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Background Although treatment-resistant and nontreatment-resistant depressed patients show structural brain anomalies relative to healthy controls, the difference in regional volumetry between these two groups remains undocumented. Methods A whole-brain voxel-based morphometry (VBM) analysis of regional volumes was performed in 125 participants’ magnetic resonance images obtained on a 1.5 Tesla scanner; 41 had treatment-resistant depression (TRD), 40 nontreatment-resistant depression (non-TRD), and 44 were healthy controls. The groups were comparable for age and gender. Bipolar/unipolar features as well as pharmacological treatment classes were taken into account as covariates. Results TRD patients had higher gray matter (GM) volume in the left and right amygdala than non-TRD patients. No difference was found between the TRD bipolar and the TRD unipolar patients, or between the non-TRD bipolar and non-TRD unipolar patients. An exploratory analysis showed that lithium-treated patients in both groups had higher GM volume in the superior and middle frontal gyri in both hemispheres. Conclusions Higher GM volume in amygdala detected in TRD patients might be seen in perspective with vulnerability to chronicity, revealed by medication resistance.

Objective Repetitive transcranial magnetic stimulation (rTMS) over the left temporo-parietal region has been proposed as a treatment for resistant auditory verbal hallucinations (AVH), but which patients are more likely to benefit from rTMS is still unclear. This study sought to assess the effects of rTMS on AVH, with a focus on hallucination phenomenology. Method Twenty-seven patients with schizophrenia and medication-resistant AVH participated to a randomized, double-blind, placebo-controlled, add-on rTMS study. The stimulation targeted a language-perception area individually determined using functional magnetic resonance imaging and a language recognition task. AVH were assessed using the hallucination subscale of the Scale for the Assessment of Positive Symptoms (SAPS). The spatial location of AVH was assessed using the Psychotic Symptom Rating Scales. Results A significant improvement in SAPS hallucination subscale score was observed in both actively treated and placebo-treated groups with no difference between both modalities. Patients with external AVH were significantly more improved than patients with internal AVH, with both modalities. Conclusions A marked placebo effect of rTMS was observed in patients with resistant AVH. Patients with prominent external AVH may be more likely to benefit from both active and placebo interventions. Cortical effects related to non-magnetic stimulation of the auditory cortex are suggested.

Benzodiazepines are widely used in France: 11.5 million of consumers (22% with 2 benzodiazepines simultaneously), 131 million of boxes of benzodiazepines were sold in 2012. Annual length of use: anxiolytic 5 months, hypnotic 3.9 months. Risk of fall, Road accident, risk of Abuse and dependence & possible increase risk of Alzheimer disease. Using the fact that spa center are an institutional place not as stigmatizing and less regressing than being in hospital and are able to reduce anxiety disorders (STOP TAG study).

Preliminary studies have suggested that balneotherapy (BT) is an effective and well-tolerated treatment for generalized anxiety disorder (GAD) and psychotropic medication withdrawal syndrome. We carried out a study in 4 spa resorts to assess the efficacy of BT in GAD.We compared BT to paroxetine in terms of efficacy and safety in a randomized multicentre study lasting 8 weeks. Patients meeting the diagnostic criteria of GAD (DSM-IV) were recruited. Assessments were conducted using the Hamilton Rating Scale for Anxiety (HAM-A) and other scales, by a specifically trained and independent physician. The primary outcome measure was the change in the total HAM-A score between baseline and week 8.A total of 237 outpatients were enrolled in four centres; 117 were assigned randomly to BT and 120 to paroxetine. The mean change in HAM-A scores showed an improvement in both groups with a significant advantage of BT compared to paroxetine (-12.0 vs -8.7; p0.001). Remission and sustained response rates were also significantly higher in the BT group (respectively 19% vs 7% and 51% vs 28%).BT is an interesting way of treating GAD. Due to its safety profile it could also be tested in resistant forms of generalized anxiety and in patients who do not tolerate or are reluctant to use pharmacotherapies.

