The utility of the autism-spectrum quotient to screen for autism spectrum disorder in adults with attention deficit/hyperactivity disorder.

The co-occurrence of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) has been reported to be highly prevalent in adults. However, very few studies have assessed the usefulness of screening instruments to detect this co-occurrence, particularly when screening for ASD in the context of ADHD. Our study aimed at assessing the utility of the autism-spectrum quotient (AQ) as a screening tool of ASD in a sample of 153 adults referred for ADHD assessment. Our results showed that the AQ is of limited use in this context as its positive predictive value was low (47%). Particularly, the more severe the attentional deficits the more likely individuals with ADHD were to be misclassified as having a co-occurring ASD based on the AQ. However, the "imagination" subscale of the AQ was able to discriminate those who met ASD criteria from those who did not, suggesting that targeting imagination impairments might be useful when assessing for the ADHD+ASD co-occurrence in clinical settings.

Neurodevelopmental Disorders: From Pathophysiology to Novel Therapeutic Approaches.

This special issue of Biomedicines on Neurodevelopmental Disorders (NDD): "From Pathophysiology to Novel Therapeutic Approaches", is a precursor of what we hope will develop into a thriving and inspiring transdisciplinary field, including genetics, psychiatry, neurology, as well as basic and applied neurosciences and molecular biology in the research area [...].

Prevalence of Polypharmacy and Inappropriate Medication in Adults With Intellectual Disabilities in a Hospital Setting in Switzerland.

Background: Polypharmacy and inappropriate prescription are frequent in vulnerable and multi-morbid populations. Adults with intellectual disability (ID) are at risk of being polymedicated because they often present with multiple comorbidities and challenging behaviors. Aim: The objective of this study was thus to evaluate the prevalence of potentially inappropriate medications (PIM) and polypharmacy in a hospital unit dedicated to adults with ID. Methods: A 10-month prospective observational study took place at a hospital unit specializing in the care of adults with ID in Geneva, Switzerland. Once a week, health and prescription data were collected and screened for PIM according to preset definitions. Results: Fourteen patients consented to participate, leading to 20 hospitalization events assessed during the study. Hospitalizations lasted 12.8 weeks on average. ID severities ranged from mild to profound, all degrees of severity being equally represented. One hundred percent of the patients were polymedicated (defined as five drugs or more prescribed simultaneously). A mean number of 9.4 drugs were prescribed per week, including 5.3 psychotropic drugs. The number of prescribed drugs remained stable throughout the hospitalizations. Antipsychotics were the most prescribed drug class (19% of all prescribed drugs), followed by benzodiazepines (13%) and laxatives (12%). A total of 114 PIM were recorded with an average of 5.7 PIM per hospitalization. Conclusions: This study showed that polypharmacy and inappropriate prescription are very common in adults with ID, even though the literature and expert positions advocate for deprescription in these patients. Specific prescribing and deprescribing guidelines are needed for that specific population.

[About the use of ketamine in emergency psychiatric settings]. / À propos de l'utilisation du traitement de la kétamine aux urgences psychiatriques.

Ketamine and its S-enantiomer, esketamine, have shown to be promising molecules for use in psychiatry. Widely investigated for the treatment of drug-resistant depression, they could be used in emergency conditions, due to their rapid onset of action, in two main conditions : 1) psychomotor agitation, and 2) acute suicidal ideation and behavior (suicidal crisis). In particular, intranasal administration offers a non-invasive, safe and very easy to administer option. An effect begins a few hours to a day after intake and lasts for about a week. These molecules present an innovative option for the future and their specific use in psychiatric emergencies.

La kétamine et son énantiomère S, l'eskétamine, se sont révélés être des molécules prometteuses pour leur utilisation en psychiatrie. Largement étudiées pour le traitement de la dépression pharmacorésistante, elles pourraient être utilisées dans des conditions d'urgence et, grâce à leur rapidité d'action, dans deux situations : 1) l'agitation psychomotrice, et 2) l'idéation et le comportement suicidaire aigus (crise suicidaire). En particulier, l'administration par voie intranasale offre une option non invasive, sûre et facile à utiliser. On observe un effet quelques heures à un jour après la prise, qui perdure pendant environ une semaine. Ces molécules représentent une option innovatrice pour le futur et pour une utilisation spécifique aux urgences psychiatriques.

TOP-ID: a Delphi technique-guided development of a prescription and deprescription tool for adults with intellectual disabilities.

