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Background Myocardial ischemia is a major cause of death in patients with renal dysfunction. In order to identify a key metabolite which may protect cardiac function following renal injury, we have recently performed a metabolomics profiling analysis of LV lysates and plasma samples derived from animals that underwent an acute kidney injury (AKI) 1 or 7 days earlier, versus sham-operated controls. The analysis revealed that the kynurenic acid (kynurenate, KYNA) metabolite levels are highly elevated in all tested experimental samples relative to control. Purpose We wished to analyze whether KYNA may protect cardiomyocytes' survival and cardiac function upon an ischemic event and if so, to characterize whether the protecting effect may be linked to better preservation of the cardiac mitochondria. Methods Cellular viability of H9C2 rat cardiac myoblasts grown under normoxic or anoxic conditions with or without KYNA was determined by flow cytometry following Annexin-PI staining. The mitochondrial structure of the cells was determined by live cell staining with green (FITC) and deep red (Cy5) mito-tracker dyes. The potential effect of the metabolite on cardiac function following acute MI was tested in a murine model by echocardiography followed by histological staining of the cardiac sections with Picro Sirius Red. Results KYNA given at 10 mM concentration hardly affected the viability of H9C2 grown under normoxia, however the metabolite rescued the viability of the anoxic cells by 63% and largely improved their mitochondrial structure. Moreover, KYNA diluted in the drinking water of post-MI animals (250mg/ml), highly enhanced their cardiac recovery compared to untreated-animals as determined by echocardiography and collagen staining. Conclusions 1. KYNA may represent a key metabolite absorbed by the heart following AKI. 2. KYNA can enhance cardiac cell viability following an ischemic event both in vitro and in vivo in a mechanism which is mediated, at least in part, by protection of the cardiac mitochondria. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Weizmann Institute-Tel-Aviv Sourasky Medical Center joint research grant KYNA's protection of cardiac cells

International audience; To compare clinical traits of suicidal vulnerability among in-patients with suicidal behavior disorder (SBD) with and without borderline personality disorder (BPD).Method: we recruited adult patients with SBD, consecutively and voluntarily hospitalized in a specialized unit for affective disorders and suicidal behavior between July and October 2016. Ninety-two inpatients having attempted suicide within the past 2 years were divided into two subgroups according to the presence or absence of BPD. Clinical vulnerability traits for suicidal behavior were assessed.Results: Half of the patients with SBD also had BPD. Patients with BPD were nine times more likely to be major suicide repeaters compared to those without. They were also more likely to display clinical and psychological vulnerability traits for suicidal behavior, even after considering potential confounders. Emotional dysregulation, shame-proneness, impulsiveness, preoccupied attachment pattern, and childhood trauma were high in both groups, but significantly increased in those with (vs. without) BPD status. Psychological traits remained stable in SBD-BPD patients, regardless of the time since the last suicide attempt (i.e. SBD in recent vs. early remission).Conclusions: Clinical and psychological traits associated with suicidal vulnerability are present in all SBD patients compared to non-suicidal populations, but comorbidity with BPD is associated with particularly high scores. BPD could be considered as a specifier for SBD diagnoses.

Resume L’etat mixte est une modalite d’expression frequente des troubles de l’humeur, dont la description clinique a ete abordee depuis plusieurs siecles mais n’a ete finement exploree que depuis quelques annees. Plusieurs auteurs proposent de redefinirses criteres diagnostiques afinde mener une strategie therapeutique adaptee. Les recommandations actuelles, proposent de traiter la depression mixte comme un etat mixte quelle que soit la polarite dominante, et par consequent selon les regles de prise en charge therapeutique de l’etat maniaque. Ainsi les traitements thymoregulateurs et antipsychotiques sont indiques et ont fait la preuve de leur efficacite. Le lithium, longtemps controverse, presente un interet therapeutique certain, notamment dans la prevention du risque suicidaire. La composante depressive de l’etat mixte, meme si elle est marquee, ne doit pas faire l’objet d’une prescription d’antidepresseurs, au risque d’aggraver les composantes d’irritabilite, d’impulsivite et d’augmenter le risque de passage a l’acte suicidaire. Par ailleurs, l’electroconvulsivotherapie represente une veritable alternative therapeutique ; les psychotherapies ont leur place dans la prevention de la rechute et dans le cadre de la psychoeducation, mais pas en phase aigue. Enfin, une evaluation precise et une prise en charge adaptee du risque suicidaire doivent etre une preoccupation constante du clinicien.

Resume L’etat mixte est un definosologique et diagnostique. La litterature a ce sujet est cependant relativement pauvre. Le traitement de l’etat mixte est diffi cile, la co- morbidite est frequente, le risque suicidaire est eleve et l’evolution est souvent pejorative. La defi nition de l’episode mixte du DSM- IV TR (« juxtaposition d’un episode maniaque et d’un episode depressif ») a ete elargie dans le DSM- 5 et les symptomes mixtes sont apprehendes sous forme de « caracteristiques specifi ques mixtes » ; defi nition qui peut s’appliquer aux episodes maniaques ou depressifs. La classifi cation de l’etat mixte comme defi ni dans le DSM- 5 est moins restrictive que celle du DSM- IV TR et demeure un defi methodologique et therapeutique. L’objectif de cet article est d’effectuer une revue de la litterature pour evaluer l’effi cacite des differentes molecules utilisees dans les etats mixtes. Les symptomes maniaques des episodes mixtes repondent bien aux antipsychotiques de seconde generation et au valproate. Il n’y a pas de difference d’effi cacite entre les differents antipsychotiques. En deuxieme intention, le lithium et la carbamazepine sont effi caces dans les etats mixtes en monotherapie mais aussi, en association avec un antipsychotique de seconde generation. L’association d’un antipsychotique avec un stabilisateur de l’humeur est effi cace dans l’etat mixte et c’est sur ce theme que les etudes ont ete les plus documentees.

