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International audience; Poor medication adherence remains frequent in schizophrenia. The present study examined the efficacy of two month-long pilot interventions using the Medication Event Monitoring System (MEMS®). Thirty-three outpatients at high risk for relapse were randomized to receive a smartphone-based intervention, a nurse-based intervention, or treatment as usual. All patients then used the MEMS® to objectively measure medication adherence over six months. No differences were observed in adherence measures or relapse rates across the three groups. When using electronic medication monitoring as an objective measure of adherence, easily-implemented interventions may not significantly improve adherence in patients at high risk for relapse.

Medication non adherence in schizophrenia is a major cause of relapse and hospitalization and remains for clinicians an important challenge. This study investigates the associations between insight, therapeutic alliance, perceived trauma related to psychiatric treatment and medication adherence in patients with schizophrenia. In this multicenter study, 72 patients were assessed regarding symptomatology, self-reported adherence with medication, insight, medication side-effects, therapeutic alliance and perceived trauma related to psychiatric treatment. Structural Equation Modeling (SEM) was used to test predicted paths among these variables. The data fit a model in which medication adherence was directly predicted by insight, therapeutic alliance and perceived trauma related to psychiatric treatment. Perceived trauma moderates the role of insight on medication adherence. The final model showed good fit, based on four reliable indices. Greater adherence was correlated with higher insight, higher therapeutic alliance and lower perceived trauma. These three variables appear to be important determinants of patient's medication adherence. Medication adherence could be enhanced by reducing perceived trauma and by increasing insight. The need for mental health providers to acknowledge patients' potentially traumatic experience with psychiatric treatment and the need to encourage greater involvement in care are discussed.

Medication Event Monitoring System (MEMS®) is considered the gold standard for the evaluation of medication adherence, yet few studies have applied this method, especially over long periods of time.To investigate medication adherence patterns in a sample of post-discharge patients with schizophrenia monitored with MEMS caps during a six-month period.Adherence to antipsychotics was prospectively investigated using MEMS among 68 patients with schizophrenia. Treatment initiation, implementation or whether or not the patient takes his dosing regimen as prescribed, persistence or the length of time between initiation and discontinuation, and treatment discontinuation were used to describe adherence. Persistence over time was described using Kaplan-Meier curves.After discharge 16% of the patients never initiated treatment. On average 37.3% of patients adhered to treatment in the first 6months. However, a strong decrease in adherence was observed over time (p0.0001), primarily due by treatment non-persistence. Only half of the patients were persistent at 6weeks, persistence further dropped to 19.0% after 6months. Among persistent patients, implementation was consistent over time with 87.8% of patients taking their medication as prescribed on any given day.Dosing profile analysis provides further evidence for the magnitude of non-adherence with antipsychotic prescriptions among post-discharge patients with schizophrenia. Using the high precision of MEMS®, dosing profiles may provide a better understanding of non-adherence patterns and help clinicians determine optimal individualized strategies.

Background Long-acting injectable (LAI) atypical antipsychotics are associated with improved adherence and reduced relapse rates in schizophrenia but reminder-based interventions may further improve outcomes. Objectives To assess an institutional medication adherence program's (IMAP) effectiveness on adherence and psychiatric hospitalizations among schizophrenia patients taking risperidone LAI (RLAI). Methods Between 2009 and 2010, we recruited patients meeting DSM-IV criteria for schizophrenia treated with RLAI receiving outpatient care from psychiatric centres in France. The IMAP consisted of calling patients 48 hours prior to their scheduled RLAI injections and within 3 days of a missed appointment. Centres applying the IMAP to ≥50% of scheduled patient injections were deemed compliant. Patients were followed up to one year for adherence (≥80% of scheduled RLAI injections received within 5 days of the scheduled date) and psychiatric hospitalizations. Results Among 506 patients recruited from 36 centres, the hospitalization rate was 32.5 per 100 person-years. 15 centres treating 243 patients were IMAP compliant and 21 centres treating 263 patients were not. IMAP compliance was associated with lower psychiatric hospitalization rates (crude RR: 0.64 [95% CI: 0.44-0.93]; adjusted RR: 0.78 [95% CI: 0.47-1.27]). Nearly 75% of patients were adherent to RLAI. While patient adherence had little impact on hospitalization rates (adjusted RR: 0.92 [95% CI: 0.59-1.44]), IMAP compliance was more effective among non-adherent (adjusted RR: 0.45 [95% CI: 0.16-1.28]) than adherent (adjusted RR: 0.88 [95% CI: 0.51-1.53]) patients. Conclusions IMAPs may improve patient adherence and reduce psychiatric hospitalizations, particularly among patients with difficulties adhering to LAI antipsychotics.

The origins of poor insight in schizophrenia are still unclear. We contrasted the changes in clinical insight, basic cognitive processes, autobiographical memory and metacognition in 63 outpatients with schizophrenia pseudo-randomly assigned to one of three cognitive remediation groups: one targeting basic cognitive processes (RECOS), a second autobiographical memory (REMAu), and a third metacognitive deficits (MBCT). Three dimensions of insight (awareness of: mental illness, benefit of treatment, psychosocial consequences) improved after treatment, regardless of the group. In addition, the REMAu and MBCT showed an improvement on other dimensions of insight (symptomatic awareness and symptomatic attribution, respectively). Poor insight and its improvement after treatment were best predicted by a combination of basic cognitive, autobiographical and metacognitive measures. This study supports a multidimensional conception of insight and recommends the combination of remediation therapies to improve clinical insight in schizophrenia.

Anomalous activations of the prefrontal cortex (PFC) and posterior cerebral areas have been reported in previous studies of working memory in schizophrenia. Several interpretations have been reported: e.g., neural inefficiency, the use of different strategies and differences in the functional organization of the cerebral cortex. To better understand these abnormal activations, we investigated the cerebral bases of a working memory component process, namely refreshing (i.e., thinking briefly of a just-activated representation). Fifteen patients with schizophrenia and 15 control subjects participated in this functional magnetic resonance imaging (fMRI) study. Participants were told that whenever they saw a word on the screen, they had to read it silently to themselves (read and repeat conditions), and when they saw a dot, they had to think of the just-previous word (refresh condition). The refresh condition (in comparison with the read condition) was associated with significantly increased activation in the left inferior frontal gyrus and significantly decreased connectivity within the prefrontal cortex and between the prefrontal and parietal cortices in patients with schizophrenia in comparison with control subjects. These results suggest that prefrontal dysfunctions in schizophrenia might be related to a defective ability to initiate (rather than to execute) specific cognitive processes.

La premiere strategie therapeutique recommandee est soit l’initiation en monotherapie d’un antipsychotique de seconde generation (AP2G) soit l’association d’un AP2G avec le lithium (Li) ou un anticonvulsivant (AC). Si vous decidez l’utilisation d’une monotherapie par AP2G : un delai avant reevaluation de 3 semaines vous est conseille ; • en cas d’absence d’efficacite, on vous recommande de • verifier l’observance, d’optimiser la posologie, et enfin d’associer un second SH.

