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Resume Introduction Seulement quelques indicateurs de resultat specifiques aux pathologies du coude et leur impact sur la capacite fonctionnelle, en usage aupres des populations francophones, sont valides et fiables. La version anglaise du « Patient-Rated Elbow Evaluation » (PREE) a ete choisie comme meilleur candidat pour la traduction. Hypothese Une version francaise de PREE (PREE-Fr) sera creee et comparee a la version originale en termes de fiabilite et validite. Methode Le PREE a ete traduit selon les recommandations de l’American Academy of Orthopedic Surgeons. Des patients souffrant de diverses pathologies du coude ont complete la version francaise du PREE (PREE-Fr), le Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) et le Mayo Elbow Performance Score (MEPS) a trois moments differents. La fiabilite test-retest du PREE-Fr a ete calculee avec 38 questionnaires completes a une semaine d’intervalle. La validite conceptuelle et la reactivite ont ete evaluees en utilisant les 29 questionnaires completes six mois apres le traitement. Resultats Les donnees amassees aupres de 54 patients montrent un coefficient de correlation intra-classe de 0,89 (CI 95 % : 0,79–0,94) pour le PREE-Fr. Pour la validite conceptuelle, le coefficient de correlation de Pearson a donne une excellente correlation entre le PREE-Fr et le QuickDASH au jour un, a une semaine et a six mois (0,89–0,96) et une correlation entre le PREE et le MEPS de bonne a excellente (0,70–0,95). La reactivite du PREE-Fr a ete evaluee et a donne une reponse moyenne normalisee de 1,03, signifiant qu’un grand changement a ete enregistre entre le jour un et six mois. Discussion Le PREE-Fr devrait etre envisage pour les populations francophones ayant une pathologie du coude, que ce soit pour la recherche ou l’evaluation fonctionnelle, puisqu’il est valide, fiable et adaptable aux changements. Niveau d’evidence scientifique II (questionnaire de validation).

Resume Contexte La violence est un probleme frequent dans les services de psychiatrie. Le niveau de violence du lieu de vie des patients n’a pas ete etudie comme une variable explicative de la violence intra-hospitaliere. Methode Nous avons mene une etude prospective dans 9 villes francaises tres contrastees du point de vue de leur niveau de violence. Les sujets eligibles etaient des patients hospitalises sous contrainte pour troubles psychotiques, dans une des unites de psychiatrie de chaque ville concernee. Au cours de leur hospitalisation, tout type de comportement agressif etait recueilli par l’Overt Aggression Scale (OAS). Resultats De juin 2010 a mai 2011, 95 patients ont ete inclus. Soixante-dix-neuf pour cent des patients ont montre un comportement violent au cours de leur hospitalisation. La violence des patients etait significativement liee : au sexe masculin, aux antecedents de violence agis par le patient, a l’abus de substances autre que la nicotine, a la presence d’un episode maniaque ou mixte, a l’intensite de la symptomatologie mesuree par la Brief Psychiatric Rating Scale (BPRS), au degre d’insight et au taux de violence a la personne des villes correspondant au secteur du patient. Dans une analyse multivariee, les seuls facteurs significativement lies a la violence des patients etaient l’abus de substance, la severite des symptomes psychotiques et le taux de violence des villes. Conclusion Cette etude suggere que la violence dans l’environnement de vie des patients est associee a une augmentation du risque de passage a l’acte violent au cours de leur hospitalisation.

Violence is a common issue in psychiatry and has multiple determiners. The aim of this study is to assess the psychotic inpatients' violence in association with the violence of the neighborhood from which the patients are drawn and to estimate the impact of this environmental factor with regard to other factors.A prospective multicenter study was led in nine French cities. Eligible patients were psychotic involuntary patients hospitalized in the cities' psychiatric wards. During their treatments, any kind of aggressive behavior by the patients has been reported by the Overt Aggression Scale (OAS).From June 2010 to May 2011, 95 patients have been included. Seventy-nine per cent of the patients were violent during their hospitalizations. In a bivariate analysis, inpatient violence was significantly associated with different factors: male gender, patient violence history, substance abuse, manic or mixed disorder, the symptoms severity measured by the BPRS, the insight degree and the city crime rate. In a multivariate analysis, the only significant factors associated with the patients' violence were substance abuse, the symptoms severity and the crime rates from the different patients' cities.These results suggest that violence within the psychotic patients' neighborhood could represent a risk of violence during their treatments.

Resume L’objectif de cet essai exploratoire multicentrique, randomise, en double insu, etait d’evaluer l’efficacite et la tolerance du milnacipran (MLN) et de la venlafaxine (VLF) administres a posologie flexible (100, 150 ou 200 mg/j en deux prises journalieres) pendant 24 semaines (dont quatre semaines de titration croissante) dans le traitement ambulatoire de l’adulte presentant un episode depressif majeur modere a severe sans risque suicidaire eleve (MINI–DSM IV-TR). Parmi les 195 patients inclus, 134 (68,7 %) ont complete l’essai. Les caracteristiques basales des deux groupes etaient similaires hormis une proportion sensiblement superieure de patients sous MLN presentant un episode severe-DSM IV (63,3 % versus 54,0 % de patients sous VLF). Le score MADRS initial (moyenne : 31,0) a progressivement diminue et de facon superposable dans les deux groupes analyses (n = 177 : 90/MLN, 87/VLF) jusqu’a semaine 24 (S24-OC ; moyenne : –23,1/MLN ; –22,4/VLF). Les taux de reponse MADRS (reduction ≥ 50 %) a S8 et S24-last-observation-carried-forward (LOCF) etaient similaires dans les deux groupes (S8 : 64,4 %/MLN, 65,5 %/VLF ; S24 : 70 %/MLN, 77 %/VLF), ainsi que les taux de remission MADRS (score ≤ 10) (S8 : 42,2 %/MLN, 42,5 %/VLF ; S24 : 52,2 %/MLN, 62,1 %/VLF). Dans les deux groupes, les evenements indesirables les plus frequents etaient nausees, sensation vertigineuse, cephalees, hyperhidrose et troubles urogenitaux masculins. MLN et VLF administres a posologie flexible (jusqu’a 200 mg/j) ont montre des profils d’efficacite et de tolerance globalement similaires dans le traitement ambulatoire au long terme de l’episode depressif majeur de l’adulte.

