Depression dexamethasone nonsuppression and negative symptoms in schizophrenia

This study compared three measures of depression in schizophrenia and their correlation with the Dexamethasone Suppression Test (DST). The degree of overlap of these three measures with negative symptoms was also examined. The Hamilton Depression Rating Scale (HDRS), the depressive syndrome score of the Present State Examination (PSE), and the Scale for the Assessment of Negative Symptoms (SANS) were administered to 50 acutely ill, hospitalized schizophrenics. Patients were diagnosed using DSM-III criteria for schizophrenia. DSM-III criteria were also used to assess the presence of a major depressive episode. Results were that DST nonsuppression was significantly associated with the presence of a major depressive episode, but not with depressive rating scale scores or with negative symptoms. It is concluded that the DST may be of value in differentiating a depressive syndrome from a negative symptom syndrome in schizophrenia.     

The dexamethasone suppression test: interaction of diagnosis, sex, and age in psychiatric inpatients

A group of 277 semiconsecutive psychiatric inpatients manifesting a depressive affect underwent an overnight 1 mg dexamethasone suppression test (DST) and a semistructured diagnostic interview according to DSM-III criteria. For major depressive syndromes (major depression with and without psychosis, bipolar depressed) the sensitivity of the DST was 63.9%, specificity 73.0%, and diagnostic confidence 72.3%. Additionally, a significant interaction between age and baseline cortisol values and nonsuppression rates was found in depressed males but not in nondepressed males nor in depressed and nondepressed females. The authors discuss the implications of these findings.     

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.     

Depression and dexamethasone suppression testing in children and adolescents

The authors compare the incidence of dexamethasone nonsuppression in a large group of child and adolescent inpatients (N = 94) diagnosed by two criteria (DSM-III and Weinberg criteria). The incidence of dexamethasone suppression test nonsuppression in patients diagnosed with DSM-III major depressive disorder (n = 33) was 55%, compared to 11% in those with no affective disorder (n = 35). This was compared to the incidence of dexamethasone suppression test nonsuppression utilizing Weinberg criteria. In addition, symptoms that to varying degrees discriminated suppressors from nonsuppressors were examined. These included change in school performance and, to a lesser degree, somatic complaints and weight and appetite changes. Differences in the diagnostic criteria are discussed.     

The dexamethasone suppression test in the clinical setting

The authors administered the dexamethasone suppression test (DST) to 47 inpatients on a clinical, nonresearch psychiatric unit who had been diagnosed according to DSM-III. Of the 30 patients with major depression, 23 (77%) exhibited nonsuppression (serum cortisol concentrations greater than 5 micrograms/dl); only 1 of the 17 patients with other diagnoses and depressive symptoms exhibited nonsuppression. There was no difference in the rate of nonsuppression between the patients with subgroups of major depression, but those with major depression and psychosis had significantly higher postdexamethasone cortisol levels than those with major depression with and without melancholia and those with diagnoses other than major depression.     

Serial dexamethasone suppression tests in psychiatric illness: Part II. A study in major depressive disorder

Weekly dexamethasone suppression tests (DSTs) were performed in 35 patients with major depressive disorder until clinical response. At initial evaluation, 65% of the patients showed nonsuppression, and 85.7% showed nonsuppression at least once during the treatment period. Normalization of the DST results usually coincided with or occurred before clinical recovery, although isolated "peaks" of DST nonsuppression occurred in 45.7% of the patients, irrespective of the clinical course. The test was not useful as a predictor of clinical recovery or relapse. Moderately ill depressed patients had significantly higher nonsuppression rates than schizophrenic or manic patients with corresponding severity scores, indicating that different factors might be associated with nonsuppression in different diagnoses. However, many abnormal DST results could neither be related to the course of the depression nor to the severity of illness; thus other factors must also be responsible for DST nonsuppression.     

The prognostic significance of HPA-axis disturbance in panic disorder: a three-year follow-up

Seventy-seven patients with DSM-III panic disorder underwent a baseline dexamethasone suppression test (DST), participated in an 8-week controlled treatment trial, and provided follow-up interviews 2-4 years later. The 20 patients who had exhibited DST nonsuppression at baseline had more symptoms of anxiety, more work and social disability, and a greater likelihood of ongoing major depression than did patients who had had normal DST results. DST nonsuppression in panic disorder apparently indicates a more persistent and chronically disabling condition.     