Dans le cadre de la creation de referentiels pouvant servir de base aux recommandations de pratiques professionnelles et/ou a une demarche d’amelioration de la qualite des soins, l’Association francaise de Psychiatrie Biologique et Neuropsychopharmacologique (AfPBN) au travers de sa section de psychopharmacologie, propose l’elaboration de Recommandations formalisees d’Experts (RfE) sur le depistage et la prise en charge du trouble bipolaire. Les RfE font partie des trois grands types de methodes participatives permettant d’aboutir a un « referentiel » les deux autres etant les Conferences de consensus (CC) et les Recommandations pour la pratique clinique (RPC). Cette demarche de constitution de Recommandations a l’origine s’est appliquee lorsque les donnees scientifiques etaient peu nombreuses, voire absentes, d’un niveau de preuve peu eleve ou conflictuel, ou lorsque les elements de reponse sont indirects ou traites seulement partiellement dans les differents travaux disponibles. Dans ce cas, le terme « accord professionnel fort » etait utilise sans reelle quantification du niveau ni du degre de convergence des avis. Or, les sujets concernes correspondent souvent a des domaines pour lesquels les pratiques s’averent peu ou mal codifiees, voire d’une grande variabilite. En raison meme de l’absence de donnees scientifiques indiscutables, une prise de position a un temps donne par un panel d’experts sur le depistage et la prise en charge du trouble bipolaire apparait donc necessaire. D’ou l’interet de mettre en place des Recommandations formalisees d’Experts elaborees dans une demarche methodologique definie, s’appuyant sur la pratique quotidienne, comprenant des « experts » de modalites d’exercice variees et reconnus pour leur expertise sur le trouble bipolaire. La demarche globale dans sa finalite s’organise en trois phases, la premiere concernant l’elaboration de la RfE, la deuxieme son applicabilite et la troisieme sa bonne diffusion.

OBJECTIVE: This study evaluates the efficacy of agomelatine, the first antidepressant to be an agonist at MT(1)/MT(2) receptors and an antagonist at 5-HT(2C) receptors, versus sertraline with regard to the amplitude of the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder (MDD). METHOD: Outpatients with DSM-IV-TR-defined MDD received either agomelatine 25 to 50 mg (n = 154) or sertraline 50 to 100 mg (n = 159) during a 6-week, randomized, double-blind treatment period. The study was conducted from 2005 to 2006. The main outcome measure was the relative amplitude of the individual rest-activity cycles, expressed as change from baseline to week 6 and collected from continuous records using wrist actigraphy and sleep logs. Secondary outcome measures were sleep efficiency and sleep latency, both derived from actigraphy, and efficacy on depression symptoms (17-Item Hamilton Depression Rating Scale total score and Clinical Global Impressions scale scores) and anxiety symptoms (Hamilton Anxiety Rating Scale total score and subscores). RESULTS: A significant difference in favor of agomelatine compared to sertraline on the relative amplitude of the circadian rest-activity cycle was observed at the end of the first week (P = .01). In parallel, a significant improvement of sleep latency (P

Objective: Morningness is a stable characteristic of individuals, related to impulsivity and novelty seeking. The evening orientation is a risk factor for psychiatric conditions such as depression and personality disorders. The authors hypothesized that adults suspected of having ADHD are more evening oriented than adults without ADHD. Method: Exploratory factor analyses were performed on the polychoric correlation matrices of the full Adult Self-Report Scale for ADHD (ASRS) and the Composite Scale of Morningness (CSM). Results: As expected, two factors for the ASRS—Inattention and Impulsivity— Hyperactivity—and three factors for the CSM were retrieved. All three CSM factors correlated negatively with ASRS Inattention, none with ASRS Impulsivity—Hyperactivity. Conclusion: Inattention is more strongly related to eveningness than is Impulsivity—Hyperactivity, and therefore eveningness may constitute an endophenotype of the predominantly inattentive subtype of ADHD. These findings need to be replicated in a patient population with a standardized assessment of sleep quality.

Background The quality of the relationship between patient and therapist can be considered a cornerstone of psychiatric practice. Nonadherence is one of the leading problems affecting antipsychotic effectiveness in schizophrenic patients and represents a poor prognostic factor for schizophrenia. Among the factors influencing adherence, the clinician's style of communication and the therapeutic relationship (TR) are recognized as key points. The measures of TR have been broadly explored in psychotherapy process but have received little attention in the treatment of severe mental illness in the context of routine mental health. Our objective was to build a self-rating scale easy to use in clinical psychiatric practice to assess TR, including drug-taking aspects and the relationship with the clinician on a day-to-day basis. A secondary objective was to assess the scale's validity and the association between TR and adherence. Methods The study was conducted with 92 consenting inpatients who met specified criteria for schizophrenia and schizoaffective disorders ( Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ). Assessments of TR were obtained by the 4-Point ordinal Alliance Self-report and an 8-cm visual analog scale completed by the patient 1 week before discharge, after the remission of acute symptomatology. Adherence behavior was estimated with a new valid and reliable questionnaire called the Medication Adherence Rating Scale . Factor analysis was performed. Results Internal consistency was assessed by calculating Cronbach α , which revealed a highly satisfactory value ( α = .91). After oblique rotation was run, 2 understandable factors were extracted that we termed empathy experienced and psychoeducation . Conclusions Therapeutic relationship with the clinician can be considered a prerequisite for positive treatment course and outcome. The detection of subpopulations characterized by determinants of poor TR could be the first step toward improving schizophrenia prognosis linked to poor adherence.

There is wide acknowledgement that apathy is an important behavioural syndrome in Alzheimer’s disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy, and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and that will be easily applied in practice and research settings. Meeting these needs is the focus of the task force work reported here.The task force includes members of the Association Française de Psychiatrie Biologique, the European Psychiatric Association, the European Alzheimer’s Disease Consortium and experts from Europe, Australia and North America. An advanced draft was discussed at the consensus meeting (during the EPA conference in April 7th 2008) and a final agreement reached concerning operational definitions and hierarchy of the criteria.Apathy is defined as a disorder of motivation that persists over time and should meet the following requirements. Firstly, the core feature of apathy, diminished motivation, must be present for at least four weeks; secondly two of the three dimensions of apathy (reduced goal-directed behaviour, goal-directed cognitive activity, and emotions) must also be present; thirdly there should be identifiable functional impairments attributable to the apathy. Finally, exclusion criteria are specified to exclude symptoms and states that mimic apathy.

Patients with bipolar disorders (BPD) display high rates of comorbidities, especially substance abuse (20-40%) and attention deficit/hyperactivity disorder (ADHD) (6%-20%). However, there are virtually no data evaluating the role of current ADHD on the global functioning of patients with BPD. The recent literature suggests that impairments in quality of life are a key prognostic feature for predicting the long course of BPD. The aim of this study was to investigate the intrinsic impact of adult ADHD and substance abuse in patients with BPD on levels of social adaptation, functioning and vitality. Seventy-three outpatients with BPD I or II, all euthymic and being treated with mood stabilizers, were evaluated using the following measures: 1) the Diagnostic Interview of Genetics Study for DSM-IV criteria; 2) the ADHD Self-Report Scale (ASRS) (screening of adult ADHD); 3) measures of quality of life: social adaptation (Social Adjustment Scale Self-Report (SAS-SR)), well-being (Short Form 36 (SF-36) Health Survey), and the Brief Psychiatric Rating Scale. In this clinical sample, 30% met the ADHD criteria and 22% were substance abusers. The results showed that the presence of ADHD in BPD patients significantly predicted a low social functioning and adaptation by comparison with BPD patients without ADHD. By contrast, we failed to detect a significant impact of substance abuse on those functional outcomes. This is the first step towards improved screening for comorbidities and an understanding of their crucial role in the prognosis of the disorder, as well as in defining new multilevel therapeutic strategies.

