Nocturnal agitation: From sleep state dissociation to sleep-related dissociative state.

Nocturnal agitation refers to a broad spectrum of symptoms from simple movements to aggressive behaviors with partial or complete loss of awareness. An accurate identification of its etiology is critical for appropriate therapeutic intervention. In children and young adults, distinguishing between non-rapid eye movement (NREM) sleep parasomnias and psychogenic non-parasomniac manifestations, a condition known as sleep-related dissociative disorder (SRDD), can be challenging. This review aims to summarize current clinical, neurophysiological, and epidemiological knowledge on NREM parasomnia and SRDD, and to present the pathophysiological hypotheses underlying these nocturnal manifestations. Sleepwalking, sleep terror and confusional arousals are the three main presentations of NREM parasomnias and share common clinical characteristics. Parasomniac episodes generally occur 30minutes to three hours after sleep-onset, they are usually short, lasting no more than few minutes and involve non-stereotyped, clumsy behaviors with frequent amnesia. The prevalence of NREM parasomnia decreases from 15-30% in children to 2-4% in adults. Parasomniac episodes are incomplete awakening from the deepest NREM sleep and are characterized by a dissociated brain activity, with a wake-like activation in motor and limbic structures and a preserved sleep in the fronto-parietal regions. SRDD is a less known condition characterized by dramatic, often very long episodes with frequent aggressive and potentially dangerous behaviors. SRDD episodes frequently occur in quiet wakefulness before falling asleep. These dissociative manifestations are frequently observed in the context of psychological trauma. The pathophysiology of SRDD is poorly understood but could involve transient changes in brain connectivity due to labile sleep-wake boundaries in predisposed individuals. We hypothesize that SRDD and NREM parasomnia are forms of sleep-related dissociative states favored by a sleep-wake state dissociation during sleep-onset and awakening process, respectively.

Evaluation of hypersomnolence: From symptoms to diagnosis, a multidimensional approach.

Hypersomnolence is a major public health issue given its high frequency, its impact on academic/occupational functioning and on accidentology, as well as its heavy socio-economic burden. The positive and aetiological diagnosis is crucial, as it determines the therapeutic strategy. It must consider the following aspects: i) hypersomnolence is a complex concept referring to symptoms as varied as excessive daytime sleepiness, excessive need for sleep, sleep inertia, or drowsiness, all of which warrant specific dedicated investigations; ii) the boundary between physiological and abnormal hypersomnolence is blurred, since most symptoms can be encountered in the general population to varying degrees without being considered as pathological, meaning that their severity, frequency, context of occurrence and related impairment need to be carefully assessed; iii) investigation of hypersomnolence relies on scales/questionnaires as well as behavioural and neurophysiological tests, which measure one or more dimensions, keeping in mind the possible discrepancy between objective and subjective assessment; iv) aetiological reasoning is driven by knowledge of the main sleep regulation mechanisms, epidemiology, and associated symptoms. The need to assess hypersomnolence is growing, both for its management, and for assessing the efficacy of treatments. The landscape of tools available for investigating hypersomnolence is constantly evolving, in parallel with research into sleep physiology and technical advances. These investigations face the challenges of reconciling subjective perception and objective data, making tools accessible to as many people as possible and predicting the risk of accidents.

[Introduction to the hierarchical taxonomy of psychopathology]. / Introduction à la taxonomie hiérarchique de la psychopathologie.

