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Antidepressants must be taken for weeks before response can be assessed with many patients not responding to the first medication prescribed. This often results in long delays before effective treatment is started. Antidepressants induce changes in the processing of emotional stimuli early in the course of treatment. In the current study we assessed whether changes in emotional processing and subjective symptoms over the first week of antidepressant treatment predicted clinical response after 4-8 weeks of treatment. Such a predictive test may shorten the time taken to initiate effective treatment in depressed patients. Seventy-four depressed primary care patients completed measures of emotional bias and subjective symptoms before starting antidepressant treatment and then again 1 week later. Response to treatment was assessed after 4-6 weeks. The performance of classifiers based on these measures was assessed using a leave-one-out validation procedure with the best classifier then tested in an independent sample from a second study of 239 patients. The combination of a facial emotion recognition task and subjective symptoms predicted response with 77% accuracy in the training sample and 60% accuracy in the independent study, significantly better than possible using baseline response rates. The face based measure of emotional bias provided good quality data with high acceptability ratings. Changes in emotional processing can provide a sensitive early measure of antidepressant efficacy for individual patients. Early treatment induced changes in emotional processing may be used to guide antidepressant therapy and reduce the time taken for depressed patients to return to good mental health.

Introduction: Lockdowns implemented in response to the COVID-19 pandemic are thought to impact mental health [1,2] Understanding the mechanisms underlying this impact is critical to mitigating it [3] We tested the hypothesis that one such mechanism involves impaired mood homeostasis (i e , failure to stabilize mood via mood-modifying activities) [4,5] Methods: In this ecological momentary assessment cohort study, students in the Netherlands reported their mood and activities 4 times a day between March 16 and 29, 2020 New and immediate lockdown measures were announced on March 23 The average change in mood an individual experienced when engaging in an activity was recorded as its pleasantness Mood homeostasis was defined as the extent to which participants preferentially engaged in pleasant activities at time t+1 when their mood was low at time t, thus stabilizing their mood Participants' history of mental illness was screened at baseline Using linear regressions we assessed (i) changes in mood homeostasis from before to during lockdown, (ii) their moderation by mental illness history, (iii) their association with changes in mood level, and (iv) their mediation by changes in range of activities undertaken How changes in mood homeostasis might impact the risk of depression was estimated using computer simulations Statistical significance was set at 2-sided P< 05 Results: Seventy-eight students were included Mood homeostasis was significantly higher before than during lockdown (0 37 vs 0 28;95% CI of the difference [0 03,0 15];P= 003) For every 0 1 point drop in mood homeostasis, average mood decreased by 1 9 points (95% CI, [1 3,3 6], P< 001) This is enough to bring someone's average mood from the population's mean to its bottom quartile The change in mood homeostasis from before to during lockdown was mediated by a reduction in the range of activities (proportion mediated: 11 9%, P< 001) Mood homeostasis dropped significantly more among people with (vs without) a history of mental illness (P< 001): from similar values before lockdown (0 31 vs 0 36;P= 37) to significantly different values during lockdown (0 13 vs 0 35;95% CI of the difference [0 11,0 33];P< 001) In computer simulations, changes in mood homeostasis attributed to the lockdown led to a 3-fold increase in the the yearly incidence of depressed mood episodes: from 9 0% (95% CI [6 6%,11 4%]) before lockdown to 28 2% (95% CI [23 6%,32 6%]) during lockdown Conclusions: Mood homeostasis appears to decrease during lockdown Larger decreases correlate with larger decreases in mood level The impact was larger for students with a history of mental illness The lack of a control group (as the lockdown was implemented nationally) is the main limitation of our study However, since the same participants were monitored before and during lockdown, the lockdown itself seems to be the most likely explanation for the observed difference Identifying interventions that increase mood homeostasis might be a promising avenue to mitigate the impact of lockdowns on mental health Table 1 No conflict of interest