Introduction Visual orientation and attention are impaired in schizophrenia. Engagement and disengagement of attention and the ability to prompt responses to a stimulus in patients before and after six weeks of risperidone were compared to controls. Methods Ten unmedicated (nine naive) schizophrenic patients, and eleven controls performed 1) A visual orienting task, the Cued Target Detection task (CTD), with the detection of a visual stimulus in valid, invalid, no cue and double cue trials, two conditions for fixation offset for a modulation of visual fixation: Gap: 200 ms before target; No Gap: simultaneous with target, 2) Choice Reaction Time (CRT 0.5 and 2 s delays). Results At baseline, patients showed longer RT than controls in CRT, but not in CTD, with in CTD, no facilitation of RT with the gap procedure. The alertness index was almost null in CTD-Gap and comparable to controls in CTD-No Gap. Efficiency to detect attended stimuli (CTD-No Gap) and warning effect (CRT 0.5 s) were negatively correlated to disorganization. After treatment, readiness to act in CRT had decreased. In CTD-No Gap, change in PANSS disorganization was correlated to an increased validity index, change in negative sub-score was correlated to decreased attention cost. Conclusion Untreated patients displayed a deficit of Gap effect and a slowing in sustained attention. Disorganization interfered with warning and visual detection. After treatment, its improvement and negative symptoms improvement were associated with better visual detection. These alterations in visual orienting provide new evidence for an oculomotor dysregulation of attentional engagement in schizophrenia.

Resume Le thermalisme, ou crenotherapie ou cure thermale, est une therapeutique meconnue en psychiatrie. Pourtant, chaque annee 10 000 patients presentant essentiellement des troubles anxieux et/ou troubles depressifs sejournent en station pour y etre traites. Des etudes preliminaires ont confirme l’interet de la crenotherapie dans ces indications. Une evaluation scientifique rigoureuse a ete menee, encadree par les centres Inserm methodologique de l’ISPED (Bordeaux II) et l’unite Inserm de l’hopital Sainte-Anne a Paris visant a evaluer comparativement la crenotherapie et la paroxetine dans une etude multicentrique randomisee sur huit semaines avec suivi observationnel sur 24 semaines. Deux cent trente-sept patients presentant un trouble anxiete generalisee (TAG) ont ete inclus et evalues a l’echelle d’anxiete de Hamilton (HAM-A). Cette etude a montre l’efficacite therapeutique de la cure thermale dans le TAG (superiorite significative de l’action therapeutique de la cure thermale par rapport a la paroxetine a S8), le maintien de son efficacite therapeutique dans le temps et son excellent profil de tolerance. Cette etude permet de proposer une nouvelle voie therapeutique pour les patients presentant un trouble anxieux, notamment pour ceux resistant aux autres therapeutiques traditionnellement proposees dans les troubles anxieux.

Conventional and atypical antipsychotics are known to induce weight gain, cause glucose and lipid impairments among schizophrenic patients. These impairments contribute to the intrinsic risk factors linked to the psychiatric pathology (sedentary state, nicotin addiction, diabetes) increasing numbers of cardiovascular complications. We propose to study ponderal modifications and presence of metabolic abnormalities in a population of schizophrenic patients treated by conventional or atypical antipsychotics, depending on the received treatment; 32 patients, whose schizophrenia diagnosis had been previously made, were consecutively included over a 4 months period. They were divided into three groups: patients treated by conventional antipsychotics (n = 6), by atypical antipsychotics (n = 16) or by a combination of both (n = 10); 6 patients (18%) display overweight problems, 4 patients (12.5%) got hypertriglyceridemia and 4 other patients (12.5%) have hypercholesterolemia. No particular drug could be directly targeted, partly because of the restricted size of our sample, but the patients presenting metabolism impairment were treated by atypical antipsychotic. The observance of these abnormalities is reflected in publications and lead to some antipsychotic treatments monitoring rules.

Resume Les auteurs se proposent d’analyser, chez des transsexuels masculins compares a une population de sujets temoins, masculins et feminins, l’identification sexuee telle qu’elle s’exprime a travers la planche III du test de Rorschach et l’echelle Mf du MMPI. L’objectif, dans cette etude exploratoire, est d’evaluer, chez ces sujets dont la conviction d’appartenir au sexe oppose est persistante et irreversible, leur position identificatoire, en les considerant selon les criteres du sexe anatomique et selon les criteres du sexe qu’ils revendiquent. Cette etude comprend 28 transsexuels masculins, soit 18 hommes biologiques traites par hormonotherapie et operes et 10 hommes biologiques non traites. Le groupe temoin se compose de 10 hommes et de 12 femmes. Tous les sujets ont passe une epreuve de niveau intellectuel verbal (test de vocabulaire de Binois-Pichot), une epreuve projective de personnalite (test de Rorschach) ainsi qu’un autoquestionnaire de personnalite (MMPI). L’analyse des resultats porte sur les deux groupes de transsexuels compares entre eux et aux deux groupes temoins. Chez ces transsexuels masculins, les donnees recueillies au test de Rorschach et au MMPI sont homogenes, temoignant d’un hyperconformisme au sexe revendique, en congruence avec les resultats des femmes temoins, et ce tant avant qu’apres l’operation.

Resume Comment peut-on predire l'activite d'un antidepresseur avec des tests psychopharmacologiques chez l'animal ? Les tests comportementaux classiques vont de l'observation du comportement au test d'antagonisme de la reserpine, et les tests utilisant des comportements chimiquement induits. De nouveaux modeles ont ete mis au point : test de « resignation acquise », test de « desespoir comportemental », modele du « stress leger repete », et separation precoce mere-enfant chez l'animal. D'autres tests sont bases sur une approche electro-physio-biologique : effets sur le trace electroencephalographique (EEG), sur le cycle de sommeil induit chez le chat. Les animaux genetiquement modifies sont un modele d'avenir.

