Psychogenic non-epileptic seizures: Chronology of multidisciplinary team approach to diagnosis and management.

While the diagnosis and management of psychogenic non-epileptic seizures (PNES) remain challenging, certain evidence-based guidelines exist, which can help to optimize patient care. A multidisciplinary team approach appears to have many benefits. Current recommendations exist for some aspects of diagnosis and management of PNES, including levels of diagnostic certainty as proposed by the International League Against Epilepsy's expert Task Force on PNES. Other aspects of clinical still care lack clear consensus, including use of suggestion techniques for recording PNES and optimal terminology, since the term "functional seizures" has recently been proposed as a possible term to replace "PNES". The present article aims to (1) review current recommendations and (2) discuss our own team's experience in managing patients with PNES. This is organized chronologically in terms of the roles of the neurologist, psychiatrist and psychologist, and discusses diagnostic issues, psychiatric assessment and treatment, and psychotherapeutic approaches.

Hypovitaminosis D is associated with negative symptoms, suicide risk, agoraphobia, impaired functional remission, and antidepressant consumption in schizophrenia.

Hypovitaminosis D has been associated with, respectively, major depressive disorder, schizophrenia (SZ), and cognitive disorders in the general population, and with positive and negative symptoms and metabolic syndrome in schizophrenia. The objective was to determine the prevalence of hypovitaminosis D and associated factors in a non-selected multicentric sample of SZ subjects in day hospital. Hypovitaminosis D was defined by blood vitamin D level < 25 nM. Depressive symptoms were assessed by the Calgary Depression Rating Scale Score and Positive and Negative Syndrome Scale Score. Anxiety disorders and suicide risk were evaluated by the Structured Clinical Interview for Mental Disorders. Functioning was evaluated with the Functional Remission of General Schizophrenia Scale. Hypovitaminosis D has been found in 27.5% of the subjects. In multivariate analysis, hypovitaminosis D has been significantly associated with, respectively, higher suicide risk (aOR = 2.67 [1.31-5.46], p = 0.01), agoraphobia (aOR = 3.37 [1.66-6.85], p < 0.0001), antidepressant consumption (aOR = 2.52 [1.37-4.64], p < 0.001), negative symptoms (aOR = 1.04 [1.01-1.07], p = 0.04), decreased functioning (aOR = 0.97[0.95-0.99], p = 0.01), and increased leucocytosis (aOR = 1.17 [1.04-1.32], p = 0.01) independently of age and gender. No association with alcohol use disorder, metabolic syndrome, peripheral inflammation, insulin resistance, or thyroid disturbances has been found (all p > 0.05). Despite some slight abnormalities, no major cognitive impairment has been associated with hypovitaminosis D in the present sample (all p > 0.05 except for WAIS similarities score). Hypovitaminosis D is frequent and associated with suicide risk, agoraphobia and antidepressant consumption in schizophrenia, and more slightly with negative symptoms. Patients with agoraphobia, suicide risk and antidepressant consumption may, therefore, benefit in priority from vitamin D supplementation, given the benefit/risk profile of vitamin D. Further studies should evaluate the impact of vitamin D supplementation on clinical outcomes of SZ subjects.

Making psychiatric semiology great again: A semiologic, not nosologic challenge.

This article analyzes whether psychiatric disorders can be considered different from non-psychiatric disorders on a nosologic or semiologic point of view. The supposed difference between psychiatric and non-psychiatric disorders relates to the fact that the individuation of psychiatric disorders seems more complex than for non-psychiatric disorders. This individuation process can be related to nosologic and semiologic considerations. The first part of the article analyzes whether the ways of constructing classifications of psychiatric disorders are different than for non-psychiatric disorders. The ways of establishing the boundaries between the normal and the pathologic, and of classifying the signs and symptoms in different categories of disorder, are analyzed. Rather than highlighting the specificity of psychiatric disorders, nosologic investigation reveals conceptual notions that apply to the entire field of medicine when we seek to establish the boundaries between the normal and the pathologic and between different disorders. Psychiatry is thus very important in medicine because it exemplifies the inherent problem of the construction of cognitive schemes imposed on clinical and scientific medical information to delineate a classification of disorders and increase its comprehensibility and utility. The second part of this article assesses whether the clinical manifestations of psychiatric disorders (semiology) are specific to the point that they are entities that are different from non-psychiatric disorders. The attribution of clinical manifestations in the different classifications (Research Diagnostic Criteria, Diagnostic Statistic Manual, Research Domain Criteria) is analyzed. Then the two principal models on signs and symptoms, i.e. the latent variable model and the causal network model, are assessed. Unlike nosologic investigation, semiologic analysis is able to reveal specific psychiatric features in a patient. The challenge, therefore, is to better define and classify signs and symptoms in psychiatry based on a dual and mutually interactive biological and psychological perspective, and to incorporate semiologic psychiatry into an integrative, multilevel and multisystem brain and cognitive approach.