Mixed states are complex manifestations of bipolar disorders. Pathophysiology of mixed states remains unclear. Several models have been proposed to understand the mechanisms underlying these mood states. These models describe mixed state either as a combinaison of depression and mania, as well as a transition between mania and depression, or mixed state as a severe type of depression or mania. Pathophysiological hypotheses involve temperaments or some personality disorders, psychiatric comorbidities as well as substance use disorders, or thyroid dysfunction. However, the formal demonstration of any specific genetic vulnerability to mixed state has not yet been provided.

Resume Les etats mixtes du DSM-IV sont devenus les manies et depressions mixtes du nouveau DSM-5. La principale nouveaute est l’apparition de neuf specifications, dont celle de mixite. Ces specifications non exclusives permettront de mieux isoler certaines categories cliniques, et ainsi de mieux y repondre sur le plan therapeutique. Une clinique dimensionnelle riche permet d’isoler un facteur de mixite, regulierement associe a un facteur anxieux et un facteur psychotique, qui sont deux autres de ces specifications. Ceci incite a la plus grande prudence dans l’etablissement d’un diagnostic, et a la plus grande vigilance dans la prise en charge de ces situations cliniques.

Resume Les perturbations du fonctionnement neurocognitif sont actuellement considerees comme un marqueur trait des troubles bipolaires et semblent presentes dans toutes les phases de la maladie. Les etudes, peu nombreuses, realisees au cours des phases thymiques (episodes depressifs, maniaques, hypomaniaques ou mixtes) montrent un fonctionnement neurocognitif qualitativement et/ou quantitativement different de la normothymie et de sujets controles sains. Nous avons cherche, au travers de ces etudes, a voir quelles sont les perturbations neurocognitives retrouvees dans les phases de manie pure et de manie mixte. Les resultats montrent qu’au cours d’un episode mixte, l’attention soutenue est significativement plus perturbee que dans la manie pure. En revanche, le pattern de reponse impulsif semble plutot caracteristique de la manie pure. Il est egalement retrouve une perturbation de la vitesse de traitement, des processus d’apprentissage et de memoire verbale et non verbale ainsi que du fonctionnement executif (fl exibilite cognitive, controle inhibiteur, raisonnement conceptuel, planification et resolution de probleme). Ce dernier domaine semble significativement plus perturbe dans la manie pure que dans la manie mixte.

Resume La position nosologique des etats mixtes a suivi le cours des modes classificatoires en psychiatrie, les etapes de l’invention de la clinique, des progres dans l’organisation des soins et notamment des decouvertes de la psychopharmacologie. La constatation clinique d’un melange de symptomes ressortant d’etats cliniques habituellement opposes est ancienne. Dans les annees 1970, une specification syndromique arretant les principales combinaisons symptomatiques de cet assortiment incongru ne parvenant pas a stabiliser ce concept nosologique, une criteriologie plus stricte etait proposee. S’averant trop restrictive, une ouverture dimensionnelle tente de repondre aux exigences d’une pragmatique de la nosologie validant l’utilite du systeme des classes. Cette alternance entre rigueur de la categorisation et retour vers une possibilite criteriologique plus souple temoigne de la recherche du plus juste equilibre entre nosologie et diagnostic. La defi nition des etats mixtes est mieux determinee par leur severite clinique et pronostique, leur gravite liee au risque de suicide, leur moindre reponse therapeutique, et l’importance de leurs comorbidites psychiatriques : anxiete, labilite affective emotionnelle, alcoolisation. Pour compenser l’insuffi sance des defi nitions categorielles et mieux rendre compte des problemes cliniques de terrain, les nouvelles definitions completent la criteriologie d’aspects dimensionnels, prenant notamment en compte le temperament.

Resume La notion d’etats mixtes est classiquement associee aux descriptions et aux categories nosologiques proposees par E. Kraepelin. Neanmoins, la presence simultanee de manifestations depressives et maniaques a pu etre decrite des l’Antiquite. L’association de ces manifestations cliniques a evidemment evolue au cours du temps, tant en termes de semiologie que de defi nition. Nous proposons ici de revenir sur quatre epoques majeures : auteurs grecs de l’Antiquite, psychiatrie prekraepelinienne (XVIIIe et XIXe siecles), apport de E. Kraepelin et enfi n approches plus contemporaines (XXe et XXIe siecles). Mais quelle que soit l’epoque consideree, deux perspectives tendent a se degager. Tout d’abord, on peut considerer les etats mixtes comme simple coincidence temporelle de symptomes, a la faveur d’un virage de l’humeur. Une seconde perspective consiste au contraire a apprehender les etats mixtes comme entite clinique autonome et stable. En temoignent les controverses psychopathologiques de la premiere partie du XXe siecle, mais aussi les modifi cations recentes proposees dans les systemes diagnostiques internationaux.

International audience; Objective The objectives are to determine the rate of potentially ă inappropriate psychotropic (PIP) prescription at discharge in the ă elderly psychiatric inpatients and to determine whether PIP is ă associated with lowered functioning outcomes. ă Methods Sociodemographic, clinical, and treatment data for all ă inpatients aged >= 65 years consecutively hospitalized during 1 year in ă 13 psychiatry departments was analyzed. PIP+/PIP- groups were defined ă according to the French-updated Beers criteria. Daily functioning was ă evaluated by the daily living (ADL) scale. Logistic regression analysis ă was used to estimate odds ratios for the association between PIP ă administration at discharge and respectively functioning and potential ă confounding factors. ă Results Data was obtained for 327 patients. Overall, 124 (37.9 %) ă patients were males, and the mean age was 73.9 years (SD=5.6); 163 ă (49.8%) patients were diagnosed with affective disorders and 89 ă (27.2%) with schizophrenia/schizotypal/delusional disorders. Overall, ă 249 (76.1 %) had one or more PIP medications, mainly anxiolytics (69.9 ă %) and hypnotics (17.2 %). In a multivariate analysis, PIP ă prescription at discharge has been associated with patient lowered ă personal care functioning, independently of age, gender, and psychiatric ă or somatic diagnoses (OR=0.88 (0.79-0.97, p=0.01). ă Conclusion In the current increasingly fragmented health care systems, ă special attention must be given to PIP prescription in older population ă suffering from psychiatric disorders. Using the Beers criteria, the ă present study demonstrates the high prevalence of PIP prescription, ă which concerns a large panel of drugs but mostly anxiolytics and ă hypnotics independently of psychiatric or somatic diagnoses and ă sociodemographic characteristics. Our study has demonstrated for the ă first time an association between PIP prescription and lowered patient ă functioning. Further longitudinal studies should confirm a potential ă causal relation.

