The dexamethasone suppression and thyrotropin-releasing hormone tests in depressed borderline patients

Borderline patients can be both a diagnostic and a therapeutic enigma. We investigated a group of 24 depressed women with borderline personality disorder or strong borderline features by DSM III criteria for the presence of either an abnormal dexamethasone suppression test (DST) or a blunted TSH response to TRH, abnormalities which have been reported in major depression. Thirteen of the 24 borderlines failed to suppress on the DST, compared with one of 14 normal women (p < 0.01). Nine of the 24 borderlines had a blunted TSH response to TRH, compared with one of 11 normal women. Neuroendocrine abnormalities were found in a total of 75% of the borderline women, independent of whether or not they met DSM III criteria for major depressive disorder. The results of this study support the notion that many borderline patients with depression have a genuine affective component to their illness, perhaps biologically similar to major depression in non-borderlines.     

The dexamethasone suppression test and antidepressant response in major depression

We conducted a prospective open pilot study of 34 consecutively admitted patients with the DSM-III diagnosis of MD who were admitted to a general psychiatric unit. Patients underwent a 1 mg DST and were randomly assigned to treatment with either maprotiline or trazodone. Antidepressant dosages were increased as tolerated clinically and according to treatment response. Results: mean final oral doses were 193 mg for maprotiline and 328 mg for trazodone. The mean treatment duration was 4.5 weeks for maprotiline and 5.9 weeks for the trazodone group. Of these 34 patients 44% showed DST nonsuppression (41% maprotiline, 45% trazodone). Seventy-six per cent of the patients responded to treatment (76% for both drugs) as defined by GAS. Eighty-seven per cent of the nonsuppressors responded to treatment (86% maprotiline, 88% trazodone) and 68% of the suppressors responded (70% maprotiline, 67% trazodone). Of the eight treatment nonresponders six showed DST suppression. The implications of these findings are discussed.     

The thyrotropin-releasing hormone and dexamethasone suppression tests in the familial classification of depression

Eighty-eight depressed patients who had received a dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) test were divided into four subgroups based on family history of psychiatric illness. Nonsuppression on the DST was found in 46% of familial pure depressive disease (FPDD) patients, 38% of sporadic depressive disease (SDD) patients, 38% of depressive spectrum disease (DSD) patients, and 50% of mixed depressive disease patients (patients with both a first degree relative with alcoholism and one with depression). A blunted thyroid-stimulating hormone response to TRH was found in 50% of FPDD patients, 56% of SDD patients, 47% of DSD patients, and 56% of mixed depressive disease patients. Neither the DST nor TRH test was found to distinguish significantly among the four familial subgroups of depression.     

Enhanced suppression of adrenocorticotropic hormone and cortisol responses to hypothalamic-pituitary-adrenal function and thyrotropin-releasing hormone tests after stressful life events in patients with major depressive disorder

BACKGROUND: It is commonly believed that there exists a relationship between the outcome of thyrotropin-releasing hormone (TRH) test, the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test and stressful life events (SLEs) in major depressive disorder. OBJECTIVE: SLEs influence the TRH and DEX/CRH tests in major depressive disorder when administered at the time of admission and improvement. Methods: The TRH and DEX/CRH tests were administered to patients hospitalized for major depressive disorders - on the 4th through the 7th hospital day and at the time of improvement. We measured DeltaMAX TSH, DeltaMAX ACTH, ACTH AUC, DeltaMAX cortisol, cortisol AUC, DeltaMAX ACTH/DeltaMAX TSH and DeltaMAX cortisol/DeltaMAX TSH. RESULTS: SLEs were significantly negatively associated with DeltaMAX ACTH, ACTH AUC and cortisol AUC at the time of admission. However, these relationships lost significance at the time of improvement. The sample (41 patients at the time of admission, 18 patients at the time of improvement) was relatively small, which may have contributed to false-negative results. CONCLUSION: SLEs may be negatively associated with the outcome of the DEX/CRH tests in major depressive disorder. The hypothalamic-pituitary-adrenal axis in the DEX/CRH test was modulated by SLEs.     

