[Identity, destiny and schizophrenia]. / Identité, destin et schizophrénie.

In his work « Phenomenology of Psychosis ¼ Arthur Tatossian tends to report the basal alteration of patients to a constrained phenomenological reduction and deducts the drive of daily life as a sensitive point of the schizophrenic experience, vulnerability and mark of his destiny. This perspective reveals the challenge of the dynamics of human identity. Going beyond the spatial figure of a split, Alfred Kraus takes up the living format of the dynamics of « role ¼, which regulates the relation of the subject to Self and others, and suggests to report symptoms and syndromes, another stake destined, to one of the variants dialectics of the balance between self and others. We return to the psychopathological intuition of the origins of psychiatric phenomenology to relate the disorder to a particular experience of the lived time, a modification of the relations between the temporal ecstasies that Bin Kimura describes as an excessive « futurisation ¼ by accentuation of the possible and impatience to exist. These approaches inform in a novel way the system of care, and far from advocating objective therapeutic applications, generate implications that can enrich and enhance care projects.

[Inclusion criteria and rating scales for RCTs in Psychiatry. The future of qualitative studies]. / Quels patients inclure et quelles échelles utiliser dans un essai clinique ? Les études qualitatives en perspective.

An inventory on the two critical dimensions that structure the Randomized Controlled Trial in Psychiatry, namely the definition of inclusion criteria for eligible patients for testing and the choice of psychometric methods of pathology assessment and its evolution during the experiment, considers the importance of increasingly numerous and precise international recommendations. Taking into account the formal constraints of industrial, questioning the cultural differences of the methodological approach of the tests, meeting the requirements of feasibility and ever increasing security, frequent cumbersome procedure often contrasts with the modest nature of the results. A better definition to include patients in randomized trials is desirable and it asks to return to the clinic studying the expectations of patients and their response to the therapeutic situation. Excessive standardization otherwise required for ensuring the objective nature of the assessment hampers the collection of original and varied clinical features of importance in the further definitions of indications. On the way to a resumption of the single case study, we can expect from qualitative methods applied to small groups of subjects, optimization principles of patient selection for the upcoming randomized trial and greater chance to address the relevant details of clinical response to the therapeutic situation. This is what has led to the discovery of psychotropic drugs and which is involved in the various modalities of the qualitative approach. For example, and beyond the exploration of clinical drug effects, the study of the experience of psychiatric inpatient care in the Healing Garden, conducted on a small group and on the basis of the narrative analysis of their experience, notes several operating thematic dimensions: a reduction in the perception of symptoms of the disease, the impression of regaining a foothold into reality, the interest of a differently perceived doctor-patient relationship, the advantage of renewed power to act and the recognition of the importance of support from others, patients recovering somehow « vitality ¼ of touch with reality. This suggests the possibility to establish an appropriate rating scale for such a specific therapeutic situation and to provide a more accurate and efficient recruitment for a comparative objective demonstration. Moreover, this construction of meaning reinforces the therapeutic benefit of treatment in Healing Garden and offers new dimensions for research.

[How may practitioners interpret the results of clinical trials?] / Comment le praticien doit-il interpréter les résultats d'un essai clinique ?

To correctly interpret the results of a randomised controlled trial (RCT), practitioners have to spot bias and other potential problems present in the trial. Internal as well as external validity of the trial are linked to the presence of such bias. The internal validity is ensured by a clear definition of the objectives of the trial. The number of patients to be included in the trial is calculated on the basis of the main objective of the trial and more precisely on the basis of the primary endpoint selected to assess the efficacy of treatment. This is the best way to ensure that the statistical significance of the result may have a clinical relevance. Internal validity depends also on the process of patients selection, the methods used to ensure comparability of groups and treatments, the criteria employed to assess efficacy, and the methods for the analysis of data. External validity refers to subjects that have been excluded from the trial, limitations of RCTs, as well as the coherence and clinical relevance of the trial. Internal validity has to be fueled by external validity.

[How to assess curative and/or preventive effects of psychotropic drugs?] / Comment évaluer l'effet curatif et/ou préventif des psychotropes ?

