the same diagnostic groups, may be taken to mean that schizoaffective disorder, depressed type, is biologically distinct from major depressive disorder but not schizophrenia. On the other hand, until further corroborated, they should probably be considered a reflection of the heterogeneity of the schizoaffective syndrome and the nonspecificity of the DST.     

Cortisol suppression per nanogram per milliliter of plasma dexamethasone in depressive and normal subjects

It has been suggested that dexamethasone pharmacokinetics may affect cortisol suppression during the Dexamethasone Suppression Test (DST). In depressed patients the cortisol response has been shown to negatively correlate with dexamethasone plasma concentrations, which also influence the sensitivity and specificity of the DST. These findings have been interpreted as weakening the utility of the DST. However, the analysis of pre- and post-1 mg DST cortisol concentrations corrected for plasma dexamethasone concentrations suggest that compared with normals (n = 52), patients with major depressive disorder (MDD) as a group (n = 71) had less suppressibility of cortisol to the same plasma dexamethasone concentrations. Moreover, when the MDD patients were evaluated based on DST status, the suppressors had cortisol/dexamethasone ratios (micrograms/dl of cortisol per ng/ml of plasma dexamethasone) similar to the normal controls, whereas the nonsuppressors had ratios that were significantly higher. These data suggest that DST non-suppression, as well as sensitivity and specificity of the DST in depression, is not only attributable to altered dexamethasone disposition, but indeed, there is a genuine reduced sensitivity of cortisol to dexamethasone that still points to an abnormality of the delayed feedback mechanism of the hypothalamic-pituitary-adrenal system in some depressed patients.     

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.     

Use of saliva cortisol in the dexamethasone suppression test

In a sample of 26 inpatients (15 primary endogenous depressives and a heterogeneous comparison group of 11 psychiatric patients), results of the dexamethasone suppression test (DST) for endogenous depression were compared when cortisol was measured in plasma (total and free) and in saliva. Results showed a close linear relationship among plasma total and free cortisol, plasma total cortisol, and saliva cortisol, and between free plasma and saliva cortisol. A saliva cortisol cutoff point of 70 ng/dl achieved the same sensitivity (67%), specificity (91%), and diagnostic confidence (91%) as the best cutoff scores of plasma total cortisol (5 μ/dl) and plasma free cortisol (0.15 μ/dl). These results suggest that saliva cortisol, which directly reflects the biologically active fraction of cortisol, can be used as a reliable and more practical index in the DST, especially in outpatients.     

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.     

Low-dose (0.5 mg) DST in manic and major depressive episodes: in relation to the severity of symptoms]