La cyamemazine (Tercian®), neuroleptique le plus prescrit en France, l’est souvent en association avec d’autres antipsychotiques. L’interet que lui portent les cliniciens resulte de son activite anxiolytique remarquable et de son impact extrapyramidal limite. Des etudes neuropharmacologiques recentes ont mis en evidence sa puissante activite antagoniste sur les recepteurs serotoninergiques, activite qui pourrait expliquer, au moins en partie, son profil therapeutique. Les travaux effectues sur les recepteurs monoaminergiques humains exprimes sur des membranes de cellules transfectees, ceux effectues sur des organes isoles ou chez l’animal entier mettent tous en evidence une plus forte affinite de la cyamemazine pour les recepteurs serotoninergiques 5HT2A que pour les recepteurs dopaminergiques D2. Les mesures effectuees en imagerie chez l’homme retrouvent cette caracteristique. La fixation moderee sur les recepteurs D2 semble ainsi expliquer la faible incidence des effets extrapyramidaux lors des traitements par la cyamemazine. Sa forte fixation sur les recepteurs 5HT2 pourrait par ailleurs participer a son activite anxiolytique constatee en clinique humaine.

Resume Le trouble explosif intermittent (TEI) a ete identifie et repertorie en tant qu’entite autonome en 1980 dans la 3e edition du Manuel diagnostique et statistique des trouble mentaux (DSM). Malgre l’evolution de ses criteres cliniques au cours des deux dernieres decennies, certaines ambiguites persistent. En effet, l’interet d’eliminer ce diagnostic en presence d’une personnalite limite ou antisociale est remis en question. D’une part, la recurrence de comportements violents n’est pas toujours retrouvee chez ces personnalites. D’autre part, accepter le diagnostic associe de TEI permet de distinguer un sous-groupe de patients auquel il est possible de proposer un traitement plus adapte. Par ailleurs, certains criteres pourraient etre inclus parmi ceux necessaires au diagnostic. Il s’agit des signes psychiques et physiques de tension precedant immediatement l’acces de violence, et des sentiments de soulagement, voire de plaisir, a l’accomplissement de celui-ci. Ces symptomes sont frequemment rapportes par les patients ayant un TEI. Contrairement aux autres troubles du controle des impulsions, de tels symptomes ne figurent pas dans les criteres diagnostiques actuels du TEI. Ce trouble debute generalement au cours de l’adolescence et se retrouve plus frequemment chez les garcons. En raison des restrictions dues aux criteres hierarchiques du diagnostic, sa prevalence est consideree comme faible. Cependant, les comportements violents dans la population des malades mentaux sont frequents. La comorbidite du TEI a ete etudiee en negligeant ces restrictions. Une forte comorbidite avec les troubles de l’humeur est notee. Certains constats sont en faveur de l’hypothese selon laquelle le TEI ferait partie du spectre des troubles de l’humeur. Les autres troubles psychiatriques frequemment associes au TEI sont les troubles de la personnalite du cluster B et les troubles anxieux. Sur le plan etiopathogenique, les etudes sont rares. Cependant, certains resultats sont interessants a considerer. Ils portent sur une dysregulation du systeme serotoninergique et sur l’existence de lesions cerebrales minimes. Ces constatations ont largement oriente le choix des medicaments proposes aux patients ayant un TEI. Il s’agit essentiellement des inhibiteurs de la recapture de la serotonine (IRS), des thymoregulateurs et des beta-bloquants. Les arguments en faveur de l’efficacite de ces classes therapeutiques dans le traitement du TEI reposent pour l’essentiel sur des rapports de cas. De veritables essais therapeutiques sont necessaires afin de confirmer l’interet de ces molecules dans cette indication. Le diagnostic de TEI permet de quantifier et de categoriser les comportements violents dans la pathologie psychiatrique. Malgre la frequence de ces comportements et leur gravite, ils restent peu etudies en comparaison des symptomes thymiques ou anxieux. L’evolution des criteres de diagnostic du TEI devrait permettre aux cliniciens de mieux reperer ces comportements et de favoriser leur prise en charge.

One of the most recurrent criticisms formulated against Gray’s Reinforcement Sensitivity Theory is the lack of a sound structural model of the postulated dimensions, i.e. ‘Anxiety’ and ‘Impulsivity’ reflecting the behavioural inhibition and approach systems, respectively. Although valuable efforts have been made and several instruments been published in the past fifteen years, most of the publications conclude that refinements are needed. This is the first paper that presents the psychometric properties of the French version of Carver and White’s BIS/BAS scales and Torrubia et al.’s SPSRQ in a sample of students. The reliabilities and the pattern of scores intercorrelations are in line with the literature. For both instruments, exploratory factor analyses reveal a two-order structure with higher-order factors representing BIS-SP and BAS-SR. The structure of the primary factors is discussed with regards to studies in non-French speaking samples. These findings add to the cross-cultural data for the BIS/BAS scales and the SPSRQ, which is an underestimated aspect of scales’ development.

Philip Gorwood,1,2 Guillaume Vaiva,3 Emmanuelle Corruble,4 Pierre-Michel Llorca,5 Franck J Baylé,1,2 Philippe Courtet61Centre Hospitalier Sainte-Anne (CMME), Paris, France; 2Centre of Psychiatry and Neuroscience, INSERM U894, University Paris-Descartes, Paris, France; 3Pôle de Psychiatrie, CHRU de Lille, Hôpital Michel-Fontan, Université Lille-Nord de France, Lille, France; 4Psychiatry Department of Bicêtre, University Hospital, INSERM U669, Paris XI University, Le Kremlin Bicêtre, France; 5CHU Clermont-Ferrand, Clermont Université, Université d’Auvergne, Clermont-Ferrand, France; 6Department of Emergency Psychiatry, CHU Montpellier, Montpellier, FranceIntroduction: Baseline values and early changes of emotional reactivity, cognitive speed, psychomotor function, motivation, and sensory perception have not been studied to any extent in unipolar depression, although they could help to characterize different dimensions of illness that are harder to capture by clinicians, give new insights on how patients improve, and offer new early clinical markers for later treatment response.Methods: About 1,565 adult outpatients with major depressive disorder receiving agomelatine completed the clinician-rated 16-item quick inventory of depressive symptoms, Clinical Global Impression, and Multidimensional Assessment of Thymic States (MAThyS) rating scales at inclusion, Week 2 and Week 6. The MAThyS includes a 20-item self-rated visual analog scale (from inhibition [0] to activation [10], with [5] representing the usual state) leading to five a priori dimensions (emotional reactivity, cognitive speed, psychomotor function, motivation, and sensory perception).Results: All MAThyS dimension scores increased from inclusion to Week 2 and from inclusion to Week 6 (P

