[New York -- Washington, September 11, 2001: the loss of illusions].
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Biomedical subjects
Publications and source records attributed to M Schittecatte.
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We have shown that clonidine, infused i.v. during the second non-REM period, was significantly less REM sleep suppressant in depressed patients than in control subjects. We have named this procedure the 'clonidine REM suppression test (CREST)'. In this report, we compare in the same sample (15 patients with primary major affective illness, 10 normal controls, 15 patients with minor depression and 15 patients with generalized anxiety) the efficacy of the CREST to separate the major depressed patients from the control subjects with the efficacy of three currently proposed biological markers of depression, i.e., the latency of REM sleep, the dexamethasone suppression test and the clonidine growth hormone stimulation test. We found that the CREST had the highest efficacy and suggest that further studies with independent and larger samples of patients and controls are needed to confirm those preliminary results and establish if the CREST could provide a new biological marker of major affective disorders.
In the present study, P300 has been recorded in 26 subjects (15 women) 1 month after an aggression without organic complications. Among our sample, 16 subjects fulfilled DSM-III-R criteria for posttraumatic stress disorder (PTSD) and 10 did not. P300 amplitude was significantly lower in the 16 PTSD subjects as compared to the 10 subjects without PTSD. This study supports information processing disturbances in PTSD.
The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients. The duration of the study was 6 weeks, with assessments every 2 weeks by means of the Montgomery and Asberg depression scale (MADRS), the Hamilton depression scale, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetine over milnacipran on most rating instruments: MADRS (P = 0.01) including five individual items, Hamilton depression scale (P = 0.002) including ten individual items, CGI of severity (P = 0.01) and therapeutical index (P = 0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran (P = 0.0008). The tolerance of the two antidepressants was very similar, with the exception of symptoms of dizziness which were more frequently reported with milnacipran (P = 0.01). These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes, whereas milnacipran possesses a plasma elimination half-life of only 7 h.
OBJECTIVE: The authors' goal was to establish, in a large multicenter sample of patients classified according to gender and menopausal status, if the growth hormone (GH) response to clonidine discriminated patients with episodes of major depression from patients with episodes of minor depression. METHOD: The GH response to intravenous clonidine administration (150 micrograms) was compared in 71 male and 140 female patients with major depressive episodes and 47 male and 53 female patients with minor depressive episodes. These patients were diagnosed according to Research Diagnostic Criteria. RESULTS: Differences in the GH response to clonidine between diagnostic groups occurred only between male patients. These results were found in the group as a whole and in each center. The GH responses to clonidine of premenopausal women differed significantly from those of postmenopausal women in each diagnostic group. CONCLUSIONS: These results confirm that gender and menopausal status are of the utmost importance in the interpretation of the clonidine GH test.
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Clonidine hydrochloride, administered intravenously (2 micrograms/kg) during the second non-rapid eye movement period, was significantly less suppressant of rapid eye movement sleep in 10 depressed patients with primary major affective illness, according to Research Diagnostic Criteria, than in three groups of matched subjects (10 normal controls, 10 patients with minor depression, and 10 patients with generalized anxiety). These results suggest that depressed patients with major primary affective illness have down-regulated alpha 2-adrenergic receptors. These findings are consistent with the cholinergic-aminergic balance hypothesis of depression and support the aminergic side of the concept. Finally, the rapid eye movement sleep response to clonidine could provide a new biological marker of affective illness.
We report a non-significantly higher growth hormone (GH) response to intravenous clonidine administration (150 micrograms) in 10 male patients with panic disorder who had never received antidepressant therapy than in 10 matched controls. These results are consistent with data suggesting a normal or increased adrenergic receptor sensitivity in panic disorder patients.
Growth hormone (GH) responses to i.v. clonidine administration (150 micrograms) were compared in untreated depressed patients and controls. There were 8 controls (6 males, 2 females), 16 patients with a major depressive episode (8 males, 8 females), and 16 matched patients with a minor depressive episode according to Research Diagnostic Criteria. Differences in the GH response to clonidine only occurred between male patients and controls. These results suggest that endocrinological variables are important in the interpretation of this neuroendocrine test. Findings in the subgroup of unmedicated male patients with a nonendogenous major depressive episode support the hypothesis of decreased noradrenergic receptor sensitivity.