Background: The limited reliability of depression diagnosis impedes research in psychiatry. This impediment is often attributed to biases in the reporting and recording of symptoms. But a fundamental and overlooked explanation may lie in the ambiguity of the very definition of depressed mood. Digital phenotyping enables isolating the effects of this ambiguity from other factors. Methods: We used data from two large independent ecological momentary assessment studies: the 58sec study for testing and the Emotion Sense study for replication. We compared the yearly incidences of depressed mood episodes from 125 interpretations of the ICD-10 criteria. We then assessed agreement between interpretations that lead to similar (and realistic) yearly incidences. Outcomes: In the 58sec and Emotion Sense studies, respectively 2042 and 2009 people reported their mood frequently for an average of 114 and 132 days. Vastly different yearly incidences of depressed mood episodes were observed for different interpretations of the ICD-10 criteria (0%–65.7% in the 58sec study, and 0.3%–52.8% in the Emotion Sense study). Interpretations leading to similar yearly incidence identified different depressive episodes (Cohen’s kappa as low as 0.25 in the 58sec study and 0.47 in the Emotion Sense study). Interpretation: A fundamental cause for the unreliability of depression diagnosis appears to lie in the ambiguity of the definition of depressed mood. Improving this definition with digital phenotyping can be achieved if measurements are combined with a representation of depressed mood along underlying dimensions. Our findings thus offer a potential bridge between conventional diagnostic practice and newer dimensional approaches to psychopathology. Funding Statement: National Institute of Health Research. Declaration of Interests: Prof Goodwin is Medical Director at P1vital products, holds shares in P1vital and P1Vital products and has served as consultant, advisor or CME speaker in the last 3 years for Beckley Psytech, Clerkenwell Health, Compass pathways, Evapharma, Janssen, Lundbeck, Medscape, Novartis, P1Vital, Sage, Servier. The other authors declare no conflict of interest. Ethics Approval Statement: The 58sec study was approved by the Ethics Committee of ESADE (Escuela Superior de Administracion y Direccion de Empresas) Business School, Barcelona, Spain. The Emotion Sense study was approved by the Research Ethics Committee of the University of Cambridge.

International audience; Bipolar disorder is associated with impaired decision-making. Little is known about how treatment, especially lithium, influences decision-making abilities in bipolar patients when euthymic. We aimed at testing for an association between lithium medication and decision-making performance in remitted bipolar patients. Decision-making was measured using the Iowa Gambling Task in 3 groups of subjects: 34 and 56 euthymic outpatients with bipolar disorder, treated with lithium (monotherapy and lithium combined with anticonvulsant or antipsychotic) and without lithium (anticonvulsant, antipsychotic and combination treatment), respectively, and 152 matched healthy controls. Performance was compared between the 3 groups. In the 90 euthymic patients, the relationship between different sociodemographic and clinical variables and decision-making was assessed by stepwise multivariate regression analysis. Euthymic patients with lithium (p=0.007) and healthy controls (p=0.001) selected significantly more cards from the safe decks than euthymic patients without lithium, with no significant difference between euthymic patients with lithium and healthy controls (p=0.9). In the 90 euthymic patients, the stepwise linear multivariate regression revealed that decision-making was significantly predicted (p

Pharmacotherapy is effective in helping many patients suffering from psychiatric and neurological disorders, and both psychotherapeutic and stimulation-based techniques likewise have important roles to play in their treatment. However, therapeutic progress has recently been slow. Future success for improving the control and prevention of brain disorders will depend upon deeper insights into their causes and pathophysiological substrates. It will also necessitate new and more rigorous methods for identifying, validating, developing and clinically deploying new treatments. A field of Research and Development (R and D) that remains critical to this endeavour is Neuropsychopharmacology which transformed the lives of patients by introducing pharmacological treatments for psychiatric disorder some 60 years ago. For about half of this time, the European College of Neuropsychopharmacology (ECNP) has fostered efforts to enhance our understanding of the brain, and to improve the management of psychiatric disorders. Further, together with partners in academia and industry, and in discussions with regulators and patients, the ECNP is implicated in new initiatives to achieve this goal. This is then an opportune moment to survey the field, to analyse what we have learned from the achievements and failures of the past, and to identify major challenges for the future. It is also important to highlight strategies that are being put in place in the quest for more effective treatment of brain disorders: from experimental research and drug discovery to clinical development and collaborative ventures for reinforcing "R and D". The present article sets the scene, then introduces and interlinks the eight articles that comprise this Special Volume of European Neuropsychopharmacology. A broad-based suite of themes is covered embracing: the past, present and future of "R and D" for psychiatric disorders; complementary contributions of genetics and epigenetics; efforts to improve the treatment of depression, neurodevelopmental and neurodegenerative disorders; and advances in the analysis and neuroimaging of cellular and cerebral circuits.