Franck Jean Baylé,1 Arnaud Tessier,2,3 Sophie Bouju,4 David Misdrahi2,3 1Sainte-Anne Hospital (SHU), Paris V-Descartes University, Paris, 2Hôpital Charles Perrens, Pôle de Psychiatrie Adulte, 3CNRS UMR 5287-INCIA, Bordeaux University, Bordeaux, 4Janssen-Cilag France, Issy Les Moulineaux, Paris, France Background: Maintaining antipsychotic therapy in psychosis is important in preventing relapse. Long-acting depot preparations can prevent covert non-adherence and thus potentially contribute to better patient outcomes. In this observational survey the main objective is to evaluate medication adherence and its determinants for oral treatment in a large sample of patients with psychosis.Methods: In this cross-sectional survey medication adherence for oral treatment was assessed by patients using the patient-rated Medication Adherence Questionnaire (MAQ). Data were collected by physicians on patients with a recent acute psychotic episode before switching to long-acting injectable risperidone. Other evaluations included disease severity (Clinical Global Impression – Severity), patients’ insight (Positive and Negative Syndrome Scale item G12), treatment acceptance (clinician-rated Compliance Rating Scale), and therapeutic alliance (patient-rated 4-Point ordinal Alliance Scale).Results: A total of 399 psychiatrists enrolled 1,887 patients (mean age 36.8±11.9 years; 61.6% had schizophrenia). Adherence to oral medication was “low” in 53.2% of patients, “medium” in 29.5%, and “high” in 17.3%. Of patients with psychiatrist-rated active acceptance of treatment, 70% had “medium” or “high” MAQ scores (P

AIn this work, the authors have analysed the principal studies on the interest in the use of benzodiazepines in schizophrenia. The first double-controlled study concerning this question was conducted in 1961. The results of the first studies are criticisable due to the variability of the diagnostic and clinical assessment criteria, as well as to the divergences between the different conclusions. Through this review of literature, the authors wish to clarify the questions and hypothesis raised specify certain therapeutic strategies. MECHANISM OF GABA-ERGIC TREATMENTS: The analysis of the principle works on this question provides evidence on the use of benzodiazepines in schizophrenia. By fixing on their receptors, benzodiazepines facilitate GABA-ergic transmission. GABA is an inhibitor neurotransmitter. The GABA stimulation induced by benzodiazepines may be at the origin of a reduction of the pre-synaptic release of dopamine in the mesolimbic region. The GABA stimulation may also delay the post-synaptic adaptation of the dopaminergic neurons to neuroleptics. This phenomenon may enhance the activity of neuroleptics in resistant schizophrenia. Benzodiazepines would also have an effect on the mesoprefrontocortical regions where neuroleptics may be less efficient. It is interesting to note that this cerebral region is particularly sensitive to stress. This effect of benzodiazepines on the mesoprefrontocortical region might explain a preferentially beneficial effect in patients who have radiographic signs consistent with prefroncortical atrophy, although this observation remains preliminary. BENZODIAZEPINES IN MONOTHERAPY: In monotherapy their action on productive and deficient psychotic symptoms is greatly discussed and not very convincing. The main studies in the use of benzodiazepines alone ) are heterogeneous for their diagnosis criteria, their methodology and their results. The conclusions of the publications are not totally clear, and different points are to be criticized: heterogeneity of assessment criteria, heterogeneity and variability of methodology, use of non standardized scales, most of the studies are open studies, variability of benzodiazepines dose. BENZODIAZEPINES IN ASSOCIATION WITH NEUROLEPTICS: In few controlled studies, most authors have underlined ) the advantage of the association of benzodiazepines with neuroleptics. This association may act either on positive symptoms (hallucinations, delusions) or on negative symptoms. The latent period and the length of the effect of benzodiazepines in the treatment of psychotic patients remain unclear. According to certain studies, the therapeutic effect may appear in a short time, and then disappear within the fourth week. The association of benzodiazepines with neuroleptics is particularly helpful for patients with great anxiety, whether they have neuroleptic intolerance or not. There is no robust convergence about the type of benzodiazepines and their optimal dose in the treatment of schizophrenia. Their use may permit a reduction in the neuroleptic dose. They could increase the plasma concentration of neuroleptics and they might act on the mesoprefrontocortical regions where there are fewer dopaminergic auto receptors. BENZODIAZEPINES AND ANXIETY IN SCHIZOPHRENIA: States of anxiety, and in particular panic disorders that would participate in the exacerbation of psychotic symptoms, would benefit from the use of benzodiazepines. Anxiety can be considered as a major symptom of schizophrenia: insecure feelings and impressions of threatening events are frequent during schizophrenia. Interpretations or brutal hallucinations can lead to the feeling of imminent catastrophe or anxiety. Nevertheless, anxious phenomenons are under-estimated for many reasons: on the one hand, positive symptoms may hide anxiety, and on the other, the symptoms that are observed in patients treated with neuroleptics are often attributed to the neuroleptic side effects rather than linked to anxiety. Benzodiazepines and catatonia - Lorazepam has demonstrated its efficacy on catatonia. This effect seems to be specific of small doses of lorazepam (

L’objectif principal de l’etude observationnelle SCOPE etait d’observer l’evolution sur deux ans d’une cohorte de 833 patients schizophrenes ou schizoaffectifs traites pour un episode psychotique aigu. Une analyse en cluster a ete realisee a l’inclusion et a permis de mettre en evidence, a partir des parametres de sexe, âge, diagnostic, duree de la maladie et scores a la CGI gravite et a l’echelle PANSS, l’existence de cinq clusters. Ceux-ci soulignent l’importance des differences liees au sexe et a l’âge dans la schizophrenie ainsi que l’heterogeneite du trouble schizoaffectif, avec des patients proches de la schizophrenie, d’autres du trouble bipolaire. Le taux de rechute dans la population totale a ete de 32,7% a 2 ans. Les donnees relatives aux taux de rechute observes dans chaque cluster sont compatibles avec les typologies de patients mises en evidence. L’utilite de cette methode d’analyse en psychiatrie est particulierement soulignee par cette etude. The main objective of the SCOPE observational study was to follow-up a cohort of 833 schizophrenic or schizoaffective patients treated for an acute state over a two-year period. A cluster analysis using the Ward method was performed at baseline using gender, age, diagnosis, length of illness, CGI-S and PANSS scores to determine clusters. Five clusters have been identified that underline the importance of gender differences in schizophrenia on one hand, and on the other, the heterogeneity of schizoaffective disorders which include patients near to schizophrenia, while other patients seem to belong to the bipolar spectrum. The two-year relapse rate in the total population was 32.7%. Data concerning relapse rates within each cluster are in line with the patient’s typology. Our results lend support to the validity of this method of analysis in psychiatry.

