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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.

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.

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.

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.

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 (

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.

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.

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.

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.