Objectives Brain imaging is now used to inform hypotheses relating not just to brain function but also the actions of drugs for depression. It can identify the relevant functional neuroanatomy of drug action and its relation to hot and cold cognition. Patients Patients with acute major depression or in recovery from same, in comparison with healthy controls. Results In the case of drugs for depression, we are limited by our understanding of the neurocognitive mechanisms involved. However, it has already been possible to show improved memory for positive descriptors for a range of drugs for depression and these are aligned in both healthy controls and patients. Brain imaging has shown corresponding early effects of drug treatment on how the amygdala responds to negative emotional stimuli. Study of cold cognition, while less developed, has attracted interest from the development of vortioxetine. Imaging studies in recovered patients and controls suggest cognitive enhancing effects of vortioxetine, which may be relevant to recovery from depression. Conclusions The challenge is to develop a coherent neurocognitive theory of depression that can explain or give context to the observed patterns of symptoms and their response to treatment. Brain imaging will play an important part in this programme of work.

Resume Objectifs Les recommandations francaises concernant la prescription de lithium ont ete publiees, mais a ce jour, il n’existe pas de synthese exhaustive recente en langue francaise des donnees de la litterature sur les effets secondaires d’un traitement par lithium. Le but de ce travail de revue est de preciser le profil toxique du lithium et de completer les recommandations francaises concernant la prescription de lithium. Materiel et methode Nous avons actualise la revue exhaustive avec meta-analyse d’essais randomises controles et d’etudes observationnelles evaluant l’association entre le lithium et tous les effets indesirables majeurs precedemment conduite par notre equipe. Nous avons explore les bases de donnees electroniques de journaux specialises, les listes et manuels de reference, et les resumes de congres et conferences. Nous avons evalue l’impact du lithium sur la fonction renale, les fonctions thyroidienne et parathyroidienne, l’apparition ou l’aggravation d’anomalies de la peau et des phaneres, d’anomalies teratogenes et sur la prise de poids. Resultats Les recherches bibliographiques ont identifie 5988 etudes. L’analyse des resumes a retenu 390 etudes. En moyenne, le taux de filtration glomerulaire et la capacite a concentrer l’urine sont respectivement diminues de –9,30 mL/min et de 15 % par rapport a la capacite moyenne maximale. La prise de lithium pourrait augmenter les taux d’insuffisance renale terminale mais le risque absolu est de l’ordre de 0,3 %. La prevalence d’hypothyroidie et le taux sanguin de l’hormone stimulatrice de la thyroide (+4,00 UI/mL) sont augmentes chez les patients traites par lithium. Le traitement par lithium est associe a une augmentation du taux sanguin de calcium et de l’hormone parathyroide. Le gain de poids associe au lithium est superieur a celui associe au placebo et inferieur a celui associe a l’olanzapine. Nous n’avons pas retrouve d’augmentation significative du risque de survenue de malformations congenitales, d’alopecie ou d’anomalies de la peau. Conclusions Le lithium est associe a une augmentation du risque de diminution de la capacite a concentrer l’urine, du risque de survenue d’une hypothyroidie, d’une hyperparathyroidie et d’une prise de poids. Chez la plupart des patients, peu de preuves attestent d’une reduction cliniquement significative de la fonction renale. Le risque de survenue d’une insuffisance renale terminale est faible et le risque d’apparition de malformations congenitales est incertain. Pendant la grossesse, il parait indispensable d’evaluer le rapport entre les benefices et les risques associes a l’arret d’un traitement par lithium. La prevalence elevee d’hyperparathyroidie impose des mesures du taux serique de calcium avant et pendant le traitement.