OBJECTIVES: Adults with an intellectual disability (AWID) are often polymedicated because of somatic and psychiatric health problems. Besides, they may display challenging behaviours, leading to off-label prescription of psychotropic drugs, without efficacy and with numerous adverse effects. In this context, a prescription/deprescription tool (Tool for Optimising Prescription in Intellectual Disability/TOP-ID) was developed to improve the care of AWID. This paper describes how TOP-ID was designed. DESIGN: Four-step consensus-based process involving a review of the literature, eight semistructured interviews and a two-round Delphi process. SETTING: Seventeen general practices and university and general hospitals from Belgium, France and Switzerland. PARTICIPANTS: Eighteen French-speaking physicians from different domains of expertise participated in the Delphi process. PRIMARY AND SECONDARY OUTCOME MEASURES: For the Delphi iteration process, consensus was defined as at least a 65% agreement between the experts. RESULTS: Two rounds were needed for the Delphi process. Eighty-one items of the tool were submitted to 18 out of 35 recruited French-speaking experts during the first round. Sixty-nine per cent of the items reached a rate of agreement of 65% or more in that round. Thirteen questions were reformulated and resubmitted for the second Delphi iteration round. All of the statements reached a rate of agreement of 65% or more in the second round. CONCLUSION: TOP-ID is the first prescription-deprescription tool developed specifically for AWIDs in French. It is intended to help prescribers document patient care in order to reduce prescription errors and to improve safety. The next steps of the project include the development of an electronic version of TOP-ID and a utility study.

Effect of Ketamine on Rumination in Treatment-Resistant Depressive Patients.

BACKGROUND: A rapid antidepressant effect of ketamine has repeatedly been documented in the literature, and identifying clinical features associated with a better response to this treatment is currently an essential question. Considering the relationship between rumination and depression and the need to identify potential predictors of response to ketamine, we analyzed the effect of a single injection of ketamine 0.5 mg/kg on rumination in treatment-resistant depressive (TRD) patients and explored whether baseline ruminative style and early improvements of rumination would predict a greater antidepressant effect of ketamine. METHODS: Ten TRD outpatients who participated in a 4-week open study on the antidepressant effect of ketamine also completed the Ruminative Response Scale the day before, the day after, and a week after ketamine administration. RESULTS: We found that in our patients, a single rapid 1-minute intravenous injection of ketamine 0.5 mg/kg was efficacious in reducing rumination, but neither severity of rumination at baseline nor early improvements of rumination after ketamine injection predicted antidepressant response. CONCLUSIONS: Our preliminary data suggest that a single injection of ketamine 0.5 mg/kg can be efficacious in reducing rumination in TRD patients but rumination does not seem to be a useful clinical predictor of response to ketamine. Larger studies are necessary to confirm these results.

[Drug management of behavioral disorders in people with developmental and intellectual disability]. / Gestion médicamenteuse des troubles du comportement de la personne en situation de handicap mental.

Behavioral disorders in people with developmental and intellectual disability are frequent but their management is rarely taught. This article is to help primary physicians prescribe drug treatment. We will also discuss the key elements of two of the most commonly used classes of drugs, taking into account the patient's co-morbidities, contraindications and the main side effects.

Les troubles du comportement chez la personne en situation de handicap mental sont fréquents, mais leur prise en charge est peu enseignée aux médecins de premier recours. Cet article a pour objectif d'aider à la prescription d'un traitement médicamenteux. Nous discutons des éléments clés des deux classes de médicaments les plus utilisés, en tenant compte des comorbidités du patient, des contre-indications et des principaux effets secondaires.

Pain interventions in adults with intellectual disability: A scoping review and pharmacological considerations.

BACKGROUND AND OBJECTIVE: Having to deal on a daily routine with prescriptions in adults with intellectual disability (ID), we systematically reviewed the literature on the specificities of pain interventions in that population, focusing on medication and trying to gather practical information on appropriate pain treatments. Given the scarcity of the literature on the topic, we also discussed the pharmacological considerations to be taken into account when prescribing analgesic drugs in that vulnerable population. DATABASES AND DATA TREATMENT: Articles on pain and ID were searched in the Medline and Google scholar electronic databases using the key words "Intellectual Disability," "Developmental Disability" and specific keywords for pharmacological and non-pharmacological pain interventions. Preset outcomes about pharmacological treatment specificity, efficacy and safety were then collected. RESULTS: One hundred and fifty-two articles were found and 16 were retained based on our inclusion and exclusion criteria. Of the 16 articles, five were topical reviews. Among the 11 remaining articles, five discussed pharmacological interventions, four considered non-pharmacological interventions and two discussed both. As anticipated, the literature matching our specific outcomes about the pharmacological treatment of pain was scarce and for the most part not designed to answer the questions of specificity, efficacy and safety of pain treatment in adults with ID. CONCLUSION: The specificity of analgesic treatments in adults with ID is a totally unexplored domain. In the absence of clinical guidelines, pharmacological facts-such as inter-individual variability in drug response, pharmacokinetic and pharmacodynamic interactions, frequent co-morbidities and ease of administration-must be systematically integrated, when prescribing in the population of adults with ID. SIGNIFICANCE: This review synthesizes the state of research on pain interventions in adults with ID and is one of the rare articles addressing the specificities of analgesic prescriptions in this population.