Background and purpose The interictal electroencephalogram (EEG) has an important role in the classification and treatment of epilepsy. In busy EEG laboratories, valuable resources are used in order to comply with current recommendations regarding the length of EEG recordings. Our aim was to examine the time to first interictal epileptiform discharge (IED) in standard and sleep-deprived EEGs. Methods Standard and sleep-deprived EEG recordings with IEDs were retrospectively reviewed during a 2-year period. Bedside EEGs and long-term video-EEGs were excluded. IED latency according to EEG type, age group and inpatient/outpatient status was analyzed with the Kaplan−Meier estimator. Results The study group included 684 patients, 372 (54%) males, aged 0.2–89 years. Standard (n = 316) and sleep-deprived (n = 368) EEGs were performed in 245 inpatients and 439 outpatients. The EEG was requested in 96% of the inpatients following a seizure. Most IEDs were recorded whilst the patients were awake (43%) or drowsy (34%). Ninety percent of the IEDs were recorded within 18.5 min, earlier in standard (14.6 vs. 21.3 min) (P = 0.024) EEGs and in inpatients (14 vs. 21.3 min) (P = 0.002). IED latency was unaffected by age. Conclusions Electroencephalogram type and admission status may be used for individual determination of the duration of EEG recording. Reducing the duration of standard and sleep-deprived EEGs may be considered especially in inpatients.

Resume Objectif L’objectif de ce travail etait de decrire les proprietes psychometriques de l’echelle des activites de la vie quotidienne (AVQ). Methodes Tous les patients, quel que soit leur âge, des deux sexes, hospitalises dans une unite de prise en charge a temps-plein dans notre etablissement public de psychiatrie entre le 1 er janvier 2008 et le 30 juin 2008, ont ete inclus dans cette etude. Le recueil de l’âge, du sexe, du statut marital, du diagnostic, de l’echelle des AVQ et de l’echelle d’autonomie sociale (EAS) a permis de tester la validite, la fiabilite, la reproductibilite et la sensibilite au changement. Resultats L’AVQ a ete complete pour 1066 patients. L’analyse en composante principale a isole une structure a deux facteurs expliquant 82 % de la variance totale. La premiere dimension representait l’autonomie des soins personnels et la seconde dimension l’autonomie sociale. On notait l’existence d’un effet plancher pour la dimension 1, pour laquelle l’unidimensionnalite n’etait pas satisfaisante. Les deux dimensions montraient un alpha de Cronbach superieur a 0,70, attestant d’une coherence interne satisfaisante. On ne notait pas de correlation de la dimension 2 de l’AVQ avec les dimensions Gestion des ressources et Vie affective et Relations sociales de l’EAS. Les scores de l’AVQ etaient lies a l’âge et au genre, mais non au statut marital et au diagnostic. L’AVQ presentait une bonne reproductibilite mais ne detectait pas de sensibilite au changement. Conclusion Les proprietes de l’echelle AVQ apparaissent insuffisantes au regard de plusieurs aspects metrologiques. Cela peut remettre en cause une utilisation destinee soit a une gestion economique et administrative de la psychiatrie, soit a la prise en charge des patients. Des recherches ulterieures doivent etre menees pour confirmer ces resultats.

Objective: To quantify the factors associated with non-adherence to medication among stable patients suffering from schizophrenia in the context of universal access to care. Methods: This naturalistic, multicentric study was conducted in 15 French public hospitals in a region of south-eastern France during a 1 week period in 2008. All consecutive outpatients with stable schizophrenia were recruited. Adherence was assessed with the 10-item Drug Attitude Inventory (DAI). Measures included socio-demographic characteristics, clinical characteristics, insight using the Scale to assess Unawareness of Mental Disease (SUMD), and therapeutic alliance using the Patient Session Questionnaire (PSQ). Regression models were used to identify the risk factors associated with non-adherence. Results: The study included 291 patients, 30% of whom were considered to be non-adherent. Non-adherence increased with duration of untreated psychosis (DUP) (OR = 1.12, 95%CI = 1.03–1.22), lack of insight only for the dimension ‘effect of medication’ (OR = 3.23, 95%CI = 1.05–9.89), and a low level of therapeutic alliance (OR = 0.45, 95%CI = 0.32–0.64). Individuals prescribed atypical antipsychotic drugs were more likely to be adherent than those prescribed typical antipsychotics (OR = 0.37, 95%CI = 0.13–1.0). Conclusions: DUP, prescription of typical antipsychotics, therapeutic alliance and insight were the most important features associated with non-adherence. This study also suggests that economic factors such as the service delivery system should not be neglected in public strategies aimed at addressing problems of non-adherence in non-universal coverage health systems.