[What place for placebo in clinical trials conducted on psychiatric patients?] / Quelle place pour le placebo dans les essais cliniques en psychiatrie ?

Placebo effect remains a crucial issue in current clinical trials. Most clinical trials rely on the hypothesis of equivalent placebo response rates in both placebo and specific drug arms ("additive model"). But contrary to this dominant and rarely questioned hypothesis, several aspects may influence placebo response. A few recent meta-analyses and reviews have shown evidence for several clinical and methodological factors, which are able to modulate placebo response. In psychiatry research, placebo response has been mainly explored through antidepressant trials. In early clinical trials, drug-placebo differences were initially significant and robust. However, more recent clinical trials have not yielded similar results, and rather show narrowed antidepressant-placebo differences. Several factors may be involved in this absence of comparability: intrinsic properties of new antidepressants, changes in clinical criteria and classifications, symptomatic remission rather than global remission criteria, industrial and institutional constraints. Moreover, results from antidepressant trials (laboratory conditions) remain hardly fully transposable to clinical routine (ecological conditions).

[Electroconvulsive therapy and level of evidence: From causality to dose-effect relationship]. / Électroconvulsivothérapie et niveau de preuve : de la causalité à la relation dose-effet.

OBJECTIVES: The first objective of this article is to summarize the history of electroconvulsive therapy (ECT) in psychiatry in order to highlight the transition from clinical level of evidence based on phenomenological descriptions to controlled trial establishing causal relationship. The second objective is to apply the criteria of causation for ECT, to focus on the dose-effect relationship criteria, and thus to analyze the conditions of application of these criteria for ECT. METHODS: A literature review exploring the use of electricity, ECT and electroencephalography (EEG) in psychiatry was conducted. The publications were identified from the Pubmed and GoogleScholar electronic databases. The scientific literature search of international articles was performed in July 2016. RESULTS: In 1784, a Royal commission established in France by King Louis XVI tested Mesmer's claims concerning animal magnetism. By doing that, the commission, including such prominent scientists as the chemist Anton Lavoisier and the scientist and researcher on electricity and therapeutics Benjamin Franklin, played a central role in establishing the criteria needed to assess the level of evidence of electrical therapeutics in psychiatry. Surprisingly, it is possible to identify the classical Bradford Hill criteria of causation in the report of the commission, except the dose-effect relationship criteria. Since then, it has been conducted blinded randomized controlled trials that confirmed the effectiveness of ECT against ECT placebos for the treatment of psychiatric disorders. At present, the dose-effect relationship criteria can be analyzed through an EEG quality assessment of ECT-induced seizures. CONCLUSIONS: EEG quality assessment includes several indices: TSLOW (time to onset of seizure activity ≤5Hz, seconds), peak mid-ictal amplitude (mm), regularity (intensity or morphology of the seizure (0-6)), stereotypy (global seizure patterning, 0-3) and post-ictal suppression (0-3). A manual rating sheet is needed to score theses indices. Such manual rating with example of EEG segments recording is proposed in this article. Additional studies are needed to validate this manual, to better establish the dose-response relationship for the ECT, and thus strengthen the position of the EEG as a central element for clinical good practice for ECT.

[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.

[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.

[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.

[Affective disorders: endocrine and metabolic comorbidities]. / Troubles affectifs et comorbidités endocrino-métaboliques.

Links between affective and endocrine-metabolic disorders are numerous and complex. In this review, we explore most frequent endocrine-metabolic comorbidities. On the one hand, these comorbidities imply numerous iatrogenic effects from antipsychotics (metabolic side-effects) or from lithium (endocrine side-effects). On the other hand, these comorbidities are also associated with affective disorders independently from medication. We will successively examine metabolic syndrome, glycemic disturbances, obesity and thyroid disorders among patients with affective disorders. Endocrinemetabolic comorbidities can be individually encountered, but can also be associated. Therefore, they substantially impact morbidity and mortality by increasing cardiovascular risk factors. Two distinct approaches give an account of processes involved in these comorbidities: common environmental factors (iatrogenic effects, lifestyle), and/or shared physiological vulnerabilities. In conclusion, we provide a synthesis of important results and recommendations related to endocrine-metabolic comorbidities in affective disorders : heavy influence on morbidity and mortality, undertreatment of somatic diseases, importance of endocrine and metabolic side effects from main mood stabilizers, impact from sex and age on the prevalence of comorbidities, influence from previous depressive episodes in bipolar disorders, and relevance of systematic screening for subclinical (biological) disturbances.

[Affective disorders and personality disorders]. / Troubles affectifs et troubles de la personnalité.

Coexistence in an individual of an affective disorder and a personality disorder is very common and there is an abundant literature on it. Articles are numerous and heterogeneous ; the results are sometimes imprecise or discordant. Some data are, despite these reserves, shared by the scientific community. The main consensus is first on a bad prognosis, with a high rate of all DSM axes comorbidities, secondly on the trap of a same phenomenology for different underlying mechanisms. A review is presented.

