Jean-Luc Cerfontaine

Intranasal oxytocin in obsessive-compulsive disorder

A 55-year patient with obsessive-compulsive disorder showed clear improvement during 4 weeks of treatment with intranasal oxytocin compared to 4 weeks of intranasal placebo. This improvement was concurrent with the development of severe memory disturbances, supporting the amnestic properties of the peptide. However, the patient also developed psychotic symptoms and a marked decrease in plasma sodium and osmolality, which may have masked the obsessive symptomatology. This case highlights the need for careful monitoring in long-term oxytocin therapy.

Use of saliva cortisol in the dexamethasone suppression test

In a sample of 26 inpatients (15 primary endogenous depressives and a heterogeneous comparison group of 11 psychiatric patients), results of the dexamethasone suppression test (DST) for endogenous depression were compared when cortisol was measured in plasma (total and free) and in saliva. Results showed a close linear relationship among plasma total and free cortisol, plasma total cortisol, and saliva cortisol, and between free plasma and saliva cortisol. A saliva cortisol cutoff point of 70 ng/dl achieved the same sensitivity (67%), specificity (91%), and diagnostic confidence (91%) as the best cutoff scores of plasma total cortisol (5 micrograms/dl) and plasma free cortisol (0.15 microgram/dl). These results suggest that saliva cortisol, which directly reflects the biologically active fraction of cortisol, can be used as a reliable and more practical index in the DST, especially in outpatients.

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.

Self-Reports of Anxiety Level and EEG Changes after a Single Dose of Benzodiazepines

A new formulation of oxazepam especially designed to increase the speed of absorption and eliminate the need to use water (freeze-dried dosage formulation; FDDF) was compared in double-blind and crossover conditions with the standard tablets of the same compound. 5 inpatients with generalized anxiety disorder received at 1-week intervals a single 30 mg dose of one of the compounds. Every 8 min for 96 min after drug intake, they completed a battery of visual analogue scales and had an EEG recording with computerized spectral analysis. Results showed a significantly more rapid onset of activity of FDDF oxazepam for both the self-reports of anxiety level (p less than 0.005) and the specific beta 2 EEG changes (p less than 0.0001), which were significantly correlated (r = -0.73; p less than 0.01). Moreover, all patients rated FDDF oxazepam as having faster onset of action in clinical change than regular tablets (p less than 0.05). This study shows the value of visual analogue scales, pharmaco-EEG, and crossover design in well-selected anxious inpatients in substantiating clinical differences between anxiolytic pharmacotherapies.

Diagnostic performance of basal free cortisol/18-hydroxy-11-deoxycorticosterone (18-OH-DOC) ratio in endogenous depression: Comparison with the dexamethasone suppression test

We assessed the 8:00 AM ratio of free cortisol/18-hydroxy-11-deoxycorticosterone (18-OH-DOC) in 56 endogenous depressive inpatients and in 22 normal volunteers. A ratio higher than 40 was associated with a diagnostic sensitivity for endogenous depression of 75%, a specificity of 95.5%, and a diagnostic confidence of 97.7%. These diagnostic results were at least equivalent to the Dexamethasone Suppression Test (DST) using a cortisol cut-off limit of 5 micrograms/dl. This may thus represent a simpler procedure than the DST in the diagnostic analysis of endogenous depression.

Prediction of Treatment Response to Selective Antidepressants from Clonidine and Apomorphine Neuroendocrine Challenges

Classically, the biochemical pathophysiology of depression is based on central disturbances in catecholaminergic and serotonergic neurotransmission (van Praag, 1980a, b). However, antidepressants are only effective in 60 to 75% of depressive disorders and their success rates are very similar in double-blind studies (Davis, 1985). Recent ‘second-generation’ antidepressants are characterised by their selective activity on neurotransmitter systems. Compounds like zimeldine, fluoxetine, or fluvoxamine selectively inhibit serotonin reuptake, while compounds like nomifensine, maprotiline, or amineptine selectively inhibit catecholamine reuptake. However, it remains quite difficult to define either by clinical or biological parameters which patients would preferentially benefit from one or the other type of antidepressants.

Diagnostic performance of the thirty-four hour dexamethasone suppression test

The performance of the dexamethasone suppression test (DST) in the diagnostic confirmation of endogenous depression was compared according to two times of blood collection--1600 hr on day 2 (usual sample) and 0800 hr on day 3 (34 hr after dexamethasone intake)--in 14 endogenous depressives and in a control group of 17 psychiatric inpatients with other diagnoses. For the day 2 (1600 hr) sample, a 5 micrograms/dl cortisol concentration represented the best cut-off score, with sensitivity of 57% specificity of 88%, and diagnostic confidence of 80%. For the day 3 (0800 hr) sample, the best cut-off score was 20 micrograms/dl, with the same sensitivity (57%) but there was a decrease of both specificity (to 76%) and diagnostic confidence (to 67%). The mean cortisol levels were much higher on day 3 than on day 2, suggesting that the inhibitory activity of dexamethasone was no longer present.