The usefulness of the dexamethasone suppression test (DST) in the prediction of treatment response to selective antidepressants was tested in 56 major depressive inpatients. Following DST, patients were randomly assigned to treatment by either nomifensine, a catecholaminergic antidepressant, or zimeldine, a serotonergic antidepressant during a 3-week period and assessed by means of the second part of the Clinical Global Impressions (CGI-2). No significant difference was present between the 27 DST suppressor and the 29 DST non-suppressor patients in their overall clinical outcome. Moreover, no preferential response to nomifensine or zimeldine was noted in any of the two groups defined according to DST status. Therefore, these results do not support the usefulness of the DST in the prediction of the treatment response to antidepressants in general and to selective antidepressants in particular.

Recent studies have examined the effectiveness of the dexamethasone suppression test (DST) in the evaluation of bulimia. In a series of 18 female bulimic outpatients without major depression, 9 (50%) failed to suppress on the DST. No significant difference was found between suppressors and nonsuppressors in personal and family histories of affective disorder, levels of anxious and depressive symptoms, psychoactive substance abuse, and severity of abnormal eating-related behaviours. In contrast, non-suppression was significantly associated with low weight. There is a trend to differentiate non-suppressors from suppressors in the current diagnosis of anorexia nervosa and in past history of anorexia nervosa. Seven patients received fluvoxamine for 8 weeks. Five patients were suppressors and showed a significant decrease in the frequency of their binges while the 2 non-suppressors did not improve. These preliminary results suggest that DST non-suppression might be typical of bulimic patients with anorexia nervosa and that pretreatment DST results might predict the response of bulimic behaviour to treatment with fluvoxamine.

In 32 patients with panic disorder with or without agoraphobia, Bmax measures of 5-HT binding in platelets did not differ from normal controls at baseline. Plasmatic cortisol levels were significantly higher than controls in the morning and in the evening measures as well as in post-dexamethasone assays. Following an 8-week treatment period with alprazolam plus behavioral guidance encouraging exposure, Bmax values did not alter but cortisol measures diminished significantly. Measures of phobic avoidance were negatively correlated with 5-HT Bmax values. Plasmatic cortisol correlated positively with the number of situational panic attacks in the month before treatment. There were no correlations between cortisol and 5-HT Bmax measures. A possible link between serotonin function and phobic avoidance is discussed. Cortisol changes were interpreted as being related to the global severity of the anxious state.

The suicide attempts were assessed in 32 schizophrenic patients on whom the dexamethasone suppression test (DST) was done twice in the course of illness: in the years 1985–91 and 1996–97. In the 1985–91 period, both baseline and post-dexamethasone cortisol levels were significantly higher in the patients with previous suicide attempts and baseline cortisol was higher in the patients who were to make a future attempt. In 1996–97, DST non-suppression was shown in more than half of the patients with a history of suicide attempt and in none of those without such history: all cortisol levels were significantly higher in the patients with a history of suicide attempt. Although the mean intensity of depression was higher in the patients with a history of suicide attempt, no association between the intensity of depression and present or previous DST non-suppression status was found. It is suggested that the hyperactivity of the hypothalamic-pituitary-adrenal axis may constitute an element of diathesis for suicidal behavior in schizophrenic patients.

Results of the dexamethasone suppression test (DST) in demented nondepressed patients have varied considerably, and there is evidence that these depend on the type of dementia, ie, Alzheimer’s disease (AD) or multi-infarct dementia (MID). AD is characterized by decreased central acetylcholine (Ach) activity, while MID is thought to be vascular in etiology. Pirecetam normalizes cerebral blood flow, along with other positive hemorheological properties. It may also increase central Ach levels. We performed the DST twice, 1 week apart, on 96 stable, demented geriatric inpatients. In 33 (21 AD, 11 MID), piracetam was started at an oral dose of 4.8 g/d 4-6 months before the first DST. The remaining 64 (39 AD, 25 MID) were untreated. Among untreated patients, those with MID were less suppressible (P < 0.001 and P= 0.01) and had more week-to-week variability (P = 0.0006) in the DST than AD patients. This is consistent with our previous findings. However, treated patients showed no difference in either postdexamethasone cortisol levels or reproducibility of DST results. We interpret these findings to mean that piracetam, by increasing central Ach, makes AD patients less suppressible on the DST, and by maintaining more constant limbic blood flow, makes MID patients more DST stable.