The dexamethasone suppression test and thyrotropin-releasing hormone stimulation test in posttraumatic stress disorder

Male veterans with posttraumatic stress disorder (PTSD) (n = 11), including 6 with concurrent major depressive disorder (MDD), were compared to veterans with MDD alone (n = 18) and to 28 controls in their response to the dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) stimulation tests. We found higher levels of 4 PM serum cortisol and lower peak thyroid-stimulating hormone (TSH) response to TRH in the MDD patients than in either the PTSD patients or controls, in spite of equivalent levels of depression for MDD and PTSD. DST suppression (cortisol less than 5 mg/dl) occurred in 90% of control, 90% of PTSD, and 78% of MDD subjects, whereas TRH blunting (dTSHmax less than 7 microU/ml) occurred in 28% of control, 27% of PTSD, and 67% of MDD subjects. Rather than blunting, four PTSD patients (36%) and only 10% of the control and MDD subjects had high TSH responses (13-24 microU/ml), which may be linked to high noradrenergic activity, since subclinical hypothyroidism seemed unlikely.     

Is the dexamethasone suppression test predictive of response to specific antidepressant treatment in major depression?

The authors attempt to correlate the response to dexamethasone suppression test (DST) with a clinical response to antidepressant drugs in 68 patients with major depression. Antidepressants that influence noradrenergic or serotonergic transmission with relative different potencies were selected and used in standard doses for 6 weeks. The response was evaluated weekly by raters blind to DST results and to antidepressant medications prescribed. The retrospective analysis failed to correlate DST response with outcome of treatment. Therefore the present results suggest that this laboratory test does not help to identify subgroups of depressed patients responding preferentially to various antidepressant drugs.     

The relation between results of thyrotropin-releasing hormone stimulation tests (TRH-ST), dexamethasone suppression test (DST) and urinary MHPG. SO4 excretion in depressive patients

Thyrotropin-releasing hormone stimulation test (TRH-ST) was performed in 68 depressive patients, 25 normal subjects and 4 schizophrenics. Dexamethasone suppression test (DST) and urinary MHPG. SO4 determination was also administered in part of this depressive patients. Our data show that some of depressive patients suffered from the dysfunction of hypothalamic-pituitary-thyroid axis, and this dysfunction was not related to the dysfunction of hypothalamic-pituitary-adrenal axis and urinary MHPG. SO4 excretion. A blunted TSH response to TRH was a "STATE MARKER" for some of depressive patients.     

Endocrine responses to thyrotropin-releasing hormone in major depressive disorders

The endocrine response to thyrotropin-releasing hormone (TRH) was studied in severely endogenously depressed patients during illness (n = 21) and after recovery (n = 18). The thyroid-stimulating hormone (TSH) response to TRH was blunted (deltaTSH less than 5 microIU/ml) in over one third of depressives during illness and remained blunted in most even after recovery. There was no correlation between multiple measures of cortisol secretion (the mean 24-hour plasma cortisol, dexamethasone suppression test, and plasma cortisol during the TRH procedure) and the TSH response during illness and after recovery. The TSH and prolactin (PRL) responses to TRH, as well as the baseline PRL, were significantly lower during illness. The role of possible abnormalities in dopamine and/or serotonin in depression contributing to these endocrine disturbances is discussed.     

Serial dexamethasone suppression tests and plasma dexamethasone levels. Effects of clinical response to electroconvulsive therapy in major depression

Serial 1-mg dexamethasone suppression tests with concurrent plasma dexamethasone assessments were conducted in 58 patients with endogenous depression treated with electroconvulsive therapy (ECT). Plasma cortisol levels decreased significantly from pretreatment to immediately posttreatment, and they declined further during the first week after the ECT course, when patients remained drug free. Plasma dexamethasone levels showed an opposite pattern of progressive increases over these three time points. The progressive changes in plasma dexamethasone and cortisol levels seen during the week after ECT indicate that alterations in the bioavailability of dexamethasone and in hypothalamic-pituitary-adrenal axis function may be incomplete immediately after the ECT course. This may partly account for previous inconsistencies in serial dexamethasone suppression test findings with this treatment modality. The major finding was that clinical response was associated with increased plasma dexamethasone levels, whereas changes in cortisol levels were independent of clinical outcome. With ECT, changes in plasma dexamethasone levels may be more related to changes in clinical state than changes in postdexamethasone cortisol levels. The extent to which clinical recovery with other treatments in depression is associated with altered bioavailability of dexamethasone and perhaps other compounds is unknown and in need of investigation.     