BackgroundElectronic medical records (EMR) are currently being implemented in psychiatric hospitals throughout Europe. The perceptions of health care professionals can contribute important information that may predict their acceptance of and desired mode of use for EMR, thus guiding EMR implementation.AimsTo develop a self-administered instrument designed to assess health care professionals’ satisfaction regarding EMR in a psychiatric hospital, based only on the professional point of view, according to the psychometric standards.MethodsThe development was supervised by a steering committee and undertaken by three standard steps. Item generation was derived from 115 face-to-face interviews with health care professionals in a French, public, psychiatric hospital. The item-reduction process resulted in a 25-item questionnaire. The validation process was based on construct validity, reliability and some aspects of external validity.ResultsThe final version of the questionnaire contained 25 items that described five dimensions, leading to a global score. The factor structure accounted for 72% of the total variance. Internal consistency was satisfactory (item-internal consistency over 0.40 and Cronbach's alpha coefficients ranged from 0.86 to 0.95). The scalability was satisfactory with INFIT statistics inside an acceptable range. Scores of dimensions were strongly positively correlated with visual analogue scale scores (all p < 0.001). External validity showed statistical associations between scores and age, gender, seniority in psychiatry and ward type. Participation rate was 66%.ConclusionThe availability of a reliable and valid questionnaire (professionals’ satisfaction questionnaire with electronic medical records [PSQ-EMR]) concerning health care professionals’ satisfaction regarding EMR in psychiatry, exclusively generated from interviews with health care professionals, enables legitimate feedback to be incorporated into EMR implementation in order to formulate a high-quality health care.

A literature search on the pharmacological treatment of acute bipolar mixed episodes in current guidelines shows that only seven of them address the acute management of mixed episodes as a separate condition, whereas the vast majority of these guidelines include the treatment of mixed episodes in the chapter of mania. As a general rule, most guidelines advise to stop antidepressant treatment and mention the superiority of valproate over lithium. Specific recommendations for the treatment of "mixed states" can be found in two guidelines, while specific recommendations for that of "mixed mania" are present in five of them. Recommendations for the treatment of "mixed depression" exist in only three guidelines. If some consensus may be found for the treatment of "mixed states" as a whole, recommendations for the treatment of "mixed mania" appear to be variable, whereas those for the treatment of "mixed depression" seem to be limited.

Resume Une revue de la litterature montre que les antipsychotiques d’action prolongee (APAP), souffrent d’un « probleme d’image » et sont souvent reserves aux patients non compliants manquant d’ insight . Une approche comprehensive n’assimile pas le manque d’ insight a l’anosognosie mais le relie a la perception par le patient du stigma attache a la maladie. Quel que soit le degre d’ insight , les patients rattachent leur espoir de mieux-etre a leur capacite d’autonomie. Beaucoup apprennent a connaitre la maladie par l’experience, ce qui fait de la relation patient–infirmier un facteur important de compliance. Lorsqu’on prend le temps d’etre attentif a son vecu, le patient reprend a son propre compte la routine de l’injection, comprise comme un moindre mal, necessaire au maintien de son autonomie. Les croyances negatives attachees au stigma sont plus reduites durant les premieres phases de la maladie. Ne faut-il pas reviser les indications des APAP en fonction de la lutte pour la norme (« agonomie ») qui caracterise le projet de vie des schizophrenes, en y incluant plus precocement les patients compliants tout en en excluant, contrairement a l’usage les patients « agonomiques purs », qui refusent en bloc stigma et traitement ?

C’est au psychiatre qu’incombe la responsabilite de l’information ; elle sera ensuite relayee par les infi rmiers, le medecin generaliste, le psychologue (lorsque le patient benefi cie d’une psychotherapie), et le travailleur social. Le psychiatre presente au patient sa maladie de facon simple et ce le plus tot possible [17], sans pour autant formuler un diagnostic precis, notamment au debut de la prise en charge. Avec l’accord du patient, il informe egalement l’entourage qui a ete souvent le premier a deceler les troubles, et a diriger le patient vers les soins. L’entourage, sollicite pour l’accompagnement au long cours du patient, est generalement tres curieux du diagnostic et du pronostic ; cependant il convient de temporiser, meme vis-a-vis des proches. Le psychiatre aide le patient a decrypter ses symptomes ; cela lui permet de justifi er l’instauration du traitement et de lui apprendre a reperer par la suite les signes d’une eventuelle rechute. Il informe sur la maladie, son histoire naturelle, son pronostic et l’ensemble des soins necessaires (traitements medicamenteux, strategies psychotherapeutiques et mesures psychosociales), en prenant en compte les principaux facteurs psychologiques, sociaux et educatifs de chaque patient. L’information porte donc sur l’ensemble des strategies ; l’abord medicamenteux Comment prescrire un APAP ?

Objective: This study was designed to analyze the language of patients with schizophrenia exhibiting negative symptoms during a 3-month period. Method: The computer-assisted ALCESTE method was used to simultaneously analyze the subjects' oral behaviour and speech patterns at various levels. Results: The tested subjects had very specific speech patterns. Most significantly, analysis of the underlying syntactic processes showed that the patients exhibited a sense of identity, however minimum, based on their own pathologies and on the surrounding world. In our previous study, no such characteristics were observed in the discourse of schizophrenia patients with delusions (exhibiting positive symptoms). This suggests that the minimum sense of identity that develops in patients with schizophrenia allows them to avoid positive symptoms. Conclusion: In studies of language production by subjects suffering from schizophrenia, it is necessary to distinguish between patients with positive symptoms and those with negative symptoms. The speech patterns of these 2 groups have to be analyzed separately, which has not been done previously, since the groups differ in too many respects.

Language, which is unique in each subject, can reflect how a patient copes with disease. The method ALCESTE used here made it possible at the same time to analyse the subject's verbal behavior and speech patterns at several levels. The present study was designed to analyse during a 3-mo. period the language production of subjects with paranoia exhibiting delusional disorder (nonbizarre delusions without any hallucination) of imaginative subtype. The subjects produced very specific speech without any semantic or syntactic impairment and disruption in language or thinking processes, but with a poverty of speech content. The main feature of the study was the analysis of the underlying syntactic processes showing that the tested patients presented a “hard” sense of identity: the patient found always a strong place for himself among the various types of discourse whatever their topics.