A cognitive model of bipolar disorder suggests that mental imagery acts as an emotional amplifier of mood and may be heightened in bipolar disorder. First, we tested whether patients with bipolar disorder would score higher on mental imagery measures than a matched healthy control group. Second, we examined differences in imagery between patients divided into groups according to their level of mood stability. Mood ratings over approximately 6-months, made using a mobile phone messaging system, were used to divide patients into stable or unstable groups. Clinician decisions of mood stability were corroborated with statistical analysis. Results showed (I) compared to healthy controls, patients with bipolar disorder had significantly higher scores for general mental imagery use, more vivid imagery of future events, higher levels of intrusive prospective imagery, and more extreme imagery-based interpretation bias; (II) compared to patients with stable mood, patients with unstable mood had higher levels of intrusive prospective imagery, and this correlated highly with their current levels of anxiety and depression. The findings were consistent with predictions. Further investigation of imagery in bipolar disorder appears warranted as it may highlight processes that contribute to mood instability with relevance for cognitive behaviour therapy., Highlights ► Patients with bipolar disorder were compared to controls on mental imagery measures. ► Patients had higher scores on several imagery measures, e.g. more vivid imagery of future events. ► Patients were divided into groups according to their level of mood stability. ► Patients with unstable (versus stable) mood had higher levels of intrusive prospective imagery. ► Prospective imagery correlated highly with current levels of anxiety and depression.

Background: In bipolar disorder (BD), little is known about how deficits in neurocognitive functions such as decision-making are related to phase of illness. We predicted that manic, depressed, and euthymic bipolar patients (BPs) would display impaired decision-making, and we tested whether clinical characteristics could predict patients' decision-making performance. Methods: Subjects (N = 317; age range: 1865 years) including 167 BPs (45 manic and 32 depressed inpatients, and 90 euthymic outpatients) and 150 age-, IQ-, and gender-matched healthy control (HC) participants, were included within three university psychiatric hospitals using a cross-sectional design. The relationship between predictor variables and decision-making was assessed by one-step multivariate analysis. The main outcome measures were overall decision-making ability on the Iowa Gambling Task (IGT) and an index of sensitivity to punishment frequency. Results: Manic, depressed, and euthymic BPs selected significantly more cards from the risky decks than HCs (p

In early March 2011 the European College of Neuropsychopharmacology (ECNP) hosted a summit to consider the implications and consequences of the abrupt withdrawal of a number of major pharmaceutical companies from key areas of neuroscience research and development in brain disorders and psychopharmacology in particular. This paper presents the recommendations of the summit plus details of the background and analyses of the problem. It will be widely circulated within Europe and elsewhere.