Resume A efficacite comparable, la tolerance constitue un critere de choix majeur du traitement antidepresseur. Or, l’evaluation des effets indesirables (EI) des antidepresseurs se heurte a de nombreuses difficultes methodologiques. Ainsi, nous avons mene une etude dont l’objectif etait de comparer 2 outils de mesure des EI des antidepresseurs : la notification spontanee (NSp) et l’echelle UKU. Cette etude a ete menee aupres de 50 patients traites depuis plus de 4 semaines par un antidepresseur appartenant a l’une des dernieres classes commercialisees : les inhibiteurs selectifs de la recapture de la serotonine et de la noradrenaline, les inhibiteurs de la serotonine et de la noradrenaline, les antidepresseurs noradrenergiques et serotoninergiques specifiques et la tianeptine. Le pourcentage de patients declarant au moins un EI est significativement plus important avec l’echelle UKU qu’avec la NSp (84 % vs 58 %, p

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

Resume Le dosage plasmatique d'antidepresseurs revele des differences importantes d'un produit a l'autre. La resorption digestive des tricycliques est importante et rapide : ils sont fortement lies aux proteines plasmatiques, a 90 %. Les nouveaux antidepresseurs n'ont pas un devenir homogene. Pour certains, agissant sur la recapture de la serotonine, leur resorption est moins importante que pour les tricycliques. La transformation metabolique des nouveaux antidepresseurs est souvent complete, avec peu de catabolites actifs. Leur elimination est urinaire et fecale. Leur demi-vie est tres variable d'un produit a l'autre, parfois tres breve ou au contraire tres longue. Le monitoring pharmacocinetique est une methode excellente pour connaitre le rapport entre la concentration plasmatique ou intraerythrocytaire et l'efficacite. Enfin, les auteurs soulignent l'existence de patients a risque a effets secondaires : les personnes âgees, les insuffisants renaux ou hepatiques et les alcooliques.

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.

This case-control study found an association between Seasonal Affective Disorder (SAD) and a single nucleotide polymorphism (intronic rs2072621) of the gene encoding GPR50 (an orphan member of the G protein-coupled melatonin receptor subfamily) in females. This may represent a gender-specific risk factor and a molecular link between melatonin and SAD.

ResumenLa adicción a diversas sustancias, incluidas las drogas y el alcohol, se origina probablemente en una combinación de factores ambientales y genéticos. Varios estudios familiares, de adopción y de gemelos apoyan la vulnerabilidad genética a la adicción a las drogas. Sin embargo, como ocurre en otros trastornos mentales, la vulnerabilidad genética a la adicción a las drogas parece compleja: estos trastornos no siguen las reglas de la herencia mendeliana. En su lugar, influyen probablemente en ellos múltiples genes de susceptibilidad, cada uno de los cuales contribuye al trastorno. Cuantos más genes son necesarios para un trastorno, más difÍcil es detectar cualquiera de ellos. El papel de los factores ambientales aumenta esta dificultad. Los estudios de asociación que han utilizado el enfoque del gen candidato pueden identificar genes de susceptibilidad para el abuso de drogas con el apoyo de la hipótesis patofisiológica de la enfermedad. Esta revisión se centrará en los estudios clÍnicos y de genética molecular en el abuso de drogas.

SummaryAddiction to various substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. The genetic vulnerability to drug addiction is supported by several familial, adoption and twin studies. However, as in other mental disorders, the genetic vulnerability to drug addiction appears complex: these disorders do not follow the rules of Mendelian inheritance. Instead, they are probably influenced by multiple susceptibility genes, each of which contributes to the disorder. The more genes necessary for a disorder, the harder it is to detect any of them. This difficulty is magnified by the role of environmental factors. Association studies using the candidate gene approach can identify susceptibility genes for drug abuse supported by the pathophysiological hypothesis of the illness. This review will focus on the clinical and molecular genetic studies in drug abuse.

BackgroundAbout one-third of patients fail to respond to initial antidepressant therapy, which suggests a need for more effective drugs.AimsTo compare the efficacy and safety of venlafaxine and paroxetine in 122 patients with non-chronic treatment-resistant depression.MethodIn-patients or out-patients satisfying DSM – III – R criteria for major depression in evolution for less than eight months, having a baseline HAM–D score 18 and a HAM – D Item 3 score < 3 were eligible. Patients were required to have a history of resistance to two previous antidepressant treatments and a CGI improvement score of 3 at the beginning of treatment. Doses were adjusted to 200–300 mg/day for venlafaxine and 30–40 mg/day for paroxetine.ResultsFor the observed-case analysis, the response rate was 51.9% for venlafaxine and 32.7% for paroxetine (P=0.044), and a remission was achieved in 42.3% of venlafaxine-treated and 20.0% of paroxetine-treated patients (P=0.01). The incidence of adverse effects was comparable between treatment groups.ConclusionsVenlafaxine showed some evidence of superiority to paroxetine in this difficult-to-treat patient population.

Anatomical, pharmacological and human post-mortem studies suggest the dopamine D3 receptor (DRD3) gene as a candidate for drug dependence. We thus performed an association study of the Bal I polymorphism at the DRD3 gene, including 54 opiate addicts and 70 controls. Opiate addicts had a higher sensation-seeking score (on the Zückerman scale) than controls (P = 0.001), particularly a subgroup (70%) who had a distinctly higher score, exceeding 24. There were no marked differences in genotypes between patients as a whole and controls. However, patients with a sensation-seeking score above 24 were more frequently homozygotes for both alleles than patients with a sensation-seeking score under 24 (P = 0.038) or controls (P = 0.034). Although obtained in a sample of limited size, these results suggest that the DRD3 gene may have a role in drug dependence susceptibility in individuals with high sensation-seeking scores. This hypothesis is consistent with the role of DRD3 in mediating responses to drugs of abuse in animals and the association of homozygosity at the Bal I polymorphism with drug abuse in schizophrenic patients (see companion article by Krebs et al).

BackgroundAmisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors. The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia.MethodThis was a multi-centre, randomised, parallel-group, double-blind study. Patients received either amisulpride (100 mg/day) or placebo over a six-month treatment period.ResultsA total of 141 patients were included, 69 received amisulpride, 72 placebo. Fifty-eight patients (41%) had received neuroleptic treatment prior to inclusion. The percentage of amisulpride patients completing the study (55%) was significantly higher than that with placebo (32%), and drop-out rates due to lack of efficacy were 27% with amisulpride and 47% with placebo. All efficacy assessments were statistically in favour of amisulpride compared with placebo. The overall incidence of extrapyramidal symptoms was comparable in both groups; only five patients started anti-Parkinsonian treatment during the study (one in the placebo and four in the amisulpride group).ConclusionAmisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms.

Background Only a few outcome measures specific to elbow pathology and the assessment of their impacts on function are valid and reliable when used in French speaking populations. The English version of the Patient Rated Elbow Evaluation (PREE) was determined to be an optimal candidate for translation. Hypothesis A French version of the PREE (PREE-Fr) will be generated and compared to its original version in terms of reliability and responsiveness. Materials and methods The PREE was translated following the guidelines of the American Academy of Orthopedic Surgeons. Patients with a variety of elbow pathologies completed the French version of the PREE (PREE-Fr), the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) and the Mayo Elbow Performance Score (MEPS) on three different occasions. The test-retest reliability of the PREE-Fr was calculated using questionnaires that were filled out with a one-week interval between them. The responsiveness was assessed using questionnaires filled out six months after treatment. Results A French version of the PREE was generated. Data gathered from 54 patients yielded an intra-class correlation coefficient for reliability of 0.89 (CI 95% : 0.79–0.94) for the PREE-Fr. For construct validity, using the Pearson correlation coefficient, we obtained excellent correlation between the PREE-Fr and QuickDASH at day one, one week and six months (0.89–0.96) while that between the PREE and MEPS was good to excellent (0.70–0.95). Responsiveness of the PREE-Fr was assessed and yielded a standardized response mean of 1.03, meaning that a large change was recorded between day one and six months. Discussion The PREE-Fr should be considered in French speaking populations for patients with elbow pathology, whether it is for research or evaluation purposes as it is valid, reliable and responsive to change. Level of evidence II (questionnaire validation).

The widespread use of antidepressants since the late 1950s and especially the ambulatory treatment of the majority of depressive patients raises the issue of the state of knowledge of the effects of these drugs on cognitive function. This review aims at synthesizing information about differential effects of antidepressants on cognitive function to facilitate good prescription. The first part of this review tries to summarize the main tasks used to explore global reactivity, attention, memory and psychomotor performances. The second part of this work presents the differential cognitive effects of antidepressants with a discrimination between substances which have a sedative impact, antidepressants with no cognitive effect, and drugs which seem to have a positive cognitive action. The differenciation is established for single and repeated administration, for healthy volunteers and depressed subjects. For each substance, the dose, the tasks selected and cognitive effect are discussed and the question of the real benefit of this cognitive impact is raised. The specificity of cognitive effects of antidepressants related to age and to the combination with alcohol are also tackled. Then the discussion raises the difficulty and the biases encountered to perform neuropsychological studies and particularly evaluation of cognitive effects of antidepressants. Finally the conclusion of this review gives some advice to select and prescribe antidepressants according to their cognitive effects.

Serotonin (HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) are commonly used as first line treatment of major depressive disorders (MDD). As compared to tricyclic antidepressants, they have proved similar efficacy and better tolerability. Milnacipran (MLN) (Ixel) and venlafaxine (VLF) (Effexor) are two SNRIs pharmacologically differing by their NA/HT ratio of potency: 1:1 and 1:30, respectively.To investigate the efficacy and safety/tolerability of MLN and VLF administered at flexible doses (100, 150 or 200 mg/day) for 24 weeks (including 4 weeks of up-titration) in the outpatient treatment of adults with moderate-to-severe MDD.Multicentre, randomised, double blind, 2-parallel-arm, 24-week exploratory trial conducted in France by 50 psychiatrists. DIAGNOSIS AND MAIN INCLUSION CRITERIA: Male or female outpatients, aged 18 to 70, meeting the DSM-IV-TR and related MINI criteria for recurrent, unipolar, moderate-to-severe MDD, with neither psychotic features nor severe suicidal risk. A Montgomery-Asberg depression rating scale (MADRS) scoreor =23 was required at inclusion. TREATMENT SCHEDULE: Patients were randomised to receive either MLN or VLF (1:1 ratio) for 24 weeks in double-blind conditions. Regardless of the treatment received, the following dosing schedule was applied: during the initial 4-week up-titration phase, the dosage was progressively increased from 25 mg/day (qd administration) to 150 mg/day (bid administration). At week 4, the dosage was either maintained at 150 mg/day, or adapted to 100 or 200 mg/day, based on the investigator's clinical judgement. At any time during the 20 following treatment weeks, the dose could be lowered for safety concerns until a minimal threshold of 100 mg/day. From Week 24, the dosage was decreased by 50mg/day every five days. After randomisation, eight assessment visits were organised at 2, 4, 6, 8, 12, 18, 24 weeks, and at study end (after the 5-15 days of down-titration and 10 days free of treatment). Efficacy evaluation ratings included the MADRS and global disease severity (CGI-S) total scores. Rates of MADRS response (reduction of initial scoreor =50%) and remission (scoreor =10) were calculated at Week 8 and Week 24 in the full analysis set as well as in the subgroups of patients with depressive disorder of severe DSM-IV intensity and with a MINI evaluation of suicidal risk (rated as required 'moderate' at the worst).Standard distribution statistics (including mean and standard deviation [S.D.]) of scores and their changes from baseline, were calculated using the observed-case (OC) approach at all assessment times for the MADRS score, and the last-observation-carried-forward (LOCF) at 8 and 24 weeks for both MADRS and CGI-S scores. MADRS response and remission rates at 8 and 24 weeks were calculated using the LOCF approach by normal approximation of the binomial distribution. Bilateral exploratory statistical tests at 5% significance level were performed for results at 8 and 24 weeks of: (i) MADRS score changes from baseline, based on the score progress at each visit (mixed model for repeated measurements [MMRM]), and (ii) global MADRS response and remission rates (Chi(2)). RESULTS AND PATIENTS: A total of 195 patients were randomly assigned MLN (n=97) or VLF (n=98) and 134 (68.7%: 61.9%/MLN and 75.5%/VLF) completed the trial. At the end of the up-titration, patients received 100 mg/day (11.4%/MLN, 10%/VLF), 150 mg/day (30.4%/MLN, 43.8%/VLF), or 200 mg/day (58.2%/MLN, 46.3%/VLF). Totals of 177 patients (90/MLN and 87/VLF) and 181 patients (90/MLN and 91/VLF) were analysed for efficacy and safety, respectively. Treatment groups were similar for baseline characteristics except a higher proportion of MLN patients with a severe depressive episode (63.3% versus 54%). RESULTS AND EFFICACY: MADRS score (mean [S.D.] initial score: 31 [4.5]) progressively decreased all along the treatment course and similarly in both groups (Week 8-OC : -18.8 [7.7]/MLN and -18.6 [7.3]/VLF, p(MMRM)=0.95 ; Week 24-OC : -23.1 [7.8]/MLN and -22.4 [7.3]/VLF, p(MMRM)=0.37 ). At week 8-LOCF, MADRS response rates were similar in both groups (64.4%/MLN, 65.5%/VLF, p(chi2)=0.88) as well as remission rates (42.2%/MLN, 42.5%/VLF p(chi2)=0.97). At week 24 they remained non clinically and statistically different between groups (response rates: 70%/MLN, 77%/VLF, p(chi2)=0.29; remission rates: 52.2%/MLN, 62.1%/VLF, p(chi2)=0.19). In both "severe depressive episode" and "MINI mild or moderate suicidal risk" subgroups (n=104 and 75, respectively), response and remission rates were non clinically different at both time points, however in the "MINI mild-to-moderate suicidal risk" subgroup, MLN tended to be more rapidly active (remission rate at week 8-LOCF: 44.7%/MLN, 35.1%/VLF). The changes in CGI-S were also indicative of a significant improvement of the global illness severity with both treatments. RESULTS AND SAFETY/TOLERABILITY: The tolerability profile of both drugs was in line with their pharmacological activity. About 70% of patients in both groups experienced at least one adverse event (AE). In both groups, the most common AEs were nausea, dizziness, headache and hyperhidrosis, and, in the male patients, genito-urinary problems: orgasmic disorders (VLF only) and dysuria (MLN only). These AEs were mostly responsible for definitive treatment discontinuation for tolerability concerns. None of the 6 serious adverse events (SAEs) on MLN and 4 of the 8 SAEs on VLF were related to the test drug.MLN and VLF at flexible doses up to 200 mg/day globally exhibited similar efficacy and tolerability profiles in the long-term treatment of adults with MDD.