The nosological position of mixed states has followed the course of classifying methods in psychiatry, the steps of the invention of the clinic, progress in the organization of care, including the discoveries of psychopharmacology. The clinical observation of a mixture of symptoms emerging from usually opposite clinical conditions is classical. In the 70s, a syndromic specification fixed the main symptom combinations but that incongruous assortment failed to stabilize the nosological concept. Then stricter criteriology was proposed. To be too restrictive, a consensus operates a dimensional opening that attempts to meet the pragmatic requirements of nosology validating the usefulness of the class system. This alternation between rigor of categorization and return to a more flexible criteriological option reflects the search for the right balance between nosology and diagnosis. The definition of mixed states is best determined by their clinical and prognostic severity, related to the risk of suicide, their lower therapeutic response, the importance of their psychiatric comorbidities, anxiety, emotional lability, alcohol abuse. Trying to compensate for the lack of categorical definitions and better reflecting the clinical field problems, new definitions complement criteriology with dimensional aspects, particularly taking into account temperaments.

Mixed states are a frequent mood state characterized by the mixture of manic and depressive symptoms. Their clinical description has been studied for centuries but has known a renewal of interest recently. Several authors intend to redefine its diagnostic criteria to develop an appropriate therapeutic strategy. Current recommendations suggest to treat mixed depression as a mixed state whatever the dominant polarity is, and therefore according to the rules of therapeutic management of the manic state. Mood stabilizers and antipsychotic medications are indicated and have proven their effectiveness. Lithium, which was considered controversial, now appears to have some therapeutic value, especially in the prevention of suicidal behavior. The depressive component of mixed states, even pronounced, should not be an argument for a prescription of antidepressants, at the risk of aggravating clinical components such as irritability and impulsivity and increasing the danger of suicide attempt. Furthermore, electroconvulsivetherapy represents a real alternative ; psychotherapies have their place in relapse prevention and psychoeducation, but not during acute phases. Finally, an accurate assessment and appropriate management of suicide risk should be a constant concern for the clinicians.

The notion of mixed states is classically associated with descriptions and categories inherited from Kraepelin. However, simultaneous descriptions of depressive and manic manifestations can be traced back to ancient times. Semiology and definitions of these clinical associations have evolved across the times. We provide here a short insight on four distinct periods: Greek authors from ancient times, pre-Kraepelinian psychiatry (18th and 19th centuries), Kraepelin's conceptualization, and contemporary psychiatry (20th and 21st centuries).

A literature search on the pharmacological treatment of acute bipolar mixed episodes in current guidelines shows that only seven of them address the acute management of mixed episodes as a separate condition, whereas the vast majority of these guidelines include the treatment of mixed episodes in the chapter of mania. As a general rule, most guidelines advise to stop antidepressant treatment and mention the superiority of valproate over lithium. Specific recommendations for the treatment of "mixed states" can be found in two guidelines, while specific recommendations for that of "mixed mania" are present in five of them. Recommendations for the treatment of "mixed depression" exist in only three guidelines. If some consensus may be found for the treatment of "mixed states" as a whole, recommendations for the treatment of "mixed mania" appear to be variable, whereas those for the treatment of "mixed depression" seem to be limited.

Neurocognitive dysfunction is increasingly recognized as a prominent feature of bipolar disorder. Cognitive function seems to be impaired across different states of bipolar illness. Nervertheless, research that studies neuropsychological functioning in acute phases is scarce. Acutely ill patients have shown dysfunctions in several cognitive areas. We reviewed the literature on neuropsychological studies of acute phases to highlight neurocognitive deficits in mixed and pure mania. The results show dysfunctions in sustained attention that are significantly more important in mixed mania rather than in pure mania. Impulsive pattern of responding seems to characterize pure manic state. We also found impairments in processing speed, verbal and spatial learning/memory and executive functions, including cognitive flexibility, inhibitory control, conceptual reasoning, planning and problem solving. Disturbance in executive functioning seems to be more important in pure mania rather than mixed mania.

DSM-IV mixed states have become the mixed mania and mixed depression in the new DSM-5. One noticeable point is the introduction of nine cations, among which the "with mixed features" specification. These non exclusive specifications may contribute to a more precise identification of mixed clinical pictures, and therefore to offer a more efficient therapeutic answer. Different dimensional approaches are widely documented. They allow the isolation of a mixed factor which is clinically associated with two other specifications: anxious distress and psychotic features. These severity markers may encourage clinicians to be alert about the risk of misdiagnosis, and cautious in the management of these clinical situations.

Mixed states present nosologic and diagnostic challenges with a relative paucity of evidence to guide treatment. Mixed bipolar states are difficult to treat and are associated with a high neuropsychiatric morbidity, a high risk of suicide and a poor outcome. In DSM- 5, the definition of mixed episode has been removed (in DSM- IV TR: "juxtaposed full manic and depressive episodes"). Mixed symptoms are captured under a broader concept called "mixed features" that is applied to mania and depression. The classification of mixed states as defined in DSM- 5 is less restrictive than in DSM- IV TR and challenges us at methodological and therapeutic levels.The aim of this paper was to conduct an overview of the literature to ascertain the efficacy of pharmacotherapy of mixed states.A systematic review of the literature was conducted using PubMed.Manic symptoms of mixed episodes seem to show a good response to second generation antipsychotics and to divalproate. There is no evidence of differential efficacy for second generation of antipsychotics (SGAs). Lithium and carbamazepine may be effective in mixed states in monotherapy and perhaps benefit in combination with SGAs as second line. Combination pharmacological treatment of SGAs and moodstabilizers are common in mixed states. This pattern has the best literature evidence.There is a few evidence to help us to choose the right treatment for patients with mixed state. In light with the DSM 5, more drugs specifically designed to treat mixed state are needed.