REM latency and awakening latency were analyzed in a sample of 26 major depressive inpatients and 8 male controls recorded for two consecutive nights. A significant inverse relationship appeared between REM latency and awakening latency in depressed patients. The relationship was more marked in male than in female patients. No significant correlation between REM latency and awakening latency was observed in male healthy volunteers. The hypothetical cholinergic supersensitivity in major depression is proposed to explain the present relationship. These results suggest that awakening latency might also be taken into account in the evaluation of sleep disturbances in depressive illness.
We have observed a significantly higher growth hormone (GH) response to clonidine administration (150 micrograms i.v.) in 14 patients with a major depressive disorder who had never received antidepressant therapy than in 14 matched depressive patients who had not received tricyclic drugs for at least 15 days. Compared with a control group of eight subjects, untreated depressed patients, as a group, had a normal response, while matched patients had markedly blunted response. Results for the group of untreated depressed patients showed that some patients had a blunted response while others had a response in the normal range. The results suggest that studies on the GH response to clonidine in psychiatric patients need to take into account the confounding and long-lasting effects of tricyclics.
The growth hormone (GH) response to clonidine administration (2 micrograms/kg) was compared in three groups of subjects: seven panic disorder patients, seven depressed patients matched for age and sex, and seven normal controls. As previously reported, patients with affective disorders show a blunted GH response to clonidine. Only one panic disorder patient had a blunted GH response to clonidine, and this patient had recently received a tricyclic antidepressant.
We assessed the length and the quality of remission of 13 unipolar endogenous depressed patients, DST non-suppressors before treatment, in a 2-year prospective study. During this period, we recorded stressful life events. Persistent dexamethasone non-suppression, after treatment and complete clinical recovery, correlated highly with early clinical relapse. All six non-normalizers but only one normalizer were rehospitalized within the following 2 years for a major depressive relapse. Persistent DST non-suppression was unrelated to any impact of drug discontinuation, the occurrence of stressful life events or the length of illness-free intervals in the patient's prior course of illness. Persistent DST non-suppression appears to have significant prognostic value.
Piribedil, a dopaminergic agonist, was administered intravenously (0.5 mg over 10 minutes) to two unipolar endogenous depressed. The two patients, a 38-year-old man and a 60-year-old woman, were matched for age and sex with two volunteers without any mental illness. Effects of piribedil on plasma levels of growth hormone and on blood pressure were studied. The two volunteers evaluated their "feelings" of anxiety and of physical comfort using visual analogue scales. The experimentation was repeated in a double blind fashion with a placebo. Piribedil induced an elevation of GH in the normal man but not in the depressed man. In contrast, no increase was noted in women. No elevation of GH was observed after placebo. Importance of factors such as depression, sexual steroid environment and influence of stress are discussed.
We assessed the length and the quality of the remission of 13 unipolar endogenous depressed DST nonsuppressors before treatment in a 2-year prospective study. During this period, we recorded stressful life events. Persistent dexamethasone non-suppression after treatment and complete clinical recovery correlated highly with early clinical relapse. All six nonnormalizers but only one normalizer were rehospitalized within the following two years for a major depressive relapse. Persistent DST nonsuppression was unrelated to any impact of drug discontinuation, to the occurrence of stressful life events or to the length of illness-free intervals in the patient's prior course of illness. Persistent DST non-suppression appears to have a significant prognostic value.
The authors briefly remind us of physiological characteristics of normal sleep and its modifications in psychiatric disorders. They draw attention to the numerous possibilities in the clinic of using electrophysiological sleep research. This is of importance in an area where few biological markers are available for the diagnosis and the treatment. Furthermore, sleep studies support the hypothesis of disturbances in circadian rhythms in affective disorders.
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