BACKGROUND: Results of previous studies and our own preliminary study suggest that the dexamethasone suppression test (DST) using 1 mg of dexamethasone might result in lower sensitivity in Japanese and Asian people with major depressive episodes, when compared to Caucasian people. We investigated the clinical utility of low-dose (0.5 mg) DST in Japanese patients with manic or major depressive episodes. METHODS: Low-dose (0.5 mg) DST was performed 276 times in 122 patients with bipolar disorder (manic or depressed) or major depressive disorder who visited the Department of Psychiatry of Osaka Prefectural General Hospital. After strict exclusion criteria were applied, the remaining 225 test results in 98 patients were analyzed. The severity of symptoms was estimated in accordance with the DSM-IV, namely, severe, moderate, mild, or in remission. A 0.5 mg dose of dexamethasone was administered orally at 20:30, and blood samples were taken the following day at 8:00 (9:00 in outpatients) and 13:00. Serum cortisol levels were measured by radioimmunoassay. Nonsuppression was considered to have occurred when at least one of the postdexamethasone cortisol values was 4.0 micrograms/dl or over. RESULTS: In manic episodes, the postdexamethasone cortisol levels were significantly correlated with the severity of the symptoms, and the postdexamethasone cortisol levels in patients with severe symptoms were significantly higher than in those in remission. The rates of nonsuppression in manic episodes with severe, moderate, mild symptoms, and in remission, were 7/8 (88%), 1/4 (25%), 1/3 (33%) and 2/7 (29%), respectively. In major depressive episodes, the postdexamethasone cortisol levels were significantly correlated with the severity of the symptoms. The rates of nonsuppression in major depressive episodes with each grading of severity were 47/58 (81%), 28/52 (54%), 14/40 (35%), 10/53 (19%), respectively. In major depressive episodes, patients aged 50 or over showed significantly higher postdexamethasone cortisol levels than patients aged under 50. In particular, patients aged between 30 and 49 showed significantly lower postdexamethasone cortisol levels than those in the other age groups. There was no significant difference between male and female patients (two-way ANOVA), but female patients with severe depressive symptoms showed significantly higher postdexamethasone cortisol levels than male patients with severe symptoms. There was no significant difference between bipolar and unipolar patients with major depressive episodes (two-way ANOVA), with the exception that the rate of nonsuppression in remission in bipolar patients was significantly different than that in unipolar patients (9/33 (27%), 1/20 (5%), respectively). Among major depressive disorders, the rate of nonsuppression was highest in those with psychotic features, followed by those with melancholia, and then by those without melancholia. Re-evaluating the cut-off point discriminating nonsuppression from suppression, it was suggested that the optimal cut-off point might differ according to age and gender, but a fixed cut-off point at 4.0 micrograms/dl was considered to be appropriate. The postdexamethasone cortisol levels of samples obtained at 13:00 were more sensitive than those obtained at 8:00 or 9:00. The exclusion criteria and the clinical meanings of DST were discussed. CONCLUSIONS: Along with the previous studies indicating a low rate of nonsuppression in Japanese and other Asians using a standard 1 mg DST, our results suggest that low-dose (0.5 mg) DST is better in Japanese, and probably in most Asian patients, than 1 mg DST.     

The dexamethasone suppression test for Japanese with eating disorders

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 measured 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 micrograms/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 less than 0.05; r = 0.75, p less than 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 less than 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.     

Plasma corticosterone and cortisol following dexamethasone in psychiatric patients

Radioimmunoassays of cortisol (F) and corticosterone (B) were carried out in 133 plasma specimens, obtained at 0800 or 1600 h on the day following administration of dexamethasone (1.0 mg), from 69 patients admitted to a psychiatric inpatient service, to test suggestions that assays of B might complement those of F in the dexamethasone suppression test (DST) in a psychiatric setting. The overall correlation between F and B was +0.80. Concentrations of B averaged 5-8% those of F. We found close agreement (80-85%) between positive (F greater than or equal to 4.5 micrograms/dl) and negative DST results for both steroids assayed by radioimmunoassay at a criterion of greater than or equal to 1.5 ng/ml for B, as well as a reasonable compromise between sensitivity and specificity of the B-DST at that criterion. Post-dexamethasone samples obtained at 1600 h showed somewhat closer agreement between the B-DST and the F-DST than at 0800 h. Inclusion of 0800 h samples added little to the rate of positive results with the F-DST but did add to those of the B-DST by about 10% or more, depending on the criterion selected for a positive B-DST. The rate of positive DSTs among 44 patients who had both steroids assayed at both times was approximately 61%, and the agreement between positive test results among these patients was 92%. In a mixed population of acutely ill, hospitalized patients with various DSM-III diagnoses, but excluding those with medical or pharmacologic contraindications to the DST, high rates of positive DST results were obtained in patients with major depressive disorders (47-58%), with little difference found among those with bipolar, non-bipolar or melancholic characteristics. High rates also were found among manic and other acutely psychotic patients, as well as others with neurotic or characterological diagnoses, but rarely in a small group of chronic schizophrenics. Thus, a positive DST as evaluated with B or F is evidently not specific for cases of major depression, but may be indicative of acute illness, possibly with affective features. The results support suggestions that a steroid suppression test based on corticosterone may be useful to aid in diagnosis of major psychiatric illnesses and might complement or substitute for the F-DST. It may be possible to avoid certain pharmacologic complications in the DST by use of a test based on suppression of B by F rather than by dexamethasone.     

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.     