We compared the rate of DST non-suppression in two samples of 26 Brazilian and 26 Belgian female depressive patients, matched for age, diagnostic subtype and severity of depression. This rate was significantly lower in São Paulo than in Liège (P = 0.04). The differences observed in DST can be explained by the complexity of familial, personal and clinical factors. A role of a latitude effect through melatonin secretion on adrenocortical function of depressed patients is also suggested.

The dexamethasone suppression test has been carried out in 111 depressed inpatients. Fasting, 8 a.m. plasma levels of Cortisol and adrenocorticotropic hormone (ACTH) were determined before and after administration of 1 mg dexamethasone. In 64 subjects multisequential (1-17,1-24,1-39) ACTH, and in 47 subjects intact (1-39) ACTH has been determined. Patients with melancholia exhibited significantly higher postdexamethasone Cortisol and intact ACTH values as compared with minor and simple major depressives. Severity of illness was significantly and positively related to postdexamethasone intact ACTH - but not to multisequential ACTH. Cortisol nonsuppressors showed higher postdexamethasone (only intact) ACTH values than Cortisol suppressors. Both postdexamethasone ACTH values were significantly and positively related with the postdexamethasone Cortisol values. We have established that Cortisol nonsuppression during melancholia is determined by an augmented escape of ACTH from suppression by dexamethasone. Intact ACTH showed the most significant clinical relevance for depression and Cortisol nonsuppression. In the clinical practice we advize the use of postdexamethasone intact ACTH in stead of plasma Cortisol or multisequential ACTH.

Low serum and urinary Cortisol has been a consistent finding in post traumatic stress disorder (PTSD). Glucocorticoid receptor numbers are increased. PTSD patients have a significantly lower adrenocorticotropic hormone (ACTH) in response to corticotrophin releasing hormone (CRH) when compared to a control group of normal volunteers. The dexamethasone suppression test exhibits an exaggerated suppression response of Cortisol to dexamethasone, when the dose utilised is lower than that utilised to test patients with depression. Increased urine levels of noradrenaline and dopamine has been noted in patients with PTSD. This is believed to be related to the hyperarousal state of PTSD.

Objective: This study investigated the frequency of abnormal Dexamethasone Suppression Test (DST) in a randomly selected group of mentally handicapped subjects. Method: Forty three subjects living in the community were selected and assessed on a variety of clinical rating scales including Hamilton Rating Scale for Depression (HDS) and Wessex Case Register Form (WCRF). DST was conducted on all the patients and the findings correlated with demographic and clinical variables. Groups defined by DST status were also compared using t-test. In subjects who showed an abnormal response, clinical assessments and DST was repeated after 3 months. Results: Only 7 of 43 subjects showed an abnormal response which did not correlate with either the severity of affective symptoms or the presence or absence of behavioural difficulties. Six of the 7 DST positive subjects were either severely or profoundly impaired on DSM-III criteria indicating that the underlying brain pathology may be pathogenetically important. This was supported by the observation that abnormal DST response was enduring at follow up. Conclusions: The findings suggest that DST may be of little value as a diagnostic tool in the mentally handicapped.