The dopamine D3 receptor gene is of potential interest in the physiopathology of affective disorder because of its expression pattern in brain structures controlling various aspects of behaviour, cognition and emotions. Moreover, it encodes for a receptor protein that is a target for psychotropic drugs, which turn out to be efficient in the treatment of this disorder. Two polymorphisms have been described at this locus (the Bal I and the Msp I Restriction Fragment Length Polymorphisms) that are useful in genetic studies. We therefore researched these polymorphisms in 60 patients suffering from bipolar affective disorder who were compared with 60 healthy volunteers. No statistical difference was observed between the whole patient sample versus the controls. However, one subgroup [homozygous for the (2-2) Bal I polymorphism] exhibits a characteristic clinical pattern consisting of: manic monopolar form of bipolar disorder, low age of onset and initiation by an acute delusional episode. A gender distribution difference for the Bal I polymorphism (chi 2 = 6.61, degrees of freedom = 1, P = 0.01) was then noted, the bipolar females being preferentially heterozygous, and the males homozygous. These results could involve the dopamine D3 receptor locus as a minor effect gene in the manic depression condition.

Objective: Progress in the science of data analysis and computer technology has led to the development of advanced methods for investigating structure discourse in the psychiatric field, where language constitutes a useful investigative and therapeutic tool. The purpose of this study was to present and use a computer-assisted method of discourse analysis (Alceste-software) to analyse the schizophrenic subject's oral contributions regularly collected for 3 months. Method: The method used consisted of modelling the main word distribution in spoken recordings pooled together and identifying the repetitive language patterns most frequently used by the speaker. Results: Four main kinds of discourse emerged from the pool of schizophrenic's speech samples, on specific topics without any lack of ability to organize the material, but the technique analysis showed that the main kinds of discourse were interspersed with unexpected ‘language satellites’ consisting of a secondary short and specific discourse which was also well planned but had no relevance to the main discourse making for a lack of cohesion in the speech samples. This method allows us direct access to the inner experience of the patient. The technique highlighted a very poor pre-syntax linked to the choice of words and a tendency to make pronoun errors, possibly reflecting some confusion between the patient herself and others, mainly her mother, especially in the discourse about childhood. Conclusion: This method of discourse analysis made it possible to investigate various language disturbances at the same time and at different levels. It is particularly adapted for analysing the schizophrenic's speech. The data obtained were consistent with the assumption that schizophrenia involves ‘thought disorders’: these ones giving rise to the language impairments.

The evolution of the kinetic parameters, maximal velocity ( V max ) and Michaelis constant ( K m ), of l-tryptophan (l-TRP) uptake into red blood cells (RBC) was studied in 30 depressed patients in a drug-free state (D0) and after 1 week (D7) and 4 weeks (D28) of a treatment involving a variety of antidepressant drugs, including SSRIs and tricyclics. At D0, 76% of patients exhibited abnormal values of V max , which were either higher (36%) or lower (40%) than the control range (control V max mean ± 1 S.D.). High and low K m values were observed in parallel with high and low V max values. At D7, individual values of V max varied drastically compared to their corresponding value at D0, whatever the pretreatment value of the parameter. The magnitude of the V max variation during the first week of treatment was found to be significantly larger in the treatment responders than in the non-responders. At D28, V max values of all the responders to treatment were within the control range, whatever their pretreatment V max value. On the contrary, non-responders had V max values that were significantly lower than those of the controls. Changes in K m followed changes in V max during antidepressant treatment. In conclusion, normalization of l-TRP transport kinetics was concomitant with a clear alleviation of depressive symptoms, indicating that RBC l-TRP uptake is dependent on clinical state. Moreover, early reactivity of the V max as soon as the first week of treatment may be useful as a predictive index of clinical outcome at D28.

Resume L’assimilation de plus en plus frequente de l’hospitalisation en psychiatrie a l’enfermement necessite une reflexion sur la portee de cette modalite de soin. L’objectif de ce travail est d’explorer le vecu et la perception des effets de cette experience au regard d’une perspective ethique. L’etude etait fondee sur une enquete par questionnaire realisee aupres de 169 patients au terme de leur sejour hospitalier. Une analyse statistique descriptive a ete realisee avec le logiciel SPSS 17.0 et les resultats examines au filtre des principes ethiques fondamentaux (autonomie, bienfaisance, non-malfaisance). Elle a mis en evidence que l’autonomisation est favorisee par l’existence de reperes dans le deroulement des soins (plus de 85 %), la liberte de circulation (82 %), l’information sur le projet therapeutique (83 %), et remise en cause surtout en matiere d’implication dans l’orientation des soins et d’information sur le mode d’hospitalisation (67 %) et la maladie (71 %). La bienfaisance est respectee tant au niveau de la disponibilite des soignants (94 %) que des effets benefiques reconnus et de l’utilite (90 %). Cependant, l’hospitalisation est une experience potentiellement chargee d’affects negatifs (vecu penible 50 %, impuissance 40 %) qui pourraient etre attenues par une ecoute plus active, ainsi qu’une information et une responsabilisation accrues des personnes hospitalisees.

Birth in late winter and spring has been consistently shown to be a risk factor of schizophrenia. The relationship of late winter/spring birth to clinical characteristics and other putative risk factors, such as family history and obstetric complications, may provide clues to etiology. Data relating to season of birth, clinical features, family history, and obstetric complications were analyzed for 192 patients with schizophrenia as defined by Research Diagnostic Criteria (including schizoaffective disorder). There was no significant association of season of birth with any of the psychopathological dimensions nor was there a significant association with obstetric variables or family history. However, winter-born schizophrenic patients who had a negative family history were more likely to have a history of obstetric complications. These findings suggest that obstetric complications associated with schizophrenia are perhaps the result of some seasonal risk factors important in those without a family history of the disorder.

