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Biomedical subjects

M Timsit-Berthier

Publications and source records attributed to M Timsit-Berthier.

At least 37 records · Page 2Linked to original sources

Comparison of adinazolam, amitriptyline, and diazepam in endogenous depressive inpatients exhibiting DST nonsuppression or abnormal contingent negative variation.

Adinazolam, a triazolobenzodiazepine that has an action similar to antidepressants in several pharmacological tests, was compared with amitriptyline and diazepam in endogenous depressive inpatients exhibiting dexamethasone suppression test non-suppression and/or abnormal contingent negative variation. Three parallel groups of 22 patients received in double-blind conditions either adinazolam (60-90 mg/day), amitriptyline (150-225 mg/day), or diazepam (30-45 mg/day) over a 4-week period, with weekly assessments by the Hamilton Rating Scale for Depression. Results showed significant superiority of amitriptyline over diazepam on total Hamilton depression scores. On the endogenomorphy subscale, amitriptyline induced significantly better improvement than both diazepam and adinazolam, whereas both amitriptyline and adinazolam exhibited significantly better antidepressant efficacy on the core symptoms of depression. Moreover, the dropout rate for inefficacy after 2 weeks of treatment was higher in the diazepam group. Taken together, these findings suggest that adinazolam has an antidepressant efficacy intermediate between amitriptyline and diazepam. Adinazolam was, however, much better tolerated than amitriptyline, and produced significantly fewer anticholinergic side effects.

Adult↗

Contingent Negative Variation in migraine.

The Contingent Negative Variation (CNV) is an event-related slow potential. It was recorded in healthy volunteers (n = 8) and in patients suffering from migraine without (n = 12) or with (n = 5) aura, during one (CNV1) and three second (CNV3) foreperiods in a forewarned reaction time task. CNV1 was recorded at the vertex while CNV3 was recorded at multiple electrode sites to assess topographical differences. Seven out of twelve migraine patients without aura had increased CNV1 amplitudes. CNV3 amplitudes were increased as well, but only at electrode positions C3 and C4 and not at Fz. CNV3, which allows for analysis of both an early and a late CNV component, could improve the discrimination of migraine without aura beyond that of CNV1. In migraine with aura all CNV parameters were at control levels, confirming previous results. The data obtained are discussed in terms of arousal, activation and stress and the "biobehavioral model of migraine" (Welch, 1986).

Adult↗

Vasopressin and vasopressin analogues for treatment of memory disorders in clinical practice.

1. Beyond its antidiuretic and vasopressor effects, vasopressin has central nervous system effects, first described in rats by David de Wied in 1965. 2. Its first clinical use in humans, in 1978, confirmed its stimulant action in normal individuals, especially in middle-aged male subjects. 3. Its utility in mnemic problems is also worht considering when the pathology is relatively recent (less than 2 years prior) and unaccompanied by major neurological lesions. Behavioral modifications, such as improvement of "sociability", "mood" improvement, independent of its effects on memory have been described, and would justify complementary clinical investigation. 4. New synthetic vasopressin derivatives which would eliminate metabolic effects while maintaining behavioral effects intact, and the definition of clinical, neuroendocrine, and neurophysiological prognostic criteria, will be the two most important paths for investigation over the next years.

Cognition↗

Inhibitory influence of oxytocin infusion on contingent negative variation and some memory tasks in normal men.

A double-blind study combining electrophysiological and psychometrical approaches was carried out to investigate the central effects of an intravenous oxytocin (OT) infusion in normal men. Contingent negative variation (CNV) was selected as the measure of central cognitive evoked potential, and the psychometric tests measured mood, vigilance and memory. OT infusion induced a significant decrease of CNV amplitude and an increase of post-imperative positive potentials in vertex derivations. A similar effect was still evidenced one week after treatment in frontal derivations, suggesting a long time effect of OT on human brain. No significant influence of OT on mood or vigilance tests was apparent; only one item of a memory test revealed a significant impairment of some mnesic performances. These observations provide new electrophysiological arguments supporting a central action of peripheral OT administration in man.

Adult↗

[Modifications of contingent negative variation (CNV) induced by oxytocin infusion].

The central effects of an intravenous infusion of oxytocin (OT), 3,680 mIU in 45 min, were investigated in 20 male volunteers in a double-blind study combining an electrophysiological and a psychometrical approach. The electrophysiological approach consisted in the simultaneous recording of the CNV (Fz-A1 and Cz-A1) and the spontaneous EEG (bipolar P3-P4) recording on which was carried out an FFT analysis. On the other hand, various psychometric tests allowed to assess memory (Rey's tests), attention (K-T test) processes and mood changes (visual analogue scales). Within the hour following the infusion, OT induced a significant decrease of CNV amplitude and an increase of the post-imperative positive component at Cz-A1. A similar effect was still observed one week later, but was more marked at Fz-A1. Neither mood nor attention tests evidenced any significant effect of OT. Only one item of the memory test PRM (item 4) revealed a significant impairment after OT infusion. There were no subjective effects reported. These observations provide new electrophysiological arguments supporting a central action of peripheral OT administration in man. This action, which may be characterized as an acceleration of CNV "habituation" is the opposite of the one described with vasopressin.