Resumen El termino «combinacion» incluye practicamente todas las modalidades en las que una medicacion puede anadirse a otra. Los otros terminos de uso frecuente son «aumento», que implica un efecto aditivo de la adicion de un segundo farmaco al obtenido de la prescripcion de un primero, y «adyuvante», que implica la adicion a un tratamiento existente, posiblemente eficaz que, por una razon u otra, no puede o no debe interrumpirse. Las cuestiones que se derivan en todas las indicaciones potenciales son: a) ?Cuanto tiempo es razonable esperar para poder demostrar la insuficiencia de la respuesta a la monoterapia?; b) ?Mediante que criterios debe definirse dicha respuesta?; c) ?Cuan optima es la dosis de la primera monoterapia y, por consiguiente, con que certeza sabemos que su falta de efecto se debe a una respuesta realmente insuficiente? Antes de considerar un tratamiento de combinacion, es preciso que se cumplan uno o mas de los criterios siguientes: a) la monoterapia solo ha sido parcialmente eficaz en los sintomas basicos; b) la monoterapia ha sido eficaz en algunos sintomas concurrentes pero no en otros, por lo que se considera que se requiere una medicacion adicional; c) en algunas circunstancias podria estar indicada una combinacion particular de novo; d) la combinacion podria mejorar la tolerabilidad porque ambos farmacos pueden administrarse por debajo del umbral de la dosis individual asociada a efectos adversos. Los responsables de las politicas sanitarias han suscitado preocupacion principalmente con el criterio a, y en principio como minimo, con el c. En la practica clinica la utilizacion de un tratamiento de combinacion refleja el desenlace, con frecuencia insatisfactorio, del tratamiento con un farmaco individual. Antipsicoticos en la mania Se dispone de pruebas apropiadas de que la mayoria de antipsicoticos examinados muestran eficacia en la mania aguda cuando se anaden al litio o al valproato para pacientes que no manifiestan una respuesta o solo una parcial al litio o al valproato como monoterapia. Los disenos de ensayos clinicos convencionales de dos grupos podrian beneficiarse de la inclusion de un tercer grupo tratado con un tercer antipsicotico. En el tratamiento a largo plazo del trastorno bipolar, en pacientes que responden de forma aguda a la adicion de quetiapina al litio o al valproato, esta combinacion reduce el riesgo posterior de recidiva de la depresion, mania o estados mixtos, comparado con la monoterapia con cualquiera de ambos solo. No se dispone de datos comparables para la combinacion con otros antipsicoticos. Antipsicoticos en la depresion mayor Se ha demostrado que algunos antipsicoticos atipicos inducen remision cuando se anaden a un antidepresivo (en general, un inhibidor selectivo de la recaptacion de serotonina [ISRS] o un inhibidor selectivo de la recaptacion de noradrenalina [ISRN]) en pacientes con trastorno unipolar en un episodio depresivo mayor que no responde a la monoterapia con un antidepresivo. La refractariedad se define como, al menos, 6 semanas sin alcanzar una respuesta predefinida adecuada al tratamiento. Todavia no se dispone de datos a largo plazo que respalden una eficacia continua. Esquizofrenia Solo se dispone de pruebas limitadas que respaldan la combinacion de dos o mas antipsicoticos en la esquizofrenia. Cualquier monoterapia debe administrarse en la dosis tolerada maxima y, antes de considerar una combinacion, deben administrarse, como minimo, dos antipsicoticos de diferente mecanismo de accion/tolerabilidad y clozapina. La adicion de un antagonista D 2/3 de alta potencia a un antagonista de baja potencia, la clozapina o la quetiapina, es la combinacion logica para el tratamiento de los sintomas positivos, aunque se requieren pruebas adicionales procedentes de ensayos clinicos metodologicamente apropiados. Otros mecanismos de accion diferentes del bloqueo D 2/3 y, por lo tanto, otras combinaciones podrian ser pertinentes para los sintomas negativos, cognitivos o afectivos. Trastorno obsesivo-compulsivo La monoterapia con un ISRS confiere un beneficio medio global en el TOC y pueden ser necesarios 3 meses hasta decidir que confiere beneficios. La adicion de un antipsicotico puede considerarse en el TOC con un trastorno de tics asociado y en el TOC refractario. Para el TOC con un deficit cognitivo (TOC con «caracteristicas psicoticas») el tratamiento de eleccion debe ser una dosis moderada o alta de un ISRS y, solo en los casos refractarios, puede considerarse un aumento con antipsicoticos. Se ha demostrado que el aumento con haloperidol y risperidona es eficaz (una reduccion de sintomas de mas del 35%) para pacientes con tics. Para el TOC refractario, hay datos que sugieren un papel especifico del haloperidol y asi mismo de la risperidona, y algunos datos con respecto a un beneficio terapeutico potencial con olanzapina y quetiapina. Antipsicoticos y efectos adversos en las enfermedades mentales graves En pacientes con enfermedades mentales graves y, en particular cuando son tratados con antipsicoticos, hoy dia los riesgos cardiometabolicos se reconocen mucho mejor y se estan realizando esfuerzos para garantizar un mejor examen de cribado de la salud fisica y prevencion.

Background Gambling can be motivated by both its hedonic value and by attempts to cope with dysphoric or stressful states. Thus, motivations constitute important mechanisms linking mood fluctuations and gambling. However, little is known about how different kinds of affective disturbance, such as mood elevation and dysphoria, motivate gambling behavior. Methods To estimate relationships between different mood experiences and gambling motivations, we recruited 4125 Internet gamblers via hyperlinks placed on gambling Web sites. Mean (SD) age of respondents was 35.5 (11.8) years, with 79.1% (3263) being male and 68.8% (2838) UK residents. We collected ratings for 11 gambling motivations. We used principal components analysis, followed by hierarchical linear regression, to model the relationships between motivation factor scores and gambling behavior, depressive symptoms, hypomanic experiences, deliberate self-harm, and alcohol and substance misuse. Results Gambling to regulate mood, gambling for monetary goals, and gambling for enjoyment were enhanced in individuals at heightened risk of problematic gambling, with mood regulation and enjoyment factors being enhanced in female compared with male problem gamblers. Lowered mood reduced the enjoyment motivation, whereas previous mood elevation enhanced it. Gambling problems alongside previous hypomanic experiences or current dysphoria enhanced gambling to regulate emotional states. Conclusions Recent theorizing argues that mood disorders and pathologic gambling may share aspects of pathophysiology. Different forms of emotional disturbance, such as mood elevation and dysphoric states, which confer heightened risk for bipolar disorder and depression, are associated with divergent motivations that might represent distinct pathways into gambling behavior.