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.

Previous studies on schizophrenia have suggested that context-processing disturbances were one of the core cognitive deficits present in schizophrenia. Schizophrenic patients have a failure either of inhibition strategy and maintenance of visuospatial information (25) in condition of contextual interference. In the present study, we explored the performances of untreated schizophrenic patients with 2 tasks exploring detection and long term retention of complex visual features and field dependence-independence tasks were selected. These abilities involve temporary maintenance of visuospatial information and executive functioning of visual working memory system. Several studies have shown that cognitive deficit may depend on schizophrenic symptomatology. However results remain controversial in determining the specific influence of negative and positive symptomatologies as well as clinical disorganization. Our goal was to explore the processing of spatial context and its relation to disorganized syndrome. This study was approved by the local ethic committee.Thirty-six schizophrenic patients were included according to DSM IV criteria (19 neuroleptic naïve, 17 unmedicated patients during more than 3 months). Thirty-six healthy controls were matched to patients for age, gender and level of education. Absence of axis 1 pathology was attested for controls with SCID-NP. Current symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) (14). Clinical disorganisation was evaluated with the disorganisation score established upon a factorial analysis of PANSS by Lepine and Lançon. Items selected to distinguish the disorganised group were abstraction, disorganization, orientation, and attention.Two tasks of embedded figures were administered individually to patients and controls. The Faverge task (Research of Figures-RF) (10) evaluates the ability to recognize the target from spatial complex geometrical figures. The Group Embedded Figure Task (GEFT - Oltman) assesses the detection and maintenance of visual target and its recognition within a complex figure. Performance between patients and controls were compared with the Student T test. The comparison of two clinical subgroups of disorganized and low disorganized patients and control group was performed with an ANOVA. Tuckey test was used for pairwise comparisons.We defined two subgroups of patients, disorganized patients (subscore 12, n=17) and low disorganized patients (subscore12, n=19). Theses 2 subgroups were similar for age and level of education. Concerning the two tasks, there was no significant difference between schizophrenic patients and normal controls. The comparison between subgroups of disorganized and low disorganized patients, for RF task, showed a decrease of correct answers with disorganized patients (p0.05). For GEFT task, disorganized patients had a decrease of correct answers p0.01) and more errors (p0.01) and omissions (p0.05). The low disorganized patients exhibited for the two tests comparable performance to controls. The disorganized patients had a decrease of right answers (p0.05) and more errors (p0.05) than controls for GEFT task and no significant difference for RF. However, with IQ (evaluated with an abstract reasoning test) introduced as covariate, only correct answers for GEFT task remain significant (p0.05).The weak performance of disorganized schizophrenic patients for two tasks RF and GEFT showed that treatment of visuospatial information was impaired in the first perceptive phase of selection and in the organization of information (RF), especially with the maintenance of visual information in memory (GEFT). By contrast, low disorganized patients demonstrated a correct analytic treatment of elementary processing and visuospatial working memory.The severity of disorganization influences the visuospatial context processing and visuospatial working memory. These results show the heterogeneity of cognitive functioning regarding to schizophrenic symptomatologies. This difficulty could be related to a problem of central executive functioning in the visuospatial component of working memory, possibly mediated by the dysfunction of dorsolateral prefrontal cortex.

