Specificity of the combined dexamethasone suppression and TRH/TSH tests in melancholia

1. Subjects for this study were 61 acute psychiatric inpatients. Forty two (42) qualified for a RDC diagnosis of Major Depressive Disorder (MDD) and 19 for other disorders.

2. After a 7–10 days drug withdrawal period patients were subjected to the dexamethasone suppression and TRH/TSH tests. TSH was measured using a RIA. Cortisol was measured using a CPB technique.

3. Eighteen (18) of the 42 MDD patients and 1 of the 19 others had an abnormal DST (sensitivity 43%, specificity 94%). Twenty two (22) depressed patients and 4 others had a blunted TSH response (sensitivity 52%, specificity 79%). Thirteen (13) depressives and none of the others had abnormal responses to both tests (sensitivity 31%, specificity 100%).

4. DST nonsuppression alone and blunted TSH response alone were not a function of severity of illness, sex, age of onset, family history or RDC subtype.

5. The 13 MDD patients with the combined neuroendocrine abnormality were more severely depressed, had longer episodes of illness, were older and had a later age of onset of their first episode.

6. Our results add support to the suggestion that serial neuroendocrine challenge studies might be of particular relevance and significance in the diagnosis and management of elderly psychotic depressed patients.     

Blunted TSH response to TRH and seizure duration in ECT

The relationship between the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) and the duration of seizures induced by electroconvulsive therapy (ECT) in depressed patients was investigated. In a balanced-order cross-over design, 16 depressed women were given 0.4 mg TRH or placebo intravenously, 20 min before ECT in the first two sessions. In the third ECT session TRH was given just prior to ECT. Thyrotropin (TSH) levels at various sampling times, as well as the duration of seizures, were measured. There was a significant inverse correlation between plasma TSH concentrations 20 min after TRH administration (deltaTSH) and seizure duration. Furthermore, when patients were categorized according to their TSH response to TRH, the group with blunted responses (deltaTSH <6 microIU/ mL, n = 7) had a longer seizure time during ECT than the group with non-blunted responses (deltaTSH > 6 microIU/mL, n = 9). Finally, the seizure duration in the group with blunted TSH responses was reduced significantly when TRH was co-administered, while it remained unchanged in the group with non-blunted TSH responses. It is concluded that a blunted TSH response to TRH might indicate a seizure susceptibility as measured by the duration of seizures induced by ECT. The fact that TRH pre-administration had a reducing effect suggests that this substance might be involved in the pathophysiology of ECT-induced seizures.     

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.     

Multiple neuroendocrinological responses in borderline personality disorder patients

ABSTRACT— Male patients suffering from borderline personality disorder (n= 13), major depression (n= 13) or schizophrenia (n= 13) were investigated on several psychopathological (HDRS, BPRS) and neuroendocrinological (DST and TSH, PRL, GH responses to TRH) parameters. Comparisons were made between the borderline group and the other groups of patients. Borderline patients differed from schizophrenics psychopathologically (BPRS) and neuroendocrinologically (DST). Also, borderline patients differed from major depressives in the HDRS, but behaved like them concerning DST. Our findings support the hypothesis that there are neuroendocrinological similarities between borderline personality disorder and major depressive patients, especially on the hypothalamo-pituitary-adrenal axis.     

Visuospatial impairment in depression: a controlled ECT study

In order to study the effect of bilateral electroconvulsive therapy (ECT) on visuospatial function in depression, a comparison was made between the performance of 20 ECT-treated patients and 20 healthy controls on a battery of neuropsychological tests including the Complex Figure Test (CFT) and the Mini-Mental State Examination (MMSE). The CFT but not the MMSE performances of depressives vs controls were impaired in pre-ECT testing. While ECT does not affect visuospatial performance, cognitive deficits are unveiled by MMSE. Possible meanings of these findings are discussed.     