Proving the efficacy of a psychotropic drug is a medical, scientific and ethical need. Psychotropic drug development is now a highly complex process, which takes several years and which is very expensive. It involves multiple steps of preclinical and clinical pharmacological refinement and testing. Methodology of studies to prove curative or preventive effect of psychotropic drugs is well codified. Preclinical studies include pharmacokinetic data, toxicology and performance in various animal models of pathology. Clinical phases are centered on randomized controlled double blind trials for demonstrating efficacy and safety/tolerability. This methodology follows strict criteria to avoid bias and to prove internal and external validity of the results. All the results from randomized controlled trials or RCTs lead to different levels of evidence of Evidence-Based Medicine (EBM): gold standard is RCTs while the lowest reference is clinical case or expert opinion. However, it is possible to level criticism at these data issued from RCTs. The main matter is that studies do not reflect the healthcare reality in daily life. For these reasons, a real debate between evaluation of efficacy and effectiveness is acute. Effectiveness refers to the overall effects of psychotropic drugs in naturalistic conditions. Furthermore, analysis of costs and financial benefits are more and more important from social and economic points of view. Official agencies and health insurances look after them very carefully. This article deals with these issues and provides examples using data from the international literature. These examples are drawn from RCTs, naturalistic studies, meta-analysis, pharmaco-economic studies and concern neuroleptics, antipsychotics, antidepressants, and mood-stabilizers.

[Negative symptoms of schizophrenia: historical aspects]. / Les symptômes négatifs de la schizophrénie: aspects historiques.

The history of negative symptoms of schizophrenia rises early days of medicine in clinical and pathophysiological differences between positive and negative and their complex joint. Forming a set of typical core of symptoms, and some feature of a syndrome belonging to a specific pathophysiological mechanism, negative symptoms of schizophrenia emerge from old descriptions of clinical pictures, related to the overall look of madness, the heart of alienation, a central sign of early dementia, gradually more precisely describing the strange nature of the autistic withdrawal and schizophrenic apragmatism. At therapeutic era, negative symptoms have taken over the positive symptoms to establish an operational criteria whose importance lies in the progressive severity of this clinical type and in their contribution to therapeutic resistance. Despite the efforts of modern typological classifications, this work rehabilitates the old concept of "unitary psychosis" by defining a common symptomatic core to multiple clinical forms of psychosis, combining deficit of emotional expression and avolition, meaning a native psychopathology and a pathophysiology possibly in a common final way, and calling the arrival of new treatment strategies.

[Negative symptoms in schizophrenia: psychotherapeutic approaches]. / Symptômes négatifs de la schizophrénie: approches psychothérapeutiques.

Although negative symptoms are recognized as a central feature of schizophrenia, their definition as well as phenomenology have long been a vexing issue. During these last years, a major progress has been made with the delineation of two underlying subdomains of negative symptoms: diminished expression and anhedonia-avolition-apathy. As current guidelines are not always in accord on the efficacy of treatments on negative symptoms, it may be tempting to re-interpret the findings of clinical trials by looking at the effects of treatments on these two subdomains. This could concern both psychotropic treatments and psychotherapeutic interventions. Furthermore, neuroimaging as well as emotional response studies have permitted to better understand the mechanism which could be at the root of diminished expression and anhedonia in schizophrenia. On this basis, new psychotherapeutic methods have been devised which, by specifically targeting these two subdomains, are likely to be more efficient on negative symptoms. Further research is warranted to test their efficacy in randomized controlled trials.

[Psychopathological aspects of negative symptoms in schizophrenia]. / Aspects psychopathologiques des signes négatifs dans la schizophrénie.

During the past ten years, research on schizophrenia has witnessed a clear emphasis on studies based on negative symptoms. This interest can be explained in terms of diagnosis, specific treatment, functional prognosis and outcome issues. However, main current approaches consider negative symptoms from an operationalist view, which implies objective and atheoretical descriptions of clinical criteria, observed from a third person perspective. And the understanding of negative symptoms in schizophrenia, still a crucial issue of mental health, remains only partial. From a different perspective, psychopathology - and notably psychiatric phenomenology -, can provide a conceptual and clinical framework, taking into account subjective experience (first person perspective), based on a global understanding of the clinical situation lived by patients with schizophrenia. In the present review, we give a brief survey on the historical aspects of the description of negative symptoms. Then, we introduce the clinical contributions raised by clinical phenomenology. We principally develop Minkowski's notion of loss of vital contact, and Blankenburg's notion of loss of natural evidence. Then we highlight the current debates which are discussed and explored in contemporary psychopathology. In conclusion, we discuss the possible articulation between objective and subjective approaches, in order to better understand pauci-symptomatic forms of schizophrenia.

[Comorbidity of affective disorders and alcohol use disorder]. / Troubles affectifs et comorbidités éthyliques.