INTRODUCTION: In clinical practice, the usefulness of diagnosis based on the Diagnostic or Statistical Manual of Mental Disorders (DSM) or the International Classification of Diseases, 11th edition, appears essential from a clinical, research, epidemiological, administrative, economic and political level. However, such diagnostic systems have shortcomings in terms of validity, little consideration of comorbidities and strong intra-class heterogeneity. On a structural level, the operationalization of its criteria is based on a reliability which has been defined a posteriori and which does not lead to improving the validity of the diagnosis but rather to the reification of the diagnostic categories. METHODS: First published in its current form in 2017, the Hierarchical Taxonomy of Psychopathology (HiTOP) constitutes a nosological alternative based on statistics. It conceptualizes psychopathology as a set of hierarchical dimensions, i.e. in "transdiagnostic" continua. The HiTOP is structured according to super-spectra, spectra, sub-factors, syndromes, components and symptoms. This comes from the current dimensional psychology and quantitative nosology. This article describes the basic principles of the HiTOP project and its potential to integrate into clinical and psychiatric research based on its advantages and limitations. RESULTS: Unlike the DSM, which is descriptive and categorical, the HiTOP is first a dimensional classification. This dimensionality describes psychiatric phenomena on continua, each dimension providing a diagnostic continuum to situate a clinical patient. This dimensionality avoids the reification of categories and it limits the dichotomy between normal and pathological. In addition, HiTOP shows a hierarchical structure: vertical refinement of dimensions allows to circumvent the problem of comorbidities, proposes a new conception of etiopathogenic mechanisms, and improves management of care. DISCUSSION: Thus, we provide an illustration of the applications of a dimensional and hierarchical classification in current clinical practice and scientific research, compared to traditional nosology. The challenges of the HiTOP arise in terms of validity, i.e. in the relation of dimensions with physiopathological mechanisms, in clinical terms, i.e. in the potential contribution of dimensions in relation to categories. Moreover, methodological challenges will be important given the inherent limitations of the HiTOP. CONCLUSION: The HiTOP allows to examine the conceptualization of psychiatric disorders, the search for explanatory mechanisms, and treatment from another perspective for psychiatry.

EEG Neurofeedback for Anxiety Disorders and Post-Traumatic Stress Disorders: A Blueprint for a Promising Brain-Based Therapy.

PURPOSE OF REVIEW: This review provides an overview of current knowledge and understanding of EEG neurofeedback for anxiety disorders and post-traumatic stress disorders. RECENT FINDINGS: The manifestations of anxiety disorders and post-traumatic stress disorders (PTSD) are associated with dysfunctions of neurophysiological stress axes and brain arousal circuits, which are important dimensions of the research domain criteria (RDoC). Even if the pathophysiology of these disorders is complex, one of its defining signatures is behavioral and physiological over-arousal. Interestingly, arousal-related brain activity can be modulated by electroencephalogram-based neurofeedback (EEG NF), a non-pharmacological and non-invasive method that involves neurocognitive training through a brain-computer interface (BCI). EEG NF is characterized by a simultaneous learning process where both patient and computer are involved in modifying neuronal activity or connectivity, thereby improving associated symptoms of anxiety and/or over-arousal. Positive effects of EEG NF have been described for both anxiety disorders and PTSD, yet due to a number of methodological issues, it remains unclear whether symptom improvement is the direct result of neurophysiological changes targeted by EEG NF. Thus, in this work we sought to bridge current knowledge on brain mechanisms of arousal with past and present EEG NF therapies for anxiety and PTSD. In a nutshell, we discuss the neurophysiological mechanisms underlying the effects of EEG NF in anxiety disorder and PTSD, the methodological strengths/weaknesses of existing EEG NF randomized controlled trials for these disorders, and the neuropsychological factors that may impact NF training success.

[Network analysis by systemic text excavation of the concept of personalized psychiatry and precision]. / Analyse en réseau par fouille de données textuelles systématique du concept de psychiatrie personnalisée et de précision.

