• Four hundred thirty-eight subjects underwent an overnight dexamethasone suppression test (DST) to standardize the test for the diagnosis of melancholia (endogenous depression). Abnormal plasma cortisol concentrations within 24 hours after dexamethasone administration occurred almost exclusively in melancholic patients. The best plasma cortisol criterion concentration, above which a DST result may be considered abnormal, was 5 ug/dL. The optimal dose of dexamethasone was 1 rather than 2 mg. Two blood samples obtained at 4 and 11 PM after dexamethasone administration detected 98% of the abnormal test results. This version of the DST identified melancholic patients with a sensitivity of 67% and a specificity of 96%. Baseline nocturnal plasma cortisol concentrations were not useful. Abnormal DST results were found with similar frequency among outpatients and inpatients with melancholia; but they were not related to age, sex, recent use of psychotropic drugs, or severity of depressive symptoms. Extensive evidence validates this practical test for the diagnosis of melancholia.

A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility.

Melancholia is thought by many investigators to have a biological basis, and biological research, particularly on abnormalities of the neuroendocrine system and of the sleep electroencephalogram, is now beginning to yield results which can help in the differential diagnosis of depressive illness. This review will focus on the most widely studied neuroendocrine disturbance: disinhibition of the hypothalamus-pituitary-adrenal cortex (HPA) system as revealed by the dexamethasone suppression test (DST).

The dexamethasone suppression test for melancholia.

• Considerable evidence suggests that the acute effects of antidepressant treatments on brain norepinephrine (NE) and serotonin (5-HT) systems cannot account fully for their delayed therapeutic action. This review evaluates the effects of long-term antidepressant treatment on biogenic amine metabolism and on various indexes of presynaptic and postsynaptic receptor function. In contrast to variable effects on NE and 5-HT turnover and on presynaptic receptor sensitivity, almost all long-term antidepressant treatments produce consistent alterations in a number of measures of postsynaptic amine receptor sensitivity. Longterm treatment has been found to reduce β-adrenergic sensitivity while enhancing responses to serotonergic and α-adrenergic stimulation, suggesting that modulation of receptor sensitivity may be a mechanism of action common to tricyclic antidepressants, "atypical" antidepressants, monoamine oxidase inhibitors, and electroconvulsive therapy. These findings provide support for hypotheses of amine receptor abnormalities in depression and indicate the need for expanded studies of amine receptor function in patients.

Receptor Sensitivity and the Mechanism of Action of Antidepressant Treatment: Implications for the Etiology and Therapy of Depression

• A modified dexamethasone suppression test (DST) has had unprecedented evaluation among biologic tests proposed for clinical use in psychiatry. It has not proved to reflect pathophysiologic changes at the level of the central nervous system or pituitary, and tissue availability of dexamethasone itself may contribute to test outcome. The sensitivity of the DST in major depression is limited (about 44% in over 5,000 cases) but is higher in psychotic affective disorders and mixed manic-depressive states (67% to 78%). The high specificity of the DST vs control subjects (over 90%) is not maintained vs other psychiatric disorders (77% specificity overall), and acute "distress" may contribute to nonsuppression of cortisol. The test may have power in differentiating severe melancholic depression, mania, or acute psychosis from chronic psychosis (87% specificity) or dysthymia (77% specificity). The DST status adds about 11% to the prediction of short-term antidepressant response. Suggestions that failure to maintain normal suppression of cortisol predicts poor outcome are not secure. Uncritical enthusiasm or excessive skepticism regarding the DST are unwarranted.

The Dexamethasone Suppression Test for Diagnosis and Prognosis in Psychiatry: Commentary and Review

• Pretreatment measures of hypothalmic-pituitary-adrenocortical (HYPAC) function in depressed, manic, and healthy normal subjects showed that nonsuppression on the dexamethasone suppression test (DST) had less positive predictive value for major diagnostic category and was more frequent in normals (8/77) than recently reported, although it was yet more frequent in depressed patients (35/111). Nonsuppression was common in manics (8/16), was similar in unipolar and bipolar depressed patients (35% and 27%, respectively), and did not segregate with melancholic, endogenous, or psychotic depression subtypes. Patterns of post-DST plasma cortisol concentration other than simple escape or nonescape from suppression were common. Nonsuppression of 9amplasma cortisol levels on the DST had as good or better diagnostic specificity as nonsuppression of any of three post-DST samples. Nonsuppression was not completely synonymous with HYPAC hypersecretion. Means of pre-DST HYPAC measures (morning plasma cortisol, urine free cortisol, and CSF cortisol levels) were elevated in depressed patients compared with normals. There were significant differences in HYPAC measures of depressed patients studied at different centers. Age correlated positively and body weight negatively with plasma cortisol level.

Pretreatment DST and hypothalamic-pituitary-adrenocortical function in depressed patients and comparison groups. A multicenter study.

• This study examines the utility of the dexamethasone suppression test (DST) in identifying a clinically meaningful subtype of depression. Forty-nine inpatients who met research diagnostic criteria for major depressive disorder underwent DSTs and standard clinical assessments and ratings. Half of those with primary depression showed escape from dexamethasone suppression and are referred to as nonsuppressors, while few of those with secondary depression had this response. Most of the nonsuppressors were rated as having a good response to treatment, while only one third of the suppressors were rated as having a good response to treatment. These data suggest that pituitary adrenal disinhibition as assessed by the DST is selectively associated with primary depression. The DST may be a marker of a depressive subtype with a specific pathophysiology or pathogenesis.

https://jamanetwork.com/journals/PSYCH/articlepdf/492350/archpsyc_37_7_002.pdf

Iris Shuey

Papers

Response to Dexamethasone and Subtype of Depression