The comorbidity of affective disorders with alcohol use disorder remains insufficiently taken into account. In spite of the well-known frequency of the addict comorbidity in most psychiatric disorders, the level of association between affective disorders and alcohol is still underestimated and poorly understood. The label of "double diagnosis" relates to a simple addition of two independent pathologies. It is suggested to consider a "dual psychopathology" combining the effects of one disorder on the other. Interactions between the two disorders commit a complex state calling a new clinical reading, an adapted therapeutic strategy through a necessary integration of care. Association of alcohol use disorder and affective disorder, particularly in bipolar disorders, is correlated with severity, unstable course, treatment resistance and a greater risk of suicide. Alcohol aggravates depression and hampers therapeutics. Alcohol and mania remain a dreaded danger. The mechanism of the comorbid association does not only refer to a behavioral strategy of compensation but seems strongly based on a shared and crossed vulnerability, related to the genetics of the 5HT carrier and gene Clock. Therapeutic limitations do suggest the implementation of an "integrated" device which supposes a new organization of care and facilitation of collaborations between Addiction and Psychiatry.

[Dissociative disorders and affective disorders]. / Troubles dissociatifs et troubles affectifs.

The phenomenology of dissociative disorders may be complex and sometimes confusing. We describe here two cases who were initially misdiagnosed. The first case concerned a 61 year-old woman, who was initially diagnosed as an isolated dissociative fugue and was actually suffering from severe major depressive episode. The second case concerned a 55 year-old man, who was suffering from type I bipolar disorder and polyvascular disease, and was initially diagnosed as dissociative fugue in a mooddestabilization context, while it was finally a stroke. Yet dissociative disorders as affective disorder comorbidity are relatively unknown. We made a review on this topic. Dissociative disorders are often studied through psycho-trauma issues. Litterature is rare on affective illness comorbid with dissociative disorders, but highlight the link between bipolar and dissociative disorders. The later comorbidity often refers to an early onset subtype with also comorbid panic and depersonalization-derealization disorder. Besides, unipolar patients suffering from dissociative symptoms have more often cyclothymic affective temperament. Despite the limits of such studies dissociative symptoms-BD association seems to correspond to a clinical reality and further works on this topic may be warranted.

[Mixed states: evolution of classifications]. / États mixtes. Évolution des classifications.

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.

[Short history of mixed states]. / Une approche historique des états mixtes.

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).

[Mixed states and schizophrenia]. / États mixtes et schizophrénie.

Because of their compilation of contrasted symptoms and their variable clinical presentation, mixed episodes have been withdrawn from the DSM. However, mixed states question not only the bonds between depression and mania, but also the distinction between bipolar disorders and schizophrenia. Indeed, doubts about the dichotomy introduced by Kraepelin between bipolar disorders and schizophrenia is as old as the nosolgy itself, as attest the later works of this author revealing his hesitations on his own classification. But findings here reviewed issued from recent technical advances, particularly in the imaging and genetic fields, offer a better understanding of the boundaries between these two disorders. Yet, when confronted to an acute episode, clinicians may find it challenging to distinguish a mixed state from a schizophrenic relapse. Indeed, there is no pathognomonic manifestation allowing to retain a diagnosis with confidence. The physician will therefore have to identify a pattern of signs, which will orient his assessment with no certainty. Thus, negative rather than affective or psychotic symptomatology appears to be useful in discriminating schizophrenia (or schizoaffective) disorders from mixed mania. However, a conclusion during this acute stage appears in definitive a formal exercise, first because the final diagnosis will only be ascertained once the symptoms are amended, and second because, according to our classifications, a mood episode, including mania and mixed mania, can be observed without ruling out the diagnosis of schizophrenia.

[Neurocognitive fuctioning in pure mania and mixed mania]. / Fonctionnement neurocognitif dans la manie pure et la manie mixte.

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.

[Pathophysiological models of mixed states]. / Modèles physiopathologiques des états mixtes.

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.

[Antimanic treatments in bipolar mixed states]. / Traitements anti- maniaques dans les états mixtes.

INTRODUCTION: 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. OBJECTIVE: The aim of this paper was to conduct an overview of the literature to ascertain the efficacy of pharmacotherapy of mixed states. METHOD: A systematic review of the literature was conducted using PubMed. RESULTS: 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. CONCLUSIONS: 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.

[Recommendations for the treatment of mixed episodes in current guidelines]. / Recommandations sur le traitement des épisodes mixtes dans les guidelines actuels.

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.

[Endophenotypes of the biorhythms and the sleep in depression]. / Endophénotypes des rythmes biologiques et du sommeil dans la dépression.