The aim of this research project was to study gender identification in male transsexuals compared to male and female controls, using the Rorschach test and the MMPI. In the international literature, many researches have shown that the nature of the human response on Rorschach card III is linked to gender identification, as is the MMPI Mf scale. Ten untreated male homosexual transsexuals and 18 treated and operated male homosexual transsexuals were compared to 10 male and 12 female controls regarding verbal IQ, human content on Rorschach card III and the MMPI Mf scale. Absence of hormonal treatment for the first group of transsexuals was checked by a blood test at the time of the psychological testing. Responses on Rorschach card III were scored according to different kinds of human contents: male (M), female (F), gender-unidentified/neutral (N), bisexual (B), feminine then masculine or the opposite (M/F), and nonhuman (NH). N, B, M/F and NH responses were rare in all Rorschach protocols. As expected, responses given by participants in the control group were significantly more consistent with their anatomical sex than with the opposite sex. Untreated transsexuals do not differ from treated and operated transsexuals on Rorschach data, and both transsexual groups give significantly more female human representations than male controls. Transsexuals' results are similar to female controls. Untreated transsexuals' mean score on the MMPI Mf scale is significantly higher than that of treated and operated transsexuals' score, in the male profile (biological sex). Both groups of transsexuals score higher on the Mf scale in the male profile than in the female profile. The mean Mf score in the male profile is significantly higher than that of male controls, whereas, in the female profile, the mean Mf score is similar to that of female controls. This study shows that for both groups of transsexuals, results are homogenous in respect of Rorschach and MMPI, showing hyper-conformism to self-perceived gender. Results in both groups are similar to results of female controls, but tend to show even more feminine gender identification. The absence of any significant difference between untreated and treated and operated transsexuals seems surprising, suggesting that the hormonal treatment has not had a major impact on gender identification processes. It would doubtless be interesting to study gender identification using even more kinds of data: all human contents in the Rorschach protocol (not just the responses given to card III), MMPI Mf scale, Draw-A-Person Test and Animal-and-Opposite Drawing Test. This would enhance result liability and could provide useful information about how gendter identification processes evolve after surgical sex reassigment.

Conventional and atypical antipsychotics are known to induce weight gain, cause glucose and lipid impairments among schizophrenic patients. These impairments contribute to the intrinsic risk factors linked to the psychiatric pathology (sedentary state, nicotin addiction, diabetes) increasing numbers of cardiovascular complications. We propose to study ponderal modifications and presence of metabolic abnormalities in a population of schizophrenic patients treated by conventional or atypical antipsychotics, depending on the received treatment; 32 patients, whose schizophrenia diagnosis had been previously made, were consecutively included over a 4 months period. They were divided into three groups: patients treated by conventional antipsychotics (n = 6), by atypical antipsychotics (n = 16) or by a combination of both (n = 10); 6 patients (18%) display overweight problems, 4 patients (12.5%) got hypertriglyceridemia and 4 other patients (12.5%) have hypercholesterolemia. No particular drug could be directly targeted, partly because of the restricted size of our sample, but the patients presenting metabolism impairment were treated by atypical antipsychotic. The observance of these abnormalities is reflected in publications and lead to some antipsychotic treatments monitoring rules.

Overall, the efficacy of the newer antidepressants: serotonin selective reuptake inhibitors (SSRI), selective serotonin/norepinephrine reuptake inhibitor (SNRI), noradrenergic and specific serotonergic antidepressant (NaSSA) and tianeptine is similar to that of the tricyclics, and so their acceptability/safety becomes a selection criterion for the clinician. However, side-effect assessment comes up against several difficulties: distinguishing between somatic symptoms caused by the depression and those caused by the treatment -- which assessment tool to use (spontaneous notification, standardized scales that are not specific for the side effects caused by psychotropic drugs, standardised scales specific for the side effects caused by psychotropic drugs, meta-analysis, etc.) -- which data sources to consult (anecdotal reports, reviews, prospective studies), and which data set to use, etc. As a result, the question of the exhaustiveness and reliability of the data consulted by the clinician can arise. We therefore conducted a comparative study in patients treated with these newer antidepressants, of 2 antidepressants side-effect assessment tools: spontaneous notification (SN) versus the UKU scale, a standardised scale specific for the side effects of psychotropic drugs.The depressed outpatients were selected from a psychiatric unit in a French psychiatric hospital and from a non-hospital consulting room. The main inclusion criteria were: male or female subjects, suffering from major depression without melancholia or psychotic features or suffering from mood disorders (according to DSM IV criteria), who had been treated for at least 4 weeks with one of the newer antidepressants. The main exclusion criteria were: any other psychiatric disorder, a serious physical disorder, treatment with neuroleptics, mood-changing drugs or other antidepressants, and patients who were not able to understand the questionnaire. The investigation was carried out by a clinical pharmacist.Fifty patients were included in the study. There were 18 men and 32 women. The mean age was 53.5 15.9 years [22 - 77], the mean period of treatment was 24 30.5 months [1 - 127] and 52% of the patients received concomitant medication with anxiolitic or hypnotic drug(s). The percentage of patients who reported at least one side effect was significantly higher for the UKU scale than for SN (84% vs 58%, p0.01). The ratio between SN and UKU scale scores was 2/3. A similar pattern was found for the total number of side effects (n=177 vs n=47, p0.001). The ratio between the total number of side effects for the SN and UKU scale was 1/4. The side effects were divided into five subgroups: psychiatric, neurovegetative, sexual, neurological and others. In all these subgroups, the number of side effects reported was significantly higher when the UKU scale was used than when SN was used. The values were as follows: psychiatric (n=44 vs n=15, p0.001), neurovegetative (n=59 vs n=15, p0.001), sexual (n=36 vs n=10, p0.001), neurological (n=11 vs n=2, p0.001) and other side effects (n=27 vs n=5, p0.001). Nineteen side effects were only reported when SN was used (for example: dry eyes, incompatibility with alcohol, euphoria...). Twenty-four side effects were only reported when the UKU scale was used (for example: increased libido, loss of bodyweight...). The side effects had no impact on daily life in most of 80% of the patients; there was no significant difference between the patient's assessment of the discomfort caused by side effects and the clinician's assessment. In 90% of cases, the side effects did not lead to any change in the treatment.The findings of this study show that the collection of data regarding side effects depends on the assessment tool used: the number of side effects reported was significantly higher when the UKU scale was used than when SN was used. However, this finding must viewed with caution, because it has been showed that checklists can induce symptoms in suggestible patients. Neurovegetative troubles are the most commonly reported side effects, and neurological troubles the least often reported. This matches the tolerability profile of these antidepressants. The disorders that were least frequently spontaneously reported were the neurological, sexual and "other" side effects. These emerged only when the clinician asked the patient about them. The 19 side effects that were only reported when SN was used were side effects that were not included in the UKU scale or that had not been present during the three days before we started the investigation. The 34 side effects that were only reported when the UKU scale was used were either side effects with no apparent link with the treatment (for example: micturition troubles) or embarrassing effects (such as increased libido).Our findings show that the collection of data on side effects depends on the assessment tool used. These findings need to be confirmed by large-scale comparative studies, and the standardization of the assessment of side effects is a question that needs to be raised.