OBJECTIVES: The current challenges of psychiatric nosology and semiology are part of an interdisciplinary and integrative framework. The paradigm of the personalized and precision psychiatry proposes to study this discipline according to new approaches and methodologies. Personalized and precision psychiatry therefore requires clarification of its concepts. To our knowledge, there is no systematic exploration of the literature on the application of the concepts of personalized and precision medicine in the field of psychiatry. This article proposes thus to explore the framework of personalized and precision medicine applied to psychiatry. METHODS: We explored the framework of personalized and precision medicine applied to psychiatry by a textual network analysis. Firstly, we performed a systematic text-mining (Natural Language Processing) from an exhaustive review of the international literature with the terms "precision psychiatry" and "personalized psychiatry". Secondly, this analysis of textual data allowed us to build a textual network which made it possible to visualize the most proximal terms (the most frequently associated in the literature). Finally, we extracted from the network the main dimensions explored in the scientific literature, and we studied the relative importance of each term by analyzing the network centrality. In addition, a brief bibliometric analysis was conducted. RESULTS: We show that personalized and precision psychiatry refers to six dimensions found in the textual network analysis which correspond to the scientific fields which study personalized and precision psychiatry: genetics, pharmacogenetics, artificial intelligence, therapeutic trials, biomarkers and staging. We explore how each dimension relates to the mechanization of psychiatric disorders. However, precision and personalized psychiatry, which tries to refine the levels of mechanistic explanations for psychiatry, suffers from a conceptual heterogeneity. Indeed, textual analysis also allows us to find terms referring to a set of heterogeneous concepts. Many methodological fields and epistemological concepts are invoked in this literature, without standardization. CONCLUSIONS: The paradox of personalized and precision psychiatry is to associate a strong conceptual heterogeneity with a well-defined mechanistic component. Heterogeneity found in literature on personalized and precision psychiatry testifies to the lack of a pluralist and integrative theoretical framework. This framework could be based on a naturalizing but non-reducing formalism, aware of the societal challenges of the sciences and their implementation in the research and clinical systems of psychiatry.

Practical considerations for the evaluation and management of Attention Deficit Hyperactivity Disorder (ADHD) in adults.

Attention deficit with or without hyperactivity disorder (ADHD) is one of the most frequent neuropsychiatric disorders, and affects 2-4% of adults. In contrast with many European countries, the identification and management of adult ADHD remains underdeveloped in France, and a subject of controversy. This review provides a practical update on current knowledge about ADHD in adults for French-speaking professionals who have to detect or manage adult patients with ADHD. ADHD is classified as a neurodevelopmental disorder in the recent update of the international diagnostic classification. While symptoms and impairment due to ADHD are frequently severe during childhood, they often evolve as children grow older, with frequent persistent disabilities in adulthood. In adulthood, the clinical presentation, as in childhood, involves the symptom triad of inattention, hyperactivity and impulsivity. However, differences are noted: hyperactivity is more often internalized, symptoms of inattention may be masked by anxiety symptoms or obsessive-like compensation strategies. ADHD is often diagnosed during childhood, but it is not rare for the diagnosis to be made later. Failure to recognise symptoms resulting in misdiagnosis, or alternatively well-developed compensation factors could be two underlying reasons for the long delay until diagnosis. Other symptoms, such as emotional deregulation or executive function-related symptoms are also usually observed in adults. In addition, in adults, ADHD is often associated with other psychiatric disorders (in 80% of cases); this makes the diagnosis even more difficult. These disorders encompass a broad spectrum, from mood disorders (unipolar or bipolar), to anxiety disorders, and other neurodevelopmental disorders and personality disorders, especially borderline and antisocial personality disorder. Substance-use disorders are very common, either as a consequence of impulsivity and emotional dysregulation or as an attempt at self-treatment. Sleep disorders, especially restless leg syndrome and hypersomnolence, could share common pathophysiological mechanisms with ADHD. ADHD and comorbidity-related symptoms are responsible for serious functional impairment, in various domains, leading to academic, social, vocational, and familial consequences. The impact on other psychiatric disorders as an aggravating factor should also be considered. The considerable disability and the poorer quality of life among adults with ADHD warrant optimal evaluation and management. The diagnostic procedure for ADHD among adults should be systematic. Once the positive diagnosis is made, the evaluation enables characterisation of the levels of severity and impairment at individual level. A full examination should also assess medical conditions associated with ADHD, to provide personalized care. In recent years, a growing number of assessment tools have been translated and validated in French providing a wide range of structured interviews and standardized self-report questionnaires for the evaluation of core and associated ADHD symptoms, comorbidities and functional impairment. The treatment of ADHD in adults is multimodal, and aims to relieve the symptoms, limit the burden of the disease, and manage comorbidities. The most relevant and validated psychological approaches are psycho-education, cognitive-behavioural therapy and "third wave therapies" with a specific focus on emotional regulation. Cognitive remediation and neurofeedback are promising strategies still under evaluation. Medications, especially psychostimulants, are effective for alleviating ADHD symptoms with a large effect size. Their safety and tolerance are satisfactory, although their long-term clinical benefit is still under discussion. In France, methylphenidate is the only stimulant available for the treatment of ADHD. Unfortunately, there is no authorization for its use among adults except in continuation after adolescence. Hence the prescription, which is subject to the regulations on narcotics, is off-label in France. This article aims to provide practical considerations for the management of ADHD and associated disorders in adults, in this particular French context.