Comorbidity in the interpretation of dexamethasone suppression test results in children: a review and report

The dexamethasone suppression test (DST) was administered as part of the initial clinical assessment to 83 children and adolescents who were consecutively referred for outpatient evaluation. All diagnoses were made clinically by a child psychiatrist according to DSM-III criteria. A weight-corrected dose of dexamethasone of 17 micrograms/kg was used. DSM-III diagnoses were made independent of DST results. Patients were stratified into four main diagnostic groups: major depressive disorder (MDD) (N = 27); attention deficit disorder with hyperactivity (ADDH) (N = 22); major depressive disorder plus attention deficit disorder with hyperactivity (MDD + ADDH) (N = 29); and psychiatric controls (PC) (N = 5). Rates of dexamethasone nonsuppression were found to be similarly elevated in children with MDD (29.6%), ADDH (22.7%), and MDD + ADDH (37.9%). All 5 psychiatric control patients had a normal postdexamethasone suppression (0%). A similar pattern of results emerged in a reexamination of the literature on available studies of DST in juveniles which revealed that children with major affective disorders, attention deficit disorder (ADDH), and anxiety disorders had comparable DST results that were significantly higher than the 5.6% rate found in normal controls. These findings provide further support for similarities in DST results between ADDH and MDD in outpatients. Although these results suggest a lack of specificity of the DST as a laboratory aid for the diagnosis of juvenile affective disorders, they are also consistent with findings indicating that the DST may be an index of clinical severity and other findings suggesting a possible association between ADDH and MDD. Despite its limitations, the DST may provide potentially useful clinical and research information regarding the pathophysiology of psychiatric disorders and in alerting clinicians to the presence of serious psychiatric disorders. The findings also stress the relevance of assessing comorbidity in interpreting DST results.     

The DST and posttraumatic stress disorder

The dexamethasone suppression test (DST) was administered to 28 male combat veterans with posttraumatic stress disorder. Six subjects (21%) were nonsuppressors. The nonsuppression rates for the subgroups with and without major depressive disorder according to the Research Diagnostic Criteria were 50% and 6%, respectively. The authors conclude that cortisol nonsuppression is rare in posttraumatic stress disorder unless there is concomitant major depression.     

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.     

Psychopathological correlates of plasma cortisol after dexamethasone suppression: A polydiagnostic approach

Seventy-seven consecutively admitted inpatients with depressive syndromes were examined with the Present State Examination and classified according to eight different operational diagnoses of endogenous depression. All patients received a 1.5 mg dexamethasone suppression test (DST). Sensitivity, specificity and the corrected predictive values of DST nonsuppression (50 or more ng/ml at 0800 hr, 1600 hr, or 2300 hr), adjusted to a 50% prevalence of endogenous and nonendogenous depression, varied considerably depending on the diagnostic definition used. The highest predictive value (89.9%) was found with the Taylor-Abrams criteria (sensitivity = 43.9%, specificity = 95.0%), and the lowest predictive value (53.3%) with DSM-III (sensitivity = 37.7%, specificity = 68.1%). Eliminating the patients with dexamethasone levels of less than 2000 pg/ml improved the diagnostic specificity of the DST for most of the eight definitions of endogenous depression. This further indicates that plasma dexamethasone levels should be analyzed in studies designed to explore the diagnostic utility of the DST. A significant, chance-corrected association between DST nonsuppression and the diagnosis of endogenous depression was found with clinical diagnosis (according to the International Classification of Diseases), and for four out of eight operational diagnoses (Newcastle Scale 1, Newcastle Scale II, Taylor-Abrams Criteria, and Vienna Research Criteria). For the other diagnoses (Research Diagnostic Criteria, DSM-III, Michigan Discriminant Index, and Hamilton Endogenomorphy Index), no significant association was found. The RDC criterion “early or intermittent awakening” was the only one out of 28 diagnostic criteria tested which was significantly associated with DST nonsuppression.     

The clinical use of the dexamethasone suppression test in DSM-III affective disorders: Correlation with the severe depressive subtypes of melancholia and psychosis

The utility of the dexamethasone suppression test (DST) as an adjunct in the diagnosis of major depression remains controversial. While the research utility of the DST has been confirmed, the clinical utility has been questioned. We studied 166 consecutive admissions to a general, non-research unit who either met DSM-III criteria for major depression or had depressive symptoms associated with other DSM-III diagnoses. Using a 5 μg/dl criterion, non-suppression of serum cortisol after dexamethasone was observed in 63% of patients with DSM-III major depression. Patients with the most severe subtypes of major depression (melancholia and psychosis) showed both the highest rate of serum cortisol non-suppression and the highest post-DST serum cortisol concentrations. These findings from the clinical setting where the test, if found useful, will be used ultimately suggest that the DST is both sensitive and specific for the diagnosis of major depression. Future research will determine the potential role of the DST as an adjunct to the clinical assessment and management of patients with major affective disorder.     