Provocative endocrine testing in recovered depressives

Twenty-eight patients underwent a series of provocative endocrine tests an average of one year after their last admission for depression. Hypersecretion of cortisol, early escape of cortisol from dexamethasone suppression, diminished growth hormone response to insulin-induced hypoglycemia and altered thyrotropin response to thyrotropin-releasing hormone reported in acute primary depression were not observed after recovery. There were no differences in these measures after recovery between previous suppressors and nonsuppressors to dexamethasone. The cortisol response to insulin-induced hypoglycemia was less than expected in 6 of 16 recovered patients tested. There were significant differences in post-dexamethasone urinary free cortisol and in basal and early post-insulin serum cortisol levels between patients who had been suppressors and those who had been nonsuppressors to dexamethasone during acute depression. Further studies need to be done to substantiate these findings. These data indicate that hormone responses in recovered depressives are largely normal, suggesting that abnormalities during depression are "state" related phenomena.     

ECT in bipolar and unipolar depression: differences in speed of response

Objectives: There is sparse evidence for differences in response to electroconvulsive therapy (ECT) between patients with bipolar or unipolar major depression, with virtually no information on speed of response. We contrasted a large sample of bipolar (BP) and unipolar (UP) depressed patients in likelihood and rapidity of clinical improvement with ECT. Methods: Over three double-blind treatment protocols, 228 patients met Research Diagnostic Criteria for UP (n=162) or BP depression (n=66). Other than lorazepam PRN (3 mg/day), patients were withdrawn from psychotropics prior to the ECT course and until after post-ECT assessments. Patients were randomized to ECT conditions that differed in electrode placement and stimulus intensity. Symptomatic change was evaluated at least twice weekly by a blinded evaluation team, which also determined treatment length. Results: Patients with BP and UP depression did not differ in rates of response or remission following the ECT course, or in response to unilateral or bilateral ECT. Degree of improvement in Hamilton Rating Scale for Depression scores following completion of ECT was also comparable. However, BP patients received significantly fewer ECT treatments than UP patients, and this effect was especially marked among bipolar ECT responders. Both BP I and BP II patients showed especially rapid response to ECT. Conclusions: The BP/UP distinction had no predictive value in determining ECT outcome. In contrast, there was a large effect for BP patients to show more rapid clinical improvement and require fewer treatments than unipolar patients. The reasons for this difference are unknown, but could reflect a more rapid build up of anticonvulsant effects in BP patients.     

Circadian variation of serum thyrotropin in endogenous depression

The circadian variation of serum thyrotropin (thyroid-stimulating hormone; TSH) was studied in nine patients with endogenous depression before and after recovery. Depressed state did not appear to influence the pattern of TSH. When 2 mg of dexamethasone was administered, serum TSH was significantly reduced for 18 hours, whereafter the effect leveled off. The TSH response to thyrotropin-releasing hormone (TRH) was evaluated 25 hours after the administration of dexamethasone and the response was found to be unchanged.     

Plasma measures of beta-endorphin/beta-lipotropin-like immunoreactivity in chronic pain syndrome and psychiatric subjects

This study compared basal concentrations of plasma beta-endorphin/beta-lipotropin-like immunoreactivity and dexamethasone suppression of cortisol in seven chronic pain patients, seven psychiatric disorder patients, and seven normal volunteers. Pain patients and psychiatric patients showed significantly higher basal concentrations of beta-endorphin/beta-lipotropin-like immunoreactivity compared to normal volunteers. Pain patients also had significantly higher beta-endorphin/beta-lipotropin-like immunoreactivity than psychiatric patients, even though there was no significant difference in severity of depressive symptomatology as assessed by Beck and Hamilton scores. Resistance to dexamethasone occurred in 57% of pain patients. These results may indicate that biological markers for depression occur in populations of chronic pain patients, or may reflect levels of central nervous system arousal in response to stress, pain, or nonaffective phenomena.     