The Composite Scale of Morningness (CSM) is a psychometrically sound instrument available in several languages, including French, aimed at arranging individuals along a continuum from high "eveningness" to high "morningness." On the other hand, impulsivity is involved in many personality disorders and is thought to be orthogonal to venturesomeness, which can be seen as a component of the broader construct of sensation seeking. We hypothesized that evening-type subjects would be more impulsive than morning-types. Self-administered questionnaires were distributed to students, and only complete forms were analyzed (194 males and 358 females). A four-way analysis of covariance showed significant effects of age, gender and impulsivity, but not venturesomeness, on morningness in the sense of a higher degree of eveningness in more impulsive subjects. In addition, the correlation coefficients in both genders were similar to those reported in smaller samples. Our findings deserve further interest because, regardless of gender, they suggest a possible physiopathological approach to impulsivity that may be accessible by circadian interventions such as midday bright light exposure or pharmacological treatments.

For schizophrenic disorders, the clinical conception of "acute state" is widely used in clinical settings to assess the effectiveness of therapeutic programs as well as epidemiological studies. Schizophrenic-specific symptomatology modification, need for hospitalization, significant change in care, disturbances in social behavior or suicide attempts were all used to define acute schizophrenic state. The decision to hospitalize is frequently used to define acute state but refers to multiple factors such as mood disorder, suicide attempts, drug abuse or social and environmental problems. Indeed, several and distinct definitions in a criteria basis form are available but no one has reached consensus. Because recognition of acute schizophrenic state remains based on the subjective clinician's advice, epidemiological and therapeutic studies fail in validity and reliability. The aim of the study was to evaluate how a population of French psychiatrists define criteria and therapeutic targets of acute schizophrenic state in their clinical practice. Psychiatrists filled out a self administered interview. At the time the interview was given, clinicians were notified that they were participating in a clinical consensus survey about schizophrenia. Six major indicators for acute state definition based on the literature data were proposed: general schizophrenic symptomatology modification (depression, anxiety, agitation, impulsivity/aggressiveness), specific schizophrenic symptomatology modification (positive symptoms, negative symptoms, disorganization), need for hospitalization, significant change in care, disturbance in social behavior and lastly, suicidal behavior. Minimal duration (1.2 or 4 weeks) of general and specific schizophrenic symptomatology modification required to define acute state were evaluated. The booklet included the 30 PANSS symptoms listed with their definitions. Among this symptom list, clinicians were instructed to select the ten criteria which they estimated best defined the acute state, followed by the ten most important target symptoms to be treated. Out of 2,369 questionnaires, 1,584 were collected on time (66.9%). Among the six majors indicators proposed to define acute state 75% of psychiatrists considered 1 to 3 criteria. Three were more frequently rated, including core schizophrenic symptomatology disturbance (68.4%), general schizophrenic symptomatology disturbance (68.0%) and suicidal behavior (64.9%). The other criteria were rated as follows: need for hospitalization (26.8%), significant change in care (18.3%), and disturbance in social behavior (29.1%). For 53.2% of psychiatrists the definition of acute state requires the presence of specific schizophrenic symptomatology for a minimal duration of one week. Two weeks with general symptomatology was required for 45.5% of psychiatrists to define acute state. Symptoms more often rated within the four first choices for acute state definition included delusions, conceptual disorganization, hallucinatory behavior and excitement. Except for grandiosity, all the PANSS positive subscale items were chosen to be included in the definition (delusions, conceptual disorganization, hallucinatory behavior, excitement, suspiciousness/persecution and hostility). Four items, including anxiety, depression, uncontrolled hostility, inner tension from the general psychopathology subscale were chosen as part of the ten most important criteria to define acute state. On the PANSS negative subscale (blunted affect, emotional withdrawal, poor relationships, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity/flow of conversation and stereotyped thinking), no item was rated to be included in the acute state definition. The highest rated symptoms among the four first choices for treatment included delusions, hallucinatory behavior, excitement and anxiety. The ten most important criteria for treatment were the same as for acute state definition with differences in frequency. Excited state, depression and suspiciousness/persecution were more rated for treatment than definition whereas delusion, hostility and conceptual disorganization were less rated as treatment target than definition criteria. In clinical practice, recognition of acute schizophrenic state is underscored by the association of specific schizophrenic symptomatology (positive symptoms, negative symptoms, disorganization) and general symptomatology (impulsivity/aggressiveness, anxiety, depression, agitation) of schizophrenia. For most clinicians, acute state definition requires specific symptom for a minimum of one week and other non-specific indicators such as suicidal behaviour have to be taken into account. With regard to PANSS criteria, most positive schizophrenic symptoms and some general schizophrenic symptoms are necessary for definition and designated as treatment priorities. Negative symptoms were not taken into account. Hallucinatory behavior is the first symptom rated in definition and is considered by psychiatrists as the absolute therapeutic priority. This survey could be a first step in the construction of an operational and consensual definition. This definition is strongly needed as a valid measurement in therapeutic and epidemiological outcome studies, which remain at least partly based on clinician subjective judgment.

ResumenObjetivo.Los investigadores intentaron explicar el solapamiento entre la ansiedad y la depresión proponiendo que algunos elementos de los cuestionarios autoadministrados estaban mal seleccionados y que ambos constructos se deben considerar más bien como muldimensionales. Así, planteamos la hipótesis de que el Inventario de Ansiedad como Rasgo (TAI) de Spielberger incluye elementos relacionados con la depresión.Método.Una muestra no clínica de 193 sujetos rellenó el TAI y la Escala Hospitalaria de Ansiedad y Depresión. Se postularon factores a partir del contenido de los elementos y se sometieron a análisis factorial confirmatorio (AFC).Resultados.Encontramos cinco factores: un factor de ansiedad de 10 elementos que contenía tres factores; un factor de falta de éxi-to que contenía cuatro elementos correlacionado con el factor de anhedonia de la HADS, y un factor de felicidad de seis elementos.Conclusión.El TAI incluye medidas de ansiedad, depresión y bienestar. Por consiguiente, el solapamiento con otras medidas de depresión puede derivar de la selección de los elementos. Este trabajo aguarda replicación en muestras normales y patológicas independientes.

Background: Depression, especially severe depression, is strongly associated with suicidality. Impulsivity is one of the main dimensions of suicidality. The objective of this study was to assess the structure of impulsivity in severe depression and its relationships to suicide attempts. Methods: 127 depressed in-patients were assessed at admission and after 4 weeks of treatment for depression and impulsivity with the Impulsivity Rating Scale (IRS) and the Impulse Control Scale (ICS) or the Baratt Impulsivity Scale (BIS). Results: Three dimensions of impulsivity were evidenced in these severely depressed patients, i.e., behavioral loss of control, nonplanning and cognitive. These three dimensions are state dependent. Recent suicide attempts in severe depression are related to loss of control and cognitive impulsivity but not to nonplanning. IRS ad ICS may assess primarily behavioral impulsivity, i.e., loss of control and nonplanning, whereas BIS may assess primarily cognitive impulsivity. Conclusions: In the future, these three dimensions should be correlated to biological and genetic markers of impulsivity [serotonergic (5-HT) system] and prospective studies should assess the predictive value of the three dimensions of impulsivity in the occurrence of suicide attempts in depressed patients.