Objectives: Cerebral abnormalities have been detected in patients with bipolar disorder (BD). In comparison to BD with a later onset, early-onset BD has been found to have a poorer outcome. However, it is yet unknown whether neuroanatomical abnormalities differ between age-at-onset subgroups of the illness. We searched for cortical folding differences between early-onset (before 25 years) and intermediate-onset (between 25 and 45 years) BD patients. Methods: Magnetic resonance images of 22 early-onset BD patients, 14 intermediate-onset BD patients, and 50 healthy participants were analyzed using a fully automated method to extract, label, and measure the sulcal area in the whole cortex. Cortical folding was assessed by computing global sulcal indices (the ratio between total sulcal area and total outer cortex area) for each hemisphere, and local sulcal indices for 12 predefined regions in both hemispheres. Results: Intermediate-onset BD patients had a significantly reduced local sulcal index in the right dorsolateral prefrontal cortex in comparison to both early-onset BD patients and healthy subjects, and lower global sulcal indices in both hemispheres in comparison to healthy subjects (p

Objective: Abnormal activations of neural networks implicated in auditory stimuli processing are hypothesized to generate auditory hallucinations (AH) in schizophrenia spectrum disorders. Because repetitive transcranial magnetic stimulation (rTMS) has the potential to modulate neural network activity, several studies have explored its use in treating medication-resistant AH, with mixed results in small-to-medium patient samples. Our aim is to apply a metaanalytic approach to exploring the efficacy of rTMS in treating medication-resistant AH. Method: A search of the electronic databases for studies comparing low-frequency (1 Hz) rTMS over the left temporoparietal cortex to sham stimulation in patients suffering from medication-resistant AH was performed. Our search was completed by cross-referencing the articles, searching the Current Controlled Trials website, and direct contact with relevant researchers. Results: From 265 possible abstracts, 6 parallel-arm, double-blind placebo-controlled and 4 crossover controlled trials, all randomized, matched the inclusion and exclusion criteria ( n = 232). The primary outcome measure (effect of active treatment on AH at the end of the treatment) was tested with a random effect model and reached a significant homogeneous ES estimate (Hedges' g = 0.514; P = 0.001; 95CI%, 0.225 to 0.804; Q = 13.022; P = 0.162). Conclusions: We found that low-frequency rTMS over the left temporoparietal cortex has a medium ES action on medication-resistant AH. This result has implications for understanding the pathophysiology of psychotic symptoms (specifically AH) and supports the use of rTMS as a complementary treatment approach in patients suffering from treatment-resistant AH. Objectif: Les activations anormales des réseaux neuraux impliquées dans le traitement des stimuli sonores produisent hypothétiquement des hallucinations auditives (HA) dans les troubles du spectre de la schizophrénie. Parce que la stimulation magnétique transcranienne répétitive (SMTr) a le potentiel de moduler l'activité du réseau neural, plusieurs études en ont exploré l'utilisation pour traiter les HA réfractaires aux médicaments, avec des résultats partagés dans des échantillons de patients de taille modeste à moyenne. Nous visons à appliquer une approche méta-analytique afin de sonder l'efficacité de la SMTr pour traiter les HA réfractaires aux médicaments. Méthode: Une recherche d'études comparant la SMTr de faible fréquence (1-Hz) sur le cortex temporo-pariétal gauche pour feindre la stimulation chez des patients souffrant de HA réfractaires aux médicaments a été menée dans les bases de données électroniques. Notre recherche a été complétée par une vérification de concordance des articles, menée au site Web des Current Controlled Trials, et par une communication directe avec les chercheurs concernés. Résultats: Sur les 265 résumés possibles, 6 essais sur groupes parallèles, à double insu et contrôlés par placebo, et 4 essais croisés contrôlés, tous randomisés, satisfaisaient aux critères d'inclusion et d'exclusion (total n = 232). La principale mesure de résultat (l'effet du traitement actif sur les HA au terme du traitement) a été testée par un modèle à effets aléatoires et a atteint une estimation de l'ampleur de l'effet homogène significative ( g de Hedges = 0,514; P = 0,001; 95 % IC, 0,225 à 0,804; Q = 13,022; P = 0,162). Conclusions: Nous acons constaté que la SMTr de faible fréquence sur le cortex temporo-pariétal gauche a une action d'ampleur d'effet moyenne sur les HA réfractaires aux médicaments. Ce résultat a des implications pour comprendre la pathophysiologie des symptômes psychotiques (spécifiquement les HA) et soutient l'utilisation de la SMTr comme méthode de traitement complémentaire chez les patients souffrant de HA réfractaires au traitement.