Disease activity assessment is an essential part of clinical management in UC, most accurately evaluated by endoscopy and biopsy, since patient symptoms may not reliably reflect activity. Published cut-offs for faecal calprotectin (FCal) in UC are largely based on prediction of relapse, rather than prediction of endoscopic or histopathologic activity.

TERMINOLOGY AND PRINCIPLES OF COMBINING ANTIPSYCHOTICS WITH A SECOND MEDICATION: The term "combination" includes virtually all the ways in which one medication may be added to another. The other commonly used terms are "augmentation" which implies an additive effect from adding a second medicine to that obtained from prescribing a first, an "add on" which implies adding on to existing, possibly effective treatment which, for one reason or another, cannot or should not be stopped. The issues that arise in all potential indications are: a) how long it is reasonable to wait to prove insufficiency of response to monotherapy; b) by what criteria that response should be defined; c) how optimal is the dose of the first monotherapy and, therefore, how confident can one be that its lack of effect is due to a truly inadequate response? Before one considers combination treatment, one or more of the following criteria should be met; a) monotherapy has been only partially effective on core symptoms; b) monotherapy has been effective on some concurrent symptoms but not others, for which a further medicine is believed to be required; c) a particular combination might be indicated de novo in some indications; d) The combination could improve tolerability because two compounds may be employed below their individual dose thresholds for side effects. Regulators have been concerned primarily with a and, in principle at least, c above. In clinical practice, the use of combination treatment reflects the often unsatisfactory outcome of treatment with single agents. ANTIPSYCHOTICS IN MANIA: There is good evidence that most antipsychotics tested show efficacy in acute mania when added to lithium or valproate for patients showing no or a partial response to lithium or valproate alone. Conventional 2-armed trial designs could benefit from a third antipsychotic monotherapy arm. In the long term treatment of bipolar disorder, in patients responding acutely to the addition of quetiapine to lithium or valproate, this combination reduces the subsequent risk of relapse to depression, mania or mixed states compared to monotherapy with lithium or valproate. Comparable data is not available for combination with other antipsychotics. ANTIPSYCHOTICS IN MAJOR DEPRESSION: Some atypical antipsychotics have been shown to induce remission when added to an antidepressant (usually a SSRI or SNRI) in unipolar patients in a major depressive episode unresponsive to the antidepressant monotherapy. Refractoriness is defined as at least 6 weeks without meeting an adequate pre-defined treatment response. Long term data is not yet available to support continuing efficacy. SCHIZOPHRENIA: There is only limited evidence to support the combination of two or more antipsychotics in schizophrenia. Any monotherapy should be given at the maximal tolerated dose and at least two antipsychotics of different action/tolerability and clozapine should be given as a monotherapy before a combination is considered. The addition of a high potency D2/3 antagonist to a low potency antagonist like clozapine or quetiapine is the logical combination to treat positive symptoms, although further evidence from well conducted clinical trials is needed. Other mechanisms of action than D2/3 blockade, and hence other combinations might be more relevant for negative, cognitive or affective symptoms. OBSESSIVE-COMPULSIVE DISORDER: SSRI monotherapy has moderate overall average benefit in OCD and can take as long as 3 months for benefit to be decided. Antipsychotic addition may be considered in OCD with tic disorder and in refractory OCD. For OCD with poor insight (OCD with "psychotic features"), treatment of choice should be medium to high dose of SSRI, and only in refractory cases, augmentation with antipsychotics might be considered. Augmentation with haloperidol and risperidone was found to be effective (symptom reduction of more than 35%) for patients with tics. For refractory OCD, there is data suggesting a specific role for haloperidol and risperidone as well, and some data with regard to potential therapeutic benefit with olanzapine and quetiapine. ANTIPSYCHOTICS AND ADVERSE EFFECTS IN SEVERE MENTAL ILLNESS: Cardio-metabolic risk in patients with severe mental illness and especially when treated with antipsychotic agents are now much better recognized and efforts to ensure improved physical health screening and prevention are becoming established.