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. © 2003 Wiley-Liss, Inc.

The low incidence of extrapyramidal effects with atypical neuroleptics has been ascribed to their 5-HT(2A)- and 5-HT(2C)-serotonin receptor antagonistic properties. On the other hand, the acute increase in striatal dopamine release by submaximal dopamine D(2) autoreceptor blockade can be respectively reduced and increased by 5-HT(2A)- and 5-HT(2C)-antagonists. Cyamemazine is a neuroleptic D(2)- and 5-HT(2A)-receptor antagonist, with small antagonistic activity at 5-HT(2C) receptors and low incidence of extrapyramidal side effects. Therefore, submaximal cyamemazine was tested in rats for its acute action on the extracellular concentrations of dopamine and dopamine metabolites (DOPAC: 3,4,dihydroxyphenylacetic acid and HVA: 4-hydroxy-3-methoxy-phenyl-acetic acid) in the corpus striatum. The serotonin metabolite 5-HIAA (5-hydroxy-indole-acetic acid) was measured in parallel. Rats prepared for microdialysis (striatum) were intraperitoneally given cyamemazine 1 mg/kg, 5 mg/kg or vehicle ( n=4 in each group). Dopamine, DOPAC, HVA and 5-HIAA concentrations in perfusates under basal conditions and after stimulation by high K(+) were measured by HPLC coupled to electrochemical detection. Cyamemazine 1 mg/kg significantly reduced extracellular concentrations of basal dopamine (-77%), DOPAC (-54%), HVA (-54%) and 5-HIAA (-65%). No such effects were seen with the dose of cyamemazine 5 mg/kg or for K(+)-evoked dopamine release. In conclusion, submaximal cyamemazine can acutely reduce basal dopamine release and metabolism in the rat striatum. Such unusual action can be explained by the original pharmacological profile of cyamemazine (potent D(2)- and 5-HT(2A)-antagonist, with small antagonistic activity at 5-HT(2C) receptors). Further experiments are required to explain the low incidence of extrapyramidal side actions with cyamemazine.

Animal studies indicate that the anxiolytic properties of the antipsychotic agent cyamemazine may result from blockade of serotonin 5-HT(2C) receptors and to a lesser extent from blockade of serotonin 5-HT(3) receptors. Here, we used human recombinant receptors to determine the relative affinity of cyamemazine for serotonin and dopamine receptor subtypes. In addition, cyamemazine was tested in other brain receptor types and subtypes which are considered to mediate central nervous systems effects of drugs. Hence, cyamemazine affinity was determined in human recombinant receptors expressed in CHO cells (hD(2), hD(3), and hD(4.4) receptors, h5-HT(1A), h5-HT(2A), h5-HT(2C), and h5-HT(7), and hM(1), hM(2), hM(3), hM(4), and hM(5) receptors), L-cells (hD(1) receptor), and HEK-293 cells (h5-HT(3) receptors) or natively present in N1E-115 cells (5-HT(3) receptors) or in rat cerebral cortex (non-specific alpha(1)- and alpha(2)-adrenoceptors, GABA(A) and GABA(B) receptors, H(3) histamine receptors), and guinea-pig cerebellum (H(1) central and H(2) histamine receptors) membranes. Similarly to atypical antipsychotics, cyamemazine exhibited high affinity for: (i) h5-HT(2A) receptors (K(i)=1.5+/-0.7 nM, mean+/-SEM, N=3) and this was four times higher than for hD(2) receptors (K(i)=5.8+/-0.8 nM), (ii) h5-HT(2C) receptors (K(i)=11.8+/-2.2nM), and (iii) 5-HT(7) receptors (K(i)=22 nM). Conversely, cyamemazine exhibited very low affinity for h5-HT(3) receptors (K(i)=2.9+/-0.4 microM). In conclusion, similarly to atypical antipsychotic agents, cyamemazine, possesses high affinity for h5-HT(2A), h5-HT(2C), and h5-HT(7) receptors, a feature which can explain its low propensity to cause extrapyramidal adverse reactions in clinical practice. The high affinity for h5-HT(2C) receptors, but not for h5-HT(3) receptors, can account for the anxiolytic activity of cyamemazine in human subjects.

Objective: Impulsivity has been found to be an important trait of personality, whose consequences are not always negative although available questionnaires focused on its ‘dysfunctional’ aspect. Method: Dickman's Functional and Dysfunctional Impulsivity questionnaire has been translated into French, and filled out by students. The tetrachoric correlation matrices were factor analysed. Results: The psychometric properties are very close to those of the English version, and we recovered both factors in males and females. The factor similarities between the genders (in our sample) and between the languages (English vs. French) are very good. The Dysfunctional scale is correlated with the Motor Impulsivity subscale of the Barratt Impulsiveness Scale, and both scales are grossly independent from Spielberger's Trait-Anxiety Inventory. Conclusion: Our results support a two-factor solution similar to the English one. Nevertheless, the validity of the functional factor remains to be investigated in further studies.

The aim of this study is to circumscribe the cognitive deficits according to schizophrenic syndromes in a population of sub-acute untreated patients. We have studied the cross-sectional correlation between cognitive deficits and schizophrenic symptoms, in a group of 24 untreated patients (including 17 neuroleptic-naive patients) with recent onset of the disease. A task of alertness, a working memory (WM) test (including two levels of difficulty) and an abbreviated version of the Wisconsin Card Sorting Test (WCST) were selected. WM deficits and poor performance on the WCST were highly correlated with disorganized symptoms, modestly with the positive syndrome and not with the negative syndrome. Thus, disorganized symptoms, more than any other, appear to be related to the impairment of executive function and WM in recent onset unmedicated patients with schizophrenia.

Resume Alors que le traitement medicamenteux de la depression peut sembler simplifie par la mise a disposition de nouveaux antidepresseurs, certains tableaux imposent des modalites particulieres de prise en charge. Ces tableaux graves de depression sont reunis sous le terme de « difficile ». Cette notion qui souligne la gravite potentielle du trouble comprend celles de severite et de resistance. Elle recouvre egalement un certain nombre de tableaux cliniques marques par des symptomes particuliers comme l’anxiete, l’agitation ou de nature psychotique. Avec le risque suicidaire, ces symptomes conduisent le plus souvent a adopter une strategie medicamenteuse specifique, generalement une association de neuroleptiques. Les etudes cliniques et therapeutiques sont peu nombreuses. Les donnees reposent en grande partie sur l’experience clinique des auteurs et le consensus d’experts.