Serial dexamethasone suppression tests in simultaneous panic and depressive disorders

Recent work suggests that the simultaneous occurrence of major depressive disorder (MDD) and panic disorder (PD) may be of relevance for clinical findings, therapeutic outcome, and prognosis. It is of interest to know whether or not this relevance extends to biological findings. We addressed this question through comparison of serial Dexamethasone Suppression Test (DST) results in patients who had either MDD alone or simultaneous MDD and PD. We were unable to describe differences between the groups.     

Growth hormone response to thyrotropin-releasing hormone and gonadotropin-releasing hormone stimulation in heroin addicts

Previous endocrine investigations have demonstrated the presence of multiple impairments of pituitary-target gland function in heroin addicts suggesting a possible hypothalamic involvement. Since the response of the pituitary to nonspecific stimuli is considered an expression of hypothalamic dysfunction, indicating a disconnection between the central nervous system and the anterior pituitary, we thought it worthwhile to study the GH response to stimulation with thyrotropin-releasing hormone (TRH) or gonadotropin-releasing hormone (GnRH) in heroin addicts. 23 male heroin addicts, aged 18-40 years, with histories of addiction to heroin alone from 8 months to 4 years, and daily i.v. heroin intakes between 200 and 2,500 mg of the drug (containing 18% pure heroin) were studied. 8 patients received TRH 500 micrograms, GnRH 150 micrograms and 5 saline only, intravenously, and GH levels were assayed radioimmunologically in bloods taken 30 min before, at the moment of stimulation and 15, 30, 60, 90 and 120 min thereafter. The results show normal base GH levels. Stimulation with TRH and GnRH induced marked GH hypersecretion in 8 of the 18 patients examined. These results suggest that the hypothalamo-pituitary function may be impaired in heroin addiction.     

Relationship between dexamethasone suppression test and contingent negative variation in major depressive patients

We tried to relate two different indexes sensitive to the perturbations induced by major depression: the Dexamethasone Suppression Test or DST (Caroll, 1982) and the Contingent Negative Variation (CNV). The question was whether abnormalities in cortisol levels, following dexamethasone would enlight the modifications observed in CNV parameters and other electrophysiological indexes (EEG spectrum, reaction time). In 61 major depressive patients, 29 being DST-non-suppressors, we calculated differences in electrophysiological variables according to DST suppression or not, but we were not able to evidence significant differences between the groups. However, there were correlations between log-transformed levels of cortisol and on the one hand, CNV slope (r = -0.34, P less than 0.03) and on the other hand, reaction time (r = 0.45, P less than 0.01). Correlations between electrophysiological variables appeared in the sole suppressors group (e.g. CNV amplitude and alpha rythm reactivity; post-imperative variation and percent beta of the EEG spectrum). These results underline the complementary aspect of the two methods.     

Weight loss, cortisol levels, and dexamethasone suppression in major depressive disorder

Appetite and/or weight loss are integral, albeit not necessary, symptoms of depression. We explored the contribution of diminished appetite and/or weight loss ascertained by history to the hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation in 120 patients with primary major depressive disorder. Significant positive relationship for both appetite and weight loss with cortisol levels in plasma and cerebrospinal fluid (CSF) were observed. Plasma cortisol levels were consistently higher in patients who noted both appetite and weight loss as opposed to patients without appetite or weight loss. Depressed patients with weight loss showed higher rates of dexamethasone-nonsuppression. Age and severity of depression influenced but did not eliminate the significance of the findings, suggesting that weight loss accounts in part for the HPA-axis function changes observed in depression.     