Kinetic parameters (Vmax and K(m)) of L-tryptophan (TRP) uptake into red blood cells (RBC) were measured in 72 drug-free depressed inpatients and 35 healthy volunteers. Mean Vmax and K(m) values were not significantly different between patients and volunteers. The frequency distributions of Vmax values, however, largely differed in the two groups: Vmax values were homogeneous in the volunteers while they were widely scattered in the depressed patients. Only 15 out of the 72 depressed patients (21%) had Vmax values within 1 SD from the mean control value. Forty-four percent of the patients (n = 32) had Vmax values above the control mean + 1 SD in 11 patients and above the control mean + 2 SD in 21 patients. Thirty-five depressed patients (n = 25) had Vmax values below the control mean - 1 SD in 8 patients and below the control mean - 2 SD in 17 patients. High and low K(m) values were observed in combination with high and low Vmax values. The alterations in kinetic parameters were neither associated with severity of depression nor with a specific diagnostic subtype of depression. The data show abnormalities in RBC L-TRP uptake in most depressed patients that likely reflect a disturbance in peripheral availability of TRP on which central serotonin synthesis closely depends.

1. A statistically significant increased risk of schizophrenia for individuals born in winter has been reported. The increase risk is of the order of 5-15 percent. The seasonal effect is more marked among females. This winter birth effect suggests some environmental agents, probably a neuropathogen one, acting on the foetus. 2. The present study sought to test the environmental damage hypothesis by application of the family history of psychiatric disorder distinction to season of birth data divided according to sex and using a control population. 3. From computer records, all patients admitted to the psychiatric department of Marseilles Timone hospital between January 1984 and December 1989 who satisfied DSM III, DSM III R criteria for schizophrenia were identified. Patients were then classified into two groups: family history of psychiatric disorder versus no family history. Division according to the sex was carried on after two groups were formed. 4. The data show (I) a significant excess of births in the early months of the year (p0.05) for all patients with no family history of psychiatric disorder, (2) a significant excess of births for females (p0.05) with no family history. 5. These results provide indirect support for the neurodevelopmental theory of schizophrenia.

Objective. The aim of this study is to assess the relationships of cardiovascular risk factors with verbal learning and memory in patients with schizophrenia. Methods and Design. cross-sectional study. Inclusion Criteria. Diagnosis of schizophrenia according to the DSM-IV-TR criteria. Data Collection. Sociodemographic information, clinical characteristics, anthropometric measurements, blood tests, and episodic memory using the California Verbal Learning Test (CVLT). Analysis. A multivariate analysis using multiple linear regressions was performed to determine variables that are potentially associated with verbal learning and memory. Results. One hundred and sixty-eight outpatients participated in our study. An association was found between the metabolic syndrome (MetS) and memory impairment on measures of verbal learning, and short- and long-term memory. Among the different components of MeTS, hypertriglycerides, abdominal obesity, and low HDL cholesterol were the only factors associated with memory impairment. Alcohol dependence or abuse was associated with a higher rate of forgetting. Conclusion. Our findings suggest that MetS and alcohol use may be linked with memory impairment in schizophrenia. These findings provide important insights into the interdependencies of cardiovascular risk factors and cognitive disorders and support novel strategies for treating and preventing cognitive disorders in patients with schizophrenia.

The aim of this study is to assess the relationships of metabolic syndrome (MetS) and inflammation with neurocognition in schizophrenia. In this cross-sectional study, we included patients with diagnosis of schizophrenia according to the DSM-IV-TR criteria. We collected socio-demographic information, clinical characteristics, anthropometric measurements, blood tests, and neurocognition measures. A multivariate analysis using multiple linear regressions was performed to determine variables that are potentially associated with neurocognition. The analyses were repeated using MetS as a dichotomised variable (< and ≥ 3 MetS criteria), a continuous variable (number of MetS criteria present), and for each component of MetS. One hundred and sixty-eight outpatients participated in our study. The prevalence of MetS was 27.4%. An association was found between the number of MetS criteria present and cognitive impairment. Among the different components of MetS, hypertriglycerides and abdominal obesity were the only factors associated with cognitive impairment. Other factors, such as smoking and alcohol dependence or abuse, also revealed a significant relationship, whereas inflammation was not associated with cognitive impairment. In conclusion, our findings suggest that MetS, alcohol use and non-smoking status are associated with cognitive impairment. These findings may support complementary therapeutic approaches in cognitive remediation that lessen the severity of cognitive impairment in schizophrenia.

Platelet tritiated imipramine binding ( B max ) was studied in 33 depressed patients, before and after 1 and 4 weeks of antidepressant treatment, and in 34 healthy volunteers. The B max was significantly lower (−21%) in drug-free depressed patients than in controls and increased significantly as early as the first week of treatment to reach the control value, in parallel with a 38% decrease in the Hamilton depression rating scale (HDRS) score. After 4 weeks of treatment, the B max was still normal and remained significantly higher than the baseline value, while the clinical state of the patients had greatly improved (a 63% decrease in the HDRS score). However, an increase in the B max also occurred in non-responders to treatment. In addition, we observed that the ability of the treatment to increase the B max depended on the pharmacological profile of the drug used. The present results show that, in patients on antidepressant medication, platelet tritiated imipramine binding normalization cannot be considered as a marker of clinical remission.

This study examined characteristics of frequent visitors to a psychiatric emergency service in a French public teaching hospital over six years. Diagnostic variability of psychotic disorders was documented.A retrospective review of the service's administrative and medical databases identified 1,285 patients with more than one visit during the period who were given at least one diagnosis of a psychotic disorder. A total of 317 patients with six or more visits (frequent visitors) were compared with 968 patients with between two and five visits (occasional visitors).Frequent visitors were significantly more likely to be single and homeless and to have diagnostic variability, substance use disorders, and personality disorders. A total of 177 patients experienced diagnostic variability, which was found mainly in three diagnostic categories: schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features.Future studies should further examine the link between increased use of emergency services and diagnostic variability.