The influence of weight loss on the dexamethasone suppression test

To evaluate the influence of weight loss on the dexamethasone suppression test (DST), we studied 61 patients with major depressive disorder as defined by the Research Diagnostic Criteria, 59 healthy normal volunteers, and 16 volunteers who lost weight by dieting. Nonsuppression on the DST was not correlated to weight loss in the depressed patients. Of the healthy volunteers, 12.5% converted to nonsuppression status. This conversion rate is not significantly different from nonsuppression rates in the normal population. Implications of these findings are discussed.     

The dexamethasone suppression test in children and adolescents with major depressive disorder: a review

The authors review the available studies on the use of the dexamethasone suppression test (DST) in children and adolescents with psychiatric disorders. For the purposes of analysis, the authors divided the studies according to the two age groups. Pooled sensitivity, specificity, and positive predictive power were calculated for each age group per diagnostic category. DST nonsuppression among subjects with major depressive disorder (MDD) in the children's group was 69.6%, with a specificity of 69.7%, whereas for adolescent subjects, DST sensitivity was 41.3%, and specificity was 79.3%. The positive predictive power of an abnormal DST result in helping diagnose MDD in the children's group was 69.7%, whereas for the adolescent group, the positive predictive power was 66.6%. The authors conclude that the evidence cannot support the routine clinical use of the DST in children and in adolescents, but there may be a research role for the DST in these patient populations.     

Low-dose (0.5-mg) dexamethasone suppression test in depressive patients

Fifty-six depressive patients underwent a low-dose (0.5-mg) Dexamethasone Suppression Test (DST). Blood samples for cortisol assay were obtained twice on day 2, and the plots of the sum of the two cortisol values formed two groups, consisting, respectively, of suppressors and nonsuppressors. Nineteen (73.1%) of 26 patients with major depressive episodes (MDE) showed nonsuppression, as well as 12 of 15 MDE patients with melancholia, 3 of 3 with psychotic features, 3 of 4 with bipolar or atypical bipolar affective disorder, and 1 of 4 without melancholia. The specificity, calculated from the data of 53 patients (excluding 3 who were already known to be false-positive on the DST) was 85.2%, and the diagnostic confidence was 82.6%. The DSTs were reexamined in the 11 MDE patients showing nonsuppression, 8 of whom became suppressors with remission of the depressive symptoms.     

Secondary agoraphobia: two case reports

Two patients with agoraphobic symptoms and major depressive disorder exhibited dexamethasone nonsuppression. Antidepressant pharmacotherapy was associated with remission of depressive symptoms and DST normalization. This improvement predated remission of agoraphobic symptoms by 1-2 months. It is suggested that agoraphobia was secondary to the depression in both cases.     

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.     

Abnormal escape from dexamethasone suppression in agoraphobia with panic attacks

Patients who met DSM-III criteria for agoraphobia with panic attacks underwent dexamethasone suppression tests (DSTs) before, during, and after treatment with alprazolam or placebo. Similarly, outpatients with major depression were given multiple DSTs as they participated in a study of desmethylimipramine efficacy. The likelihood of an abnormal escape from dexamethasone was similar in the two diagnostic groups; nonsuppression was somewhat more likely among patients with primary depression, but comparisons with agoraphobic groups remained statistically insignificant. These results apparently did not reflect misclassification of primary depression patients as agoraphobics since a history of major depression was not related to the likelihood of nonsuppression within that group. Moreover, change in DST results during treatment reflected clinical change among agoraphobics. After a review of relevant followup and family studies, we conclude that panic disorder and primary depression are separate illnesses and that hypothalamic-pituitary-adrenal axis hyperactivity is an epiphenomenon of both.     

The dexamethasone suppression test in demented outpatients with and without depression

The dexamethasone suppression test (DST) was given to 33 elderly, male outpatients, previously diagnosed by DSM-III criteria as having dementia. Fifteen of these patients also had signs and symptoms of depression and, except for the presence of organic mental syndrome, would have met DSM-III criteria for major depressive episode. Of these 15 depressed, demented patients, 40% had abnormal DST results. None of the 18 patients who had dementia alone had abnormal DSTs. Our data suggest that in elderly, demented outpatients, an abnormal DST may be associated with concomitant depression.