Compelling evidence that tobacco-smoking is a form of drug addiction exists. The aim of this study is to determine the following: (1) prevalence of tobacco-smoking and of nicotine dependence in French psychiatric patients; (2) rates and patterns of tobacco smoking and of nicotine dependence according to diagnosis; (3) relationship between current smoking status and antipsychotic medications; and (4) relationship between cigarette smoking and neurological side effects induced by neuroleptics. A population of 711 psychiatric in- and outpatients was assessed using: (1) a detailed smoking self-questionnaire for smoking history and nicotine dependence; and (2) a questionnaire for staff covering treatments and DSMIII-R diagnoses. Data were analyzed using chi2 analysis of variance (ANOVA) tests (one factor) for quantitative comparisons between groups of patients, and analysis of covariance (ANCOVA) test with age covariate was performed for age-dependent variables. Prevalence of smoking in the population of psychiatric patients was significantly higher than in the French general population. Diagnoses among current smokers were mainly substance-related disorder and schizophrenia. The authors established correlations between prevalence of smoking and age, sex, marital and socioeconomic status, alcohol use, coffee consumption and other psychoactive substance use or abuse. The authors did not find relationship between smoking prevalence and institutionalization. Neuroleptic neurological side effects were significantly fewer among smokers compared to nonsmokers. However, the rate of smokers was significantly higher in psychiatric patients receiving neuroleptic drugs. Nicotine abuse in psychiatric patients, and especially in schizophrenic patients, could support the hypothesis that smoking is consistent with self-medication.

International audience; Anxiety in schizophrenia possesses specific features and is difficult to assess because no specific evaluating tool is currently available. The aim of this study was to develop and validate a hetero-assessment-based scale to specifically measure anxiety in schizophrenia. A literature review and a survey among psychiatrists allowed the selection of 29 items from 4 previous scales evaluating anxiety. Factor analysis allowed building up a final 22-item composite scale of anxiety evaluation in schizophrenia (SAES), which was then validated in 147 schizophrenic patients. One hundred and forty-seven (147) schizophrenic patients (70.8 % male, mean age = 36.9 years) were included in the study. Principal component analysis of the SAES revealed three factors, namely ''expressed and perceived anxiety,'' ''somatic anxiety,'' and ''anxiety and environment''. All total and factor scores of the SAES were significantly correlated (p \ .001) with total and factor scores of the original scales. Finally, the SAES showed good inter-rater reliability [intra-class correlation coefficient (ICC) = .82]. In conclusion, a specific tool for evaluating anxiety in schizophrenia (SAES) was developed and validated in a sample of schizophrenic patients. The SAES can be useful to investigate clinical, psychopatho-logical, and therapeutic aspects of anxiety in schizophrenia.

SummarySince reports have underscored that panic attacks (PA) may be an identifiable state occurring in schizophrenia, we studied the symptomatology of PA in a group of schizophrenic patients. Of 40 patients (21 males and 19 females) attending a clinic for maintenance therapy of schizophrenia, 19 (36.8%) had a lifetime history of PA. Seven among those 19 patients (36.8%) had or had had spontaneous panic attacks, not related to phobic fears or delusional fears, and for the 12 remaining patients, the PA were related to paranoid ideas. Moreover, the paranoid subtype of schizophrenia tends to be more often associated with a history of panic attack than other subtypes of schizophrenia (52.6% vs 23.8%; χ2 = 3.5, P = .06). It seems that there are at least two types of PA in schizophrenic patients. The first one could be independent from the psychotic feature, with no psychopathological link. The second kind of PA could be directly related to a schizophrenic disorder, and found in patients with the paranoid subtype.

Même si le concept d'impulsivité demeure sujet à controverses, de nombreuses d'approches ont été tentées pour mesurer cette dimension. Seules les mesures psychométriques possèdent une bonne validité consensuelle et semblent aujourd'hui opérationnelles en routine. Barratt a élaboré la plus ancienne échelle mesurant spécifiquement l'impulsivité. De nombreuses révisions ont permis d'en améliorer la validité. Nous avons traduit en français sans difficultés majeures la dixième version validée de cette échelle (Barratt Impulsivity Scale [BIS-10]) et exploré sa structure factorielle. Nous l'avons assortie d'un autoquestionnaire évaluant l'anxiété. Nous avons recruté au sein de la population générale 280 sujets âgés en moyenne de 36,9 ans (18 à 79 ans). L'âge des sujets exerce une influence faible mais significative sur les scores d'impulsivité. L'analyse en composantes principales (ACP) montre que les 9 premiers facteurs expliquent 55,6% de la variance. Une nouvelle ACP sur ces facteurs de premier ordre permet d'extraire 3 facteurs de second ordre. Ceux-ci correspondent bien au regroupement proposé par Barratt. Nos résultats confortent ceux de l'analyse initiale de l'échelle qui n 'ont pu être reproduits par la suite. Il s'agit, à notre connaissance, de la première traduction française d'un instrument qui évalue spécifiquement l'impulsivité et dont la structure factorielle a été étudiée dans la population générale.

Poor adherence is one of the leading problems affecting the effectiveness of treatment in schizophrenia. It is an identified factor for relapse and hospitalizations with major social and economic consequences. Various determinants of poor adherence have been identified but few studies investigate the role of therapeutic alliance on medication adherence in routine mental healthcare.To investigate links between therapeutic alliance insight and medication adherence in routine care and community psychiatry.In this cross-sectional study, 38 inpatients that met ICD-10 criteria for schizophrenia or schizoaffective disorder were recruited and independently interviewed just before discharge. Various rating scales were used: the self-reported 4-Point ordinal Alliance Scale (4PAS), the Medication Adherence Rating Scale (MARS) and the Scale to assess Unawareness of Mental Disorder (SUMD). In addition, we investigated the relationships between medication adherence and clinical variables through uni- and multivariate analysis.Therapeutic alliance was significantly correlated with adherence (r = 0.663, P0.0001) and insight (r =-0.664, P0.0001). Poor adherence was associated in patients with substance or alcohol use disorders (5.4 vs. 2.9, P = 0.0075, t = 2.83). No significant difference was found between the demographic characteristics of the sample, the characteristics of the treatments and adherence.A weak therapeutic alliance and low insight are associated with poor adherence in patients with schizophrenia or schizoaffective disorder who were hospitalized. Specific psycho-educational programs to improve therapeutic alliance and insight should be implemented to achieve better therapeutic adherence and outcome.

OBJECTIVE: The authors compared impulsivity, sensation seeking, and anhedonia in a group of schizophrenic patients with and without lifetime substance abuse or dependence. METHOD: Patients (N=100) with schizophrenia or schizoaffective disorder (per DSM-III-R criteria) were assessed with the Composite International Diagnostic Interview’s section on psychoactive substance use disorder, the Positive and Negative Syndrome Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale. RESULTS: The mean scores for impulsivity and sensation seeking were higher in the group with substance abuse (N=41) than in the group without substance abuse (N=59). No significant difference between groups was found regarding physical anhedonia. CONCLUSIONS: As in the general population, high levels of impulsivity and sensation seeking are associated with substance abuse in patients with schizophrenia.