Hypothalamic-pituitary-adrenal axis abnormality and ECT response

Response to electroconvulsive therapy (ECT) was assessed in 42 depressed patients grouped by dexamethasone suppression test (DST) response. Patients with initially abnormal DST results had better outcomes according to global ratings that did patients with initially normal DST results; final Hamilton Rating Scale scores did not distinguish these two groups, however. No group had an outcome that was clearly poor; only three (14.3%) patients with initially normal DST results were rated as unimproved at discharge. The results of this and other studies attempting to predict response to ECT are sensitive to the heterogeneity of patients referred for ECT, the timing and type of outcome assessment, and the differential action of placebo effects.     

The use of ECT in intellectual disability

The present survey examines the use of electroconvulsive therapy (ECT) by consultant psychiatrists working with people with intellectual disability in Trent Region, UK, which has a population of 4.7 million people. In the first phase of the study, all consultants in the area were sent a questionnaire to find out how many patients had been given ECT during the previous 5 years. Some 92% of the consultant psychiatrists returned the questionnaires. Eight patients were given a total of 122 ECTs, which is low when compared with the use of ECT by general adult psychiatrists. The second phase of the research involved a study of the individual medical case notes to obtain information about individual indications for ECT, outcome and consent issues. The commonest indication for ECT was depression, and the best response was obtained when the clinical picture was dominated by biological and/or psychotic symptoms.     

Relationship between prolactin responses to ECT and dopaminergic and serotonergic responsivity in depressed patients

The prolactin (PRL) increases in plasma, induced by the electrical stimulus during electroconvulsive therapy (ECT), is a consistent finding that can be studied in order to obtain information about its actions on the brain neurotransmitter systems, the most probable candidates being the serotonergic and the dopaminergic system. Central serotonergic and dopaminergic responsivity may also be assessed using neuroendocrine challenge tests. In this study, we measured the PRL responses during the first ECT of a therapeutic course in 15 male depressive patients, of mean age 49.2 ± 14.5 (range 22 to 68 years), and score in the HDRS of 29 ± 8 (range 18 to 43 points). Before the ECT course, we assessed the central serotonergic and dopaminergic responsivities, by measuring the PRL responses to the administration of the serotonin uptake inhibitor clomipramine (CMI) intravenously, and, two days later, the PRL responses dopamine receptor blocker haloperidol (HAL), administered intramuscularly. The CMI and HAL tests were also performed in 15 healthy male subjects. The PRL responses to CMI of the patients were blunted compared to healthy controls, while the PRL responses to HAL were not significantly different from controls. Searching for correlations among the maximal PRL responses to the three stimuli in the patient's group, we found that the PRL responses to ECT were significantly correlated to the PRL responses to i. m. HAL (r = 0.8205, N = 15, p < 0.001) and not to the PRL responses to i. v. CMI (r = 0.1713, n. s.). It is suggested that the rises in PRL during ECT reflect the responsivity of the hypothalamus-pituitary dopaminergic system, and seem to be the result of a transient decrease in the inhibitory dopaminergic input of the hypothalamus to the pituitary lactotrophs, caused by the electrical stimulus and the subsequent seizure. Received: 5 March 2002 / Accepted: 15 July 2002     

The change in electrical energy delivered to aged patients over a course of moderate dose unilateral electroconvulsive therapy

Background: To prove effective, the electrical energy delivered as part of unilateral electroconvulsive therapy (ECT) must exceed the seizure threshold. Although high dose treatment (six times the threshold) is most effective, it results in more cognitive deficits to which aged patients are especially vulnerable. As a compromise, Australian psychogeriatricians often prescribe moderate dose (three times the threshold) treatment. However, older patients' thresholds sometimes rise steeply as treatment progresses. If energy levels are kept low to make treatment safer, the result might be that patients' recovery is delayed. We report here on changes in prescribed energy over a course of six unilateral treatments. Methods: A retrospective review of data collected routinely on 42 depressed patients aged ≥65 years given moderate dose unilateral ECT in five aged psychiatry services in Victoria, Australia. Results: Prescribed energy rose with time, but only 31% of patients reached high dose levels by their sixth treatment. Conclusions: We cannot comment on the safety or effectiveness of moderate dose ECT. We focus instead just on changes in prescribed energy levels. These did not rise quickly in most cases, suggesting that moderate dose ECT cannot be dismissed as a treatment option simply because of the rate of change in electrical stimulation.     