Les convergences épidémiologiques, cliniques et biologiques, entre trouble panique et dépression laissent à penser que ces 2 phénomènes pourraient être sous-tendus par un même mécanisme physiopathologique. Des travaux récents retrouvent chez des patients présentant un trouble panique une diminution de la réponse de l'ACTH à la stimulation par le CRF (corticotropin-releasing factor) exogène comparable à celle observée dans la population des déprimés endogènes. Ces résultats suggèrent l'existence dans le trouble panique, comme dans la dépression, d'un hyperfonctionnement de l'axe hypothalamo-hypophyso-surrénalien sous l'influence d'une hypersécrétion de CRF endogène. Afin de vérifier cette hypothèse, les auteurs ont pratiqué un test de stimulation par le CRF et un test de freinage par la dexaméthasone (DST) chez 10 patients non déprimés présentant un trouble panique ou une agoraphobic avec attaques de panique. Les résultats du DST n'apparaissent pas différents de ceux habituellement retrouvés chez le sujet sain. La comparaison des taux de base de Cortisol et d'ACTH retrouvés dans le groupe « panique » et chez 7 sujets témoins ne montre pas de différence. Enfin, si la réponse du Cortisol à la stimulation par le CRF exogène n'apparaît pas significativement différente de celle observée chez les témoins, on note une augmentation de la réponse de l'ACTH chez les sujets présentant des attaques de panique. Ces résultats sont en contradiction avec ceux des travaux précédemment cités et semblent infirmer l'existence dans les troubles anxieux paroxystiques d'une hypersécrétion chronique de CRF endogène. Ces discordances peuvent, certes, peut-être s'expliquer par des différences dans les populations étudiées et dans les méthodes utilisées. L'augmentation de la réponse de l'ACTH à la stimulation par le CRF exogène observée dans cette étude chez les patients présentant des attaques de panique se montre cepcndant compatible, contrairement aux autres travaux, avec les théories habituellement admiscs et impliquant une hyperactivité noradrénergique centrale dans l'étiopathogénie des troubles anxieux.

Dexamethasone suppresson test (DST) was administered to 26 chronic schizophrenic inpatients who were on stable doses of neuroleptics for over 3 months. Clinical assessments were made on the Brief Psychiatric Rating Scale (BPRS), the Manchester Scale (KGV) and the Scale for the Assessment of Negative Symptoms (SANS). Patients’ neuroleptic treatment was then stopped for 4 weeks and the clinical assessements and the DST repeated. Thirty two percent of the patients showed DST non-suppression which was mostly stable over the 4-week period of the study and was unaffected by the neuroleptic treatment. Contrary to some reports in the literature, the clinical rating scores (including those for depression and negative symptoms), in our patients, showed no relationship with the DST status. We suggest that the DST abnormality in chronic schizophrenies may result from two quite different mechanisms: one due to stress assoeiated with transient psychopathology such as agitation, anxiety, depression or psychotic perturbation which is transient, the other resulting from structural abnormalities in the brain and which remains stable over time.

Several lines of evidence suggest that bulimia - the syndrome of compulsive binge-eating - may be related to major affective disorder. First, high rates of major affective disorder have been found both among bulimic patients and their relatives. Second, neuroendocrine abnormalities, similar to those found in major affective disorder, have been reported in bulimia. Finally, several antidepressant medications have been shown to be effective in the treatment of bulimia.

To investigate further the relationship between bulimia and major affective disorder, we evaluated 105 consecutive patients (101 women, 4 men), meeting DSM III criteria for bulimia, referred to our center, for the following: (1) rates of current or past major affective disorder and other psychiatric disorders, by DSM III criteria, using the NIMH Diagnostic Interview Schedule (n = 105); (2) family history of psychiatric disorders among first-degree relatives, by DSM III criteria (n = 101); (3) response to the 1 mg oral overnight dexamethasone suppression test (DST) with postdexamethasone plasma cortisol level measured at 16 00 h (n = 43); and (4) response to open trials of antidepressant medications, front several different classes - particularly tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, and trazodone (n = 50).

The results of these studies were as follows: (1) the bulimic patients displayed a 77% lifetime prevalence rate of major affective disorder by DSM III criteria; (2) the morbid risk for major affective disorder among the firstdegree relatives of the bulimic probands was 0.29, similar to the 0.19 morbid risk found among the first-degree relatives of 40 probands with bipolar disorder, but significantly higher than the 0.03 morbid risk found among the first-degree relatives of 46 schizophrenic probands (P<0.001); (3) the bulimic patients showed a 40% rate of nonsuppression to the DST (16 00 h postdexamethasone plasma cortisol Level≥5.0 mcg/dl), significantly higher than the 9% rate of nonsuppression found among 22 normal control subjects (P<0.02); and (4) after one or more trials of antidepressant medications, 38% of the bulimic patients achieved a remission of symptoms (cessation of bingeeating episodes), 34% achieved a marked response (75-99% reduction in the frequency of binge-eating episodes), 16% achieved a moderate response (50-74% reduction in the frequency of binge-eating episodes), and 12% had no response (less than a 50% reduction in the frequency of binge-eating episodes).