Previous studies testing the functional polymorphism in the promoter of the serotonin-transporter gene (5HTTLPR) in various psychiatric conditions have suggested that the association could be with an intermediate phenotype, impulsivity and/or violence rather than with a diagnosis. Schizophrenia is associated with a high risk of suicide, especially in patients with high impulsivity. We examined whether this polymorphism could be associated with violent suicide and/or impulsivity in schizophrenic patients. We genotyped the 5HTTLPR polymorphism in 185 unrelated schizophrenic patients from a French Caucasian population. The genotype frequencies significantly differed between patients who made violent suicide attempts and both, those who attempted suicide with a non-violent method (P = 0.013) and those who never attempted suicide (P = 0.026). The genotypes containing the low activity "short" allele was significantly more frequent in violent suicide attempters (P = 0.007) than in non-violent suicide attempters. No evidence was found for an association either with schizophrenia itself, when compared to gender and ethnically matched controls (n = 159) or with impulsivity, assessed using Barratt's Impulsivity Scale. Although replication studies are warranted, these results in schizophrenia further support the hypothesis that 5HTTLPR polymorphism is a risk factor for violent suicidal behavior.

Abuse of cannabis is frequent among the young and is suspected to precipitate schizophrenia in vulnerable subjects. Cannabinoid receptor (CB1) is particularly concentrated in dopamine-modulated areas of the nervous system. An association between an AAT polymorphism of the CB1 gene and intravenous drug abuse has been previously reported, but not with schizophrenia. In a French Caucasian population, we compared the distribution of a single-base polymorphism revealed by MspI within the first exon of the CB1 gene in patients with schizophrenia (n = 102) and ethnic- and gender-matched controls (n = 63). No significant difference was seen in the allele or genotype distribution between the whole sample of schizophrenic patients and controls. However, we found a borderline lack of allele g and a significant lack of gg genotype in the non-substance-abusing patients compared to substance-abusing patients, the latter being similar to the controls. These results are the first report of an significant association between CB1 receptor and a subtype of schizophrenia. Studies are needed to confirm and further explore the precise role of the cannabinoid system in schizophrenia.

Buprenorphine has a partial morphine-agonist pharmacological profile. It is proposed as alternative to methadone in opiate drug addicts with greater safety of use and less cost in terms of public health. The aim of this study was to determine the clinical factors of response to this molecule.The study was conducted in 73 patients treated for 3 months with adaptable doses. Mean dose was 8.5 mg/d (range: 3 to 16 mg/d). Response to treatment was defined as: still in the study at 3 months and absence of opiates in 75% of urinary samples over the past month.Forty-eight patients responded and 25 did not. The determinating clinical variables of response were: opiate drug addiction less than 10 years, high score on the Addiction Severity Index (ASI), absence of depression according to the Minnesota Multiphasic Personality Inventory (MMPI) and low rate of disinhibition on Zukerman's sensation seeking scale. Conversely, the dose of buprenorphine within the limits specified in the Marketing Authorisation did not intervene in the response.In view of its partial agonist effect, administration of buprenorphine must be reserved for patients addicted to opiates for less than 10 years, non-depressive and with low disinhibition on Zukerman's scale.

International audience; A role of histaminergic neuronal systems in schizophrenia was suggested by an association with several polymorphisms located in the coding region of the histamine H2-receptor (H2R) gene (Orange et al, Mol Psychiatry 1996; 1: 466–469). Using either the reference method of direct sequencing or restriction endonuclease digestion of PCR products amplified from DNA, we could not confirm the existence of these polymorphisms in 53 Swedish controls, 52 French controls and 88 French schizophrenics. In contrast, we detected a G543A transition in the coding region of the gene that was not found in the British population. This allelic variation, which was observed in 15% of the controls with no homozygotes, did not change the amino acid sequence of the receptor. We also analyzed a 1.8-kb nucleotide sequence of the promoter region in which we detected two additional polymorphisms that may modulate the expression of the H2R gene. The first one was a A-592G transition located in the minimal promoter of the gene and found in ˜10% of controls with no homozygotes. The second one was a G-1018A transition located in an enhancer element of the promoter and was found in ˜20–30% of controls (with ˜2–4% homozygotes). DNA analysis of the 88 French schizophrenic subjects revealed that the incidence of the three polymorphisms was not significantly different in this population. In conclusion, the present findings may suggest a surprisingly high variability of the H2R gene polymorphisms in different geographical areas but do not support an association of these allelic variations with schizophrenia.

Clinical symptoms of bipolar disorders onset act as a prognostic risk-factor. Discrepancies of data are related with geographical or cultural conditions. Within a patient population of bipolar (ICD 10) in and out patients of a psychiatric department, manic or hypomanic disorders initiate the space disease in 33% of the cases theses features are similar within the western psychiatric population. In a maghrebian population this proportion reaches 50%. A percentage of 65% of bipolar 1 patients was found within our sample. Sex ratio is 1 for bipolar 1, when, for bipolar 2 disorders sex-ratio was superior to 1, in favor of females. Mean age of the first episode of the disease was younger for patients with a familial history of the disease.