The use of melatonin in adult psychiatric disorders: Expert recommendations by the French institute of medical research on sleep (SFRMS).

Melatonin is a hormone secreted by the pineal gland at night. This hormone has many physiological functions, the main one being to synchronise individuals' biological rhythms. Exogenous melatonin has the same chronobiotic action, even at small doses (0.125mg). In addition, a sleep-inducing (soporific) action appears to occur in a dose-effect relationship, i.e. as the dose increases. In psychiatric disorders, these two effects could have interesting applications in clinical practice. The French institute of medical research on sleep (SFRMS) appointed a group of experts to conduct a consensus conference to study the indications of melatonin and the conditions of its prescription. An account of the conclusions on adult psychiatric disorders (presented orally at the Congress on Sleep in Marseille, 23 November 2017) is given here. Exogenous melatonin proves to be useful among patients with a stabilized psychiatric disorder or in remission, to prevent relapse in case of associated complaints of insomnia, poor quality sleep or delayed sleep phase syndrome. During acute phases, melatonin could be used as an adjuvant treatment when there are insomnia symptoms, in mood disorders (bipolar disorder, major depressive disorder, seasonal affective disorder), in attention deficit hyperactivity disorder (ADHD), in peri-surgical anxiety and in schizophrenia. In somatoform disorders, melatonin is a possible treatment for painful symptoms in fibromyalgia, irritable bowel syndrome, functional dyspeptic syndrome and temporomandibular joint dysfunction.

EEG neurofeedback research: A fertile ground for psychiatry?

The clinical efficacy of neurofeedback is still a matter of debate. This paper analyzes the factors that should be taken into account in a transdisciplinary approach to evaluate the use of EEG NFB as a therapeutic tool in psychiatry. Neurofeedback is a neurocognitive therapy based on human-computer interaction that enables subjects to train voluntarily and modify functional biomarkers that are related to a defined mental disorder. We investigate three kinds of factors related to this definition of neurofeedback. We focus this article on EEG NFB. The first part of the paper investigates neurophysiological factors underlying the brain mechanisms driving NFB training and learning to modify a functional biomarker voluntarily. Two kinds of neuroplasticity involved in neurofeedback are analyzed: Hebbian neuroplasticity, i.e. long-term modification of neural membrane excitability and/or synaptic potentiation, and homeostatic neuroplasticity, i.e. homeostasis attempts to stabilize network activity. The second part investigates psychophysiological factors related to the targeted biomarker. It is demonstrated that neurofeedback involves clearly defining which kind of relationship between EEG biomarkers and clinical dimensions (symptoms or cognitive processes) is to be targeted. A nomenclature of accurate EEG biomarkers is proposed in the form of a short EEG encyclopedia (EEGcopia). The third part investigates human-computer interaction factors for optimizing NFB training and learning during the closed loop interaction. A model is proposed to summarize the different features that should be controlled to optimize learning. The need for accurate and reliable metrics of training and learning in line with human-computer interaction is also emphasized, including targeted biomarkers and neuroplasticity. All these factors related to neurofeedback show that it can be considered as a fertile ground for innovative research in psychiatry.

[What do virtual reality tools bring to child and adolescent psychiatry?] / Qu'apportent les outils de réalité virtuelle en psychiatrie de l'enfant et l'adolescent ?