Thus, on each of the four indices evaluated, patients with bulimia were similar to patients with major affective disorder, but were distinguishable from patients with other psychiatric disorders and from normal Controls. These results are consistent with the hypothesis that bulimia may be closely related to major affective disorder.

The thyrotropin-releasing hormone (TRH) test was carried out in 231 depressed patients undergoing a dexamethasone suppression test (DST), and in 63 psychiatric control patients. The patients were classified according to DSM-III. Thyrotropin-secreting hormone (TSH) was determined in basal conditions, 20 and 60 min after the administration of 200 μg TRH. The Δ max TSH values (peak TSH response minus basal TSH) showed no significant difference between psychiatrie Controls and patients with major depression (296.00X2, 296.00X3, 296.00X4) or with depression (major and minor depression; 300,40, 296,82, 309.00). Consequently, the TRH test is not specifie either for depression or for major depression. Within the selected group of depressive patients, major depressives showed significantly (P<0.005) lower Δ max TSH responses than minor depressives. The TRH test could barely be used as a clinical diagnostic aid for major depression, since the predictive value for a positive test resuit was too low (maximal 70.2%). To separate major from minor depression, a single DST was more suitable than the TRH test or the combination of both tests. Age showed a negative correlation (P<0.005) with the Δ max TSH responses and could be considered as a predisposing factor for a blunted TSH response to TRH in depressive patients.

Une hyperactivité de l’axe hypothalamo-hypophyso-cortico-surrénalien est souvent objectivée dans les dépressions majeures ou endogènes, particulièrement par le test de freinage à la dexaméthasone (DST).

Certaines hypothèses évoquent un dysfonctionnement noradrénergique pour expliquer cette anomalie.

Afin de rechercher les liens entre l’axe HPA et une anomalie du métabolisme de la noradrénaline (NA) cérébrale, 47 déprimés majeurs ont été étudiés.

Pour chaque déprimé étaient mesurés l’excrétion urinaire du MHPG de 24 heures et un test de freinage à la dexaméthasone était effectué.

Aucune corrélation n’est retrouvée entre l’âge et la sévérité de la dépression d’une part et d’autre part, l’excrétion du MHPG et les chiffres de cortisolémie pré et post dexaméthasone. Par contre, il existe une corrélation positive entre l’âge et l’excrétion du MHPG et entre l’âge et la cortisolémie post dexaméthasone, entre la durée du sevrage thérapeutique et la cortisolémie pré dexaméthasone et surtout, entre la cortisolémie pré DST et post DST.

Aucune corrélation ne peut âtre retrouvée entre l’excrétion du MHPG et la cortisolémie maximale post dexaméthasone.

Il n’y a pas de différence d’excrétion urinaire du MHPG entre les suppresseurs et les non suppresseurs qui sont au nombre de 19 (40 %).

Lorsque les déprimés sont séparés en hauts excréteurs et bas excréteurs de MHPG, il existe une tendance significative des déprimés hauts excréteurs à présenter un pourcentage supérieur de non suppresseurs.

L’étude ne confirme pas l’hypothèse hyponoradrénergique de l’échappement à la dexaméthasone. Elle tend plutôt à démontrer une association entre une hyperactivité de l’axe HPA et une excrétion urinaire élevée de MHPG.

De nombreux facteurs peuvent peut-âtre expliquer les difficultés à mettre en évidence les liens entre l’échappement au freinage par la dexaméthasone et une anomalie du métabolisme de NA cérébrale lorsque des mesures biologiques périphériques sont utilisées.