Brain↗

[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.

Adult↗

Blunted response of growth hormone to clonidine and apomorphine in endogenous depression.

We measured the growth hormone (GH) response to clonidine (an alpha-2-adrenergic agonist) and to apomorphine (a dopaminergic agonist) in 15 major endogenous and 15 minor depressive in-patients matched for gender and age. Results showed a significantly smaller GH response in the major depressives to both clonidine (P less than 0.01) and apomorphine (P less than 0.001). No significant difference existed between the two groups with regard to changes in blood pressure and pulse rate during either test. While major depressives showed a trend toward smaller sedative side-effects than minor depressives after clonidine, they showed significantly smaller sedative and gastro-intestinal side-effects after apomorphine. No significant correlation was present either in the major depressive or in the minor depressive group between the GH responses following clonidine and apomorphine challenges. These results support the hypothesis of both noradrenergic and dopaminergic neurotransmitter disturbances in major depression, with individual variability with regard to those biochemical anomalies.

Adult↗

Neuroendocrine evaluation of catecholaminergic neurotransmission in mania.

Several lines of evidence suggest catecholamine overactivity (noradrenergic and/or dopaminergic) in mania. We studied the growth hormone (GH) response to clonidine (an alpha-adrenergic agonist) and apomorphine (a dopaminergic agonist) in seven inpatients meeting Research Diagnostic Criteria for mania. They had been completely drug free for at least 3 months before the neuroendocrine procedures and were age- and sex-matched to seven major depressive and seven minor depressive inpatients, drug free for at least 2 weeks. GH was assayed every 20 min for 40 min before and 120 min after either clonidine (0.15 mg i.v.) or apomorphine (0.5 mg s.c.), with an interval of at least 2 days between the tests. The three groups differed significantly in the GH peak response: after clonidine (mean +/- SD), 3.2 +/- 2.4 ng/ml in manics, 3.2 +/- 2.4 ng/ml in major depressives, and 13.2 +/- 8.7 ng/ml in minor depressives; after apomorphine, 10.5 +/- 7.4, 3.2 +/- 1.9, and 26.9 +/- 15.8, respectively. While there were significant differences between manics and minor depressives and between major and minor depressives after both clonidine and apomorphine, manics did not significantly differ from major depressives on either test. These results do not provide neuroendocrine support to the catecholaminergic hypothesis of manic disorders.

Adult↗

[Value of the study of contingent negative variation in migraine and tension headache].

The aim of this study was to display the result obtained by the contingent negative variation (CNV) recording in patients suffering from headache. Eighty-five patients were taken into account: 59 with migraines (M) and 26 with tension headache (TH). A typical CNV pattern (high CNV amplitude with no habituation) differentiated M from TH. Moreover, psychological data were collected through Rorschach ink blot test among 42 headache sufferers (31 M and 11 TH). The typical Rorschach repressive pattern of alexithymia was found as well in M as in TH while CNV amplitude was significantly higher in the 31 M (-25 microV) than in the 11 TH (-19 microV FP less than 0.04). Biochemical data collected among 28 patients (17 M and 11 TH) revealed a positive correlation between CNV amplitude and plasma level of noradrenaline, regardless of the type of headache (r = 0.58; P less than 0.01). Thus, besides psychological factors, catecholaminergic mechanisms seem implicated in the determination of the CNV pattern in migraine. CNV may help the clinician both to specify diagnosis and to decide between the many therapeutic strategies available.

Adult↗

Contingent negative variation in headache.

Contingent negative variation (CNV), an event-related slow cerebral potential, was analyzed in 79 consecutive headache patients. Compared to normal controls (n = 33), CNV did not differ in tension headache (n = 21) or in combined headaches with a predominant tension component (n = 13). The mean amplitude of CNV was significantly (p less than 0.001) increased in migraine (n = 29) as well as in combined headache with predominant migraine (n = 16). All migraineurs were studied between attacks and without prophylactic treatment. CNV may be a useful diagnostic test in headache. Its increased amplitude in migraine might reflect central catecholaminergic hyperactivity.

Adult↗

Contingent negative variation and efficacy of beta-blocking agents in migraine.

Thirty-three patients with common migraine underwent contingent negative variation (CNV) recordings before receiving prophylactic beta-blocker treatment with either metoprolol (27 patients) or propranolol (6 patients) at mean daily dosages of 110 mg and 122 mg, respectively. After 3 months the therapeutic efficacy of the beta-blocker was assessed in each patient by means of a global severity score and compared with the initial CNV recordings. The mean clinical improvement was 62%. A significant positive correlation was found between CNV amplitude before prophylaxis and the clinical response to beta-blockers: patients with higher CNV tended to respond better to therapy. Eight of 10 patients with a CNV amplitude higher than -25 microV had a more than 50% reduction of the severity score--that is, a good or excellent response to the beta-blocking agent--whereas only 2 of 9 patients with an amplitude lower than -20 microV had a good response.

Adrenergic beta-Antagonists↗