Ventricular size, the dexamethasone suppression test and outcome of severe endogenous depression following psychosurgery

To assess the possible significance of cerebral ventricular size and the dexamethasone suppression test (DST) in the outcome of severe endogenous depression, 28 patients were followed up and reviewed 1 year after stereotactic subcaudate tractotomy. Neither ventricular size nor the dexamethasone suppression test predicted either a good or poor outcome. There was no relationship between ventricular size and the DST results.     

The treatment of psychotic depression in later life: a comparison of pharmacotherapy and ECT

Objective. Response to combination pharmacotherapy and to electroconvulsive therapy (ECT) was evaluated in elderly patients with psychotic depression. Method. Twenty-five patients, aged 60 years and older, with DSM-III-R unipolar psychotic major depression, were treated in an open, non-randomized fashion with either 6 weeks of nortriptyline and perphenazine (N=8) or ECT (N=17). Response was defined as a Hamilton score of ≤10 and the absence of delusions and hallucinations. Patients who failed to respond to combined antidepressant–antipsychotic medication underwent 2 weeks of lithium augmentation. Results. Two (25.0%) patients responded to the first 6 weeks of pharmacotherapy whereas 15 (88.2%) patients responded to ECT (Fisher's exact test, p=0.004). Even after lithium augmentation, there was a trend for patients to be less responsive to medication than to ECT (50.0% versus 88.2%, Fisher's exact test, p=0.059). Survival analysis, based on 8 weeks of observation, demonstrated that patients took longer to respond to pharmacotherapy than to ECT (mean (SE) of 7(0) weeks versus 4(0) weeks; log rank χ²=10.43, df=1, p=0.001). Conclusions. We found that elderly patients with psychotic depression had a significantly lower frequency of response to nortriptyline and perphenazine than to ECT. However, patients responded more slowly to pharmacotherapy than to ECT and longer duration of treatment may have improved the outcome of the medication group. These findings suggest the need for a randomized controlled trial comparing the efficacies of drug treatment and ECT in late life psychotic depression. © 1998 John Wiley & Sons, Ltd.     

Insulin-like growth factor I in depressed patients and controls

To explore the role of the somatomedin-mediated long-loop negative feed-back mechanism in altered growth hormone (GH) secretory dynamics associated with depression, plasma IGF-I concentrations were measured in 34 patients with a major depressive episode and matched healthy subjects. Compared with controls, depressed patients exhibited significantly increased plasma IGF-I concentrations. In the patient group plasma IGF-I concentrations were positively correlated with the maximum post-dexamethasone plasma cortisol concentrations. Our data suggest that increased plasma IGF-I concentration may reflect diurnal GH hypersecretion, contribute to deficient GH responses to dynamic challenges, and indicate an interrelationship between the hypothalamic-pituitary-somatotropic (HPS) and -adrenocortical (HPA) system regulation in depression.     

Dexamethasone suppression test and TRH test in endogenous depression

Dexamethasone suppression test (DST) and thyrotropin releasing hormone (TRH) stimulation test were performed in 34 patients with endogenous depression. Compared with 33 psychiatric controls (limit of discrimination for serum cortisol of 275 nmol/l = 10 micrograms/100 ml) the specificity of the DST was 91% and the sensitivity was 65%. Compared with 24 healthy subjects the sensitivity of the TRH test was 24%, and the combined sensitivity for the DST and the TRH test was 76%. In contrast to the TRH test the DST showed a significant relationship (r = 0.54, P less than 0.01) to the Hamilton Rating Score. Repeating the tests after clinical recovery parallel changes of the two tests were found in 14 of 19 patients with abnormal DST in the depressed phase. In the remaining five patients the DST normalized, while the TRH test remained unchanged. It is suggested that both the apparent higher diagnostic sensitivity and the higher rate of normalization after clinical recovery of the DST is due to the dependency of the severity of depression.