Premorbid functioning may be associated with treatment response, but this is confounded by a lack of prospective longitudinal data and controls for medication compliance. This study tested the hypothesis that good premorbid functioning will be associated with better antipsychotic treatment response after controlling for drug adherence by using a long-acting injectable antipsychotic. This was a 6-month, open label, multicenter, phase IV trial in recent-onset schizophrenia treated with flexible doses of risperidone long-acting injectable (25-50 mg every 14 days). Premorbid functioning was assessed with the Premorbid Adjustment Scale (PAS)-Structured Interview; efficacy was evaluated with clinician-rated Positive and Negative Syndrome Scale, Clinical Global Impression scale of Severity of Illness, Clinical Global Impression scale of Change, Global Assessment of Functioning Scale, and trial participant completed SF-36. Analyses controlled for baseline scores and demo-graphics. With the use of a priori PAS scoring criteria, the participants' premorbid functioning was categorized as stable-good (n = 142), stable-poor (n = 116), and deteriorating (n = 36). At baseline, the stable-good group had the best functioning on most efficacy measures. All groups showed significant improvement on efficacy measures with treatment. Improvement was significantly higher for the stable-good group. The PAS global assessment of highest level of functioning scale (excellent, n = 75; good, n = 117; fair, n = 78; and poor, n = 31) showed a strong association with baseline functioning and improvement and had a significant linear association with meeting Remission in Schizophrenia Working Group symptom criteria at baseline (P = 0.003) and attained and sustained remission for 3 months during study (47.7%, 49.3%, 29.6%, and 22.2%; P = 0.006). Good premorbid functioning corresponds with better treatment response in recent-onset psychosis as captured on both clinician and patient-reported measures.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects up to 4% of the adults in the general population. The Utah criteria were devised in the 1970s to help a retrospective diagnosis of ADHD during childhood, a necessary but not sufficient condition for diagnosing ADHD at adulthood. A sample of 466 adults was collected from a referral center and a large university. We investigated the psychometric properties (reliability and factor structure) of the original WURS-25 and the WURS-K, two shortened versions of the Wender Utah Rating Scale. These scales have similar psychometric properties; both have a 3-factor structure with only the first two factors highly and positively correlated. The third factor in the WURS-K, antisocial behavior, is less specific to the construct of ADHD than the third factor in the WURS-25, mood/self-esteem. The 18-item Adult ADHD Self-Rating Scale (ASRS) was used as a screening tool for actual ADHD. The composite total scores and the factorial scores correlated moderately with ASRS total and subscores. Research is warranted to assess the cutoff scores against a diagnosis of ADHD using a structured interview.

Recombinant human liver microsomal enzymes of the cytochrome P450 family (CYP1A2, CYP2A6, CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1) were used to determine the metabolic fate of the antipsychotic anxiolytic agent cyamemazine. An LC/MS-MS tandem methodology was developed specifically for identifying the presence of cyamemazine and its metabolites in reaction media. All P450 enzymes investigated, with the exception of CYP2A6 and CYP2E1, degraded cyamemazine, albeit to a different extent, with CYP1A2, CYP2C8 and CYP2C19 being the most efficient (>80%). However, in microsomes prepared from native human hepatocytes, only relatively specific competitors (inhibitors and/or substrates) of CYP1A2, CYP2C8, CYP2C9 and CYP3A4 reduced notably the degradation cyamemazine. The main routes of cyamemazine biotransformation are N-mono-demethylation (CYP1A2, CYP3A4 and CYP2C8) and mono-oxidation (either S-oxidized or hydroxylated derivatives which could not be discriminated because characterized by the same mass value) by CYP1A2 and CYP2C9. Secondary metabolic routes yields N,N-di-demethylated and N-demethylated mono-oxidized products. Thus, under in vitro conditions, cyamemazine is extensively degraded by at least four distinct P450 enzymes, into two primary hydrophilic metabolites. These results suggest that cyamemazine detoxification process is unlikely to be significantly impaired by co-administration of therapeutic agents that are substrates of the CYP metabolic system.

Although impulsivity is recognised as a major psychopathological feature, its cognitive correlates remain controversial. We evaluated readiness to act induced by a warning signal and attentional engagement in healthy impulsive participants.People with high impulsivity scores (HI) and low impulsivity (LI) scores on Barratt's Impulsivity Scale (BIS) were selected among 1250 students from top and bottom deciles. Subjects with personal or family of lifetime Axis I disorders were excluded. Motor preparation was evaluated by a Choice Reaction Time task (CRT) with a randomly presented warning signal with a delay before target of 500 ms or 2000 ms depending on the trial block. Attentional engagement and maintenance of fixation was evaluated by a Cued Target Detection task (CTD) comparing cued (valid, invalid, or double cue) and uncued trials and contrasting fixation offset (gap) or maintenance (overlap) conditions.HI, but not LI participants had a shortened reaction time in the 2000 ms condition of CRT with warning signal, indicating a persistent readiness to act. In contrast to LI, HI showed a decreased reinforcement of attention in the overlap condition of CTD with a hyperreactivity to all types of visual stimuli.Impulsivity per se appears to be associated with hyperreactivity to warning or cue signals and on inability to maintain attentional fixity.

Comorbidity is very frequent in bipolar disorders. The most frequently psychiatric disorders associated with bipolar disorders are substance use disorders (particularly alcohol abuse) and anxiety disorders. Obsessive-compulsive disorder, impulse control disorders, personality disorders and eating disorders co-occur also with bipolar disorder. Comorbidity complicates the diagnosis and the treatment of bipolar disorder and worsen the prognosis. For every bipolar patient, it is necessary to search for a comorbid psychiatric disorder, and vice-versa. There is a noticeable paucity of controlled studies to guide selection of the most effective treatment approches for these patients. The expert consensus guidelines about treatment of bipolar disorder propose divalproex as first-line treatment when bipolar disorder co-occurres with substance abuse, panic disorder or posttraumatic stress disorder.

Cyamemazine (Tercian) is an antipsychotic drug with anxiolytic properties. Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT(2A) receptors, which was fourfold higher than its affinity for dopamine D(2) receptors (Hameg et al. 2003).The aim of this study is to confirm these previous data in vivo in patients treated with clinically relevant doses of Tercian.Eight patients received 37.5, 75, 150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D(2) and serotonin 5-HT(2A) receptor occupancies (RO) were assessed at steady-state plasma levels of cyamemazine with positron emission tomography (PET), using [(11)C]raclopride and [(11)C]N-methyl-spiperone, respectively. The effective plasma level of the drug leading to 50% of receptor occupancy was estimated by fitting RO with plasma levels of cyamemazine at the time of the PET scan.Cyamemazine induced near saturation of 5-HT(2A) receptors (RO=62.1-98.2%) in the frontal cortex even at low plasma levels of the drug. On the contrary, occupancy of striatal D(2) receptors increased with plasma levels, and no saturation was obtained even at high plasma levels (RO=25.2-74.9%). The effective plasma level of cyamemazine leading to 50% of D(2) receptor occupancy was fourfold higher than that for 5-HT(2A) receptors. Accordingly, individual 5-HT(2A)/D(2) RO ratios ranged from 1.26 to 2.68. No patients presented relevant increased prolactin levels, and only mild extrapyramidal side effects were noticed on Simpson and Angus Scale.This in vivo binding study conducted in patients confirms previous in vitro findings indicating that cyamemazine has a higher affinity for serotonin 5-HT(2A) receptors compared to dopamine D(2) receptors. In the dose range 37.5-300 mg, levels of dopamine D(2) occupancy remained below the level for motor side effects observed with typical antipsychotics and is likely to explain the low propensity of the drug to induce extrapyramidal side effects.