Effect of recovery on the cortisol circadian rhythm of depressed patients.
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Biomedical subjects
Publications and source records attributed to G Darcourt.
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The 24-hour patterns of body temperature and plasma thyrotropin (TSH) were measured in eight bipolar patients in both depressed and recovered (after 3 weeks of treatment) states and in eight normal control subjects. Clear circadian patterns were detected for both temperature and TSH. Nocturnal body temperature was increased and the nocturnal surge of TSH was blunted during depression; these abnormalities were corrected after recovery. The inverse relationship between changes in body temperature and TSH levels at night suggests that changes in thermoregulation may be responsible for the neuroendocrine disturbance and may play a role in the pathophysiology of depression.
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The chronobiological hypotheses of depression are based on epidemiological, biological as well as therapeutical pieces of evidence. The seasonal pattern of depression and suicide rates tend to link affective disorders and the daylight duration. Disturbances of circadian rhythms have been reported in endogenous depression. Treatments of depression, such as manipulations of the sleep/wake cycle, phototherapy or tricyclics, may involve chronobiological mechanisms on endogenous pacemakers. Beside the phase advance hypothesis of depression, present data seem to involve a disturbance of the mechanisms of entrainment of the internal clocks by external synchronizers. Other psychiatric illnesses may thus be linked to chronobiological abnormalities.
The aim of this study was to evaluate the acute effects of 5-methoxypsoralen (5-MOP) on the melatonin secretion in humans. Eleven normal volunteers were investigated before (drug-free) and after 6-day periods of treatment with oral 5-MOP, first administered daily at 9 A.M. and after a 1-week free interval administered daily at 9 P.M. Under nyctohemeral conditions, the plasma melatonin levels were evaluated over a 24-h period in each session by hourly blood samples and radioimmunoassay. The sensitivity of the retina to light was also evaluated by means of electroretinography performed at 11 A.M. before and after a morning administration of 5-MOP. Plasma levels of melatonin were significantly increased from the second hour after 5-MOP administration. The hourly mean levels were significantly higher after 5-MOP administration compared to baseline values. This increased secretion was more pronounced after evening than after morning administration. Also, 5-MOP increases the sensitivity of the retina to light under photopic conditions and in the early stages of the dark adaptation period, as observed under scotopic conditions.
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The circadian rhythm of plasma norepinephrine (NE) was investigated in the depressed (major affective disorder, DSM III; n = 12), recovered (after 3 weeks of treatment using usual antidepressant drugs; n = 12) and normal (volunteers, age and sex matched; n = 10) states. Data analysis (based on the evaluation of circadian parameters, on the chronogram method and on the chronobiological analysis) revealed a clear NE circadian rhythm in normal subjects, a rhythm which was disturbed in depression, with amplitude reduction and abnormal phase position. These abnormalities tended to disappear during recovery since circadian parameters were similar to those of controls. These circadian abnormalities could be linked to the impairment of the peripheral and central catecholaminergic systems. They may also support the chronobiological hypothesis of affective disorders.
The 24-hr patterns of plasma thyrotropin have been observed in 12 endogenous depressed patients in both depressed and recovered states and in 13 normal subjects. A clear circadian rhythm was detected in controls with high values at night. In depression, the circadian rhythm was altered with amplitude reduction and blunted nocturnal secretion, abnormalities particularly relevant in bipolar patients. This flattened profile could be linked to the blunted response of TSH to TRH administration reported in depressed patients. Normal nyctohemeral patterns have been restored after recovery. These chronobiological abnormalities as well as their normalization under antidepressant drugs seem to be similar to those reported for various parameters (e.g. temperature, cortisol, etc) in depression which could support the chronobiological hypothesis for affective disorders.
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The authors have studied the neurological tolerance from the combination of lithium-psychotropic drugs from 265 associated cures carried out on 132 patients between 1971 and 1978. The risk of neurological inability to assimilate is not greater when haldol is combined with lithium by comparison with other combinations where it is not included. Only the presence of cerebral organicity presents a risk factor. The 117 associated cures were preceded by preliminary treatments during which either the lithium or the psychotropic drugs were used to the same extent during the treatment. This series seems to allow on one hand to demonstrate that the incidence of neurological signs is multiplied by two by the combination, on the other hand to note that the intensity of the neurotoxic effects increases.
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During a double-blind trial about using TRH perfusions, the authors didn't established any antidepressive effect. On the other hand they observed an anxiety reaction under a 1,200 microgram in perfusion. The study of the basic level of T3, T4, T.S.H. and Prolactin corroborated the normality of the biological evaluation among the depressed. No difference of the hormonal response under T.R.H. was established depending on different types of depression. The authors reported that the Prolactin respons is higher among the subjects for whom the T.R.H. was the more distressing.
The authors report the observations of 12 patients who have been treated by haloperidol at a dose of 60 mg per os each day during periods from 15 to 106 days. They presented severe paranoid reaction with excitement. This treatment was insufficient to calm down the agitation and had to be completed by an increase of the doses in one case and by the association of an other neuroleptic in the other cases. The tolerance was always good.
From the book "The Analysis of the self" by Heinz KOHUT, recently translated into French, the author studies how several notions coming from the psychanalysis of those cases may be used in practical psychiatry, more particularly the notions of: self-object, grandiose self, double cleavage, independance of the development of the libido and narcissim.
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