Topological network mechanisms of clinical response to antidepressant treatment in drug-naive major depressive disorder

AimThere is rapidly increasing evidence that remission of MDD is associated with substantial changes in functional brain connectivity. These New data have provided a holistic view on the mechanism of antidepressants on multiple levels that goes beyond their conventional effects on neurotransmitters.MethodThe study was approved by the Local Ethics Committee of Istanbul Medipol University (10840098-604.01.01-E.65129) and followed the Helsinki Declaration principles. In our study, we have evaluated the effect of six weeks of treatment with antidepressants (escitalopram and duloxetine), and tested the underlying brain functional connectivity through a Graph analysis approach in a well-defined first-episode, drug-naive, and non-comorbid population with MDD.ResultsBeyond indicating that there was a significant correlation between the antidepressant response and topological characteristics of the brain, our results suggested that global rather than regional network alterations may be implicated in the antidepressant effect.ConclusionDespite the small-sample size and non-controlled study design, our study provides important and relevant clinical data regarding the underlying mechanisms of the antidepressants on topological dynamics in the human brain.     

Effects of antidepressant withdrawal on the dexamethasone suppression test

Withdrawal of antidepressant medications may be a source of variance in dexamethasone suppression test (DST) results. We investigated this issue retrospectively through the serial analysis of postdexamethasone plasma cortisol concentrations and clinical severity in 15 patients and 9 control subjects before, during, and after antidepressant withdrawal. Postdexamethasone cortisol concentrations were significantly higher during the antidepressant withdrawal phase. Drug-withdrawal subjects also had an increased frequency of DST nonsuppression. Recent withdrawal of antidepressants requires further study as a possible source of variance for hypothalamic-pituitary-adrenal measures.     

Simultaneous use of thyrotropin-releasing hormone test and combined dexamethasone/corticotropine-releasing hormone test for severity evaluation and outcome prediction in patients with major depressive disorder

We performed a prospective study designed to examine whether or not evaluation of the severity and prediction of treatment outcome in major depressive disorder would be enabled by simultaneous use of the thyrotropin-releasing hormone (TRH) test and the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test. We studied consecutive patients hospitalized for major depressive disorder. The patients received the TRH test and the DEX/CRH test on the 4th through the 7th hospital days and at the time of improvement. None of the indices in these tests at the time of admission correlated with the Hamilton rating scale for depression (HRSD) or the Global Assessment for Function (GAF). However, since the DeltaMAXACTH, ACTHAUC, DeltaMAXcortisol, and CortisolAUC showed significant decreases at the time of improvement compared with the time of admission, suggesting that the DEX/CRH test can be a state marker. DeltaMAXTSH showed no significant change. Prediction of improvement within 3 months after admission was not possible with either test alone. However, the quotient which divided DeltaMAXACTH by DeltaMAXTSH was predictive of clinical improvement with a sensitivity of 50% and a specificity of 100%. The simultaneous use of the TRH test and the DEX/CRH test seems to provide a more useful biological marker than the separate use of either test alone in patients with major depressive disorder.     

Effects of age and diagnosis on thyrotropin response to thyrotropin-releasing hormone in psychiatric patients

The thyrotropin (thyroid-stimulating hormone; TSH) response to thyrotropin-releasing hormone (TRH) was studied in 64 age-matched healthy volunteers, 44 patients with endogenous depression, and 21 patients with schizophrenia. A significant negative correlation between delta TSH and age was found both in healthy subjects and in depressed patients. We based our comparison on normal ranges for delta TSH calculated from the delta TSH values in the healthy subjects related to age. It was then seen that blunted TSH response to TRH does not occur significantly more often in depression (13.6%) than in healthy controls (4.7%). Blunted TRH test results were also found in a considerable number of severely ill schizophrenic patients (19%). Application of an improved radioimmunoassay revealed a highly significant correlation between TSH values at baseline and after stimulation, and showed decreased baseline TSH levels in subjects with blunted TRH test results.