Chronobiological markers of depression display a biological desynchronization which participates in the pathogenesis of depression. Mood disorders and clock genes have shown significant associations suggesting a possible pathogenetic link between them, providing a privileged base for exploring biorhythmic endophenotypes. They would be useful indicators of vulnerability mechanisms, giving rise to new therapies and prevention programs. Two ways of research are of interest: the study of the genetic determinants of cholinergic hypersensitivity generating REM sleep pressure in depression, and the analysis of clinical response to sleep deprivation suggesting an exploration of links between genomic function of arousal and mood regulation. To date, the empirical principle of behavioral stimulus control reaches the level of the available eco-instrumental synchronization procedures.

[Temperamental endophenotypes]. / Les endophénotypes tempéramentaux.

Temperament has been defined as the heritable biologically determined core of personality that remains stable throughout the life span and establishes the baseline level of reactivity, mood, and energy of a person. If the link between temperament and mental disorder goes back to the Greco-Roman medicine, Kraepelin was among the first authors to pay attention to the temperamental bases of bipolar disorder. He proposed four temperamental types that he described in the premorbid histories of the majority of manic-depressive patients, and found overrepresented in the biologic relatives of these patients. Building on this ancestry, Akiskal formulated the modern concept of affective temperament, and described five temperaments: depressive, hyperthymic, cyclothymic, irritable, and anxious. According to Akiskal's model, bipolar disorder lies along a continuum from temperament to full-blown episodes of affective illness. A series of recent studies have shown the role played by temperaments in the outbreak of bipolar episodes, their clinical presentation, as well as the illness course and comorbidities. Furthermore modern familial and genetic studies have confirmed the first observations of Kraepelin. It has been recently proposed that affective temperaments may carry distinct evolutionary advantages on the individual or a group level, so that affective disorders would be genetic reservoirs for adaptative temperaments and the price to be paid for the chance of exceptionality. Apart from these theoretical perspectives, paying attention to temperamental components may have important implications for the treatment of bipolar disorder. Finally recent studies confirmed as well, that the concept of affective temperament fulfilled the criteria required to be considered as an endophenotype.

[Are catatonia and neuroleptic malignant syndrome related conditions?]. / Existe-t-il un lien entre catatonie et syndrome malin des neuroleptiques ?

INTRODUCTION: Catatonia and neuroleptic malignant syndrome are both conditions that can compromise survival and whose successful treatment depends on early diagnosis. OBJECTIVE: Distinguishing between these two conditions is difficult in a clinical setting and is further complicated by diagnostic criteria overlap. Are they both variations of a single disorder or two distinct conditions that happen to share certain characteristics? The goal of this paper is to review the available published data concerning the existence of a link between these two conditions and to specify the nature of the link between them. METHOD: We identified relevant articles from the PubMed registry by cross-referencing "catatonia" and "neuroleptic malignant syndrome". The articles returned were selected according to language (English and French) and publication date (before November 2007). RESULTS: Opinions are clearly divided concerning the existence of a link between these two conditions. The most commonly held opinion is that catatonia and neuroleptic malignant syndrome are two entities on the same spectrum. There are, however, no less than five different hypotheses concerning the nature of the link between them: first hypothesis: neuroleptic malignant syndrome is a drug-induced form of catatonia; second hypothesis: neuroleptic malignant syndrome is a drug-induced form of malignant catatonia; third hypothesis: neuroleptic malignant syndrome and malignant catatonia are one and the same; fourth hypothesis: catatonia is a risk factor for neuroleptic malignant syndrome; fifth hypothesis: neuroleptic malignant syndrome is a heterogeneous syndrome that includes both catatonic and non-catatonic responses to antipsychotic drugs. Other research maintains that catatonia and neuroleptic malignant syndrome are two distinct conditions. This point of view has fewer proponents, but benefits from historical, clinical and neurobiological studies that comfort this hypothesis. A careful clinical examination should in theory enable the distinction between these two entities and various neurobiological hypotheses are put forward to explain the differences between them. ANALYSIS AND DISCUSSION: The analysis of the data does not enable the elaboration of a single consensus on the existence of a link between catatonia and neuroleptic malignant syndrome. Additionally, the different hypotheses' level of scientific proof is insufficient to confirm or reject them. We only have at our disposal isolated case studies or studies with varying diagnostic criteria. CONCLUSION: A review of the literature does not enable us to confirm or invalidate a link between catatonia and neuroleptic malignant syndrome. However, answering this question would have direct consequences, since the suggestion of a link has led to the contraindication of neuroleptics for the treatment of catatonia, which contraindication has been extended on principle to the use of all newer antipsychotic medication. But since the link between catatonia and neuroleptic malignant syndrome has not been established according to scientific criteria, should the contraindication of atypical antipsychotic drugs be maintained in the treatment of catatonia?