Benzodiazepines should be prescribed on a short-term basis, but a significant proportion of patients (%) use them for more than 6 months, constituting a serious public health issue. Indeed, few strategies are effective in helping patients to discontinue long-term benzodiazepine treatments. The aim of this study was to assess the feasibility and the impact of a program including cognitive behavioural therapy, psychoeducation, and balneotherapy in a spa resort to facilitate long-term discontinuation of benzodiazepines. We conducted a prospective multicentre cohort study. Patients with long-term benzodiazepine use were recruited with the aim of anxiolytic withdrawal by means of a psychoeducational program and daily balneotherapy during 3 weeks. The primary efficacy outcome measure was benzodiazepine use 6 months after the program, compared to use at baseline. A total of 70 subjects were enrolled. At 6 months, overall benzodiazepine intake had decreased by 75.3%, with 41.4% of patients completely stopping benzodiazepine use. The results also suggest a significantly greater improvement in anxiety and depression symptoms among patients who discontinued benzodiazepines compared to patients who only reduced their use. Our findings suggest that balneotherapy in association with a psychoeducative program is efficient in subjects with benzodiazepine addiction.

This open, multicenter, prospective study in France assessed the efficacy and tolerability of escitalopram in patients with depression, with or without comorbid anxiety. Escitalopram was administered over a 12-week treatment period to 790 depressed patients, including 482 patients with at least one concomitant anxiety disorder. The study was completed by 649 patients. At baseline, the mean Montgomery-Asberg Depression Rating Scale (MADRS) total score was 31.5 and decreased to 12.4 at end point (last observation carried forward [LOCF]). The MADRS score decreased by 20.5 points in patients with no anxiety disorder and by 18.3 points in patients with at least one concomitant anxiety disorder. The mean Hamilton Anxiety Rating Scale (HAM-A) total score at baseline was 25.6, which decreased to 10.8 at end point (LOCF). The HAM-A score decreased by 13.8 points in patients with no anxiety disorder and by 15.5 points in patients with at least one anxiety disorder. Adverse events were reported by 246 patients (31%). The most frequent adverse events were nausea in 65 patients (8%) and headache in 38 patients (5%); 61 patients (8%) discontinued treatment due to adverse events. Escitalopram was well tolerated and efficacious in reducing symptoms of depression in patients with or without comorbid anxiety over a 12-week treatment period.

Background Beneficial effects of repetitive transcranial magnetic stimulation (rTMS) were demonstrated by many controlled studies in major depression. Moreover, this promising and non invasive therapeutic tool seems to be better tolerated than electroconvulsive therapy. Vascular depression is a subtype of late-life depression, associated with cerebrovascular disease and means a poorer response to antidepressant treatment. We employed rTMS over the left prefrontal cortex in 11 patients with late-onset resistant vascular depression. The primary purpose of this two-week open study was to examine antidepressant efficacy of rTMS in vascular depression. The secondary aim was to evaluate cognitive effects of rTMS in our sample. Methods Clinical status, as measured with the Hamilton Depression Rating Scale (HDRS), and cognitive effects, as evaluated by neuropsychological tests, were assessed at baseline and after two weeks of rTMS. Brain measurements to obtain an index of prefrontal atrophy were performed at both the motor cortex and prefrontal cortex. Results Five out of 11 resistant patients with late-onset vascular depression were responders. They showed a clinically meaningful improvement in HDRS scores, with a decrease of 11, 4 points (p