The kinetic characteristics of platelet L-tryptophan uptake were investigated in 23 untreated depressed patients and 18 healthy volunteers. A significant increase of 50% in the apparent Michaelis constant (Km) was observed in depressed patients compared with controls, without significant change in the maximal velocity (Vmax). After 1 month of successful antidepressant treatment the mean Km value decreased significantly and reached the control value. This result raises the possibility that the decrease in platelet tryptophan uptake affinity is a state-dependent marker for depression. It is likely that the transport alteration results in a decrease in platelet tryptophan accumulation. The effect of this peripheral membrane defect on brain serotonin function is discussed.

ResumenPara someter a prueba la hipótesis de que un número mayor de nacimientos en verano es un factor de riesgo para el síndrome de déficit, se estudió el mes de nacimiento en 53 pacientes esquizofrénicos con déficit en comparación con 158 pacientes sin déficit. No se observaron diferencias significativas desde el punto de vista del mes o la estación de nacimiento entre los pacientes con y sin déficit, lo que indica que los nacimientos en verano pueden no ser un factor de riesgo para la esquizofrenia de déficit.

Deficits in social functioning are an important core feature of mental health. Recently in France, the Activities Daily Life (ADL) scale has been proposed by the French authorities to assess social functioning for all hospitalized patients in a psychiatric ward. The perspective is to use this scale in the financing and organization of mental health services in France. The ADL scale is a 6-item (dressing/undressing, walking/mobility, eating/drinking, using toilets, behaviour, relationships/communication) heteroquestionnaire completed by a health care professional at the beginning of each hospitalization, assessing functioning of patients suffering from mental health diseases. However, limited consensus exists on this scale. The psychometric properties of the ADL scale have not been assessed. There is a pressing need for detailed examination of its performance. The aim of this study was to explore ADL psychometric properties in a sample of hospitalized patients in a psychiatric ward.We retrospectively analyzed data for all episodes of care delivered to hospitalized patients in a psychiatric ward in our French Public Hospital from January 1, 2008 to June 30, 2008. The study involved retrospective review of administrative and medical databases. The following data were collected: age, gender, diagnoses based on the International Classification of Diseases - 10th version, ADL scale and Assessment of Social Self-Sufficiency scale (ASSS). The psychometric properties were examined using construct validity, reliability, external validity, reproducibility and sensitivity to change. Data analysis was performed using SPSS 15.0 and WINSTEP software.A total of 1066 patients completed the ADL scale. Among them, 49.7% were male, mean age was 36.5 ± 10.8, and 83.5% were single. Schizophrenia, schizotypal and delusional disorders (40.0%), mood disorders (27.9%) and mental and behavioural disorders due to psychoactive substance use (12%) were the most common diagnoses. Factor analysis with varimax rotation identified a 2-factor structure accounting for 82% of the total variance. The first dimension (ADL 1) comprised four items and represented personal care activities. The second dimension (ADL 2) comprised two items and represented social functioning. A floor effect was reported for ADL 1 and its unidimensionality was not satisfactory: two items showed an INFIT statistic outside the acceptable range. Internal consistency was satisfactory for the two dimensions: each item achieved the 0.40 standard for item-internal consistency. The correlation of each item with its contributory dimension was higher than with the other (item discriminant validity). Cronbach's alpha coefficients ranged over 0.70 in the whole sample. Concerning external validity, positive correlations were not systematically found between ADL and ASSS dimensions. The score of ADL 1 had medium to high correlations with four dimensions scores of the ASSS, while the score of ADL 2 were not at all or weakly correlated with ASSS dimension scores. Globally, ADL did not cover sentimental life and social relationships. There were statistical associations between ADL and age or gender: women and subjects older than 60 had a higher level of dependency. We didn't find any association with marital status or diagnoses. The ADL scale presented a good reproducibility but was not sensitive to change.The psychometric properties of the ADL scale were not sufficient for several parameters such as validity or sensitivity to change, contrary to other available French scales. The use of a heteroquestionnaire rather than a self-administered questionnaire should be discussed by professionals and the French authorities. These results should be taken into account in the use of the ADL scale for the economic and administrative management of psychiatry. Further research should be conducted to confirm these results.

This paper focuses on the questions asked to practitioners regarding compliance to new long-acting atypical antipsychotics (LAAA): how does the comprehensive approach of patients' and carers' attitudes facing treatment challenge it?A review of recent literature shows that LAAA, are still suffering from an "image problem". We aim to describe these negative beliefs and suggest that LAAA indications be reconsidered.Following a comprehensive approach, we interpreted our review on the basis of anthropological criteria. We focused on value-based health and disease models that organize the attitude of patients and carers regarding the depot injection.Multiple negative beliefs attached to the pain, side-effects, and stigmas are well-known to impair adhesion to treatment. Carers understand disease as a lack of insight. Patients experience it as a threat for the Self and a loss of autonomy. The nurse-patient relationship involving injections is an important factor of compliance. When time is devoted by the carer to paying attention to the patient's experience, in order to perceive the patient as a participant, patients are more likely to adopt the injectable route themselves. By doing so, the patient considers the injection as a "protective net" a "lesser evil" by integrating it within his(her) biography.A comprehensive approach links the lack of insight to the patient's perception of stigma. Hope for recovery is related by the person him(her)self to his(her) own ability for autonomy. Persons with schizophrenia usually struggle for norms (agonomia). This trend has to be taken into account. LAAA are better indicated when patients are compliant. There is no indication when patients are "pure agonomics" and fight to deny both stigma and medication.