Comparison of plasma cortisol and corticosterone in the dexamethasone suppression test for melancholia

The suppression of plasma corticosterone (B), measured by radioimmunoassay (RIA), was compared to simultaneous suppression of plasma cortisol (F), measured as total corticoids by a competitive protein binding (CPB) assay, in the overnight dexamethasone suppression test (DST). Baseline plasma B concentrations in IO control subjects were 4.04 ± 1.07 ng/ml (X ± S.D.) at 0800 hr and 1.51 ± 0.68 ng/ml at 1600 hr. Post-dexamethasone 1600 hr B levels in the controls were 0.46 ± 0.29 ng/ml. An early escape of plasma B (> 1.2 ng/ml), like that of F (> 5 μg/dl), during the overnight 24 hr 1.0 mg dose DST was noted in patients with melancholia (endogenous depression).Half-hourly catheter samples in a normal subject stimulated to escape from dexamethasone suppression showed that in general, plasma B concentrations parallel plasma F concentrations over a 12 hr period. Repeated weekly DSTs on two patients with different psychiatric diagnoses resulted in B: F correlations of 0.74 and 0.60. Overall agreement between B- and F-DST outcomes in all categories tested at 1600 and 2300 hr was 93%; the agreement in the melancholic and non-endogenous depressed groups was 100%.Post-dexamethasone, both B and F were suppressed 55–60% below the criterion level in controls. In those patients who escaped from dexamethasone suppression, the percentage increase in plasma B above the criterion level was significantly greater (+ 55%) than the corresponding percentage change in plasma F. Most patients with borderline abnormal F-DSTs (3.5–4.9 μg/dl) exhibited clearly abnormal B-DSTs (> 1.2 ng/ml). We conclude that the use of dexamethasone suppression of plasma B (using 1.2 ng/ml as the abnormal criterion value) is an additional indicator of an abnormal DST in depressed patients.     

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.     

Serial dexamethasone suppression tests in initial suppressors and nonsuppressors treated with electroconvulsive therapy

Four different methods of quantifying the 1-mg Dexamethasone Suppression Test (DST) were contrasted with serial testing in endogenous depressives receiving electroconvulsive therapy (ECT). Of three continuous measures in 38 patients with pretreatment DSTs, only the log-transformed value for plasma cortisol was normally distributed, indicating that it possessed superior psychometric properties. Pretreatment Hamilton Depression Rating Scores (HAM-D) correlated positively with pretreatment DST status, with a similar association noted between posttreatment DST status and HAM-D scores. There was no uniform effect of ECT on the DST. Although pretreatment nonsuppressors showed a trend toward decreased postdexamethasone cortisol values, initial suppressors (cutoff: 5 micrograms/dl) evidenced a significant increase in these values, and 35.3% of initial suppressors were nonsuppressors at final DST assessment. These trends were noted in the DST assessment done following the third ECT treatment, suggesting an effect of regression to the mean. The findings highlight the importance of following initial DST suppressors in studies of this type.     

Dexamethasone suppression test in schizophrenia: its relation to monoamine metabolism in hypothalamic-pituitary-adrenal axis

The metabolic disturbances of monoamine in the hypothalamic-pituitary-adrenal axis (HPA axis) was examined in patients with chronic schizophrenia showing nonsuppression of the dexamethasone suppression test (DST). Subjects were 16 male chronic schizophrenics consisting of 8 DST suppressors and 8 nonsuppressors. All the patients were orally given the 5HT precursor, L-5-hydroxytryptophan (L-5HTP, 3 mg/kg) and the alpha 2-adrenergic agonist, clonidine (3 micrograms/kg), and the concentrations of plasma prolactin, cortisol, human growth hormone, and blood 5HT were measured chronologically. As a result, all of the DST nonsuppressors showed no increased response of prolactin after L-5HTP loading. Moreover, in the DST nonsuppressors, the secretion response of cortisol after L-5HTP loading was delayed compared with that of the suppressors. However, no different response between the DST suppressors and the nonsuppressors was observed after a loading dose of clonidine. These results suggest that there might be a metabolic disturbance of 5HT in the HPA axis of chronic schizophrenics showing DST nonsuppression.