Objective The principal objective was to compare the effects of milnacipran, an antidepressant characterized by a dual-action on serotonin and noradrenaline reuptake, with placebo on memory, attention and psychomotor performance in healthy volunteers. The secondary objective was to evaluate the effects of milnacipran on mood, anxiety and vigilance in these subjects. Methods In a double-blind crossover randomized trial, milnacipran (50 mg b.d.) or placebo was administered during two periods of 7 days separated by a washout period of 7 days. Memory tests (recall of words, images and coloured bars), tests to evaluate attention and vigilance (squares test, critical flicker fusion test and choice reaction time test) and visual analogue scales for affect and sleep were used. Results There were no significant differences between milnacipran and placebo groups with respect to the psychomotor functions tested. No differences were observed in the Norris scales for vigilance, anxiety or satisfaction or in the sleep questionnaire (sleep latency, sleep quality and waking). Conclusion Milnacipran, administered at 100 mg per day for 7 days to healthy volunteers, had no effects on cognitive functions. Copyright © 2004 John Wiley & Sons, Ltd.

Resume Les prescripteurs souhaitent savoir comment choisir un antidepresseur, grâce a des arguments objectifs : symptomatologique, biologiques ou bases sur l'experience. Les traits « endogene » de la depression d'une part ou les aspects nevrotiques d'autre part, peuvent orienter le choix de l'antidepresseur. Parmi les facteurs biologiques, les deux catabolites de la noradrenaline (MHPG et DHPG) sont mentionnes ainsi que le taux de tryptophane ou d'acide homovanillique comme possibles indicateurs. Des tests neuroendocriniens tels le test de frenation a la dexamethasone ou la stimulation par la thyrostimulin releasing hormone (TRH) sont discutes. Jusqu'a maintenant, aucun indice biologique n'est entre dans la pratique comme permettant de predire la reponse therapeutique a un traitement antidepresseur.

Resume La stimulation magnetique transcrânienne (TMS) est une technique d’investigation du systeme nerveux qui possede, en applications repetees, un potentiel therapeutique, notamment en psychiatrie. Les effets physiologiques et neuroendocriniens induits par la TMS repetee chez l’animal sont voisins des effets entraines par les antidepresseurs. En particulier, la TMS semble modifier la liberation de neuromediateurs impliques dans les etats depressifs (serotonine, dopamine). Ces proprietes ont fait proposer la TMS repetee comme un traitement potentiel de la depression. Plusieurs etudes randomisees en ont maintenant evalue les effets dans cette indication et montrent le plus souvent des resultats statistiquement significatifs, bien que cliniquement parfois modestes. Cependant, les effets therapeutiques dependent de divers parametres comme l’excitabilite corticale et le metabolisme cerebral regional, qui generalement ne sont pas pris en compte. En dehors de la depression, les essais portent sur un nombre reduit de malades. Dans la schizophrenie, la TMS a permis de montrer des anomalies de l’excitabilite corticale, et d’ameliorer la symptomatologie, supprimant par exemple la perception des hallucinations auditives. La maladie de Parkinson, les tics et le syndrome de Gilles de la Tourette, les troubles obsessionnels compulsifs et la manie ont egalement fait l’objet d’essais prometteurs mais preliminaires. Des etudes randomisees plus larges doivent maintenant evaluer les differents parametres intervenant dans les effets therapeutiques, de facon a optimiser la procedure de traitement et de mieux comprendre la physiopathologie de divers troubles neuropsychiatriques.

1. Plasma Homovanillic Acid (p HVA) levels were measured by HPLC (high performance liquid chromatography) in 5 schizo-affective depressed patients receiving a standardized treatment. (lithium, chlorpromazine and clomipramine) during 4 weeks. 2. Four patients were pretreated, without a washout period. 3. No significant difference was observed between patients and normal controls at baseline. Under treatment, pHVA levels increased (p

A decreased thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) has been noted in major depression. Some authors found a positive correlation between baseline TSH levels and TSH response to TRH, especially with sensitive assays of TSH. Serum TSH was assayed by a sensitive method in 55 depressed patients and 38 healthy volunteers. Patients were subclassified according to DSM-III as suffering from major depression (n = 40) and non-major depression (n = 15). The patients' mean score on the Hamilton Rating Scale for Depression (HRSD) was 50 (SD = 10). The TSH value was significantly lower in depressed patients compared with healthy control subjects, and in major compared with non-major depression. No differences in TSH levels distinguished the various subtypes of major depression. There was a significant negative correlation between global HRSD scores and TSH concentrations. The most anxious patients tended to have significantly lower TSH values compared with the least anxious subjects. Total HRSD insomnia scores correlated negatively with TSH concentrations after log transformation. The sensitive determination of TSH may also provide an index of thyroid function in depression that is simpler to implement than measurements of the TSH response to TRH.