Resume L'auteur rappelle les principes de base de l'Evidence Based Medicine, soulignant son interet ethique mais aussi ses limites. Il donne un exemple d'elaboration de recommandations pour le traitement du trouble bipolaire a partir d'un consensus d'experts mis en place par la British Association for Psychopharmacology. L'elaboration de ces recommandations a suivi les principes de l'EBM.

Background Cognitive dysfunction persists in the euthymic phase of bipolar disorder and may provide a marker of underlying neuropathology and disease vulnerability. This study aimed to replicate a deficit in sustained attention in euthymic bipolar patients and investigate sustained attention in first-degree relatives of bipolar probands and in remitted patients with major depressive disorder. Methods The rapid visual information processing (RVIP) task was used to measure sustained attention in 15 euthymic patients with bipolar disorder and 15 control subjects in experiment 1 and in 27 first-degree relatives of bipolar probands, 15 remitted patients with major depressive disorder, and 46 control subjects in experiment 2. Results Sustained attention deficit was confirmed in the euthymic bipolar patients in experiment 1, but the deficit was not statistically significant in remitted major depressed patients or in the relatives of bipolar probands. Conclusions A deficit of sustained attention is not present in patients with recurrent major depression tested during remission nor is it discriminable in the first-degree relatives of bipolar probands. Thus, the confirmed abnormality in euthymic bipolar patients may be acquired as a consequence of bipolar illness. However, future studies of relatives will require larger sample sizes to exclude or utilize small genetic effects.

BACKGROUND: Antidepressant drugs can promote remission from acute depressive episodes. Our aim was to establish how long such treatments should be continued to prevent relapse. METHOD: We did a systematic overview of evidence from randomised trials of continuing treatment with antidepressants in patients with depressive disorders who have responded to acute treatment. Medline, Embase, Cinahl, PsycLIT, Psyndex, and Lilacs were searched. FINDINGS: Data were pooled from 31 randomised trials (4410 participants). Continuing treatment with antidepressants reduced the odds of relapse by 70% (95% CI 62-78; 2p

Bipolar disorder is a devastating and chronic mood disorder, which can require life-long treatment. The vast majority of patients will suffer relapse of symptoms in the absence of effective therapy. Of those patients receiving treatment, compliance to medication regimens is poor. Non-compliance, when associated with lithium treatment in particular, increases the risk of recurrence of illness. Problems associated with withdrawal serve as powerful stimuli to develop alternatives to lithium monotherapy. Conventional placebo-controlled studies of treatments are difficult in patients with bipolar disorder. Large-scale, pragmatic and clinically relevant trials should be employed to assess existing and novel treatments for bipolar disorder. These can only develop out of genuine clinician and patient uncertainty and the creation of a trial culture in everyday practice.

The polymorphism of a variable number tandem repeat (VNTR) region of the serotonin transporter gene consists of three alleles containing, respectively, 9 (STin2.9), 10 (STin2.10) and 12 (STin2.12) copies of a repetitive element. The frequencies of the three alleles in 384 individuals presenting after deliberate self harm were the same as a group of 346 controls. However, ratings of anxiety (and state anger) were higher in those patients with genotypes including the shorter repetitive elements. The findings support the hypothesis that, in this group of patients with low rates of severe psychiatric disorder, allelic variation in the serotonin transporter gene may contribute to the expression of anxiety symptoms.