Objective and Method: The authors compared the effects ofacetorphan, an enkephalinase inhibitor, with those of clonidine for the treatment of the opioid withdrawal syndrome. Nineteen patients addicted to heroin or synthetic opiates who were undergoing drug withdrawal and displayed a withdrawal syndrome according to DSM-III criteria were studied for 5 days in a hospital setting. In a double-blind trial, 10 subjects were given acetorphan intravenously and nine were given clonidine; objective signs and subjective symptoms of withdrawal were recorded. Results: On several objective signs, the effect of acetorphan was more marked than that of clonidine, whereas the two drugs exhibited similar efficacy with respect to the subjective components of withdrawal. No side effect was noted in the subjects who received acetorphan. Conclusions: Enkephalinase inhibition may constitute a novel and safe therapeutic approach to the opioid withdrawal syndrome. (Am J Psychiatry 1991; 148:627-629)

According to the ICD 10 only acute psychotic disorders and transitory acute disorders are specified, whereas DSM IV index, in the same class, schizophreniform disorder, schizoaffectif disorder and atypical psychosis. State biological markers of these disorders are present during the acute episode and disappear with it. A few studies concerns trait predispositional markers of these acute psychotic disorders. In addition, several studies of acute psychotic states are indexed as a partition of usual schizophrenic disorder, as a simple occurrence of that chronic disease. From the biological point of view, dysfunctions of norepinephrine and dopaminergic metabolisms are reported within these acute schizophrenic disorganisation, especially hyperdopaminergia, causality, consequence or evidence of the state syndrome. Those kinds of data are also reported in mood disorder with delusional symptoms. A hypothetic dysregulation of the balance between oxydation and antioxydation system has been searched in these acute states of schizophrenia. From the electrophysiologic perspective, no abnormalities are found for ocular movement functions during these acute psychotic disorders. Besides the clouding of consciousness of confusional states, neuropsychological abnormalities are reported: attention disorders, lack of inhibition of non relevant informations, abnormalities of working memory. Brain imaging can substantiate a diminution of the caudate nucleus size and a possible increase of D2 receptors number. Also, in these acute psychotic states abnormalities of humoral and cellular immunologic system have been found. Lastly, street drugs can originate confusional states and depersonalization, through their serotoninergic, dopaminergic and anticholinergic properties. Ethical drugs can also create an acute psychosis disorder: individual vulnerability and somatic disease cooccurrence act as risk-factors.

About 30% of depressed patients exhibit depression that is resistant to antidepressant treatment. This resistance may be primary or associated with a concomitant psychiatric or somatic disease. Venlafaxine has shown potent efficacy in certain severe depressions in in-patients and in patients presenting with resistant depression in an open-label study. It was considered of interest to compare, under double-blind, the efficacy of venlafaxine (200 to 300 mg/day) and that of paroxetine (30 to 40 mg/day) (for 6 weeks) in 123 patients presenting with major depression resistant to two correctly conducted antidepressant treatments in the course of an episode of depression of duration not exceeding 8 months. The patients were required not to present with organic disease, particularly endocrine disease. After 28 days of treatment, half of the patients receiving venlafaxine and one third of the patients receiving paroxetine showed a 50% reduction in their total score on the Hamilton scale. In addition, the percentage of patients presenting with remission was significantly higher in the group receiving venlafaxine (42%) compared to that receiving paroxetine (20%). These results require confirmation over the long term and in other forms of resistant depression.

SCHIZOPHRENIA: The long-standing dopaminergic hypothesis is based on well-established findings, mainly related to a dysfunction of the mesolimbic C2 and D3 receptors, negative signs of prefrontal hypodopaminergia concerning the D2 and D4 receptors. Immune disorders are also involved as well as a possible neurodevelopmental component. Finally genetic factors play an important role.Three monoaminergic systems appear to be implicated: the catecholaminergic, serotaminergic and homovanilic systems. It is not known whether the disorder of the serotaminergic system results from pre-existing fragilization or a symptom-related modification.According to the chronobiology hypothesis, certain biological rhythms (cortisol, temperature, perhaps melatonin) are desynchronized, a disequilibrium which disappears after cure. The fragilization hypothesis is based on the progressive development of a stress-related pathological organization in the hippocampo-hypothalamo-adrenal axis.The development of new psychotropes remains a challenge to meet the unsatisfied demands in psychiatrics. Drugs with rapid action and minimal side effects are needed.

Behavioural modifications induced by psychotropic drugs results primarily from their pharmacological properties. According to classification of psychotropic drugs, sedative compounds contrast with psychostimulating medications. Behavioural effects of psychotropic drugs depend on dosing, subject's status (patient or healthy volunteer), acute or chronic administration, and environment. Some psychotropic compounds, particularly sedative drugs, decrease the level of mental alertness and cognitive functioning. But those deleterious effects tend to disappear during the course of a repeated administration. Some psychotropic drugs, especially benzodiazepines, induce a tolerance effect, eventually a psychic or a physiological dependence state evidenced by withdrawal reactions. Such similar dependence processes have been reported with other psychotropic drugs. Forensic problems have been attributed to some psychotropic compounds, like benzodiazepines: paradoxical aggressive reactions, psychomotor automatism; Psychotropic drugs usually can confer a positive effect on behaviour owing to their therapeutic action by the way of improving the illness and consequently the life of patients in the cases of depression, anxiety or schizophrenia.

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.

The prevalence rate of transsexualism varies from 1 to 50,000, to 1 to 100,000. Although it remains an infrequent affliction, transsexualism generates usually major suffering and may be responsible of many complications like suicide, self-mutilations, affective disorders and social disabilities. Since the first descriptions of Esquirol in the nineteenth, the medical community has always been questioned on medical, legal, social or ethical aspects of transsexualism. The aetiology of the trouble is still unknown. In the absence of biological marker, the syndrome of transsexualism can be defined only with clinical criteria. The main differential diagnosis are sexual ambiguities and psychotic disorders. For the specialists, satisfying the patients demand of a surgical and social reassignment still remains the only way to improve their clinical condition and avoid the onset of many dramatic complications. Without any treatment, the evolution of the trouble is chronic, without remission. Longitudinal studies of transsexual patients with a five year follow-up demonstrated subjective improvement in two thirds of the patients and don't find either higher rates of suicides nor psychotic decompensations after surgery and hormonotherapy. Clinical and neuropsychological studies of sexually differentiated cognitive abilities of transsexual patients, before and after hormonotherapy, could allow us in improving the understanding of sexual differences of the brain.