Recent studies on schizophrenia led to the conclusion that 20% to 30% of schizophrenic patients do not respond to neuroleptics treatments. The majority corresponds to the deficit or negative subtype. In this preliminary, prospective study, we examined immunoglobulin (Ig) G and M autoantibody levels in responder and nonresponder schizophrenic patients

International audience; Neuroimaging studies of patients with treatment-resistant depression (TRD) have reported abnormalities in frontal and temporal regions. We sought to determine whether metabolism in those regions might be related to response to repetitive transcranial magnetic stimulation (TMS) in patients with TRD. Magnetic resonance images and baseline resting-state cerebral glucose uptake index (gluMI) obtained using 18F-fluorodeoxyglucose positron emission tomography were analyzed in TRD patients who had participated in a double-blind, randomized, sham-controlled trial of prefrontal 10Hz-TMS. Among the patients randomized to active TMS, 17 responders, defined as having 50% depression score decrease, and 14 nonresponders were investigated for pre-stimulation glucose metabolism and compared with 39 healthy subjects using a voxel-based analysis. In nonresponders relative to responders, gluMI was lower in left lateral orbitofrontal cortex (OFC), and higher in left amygdala and uncinate fasciculus. OFC and amygdala gluMI negatively correlated in nonresponders, positively correlated in responders, and did not correlate in healthy subjects. Relative to healthy subjects, both responders and nonresponders displayed lower gluMI in right dorsolateral prefrontal (DLPFC), right anterior cingulate (ACC), and left ventrolateral prefrontal, cortices. Additionally, nonresponders had lower gluMI in left DLPFC, ACC, left and right insula, and higher gluMI in left amygdala and uncus. Hypometabolisms were partly explained by gray matter reductions, while hypermetabolisms were unrelated to structural changes. The findings suggest that different patterns of frontal-temporal limbic abnormalities may distinguish responders and nonresponders to prefrontal magnetic stimulation. Both preserved OFC volume and amygdala metabolism might precondition response to TMS.

SummaryA study was performed in young healthy volunteers in order to test the possible action of tianeptine, a new antidepressant drug, on cognitive performances. Attention tests, memory tests, a non-verbal inductive reasoning test and a sleep questionnaire were used in this double-blind placebo-controlled crossover study. The two one-week drug administration periods were separated by a one-week wash-out period. The methodology permitted us to evaluate the learning effect during the familiarization with the tests and to clear the results of the study from this parameter which could possibly distort analysis. For this large range of tests, the results showed that tianeptine did not affect the level of functioning of the volunteers after their familiarization with the tests. These results are in contrast with those obtained by different authors with classical tricyclic antidepressants.