[Facilitating access to somatic care for adults suffering from severe mental disabilities]. / Pour un accès facilité aux soins somatiques des adultes en situation de handicap mental sévère.

For the purpose of improving the management of somatic disorders among patients suffering from severe intellectual development and autism spectrum disorders, a specific admissions mechanism has been implemented at Geneva University Hospitals (HUG). The Adult Psychiatric Hospital Unit (UPHA), a complex intervention unit, collaborates with HUG's Disability Program. From May 2018 to May 2019, 29 requests for hospitalizations were accepted. These requests primarily originated from private practice physicians (42 %). In some cases, immediate admissions were urgently organized, and in others a 13-day waiting period was imposed. Hospitalizations were adapted to the patient: more often than not, these were short (48 %), with 6 hospitalizations extended for an average 103-day period. A clinical case illustrates the healthcare management provided.

Afin d'améliorer la prise en charge somatique des patients avec troubles sévères du développement intellectuel et du spectre de l'autisme, un dispositif d'accueil a été mis en place aux Hôpitaux universitaires de Genève (HUG). Dans ce dispositif, l'Unité de psychiatrie hospitalière adulte (UPHA), une unité d'intervention complexe (UIC), collabore avec le Programme Handicap des HUG. De mai 2018 à mai 2019, 29 demandes d'hospitalisation pour soins ou bilans somatiques, évaluées en amont, ont été acceptées. Ces demandes venaient prioritairement des médecins de ville (42 %). Un accueil rapide a été organisé en urgence ou avec un délai moyen de 13 jours. Les séjours étaient adaptés : le plus souvent courts (48 %), 6 séjours ont été prolongés, avec une durée moyenne de séjour de 103 jours. Un cas clinique illustre le type de prise en charge.

Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: The antidepressant effect of ketamine is associated with increased activity in the reward circuitry of the brain and a suppression of circuitry that mediates perceptual processing of negative emotions. The duration of ketamine effect on these brain structures remains to be defined. WHAT THIS ARTICLE TELLS US THAT IS NEW: As expected, ketamine administration led to an improvement in mood and global vigilance. The improvement in mood was accompanied by an increased recruitment of the orbitofrontal cortex, ventral striatum, medial substantial nigra and ventral tegmental area, structures that are part of the reward circuitry.Responses in the mesolimbic structures (amygdala, medial substantial nigra and ventral tegmental area, orbitofrontal cortex) to negative stimuli were decreased after ketamine administration.The data are consistent with the premise that ketamine induces sustained changes in the mesolimbic neural circuits to reset pathological reward and emotional processing. BACKGROUND: Ketamine rapidly improves maladaptive mood states in major depressive disorder, and some of the neural substrates underlying this therapeutic effect have been identified. This study aimed to identify functional changes within neural networks that may underlie the impact of ketamine on both reward and emotional processing in patients with treatment-resistant major depression. METHODS: Ten adult patients with a Montgomery-Åsberg Depression Rating Scale score above 25 were enrolled to receive a single intravenous administration of ketamine (0.5 mg/kg). Patients' performance along with related neural network activations were analyzed in a game-like reward task and in an emotional judgment task using functional magnetic resonance imaging 1 day before and 1 and 7 days after ketamine administration. RESULTS: A significant correlation (R = 0.46, P = 0.03) between the improvement of depression scores and the enhanced reaction time for positive items was found in the game-like reward task 1 day after ketamine administration. This enhanced sensitivity for rewarded items was accompanied by increased activity of reward-related brain regions, including the orbitofrontal cortex, ventral striatum, and the ventral tegmental area, an effect that persisted up to 1 week after ketamine injection. In the emotional judgment task, it was found that ketamine rapidly modified local brain activities in response to emotionally negative, positive, or neutral stimuli in the amygdala, insula, anterior cingulate cortex, and in the ventral tegmental area. CONCLUSIONS: Single bolus ketamine administration rapidly triggers lasting changes in mesolimbic neural networks to improve pathologic reward and emotional processing in patients with major depressive disorder.