Virtual reality is a relatively new technology that enables individuals to immerse themselves in a virtual world. It offers several advantages including a more realistic, lifelike environment that may allow subjects to "forget" they are being assessed, allow a better participation and an increased generalization of learning. Moreover, the virtual reality system can provide multimodal stimuli, such as visual and auditory stimuli, and can also be used to evaluate the patient's multimodal integration and to aid rehabilitation of cognitive abilities. The use of virtual reality to treat various psychiatric disorders in adults (phobic anxiety disorders, post-traumatic stress disorder, eating disorders, addictions…) and its efficacy is supported by numerous studies. Similar research for children and adolescents is lagging behind. This may be particularly beneficial to children who often show great interest and considerable success on computer, console or videogame tasks. This article will expose the main studies that have used virtual reality with children and adolescents suffering from psychiatric disorders. The use of virtual reality to treat anxiety disorders in adults is gaining popularity and its efficacy is supported by various studies. Most of the studies attest to the significant efficacy of the virtual reality exposure therapy (or in virtuo exposure). In children, studies have covered arachnophobia social anxiety and school refusal phobia. Despite the limited number of studies, results are very encouraging for treatment in anxiety disorders. Several studies have reported the clinical use of virtual reality technology for children and adolescents with autistic spectrum disorders (ASD). Extensive research has proven the efficiency of technologies as support tools for therapy. Researches are found to be focused on communication and on learning and social imitation skills. Virtual reality is also well accepted by subjects with ASD. The virtual environment offers the opportunity to administer controlled tasks such as the typical neuropsychological tools, but in an environment much more like a standard classroom. The virtual reality classroom offers several advantages compared to classical tools such as more realistic and lifelike environment but also records various measures in standardized conditions. Most of the studies using a virtual classroom have found that children with Attention Deficit/Hyperactivity Disorder make significantly fewer correct hits and more commission errors compared with controls. The virtual classroom has proven to be a good clinical tool for evaluation of attention in ADHD. For eating disorders, cognitive behavioural therapy (CBT) program enhanced by a body image specific component using virtual reality techniques was shown to be more efficient than cognitive behavioural therapy alone. The body image-specific component using virtual reality techniques boots efficiency and accelerates the CBT change process for eating disorders. Virtual reality is a relatively new technology and its application in child and adolescent psychiatry is recent. However, this technique is still in its infancy and much work is needed including controlled trials before it can be introduced in routine clinical use. Virtual reality interventions should also investigate how newly acquired skills are transferred to the real world. At present virtual reality can be considered a useful tool in evaluation and treatment for child and adolescent disorders.

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.

Birth by cesarean section and schizophrenia: results from the multicenter FACE-SZ data-set.

Children born by cesarean section ("c-birth") are known to have different microbiota and a natural history of different disorders including allergy, asthma and overweight compared to vaginally born ("v-birth") children. C-birth is not known to increase the risk of schizophrenia (SZ), but to be associated with an earlier age at onset. To further explore possible links between c-birth and SZ, we compared clinical and biological characteristics of c-born SZ patients compared to v-born ones. Four hundred and fifty-four stable community-dwelling SZ patients (mean age = 32.4 years, 75.8 % male gender) were systematically included in the multicentre network of FondaMental Expert Center for schizophrenia. Overall, 49 patients (10.8 %) were c-born. These subjects had a mean age at schizophrenia onset of 21.9 ± 6.7 years, a mean duration of illness of 10.5 ± 8.7 years and a mean PANSS total score of 70.9 ± 18.7. None of these variables was significantly associated with c-birth. Multivariate analysis showed that c-birth remained associated with lower CRP levels (aOR = 0.07; 95 % CI 0.009-0.555, p = 0.012) and lower premorbid ability (aOR = 0.945; 95 % CI 0.898-0.994, p = 0.03). No significant association between birth by C-section and, respectively, age, age at illness onset, sex, education level, psychotic and mood symptomatology, antipsychotic treatment, tobacco consumption, birth weight and mothers suffering from schizophrenia or bipolar disorder has been found. Altogether, the present results suggest that c-birth is associated with lower premorbid intellectual functioning and lower blood CRP levels in schizophrenia. Further studies should determine the mechanisms underlying this association.

Keep calm and carry on: Mental disorder is not more "organic" than any other medical condition.