The aim of this study was to determine the benefit/risk ratio of long-term treatment with medifoxamine, a non-tricyclic, non-monoamine oxidase inhibitor agent, and fluoxetine in patients with acute depressive episode and at high risk of relapse and/or recurrence. The study involved a 12-month double-blind, randomised, parallel-group design with a multicentric trial setting conducted by 64 participating physicians. 155 and 158 patients of either gender, aged between 18 and 70 years, were allocated to fluoxetine and medifoxamine, respectively. All patients had an acute depressive episode defined by the presence of at least five of the DSM III-R criteria with a minimal score of 25 on the Montgomery and Asberg Depression Rating Scale (MADRS). All subjects had at least one previous documented depressive episode in their medical history. The main outcome criterion consisted of good therapeutic response defined by a sustained 50% reduction of the Clinical Global Impression (CGI) score combined with the absence of any serious or troublesome (i.e. intensity motivating study discontinuation) events. In the fluoxetine and medifoxamine groups, respectively, 45.2% and 43% of the randomised patients completed the 12-month follow-up period with no major differences between groups regarding the reasons for treatment withdrawal. With each treatment 58% of the patients reached at least a 50% decrease in their CGI score, with no differences on the evolution of the MADRS, Hamilton Anxiety Rating Scale (HARS), the Self Rating Depression Scale of Zung (Zung scale) and Scott depression visual analogue scale (VAS) scores on average. According to the main efficacy criterion, 26% of the patients in the fluoxetine group were considered as responders compared with 36% in the medifoxamine group (p = 0.047). When only serious adverse effects were considered in combination with CGI scores to define response rates, the respective percentages were in favour of medifoxamine but the difference (45 vs 53%) was not significant. Results with medifoxamine were better in the elderly whereas, with fluoxetine, best responses were observed in younger patients. In conclusion, medifoxamine was an active and well tolerated drug in the continuation and maintenance treatment of depression. Its benefit/risk ratio appeared to be superior to fluoxetine, but this difference was mainly based on the occurrence of less minor adverse effects, a potential advantage not sufficient to favour better compliance with long-term therapy. Nevertheless, efficacy and tolerance of medifoxamine merits further evaluation in specific elderly populations.

The thyrotropin-releasing hormone (TRH) test was performed in 100 depressed patients, including 73 patients with a major depressive episode (MDE) according to DSM-III. Thirty-one patients subsequently received an antidepressant with a predominant serotoninergic action (indalpine or citalopram), and 27 patients received a noradrenergic antidepressant (maprotiline). The diagnostic value of the TRH test was not conclusive for any of the subgroups of depressed patients: MDE, MDE with melancholia or MDE in bipolar patients. Similarly, the value of the TRH test in the choice of antidepressant treatment according to the monoaminergic action was not convincing. These results are discussed in the light of the data of the international literature.

Introduction: Although previous studies have shown that lithium modifies eye movements or psychomotor speed, no studies have ever explored the predictive saccades or memory guided saccades during lithium administration. We took the objective to determine the influence of lithium in pseudo-random, predictive or memory-guided saccades in healthy subjects with a view to detect reduced psychomotor speed, inability to anticipate incoming events, or working memory deficits. Methods: A ten day lithium-placebo randomized double-blind cross-over pilot study was carried out with 12 healthy male volunteers. The cognitive assessment included pseudo-random, predictive and memory guided saccades before and after lithium and placebo periods. A biological assay substantiated the lithium effect on TSH and thyroid hormones. Results: There was no change in pseudo-random or memory guided saccades when comparing lithium or placebo administration. However the ratio of anticipated saccades decreased under the lithium sequence while it remained stable under placebo. Also, subjects having lithium serum levels of > 0.5 meq/l had longer latencies in anticipated saccades. Conclusion: The findings do not support a major effect of lithium on alertness or on working memory, although the dosage and duration of lithium was sufficient to modify TSH blood level. Nevertheless, lithium treatment was associated with decreased anticipation in predictive saccades, suggesting this could reflect a reduced ability to anticipate quick motor movements and could be related to the well-known effect of lithium as an anti-impulsive medication.

In a 4-week study of 14 drug-free schizophrenic patients (according to DSM-III-R), free and conjugated fractions of plasma homovanillic acid (pHVA) were repeatedly measured. Free HVA levels decreased during the first 2 h of haloperidol intake (P < 0.03). Conjugated HVA levels slowly decreased during the following weeks (P < 0.05), while free HVA levels remained stable. After 4 weeks, free HVA levels remained unchanged 2 h after morning haloperidol intake, but conjugated HVA levels tended to increase. In haloperidol responders, at baseline the free/total HVA ratio was significantly higher than that in non-responders (P < 0.01). Tolerant patients, i.e. those whose post-treatment free HVA levels decreased below pre-treatment levels, were not found to respond better to haloperidol than non-tolerant patients. The balance between free and conjugated pHVA may be a better reflection of the action of haloperidol than free pHVA levels and it may be of prognostic value in terms of drug response.