Ten healthy volunteers were examined with single photon emission tomography and 99mTc-exametazime. They were studied on 2 occasions, during a 2- and a 3-sound auditory discrimination (oddball) task. Twenty healthy volunteers were used as controls, studied once at rest. During the 2-tone task there was a bilateral posterior (occipito-) temporal and medial frontal activation, a left pericentral increase, and posterior cingulate suppression. During the 3-sound task activation was again found in posterior (occipito-) temporal, medial frontal cortex, left pericentral, with a small non-significant reduction in posterior cingulate uptake. Compared with the 2-tone task, there was a trend towards higher activity in left medial frontal, right posterior temporal and posterior cingulate cortex in the 3-sound task. P3b amplitudes were negatively correlated with posterior cingulate tracer uptake during both tasks. Positive correlations with P3b amplitudes were found in various frontal and temporal regions. These results are consistent with more invasive localisation studies of P3b. Posterior cingulate cortex appears to be inhibited during the oddball tasks, the more so, the more restricted the range of stimuli, and the greater the task-related recruitment of neurones (P3b amplitude). As expected from its more frontal distribution, P3a amplitude was positively correlated with anterior cingulate tracer uptake, and negatively correlated with temporal cortical activity.

The associations between personality dimensions of the Eysenck Personality Questionnaire and individual differences in the regional uptake of 99mTc-Exametazime in brain were studied in 51 healthy volunteers. Extraversion was significantly correlated (r = 0.46, P

The aim of this study was to determine the effects of sex, corticosterone and oestradiol-17 beta on the hypothermia and motor behavioural syndrome induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat. The hypothermia, but not the behavioural syndrome induced by 8-OH-DPAT was significantly greater in female compared with male rats. Adrenalectomy in male rats enhanced the hypothermic response, an effect prevented by corticosterone implants. Ovariectomy significantly attenuated the hypothermia induced by 8-OH-DPAT, an effect prevented by oestradiol-17 beta implants. Neither type of steroid manipulation affected the behavioural syndrome. These results show that sex, corticosterone and oestradiol-17 beta modulate the hypothermic response to 8-OH-DPAT in the rat, with corticosterone and oestradiol-17 beta having opposing effects.

We examined 20 actively psychotic unmedicated schizophrenic patients and 20 matched control subjects by using single-photon emission, computed tomography (SPECT) with 99mtechnetium-exametazime. Patients showed a hyperfrontal pattern of tracer uptake with significant relative increases in superior prefrontal cortex. This abnormality was less pronounced in patients with higher symptom scores for psychomotor poverty. In addition, patients showed associations between certain schizophrenic syndrome scores, such as psychomotor poverty, disorganization, and reality distortion, and tracer uptake to a number of cortical and subcortical brain regions. This syndrome-related pattern of tracer uptake was, at least in part, consistent with similar associations previously reported in chronically medicated schizophrenic patients. SPECT therefore provides a readily available method to examine the relationship between symptom pattern and regional brain metabolism in psychotic patients. Any observed patterns of association will depend on the current mental and medication status of the patients examined.

Thyroid and adrenal function was assessed in euthymic bipolar patients, stable on prophylactic lithium for at least 1 year, before and after lithium discontinuation in a randomised double-blind placebo-controlled trial. All hormonal measurements were within the reference range, but a significant increase (P less than 0.001) in plasma thyroxine (T4) levels and a decrease (P less than 0.01) in TSH levels were observed 1 month after lithium withdrawal; cortisol concentrations showed a non-significant decrease in the same period. No relationship could be demonstrated between the magnitude of the change in hormone levels and the probability of relapse of manic symptoms. In the second part of this study, inositol was added for 11 days to the diets of bipolar patients being treated with prophylactic lithium and normal controls. No modification was shown in T4 and TSH in either group before or after inositol administration. Inositol did not alleviate other side-effects such as tremor and thirst in the patient group. This result suggests that short-term dietary inositol is not equivalent to lithium withdrawal and is of no value in reducing hormonal and other adverse effects of lithium prophylaxis.

Hypersecretion of cortisol is associated with depression. Because corticosterone may show greater responsiveness than cortisol to exogenous ACTH in depression and it has behavioural effects in rodents, we determined whether depression is also associated with hypersecretion of corticosterone. Both cortisol and corticosterone were significantly elevated in depression, with greatest differences from control subjects during the afternoon and evening. The ratio of corticosterone/cortisol was constant and similar throughout the day in both depressed patients and controls. We conclude that there is no disproportionate endogenous hypersecretion of corticosterone in depression.