Psychiatry as a discipline should no longer be grounded in the dualistic opposition between organic and mental disorders. This non-dualistic position refusing the partition along functional versus organic lines is in line with Jean Delay, and with Robert Spitzer who wanted to include in the definition of mental disorder discussed by the DSM-III task force the statement that "mental disorders are a subset of medical disorders". However, it is interesting to note that Spitzer and colleagues ingeniously introduced the definition of "mental disorder" in the DSM-III in the following statement: "there is no satisfactory definition that specifies precise boundaries for the concept "mental disorder" (also true for such concepts as physical disorder and mental and physical health)". Indeed, as for "mental disorders", it is as difficult to define what they are as it is to define what constitutes a "physical disorder". The problem is not the words "mental" or "organic" but the word "disorder". In this line, Wakefield has proposed a useful "harmful dysfunction" analysis of mental disorder. They raise the issue of the dualistic opposition between organic and mental disorders, and situate the debate rather between the biological/physiological and the social. The paper provides a brief analysis of this shift on the question of what is a mental disorder, and demonstrates that a mental disorder is not more "organic" than any other medical condition. While establishing a dichotomy between organic and psychiatry is no longer intellectually tenable, the solution is not to reduce psychiatric and non-psychiatric disorders to the level of "organic disorders" but rather to continue to adopt both a critical and clinically pertinent approach to what constitutes a "disorder" in medicine.

[How to characterize and treat sleep complaints in bipolar disorders?] / Comment caractériser et traiter les plaintes de sommeil dans les troubles bipolaires ?

OBJECTIVES: Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD. METHODS: We examined the international scientific literature in June 2016 and performed a literature search with PubMed electronic database using the following headings: "bipolar disorder" and ("sleep" or "insomnia" or "hypersomnia" or "circadian" or "apnoea" or "apnea" or "restless legs"). RESULTS: Patients with BD suffer from sleep and circadian rhythm abnormalities during major depressive episodes (insomnia or hypersomnia, nightmares, nocturnal and/or early awakenings, non-restorative sleep) and manic episodes (insomnia, decreased need for sleep without fatigue), but also some of these abnormalities may persist during remission. These remission phases are characterized by a reduced quality and quantity of sleep, with a longer sleep duration, increased sleep latency, a lengthening of the wake time after sleep onset (WASO), a decrease of sleep efficiency, and greater variability in sleep/wake rhythms. Patients also present frequent sleep comorbidities: chronic insomnia, sleepiness, sleep phase delay syndrome, obstructive sleep apnea/hypopnea syndrome (OSAHS), and restless legs syndrome (RLS). These disorders are insufficiently diagnosed and treated whereas they are associated with mood relapses, treatment resistance, affect cognitive global functioning, reduce the quality of life, and contribute to weight gain or metabolic syndrome. Sleep and circadian rhythm abnormalities have been also associated with suicidal behaviors. Therefore, a clinical exploration with characterization of these abnormalities and disorders is essential. This exploration should be helped by questionnaires and documented on sleep diaries or even actimetric objective measures. Explorations such as ventilatory polygraphy, polysomnography or a more comprehensive assessment in a sleep laboratory may be required to complete the diagnostic assessment. Treatments obviously depend on the cause identified through assessment procedures. Treatment of chronic insomnia is primarily based on non-drug techniques (by restructuring behavior and sleep patterns), on psychotherapy (cognitive behavioral therapy for insomnia [CBT-I]; relaxation; interpersonal and social rhythm therapy [IPSRT]; etc.), and if necessary with hypnotics during less than four weeks. Specific treatments are needed in phase delay syndrome, OSAHS, or other more rare sleep disorders. CONCLUSIONS: BD are defined by several sleep and circadian rhythm abnormalities during all phases of the disorder. These abnormalities and disorders, especially during remitted phases, should be characterized and diagnosed to reduce mood relapses, treatment resistance and improve BD outcomes.

[Noninvasive cerebral stimulation for treatment of ADHD: A review of the literature]. / Stimulation cérébrale non invasive dans le traitement du trouble déficit de l'attention avec ou sans hyperactivité : une revue de la littérature.