[Affective disorders and impulsivity]. / Troubles affectifs et impulsivité.

Impulsivity is a complex and important phenomenon in mood disorders. Impulse control disorders, as defined in DSM, are more frequent in mood disorders especially in Bipolar Disorder type I, and are associated with a more severe course of illness. Dimensional studies demonstrate that impulsivity is a core manifestation of bipolar disorder both as state- and trait-dependent markers in patients. Comorbid substance use disorders are often associated with a higher level of impulsivity whereas the relation between suicidal behaviors and higher impulsivity remains uncertain. Moreover, neuropsychological tests were used to study correlation between clinical impulsivity and laboratory measurements of impulsivity. Level of correlation remains weak and several explanations are proposed in the literature.

[Do sleep abnormalities contribute to cardiovascular risk in bipolar disorders?]. / Les anomalies du sommeil peuvent-elles participer au risque cardio-vasculaire des troubles bipolaires ?

OBJECTIVES: The aim of this review is to summarize the state of knowledge concerning the relationship between cardiovascular risk, sleep abnormalities, and emotional reactivity in patients with bipolar disorder (BD). METHOD: A scientific literature search of international articles was performed during August and September 2014 using the PubMed electronic database. We used the following MeSH terms : "Bipolar Disorders", "Cardiovascular risk", "Emotional reactivity", "Sleep apnea", and "Sleep disorder". RESULTS: Obstructive sleep apnea (OSA) is a sleep disorder strongly associated with BD, which tends to fragment sleep. OSA is associated with an increased cardiovascular risk. Furthermore, emotional hyper-reactivity is favored by "hostility" temperaments, BD and sleep deprivation. The combination of these factors interacts and also results in an increased cardiovascular risk. Taken as a whole, both sleep disorders and emotional hyper-reactivity seem to increase the risk of cardiovascular diseases in BD. CONCLUSION: These data emphasize the central role of sleep abnormalities and emotional reactivity in the vulnerability of BD to express cardiovascular diseases. From a clinical point of view, these data also emphasize the importance of identifying and care for sleep abnormalities in BD in order to improve BD outcome.

[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 and neuroimaging]. / États mixtes et neuroimagerie.

Despite the growing number of neuroimaging studies in bipolar disorder over the past years, the brain regions involved in mood dysregulation in this disease are still poorly understood. If some neurofunctional abnormalities seem to be independent of mood state, others were preferentially associated with mania or depression, involving the amygdala and other limbic regions as well as ventral frontal regions, with a likely hemispheric lateralization of these abnormalities according to the thymic state that was examined. Very few imaging studies became interested in bipolar patients in a mixed state, making it harder to connect brain malfunction to a given mood state. However, data obtained so far support the hypothesis of a lateralization of brain abnormalities in relation to bipolar symptomatology, suggesting that neurofonctional abnormalities preferentially located in the right ventral frontal and limbic areas may underlie the depressive component, associated with abnormalities of the left similar regions for the manic component. Identification of brain dysfunctions that may explain the emergence of mixed symptoms will likely provide useful information to better understand the respective roles of each hemisphere in the pathophysiology of bipolar disorder.

[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.

[Clinical description of mixed mania]. / Clinique des manies mixtes.

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 depressions: clinical and neurophysiological biomarkers]. / Épisodes dépressifs mixtes : clinique et biomarqueurs neurophysiologiques.

Epidemiological studies of major depressive episodes (MDE) highlighted the frequent association of symptoms or signs of mania or hypomania with depressive syndrome. Beyond the strict definition of DSM-IV, epidemiological recognition of a subset of MDE characterized by the presence of symptoms or signs of the opposite polarity is clinically important because it is associated with pejorative prognosis and therapeutic response compared to the subgroup of "typical MDE". The development of DSM-5 took into account the epidemiological data. DSM-5 opted for a more dimensional perspective in implementing the concept of "mixed features" from an "episode" to a "specification" of mood disorder. As outlined in the DSM-5: "Mixed features associated with a major depressive episode have been found to be a significant risk factor for the development of bipolar I and II disorder. As a result, it is clinically useful to note the presence of this specifier for treatment planning and monitoring of response to therapeutic". However, the mixed features are sometimes difficult to identify, and neurophysiological biomarkers would be useful to make a more specific diagnosis. Two neurophysiological models make it possible to better understand MDE with mixed features : i) the emotional regulation model that highlights a tendency to hyper-reactive and unstable emotion response, and ii) the vigilance regulation model that highlights, through EEG recording, a tendency to unstable vigilance. Further research is required to better understand relationships between these two models. These models provide the opportunity of a neurophysiological framework to better understand the mixed features associated with MDE and to identify potential neurophysiological biomarkers to guide therapeutic strategies.