Autoantibodies reacting with cell constituents other than antinuclear antibodies have seldom been reported in the literature on schizophrenia. Serum of 41 DSM-III-R schizophrenic patients was examined for the presence of various autoantibodies and compared with that of healthy volunteers (n = 10) and hospitalized controls. Titers of IgG, IgA and IgM autoantibodies directed against actin, tubulin, myosin, DNA, thyroglobulin, elastin, albumin, DNA and trinitrophenyl groups were determined using enzyme immunoassay. IgG and IgA titers were significantly decreased in schizophrenic patients. These results contrast with those obtained with various other autoimmune and nonautoimmune diseases in which titers are either unchanged or increased. A significant increase of various autoantibody levels was observed in the paranoid subgroup of schizophrenics compared with the disorganized subgroup. These autoantibodies possess characteristics similar to those of natural autoantibodies, which seem to play several biological roles.

Cortical excitability is modified in schizophrenia [1] but the effect of antipsychotic drugs has been disputed. In particular, patients receiving olanzapine and risperidone showed less cortical disinhibition compared to untreated schizophrenic subjects [2]. However, despite the observed increase, the Resting Motor Threshold (RMT) remained inferior to the RMT in normal controls, and the Transcallosal Conduction Time (TCT) did not change.There is no comparative study of the effect of clozapine, an effective antipsychotic with proconvulsant properties.We studied cortical excitability by transmagnetic stimulation in stabilized schizophrenic patients treated by clozapine (n=10), olanzapine (n=10) compared to healthy volunteers (n=10).The aim of this study was to extend previous research into inhibitory deficits in schizophrenia and to compare the effect of clozapine and olanzapine on neurophysiological parameters such as RMT, Intracortical Inhibition (ICI), Intracortical Facilitation (ICF), Cortical Silence Period (CSP) and Transcallosal Inhibition (TI).In clozapine treated patients, the RMT and ICI were significantly lower (p

Abnormalities of noradrenaline metabolism and of the activity of hypothalamic-pituitary adrenal axis (HPA) have been reported in depression. To study the possible relationship between these 2 parameters, urinary excretion of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and Dexamethasone Suppression Test (DST) were analyzed in 58 depressed patients. A positive correlation was found between the age of depressed patients and 24-h urinary excretion of MHPG. Twenty-two patients (38%) were DST non suppressors. Pre-DST plasma cortisol levels were significantly higher in non suppressors than suppressors. No difference was found however between urinary MHPG levels in suppressors and non suppressors. There was no correlation between pre-DST plasma cortisol and levels of urinary excretion of MHPG. These results do not support the hypothesis of a relationship between these 2 parameters. However, when depressed patients were separated into two groups according to urinary excretion of MHPG ("high MHPG" and "low MHPG"), the "high MHPG" group included significantly more non suppressors then the "low MHPG" one. This result is not sufficient to demonstrate of link between HPA system activity and central noradrenaline metabolism.

It has recently been suggested that the plasma level of homovanillic acid (HVA) may provide an index of central dopaminergic activity in humans. Clinical studies have shown that in schizophrenic patients, plasma HVA levels increase with the severity of psychopathology. However, these studies only considered the plasma free HVA fraction whereas investigations on conjugated HVA in humans are sparse and results remain controversial. The aim of this study was to measure both plasma free and conjugated HVA in healthy volunteers and drug-free schizophrenic patients. The mean values and the ranges of plasma free HVA in volunteers and patients were similar to those described in the literature. A substantial and significant increase in plasma free HVA was observed in schizophrenic patients compared with normal subjects. In contrast, plasma conjugated HVA was significatively decreased in schizophrenics. The plasma total HVA was nevertheless higher in schizophrenics compared with controls. No significant correlations were observed between plasma HVA levels and the clinical features of schizophrenic patients rated by various psychiatric scales. These findings suggest that there is an imbalance between plasma free and conjugated HVA in schizophrenic patients, who present an increase in total HVA when compared with controls. Paranoid schizophrenic patients, who present mainly positive symptoms, show the most marked plasma free/conjugated HVA imbalance.