OBJECTIVES: The aim of this review is to summarize the available data in the literature about the therapeutic applications of transcranial magnetic stimulation and transcranial direct current stimulation in attention-deficit hyperactivity disorder (ADHD). METHOD: The scientific literature search of international articles was performed in February 2016 using the PubMed electronic database. The following MeSH terms were employed: "attention-deficit disorder with hyperactivity" AND "transcranial magnetic stimulation", "attention-deficit disorder with hyperactivity" AND "transcranial direct current stimulation". RESULTS: Five studies were retained by the literature search and were included in the review about rTMS and ADHD. Except for one study, they all showed significant positive effects of rTMS on ADHD. Four studies were retained by the literature search and were included in the review about tDCS and ADHD. Three of them showed significant positive effects of tDCS on ADHD. Two of them used tDCS during sleep at a frequency<1Hz. Only low-level evidences are available to support treatment with rTMS or tDCS in patients with ADHD. Indeed, randomized controlled trials are rare in this field of research. CONCLUSION: Additional studies are needed to confirm the efficacy of rTMS and tDCS in ADHD. rTMS could be used as an alternative therapy when methylphenidate is not well tolerated or shows an insufficient efficacy. Nevertheless, the optimal target, frequency and duration remain to be determined. tDCS can modulate attention in healthy subjects but data are insufficient in ADHD to conclude. It could be interesting to study its use in association with cognitive remediation to enhance its cognitive efficacy.

Neurofeedback: One of today's techniques in psychiatry?

OBJECTIVES: Neurofeedback is a technique that aims to teach a subject to regulate a brain parameter measured by a technical interface to modulate his/her related brain and cognitive activities. However, the use of neurofeedback as a therapeutic tool for psychiatric disorders remains controversial. The aim of this review is to summarize and to comment the level of evidence of electroencephalogram (EEG) neurofeedback and real-time functional magnetic resonance imaging (fMRI) neurofeedback for therapeutic application in psychiatry. METHOD: Literature on neurofeedback and mental disorders but also on brain computer interfaces (BCI) used in the field of neurocognitive science has been considered by the group of expert of the Neurofeedback evaluation & training (NExT) section of the French Association of biological psychiatry and neuropsychopharmacology (AFPBN). RESULTS: Results show a potential efficacy of EEG-neurofeedback in the treatment of attentional-deficit/hyperactivity disorder (ADHD) in children, even if this is still debated. For other mental disorders, there is too limited research to warrant the use of EEG-neurofeedback in clinical practice. Regarding fMRI neurofeedback, the level of evidence remains too weak, for now, to justify clinical use. The literature review highlights various unclear points, such as indications (psychiatric disorders, pathophysiologic rationale), protocols (brain signals targeted, learning characteristics) and techniques (EEG, fMRI, signal processing). CONCLUSION: The field of neurofeedback involves psychiatrists, neurophysiologists and researchers in the field of brain computer interfaces. Future studies should determine the criteria for optimizing neurofeedback sessions. A better understanding of the learning processes underpinning neurofeedback could be a key element to develop the use of this technique in clinical practice.

[Serious game as a therapeutic tool in psychiatry: A systematic review]. / Le serious game : applications thérapeutiques en psychiatrie.

CONTEXT: The growing field of new technologies offers new ways to tackle psychiatric disorders (e.g. virtual reality therapy, neurofeedback, etc.). Serious games (SG) are computer applications combining serious aspects with the fun side of video games. This kind of new media could find applications to treat psychiatric disorders. OBJECTIVE: This paper summarizes available data in the literature about therapeutic interventions using SG in psychiatry. METHOD: A Medline search was conducted in May 2014 using the following Medical Subject Headings (MESH) terms: "video games", "mental disorders", and "psychotherapy". RESULTS: Only 10 relevant references were identified according to our inclusion criteria. These studies show that SG are very interesting tools to improve the management of psychiatric disorders. However, only low-level evidence is available to support treatment with SG in patients suffering from psychiatric disorders. Indeed, randomized controlled trials are rare in this field of research. CONCLUSION: SG provide promising therapeutic innovations for the management of psychiatric disorders. Moreover, they could easily be developed in accordance with current dimensional approaches. Finally, major issues to facilitate the implementation of future work on SG in psychiatry are discussed.

[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.