Efficacy and Safety of a Rapid Intravenous Injection of Ketamine 0.5 mg/kg in Treatment-Resistant Major Depression: An Open 4-Week Longitudinal Study.

BACKGROUND: Ketamine has been documented for its rapid antidepressant effects. However, optimal dose and delivery route have not yet been thoroughly investigated. The objectives of this study were to document the safety and test the antidepressant and antisuicidal effects of a single rapid 1-minute injection of ketamine 0.5 mg/kg in treatment-resistant depression (TRD). METHODS: Ten patients with TRD were included in an open, noncontrolled 4-week study and received a rapid intravenous dose of ketamine 0.5 mg/kg. Main outcome measure was the Montgomery-Åsberg Depression Rating Scale and suicidality was assessed using the Scale for Suicide Ideation. RESULTS: Rapid injection of ketamine elicited transient increase of blood pressure and altered states of consciousness in all patients and mild psychotomimetic effects in 4 patients, which all resolved without any intervention. Decrease of depression severity was observed from 40-minute postinjection until day 15. Eight patients became responders within 1 day and all were nonresponders after 4 weeks. The decrease of suicidal ideation was significant until day 7. Analysis indicated that higher severity of depression and anxiety at baseline predicted a larger Montgomery-Åsberg Depression Rating Scale decrease after 4 weeks. CONCLUSIONS: This study suggests that in well-controlled medical settings with adequate monitoring, a single rapid 1-minute injection of ketamine 0.5 mg/kg can be well tolerated and is efficacious in rapidly reducing depression symptoms and suicidal thoughts in outpatients with TRD. These findings are relevant to the practice of general clinical psychiatry and emergency departments were ketamine can have a place in acute management of TRD. Larger studies are necessary to confirm these results.

[Intellectual disability: contribution of genetic studies to the etiological diagnosis]. / Handicap intellectuel : apport de la génétique pour le diagnostic étiologique.

The multidiscipinary care of patients with intellectual disability requires a structured and systematic etiological process. Today, advances in technology make it possible to perform diagnostic genetic analyzes that are highly contributive in this process. The CGH-array (Comparative Genomic Hybridization array) makes it possible to search for chromosomal anomalies with a very high level of resolution; high throughput sequencing can detect gene abnormalities on the whole exome or on a panel of genes. For the patient the detection of genetic anomalies aims to improve the quality of care; for related parties, genetic counseling is systematically offered.

La prise en charge multidisciplinaire des patients présentant un handicap intellectuel impose la mise en œuvre d'une démarche étiologique structurée et systématique. Les avancées technologiques permettent aujourd'hui la réalisation d'analyses génétiques diagnostiques très contributives. Le CGH-array (puce d'hybridation génomique comparative) permet de rechercher des anomalies chromosomiques avec un très haut niveau de résolution; le séquençage à haut débit permet de détecter des anomalies géniques sur l'exome entier ou sur un panel de gènes. Pour le patient, la détection d'anomalies génétiques a pour objectif d'améliorer la qualité de la prise en charge; pour les apparentés, un conseil génétique est systématiquement proposé.

Novel NEXMIF pathogenic variant in a boy with severe autistic features, intellectual disability, and epilepsy, and his mildly affected mother.

Intellectual disability (ID) and autism spectrum disorders are complex neurodevelopmental disorders occurring among all ethnic and socioeconomic groups. Pathogenic variants in the neurite extension and migration factor (NEXMIF) gene (formerly named KIAA2022) on the X chromosome are responsible for ID, autistic behavior, epilepsy, or dysmorphic features in males. Most affected females described had a milder phenotype or were asymptomatic obligate carriers. We report here for the first time mother-to-son transmission of a novel NEXMIF truncating variant without X-inactivation skewing in the blood. Truncating gene variant leads to symptomatic mother to severely affected son transmission. Our findings emphasize that NEXMIF sequencing should be strongly considered in patients with unexplained autism spectrum disorder, ID, and epilepsy, irrespective of gender. Such testing could increase our knowledge of the pathogenicity of NEXMIF variants and improve genetic counseling.

Development of inhibitory synaptic inputs on layer 2/3 pyramidal neurons in the rat medial prefrontal cortex.

Inhibitory control of pyramidal neurons plays a major role in governing the excitability in the brain. While spatial mapping of inhibitory inputs onto pyramidal neurons would provide important structural data on neuronal signaling, studying their distribution at the single cell level is difficult due to the lack of easily identifiable anatomical proxies. Here, we describe an approach where in utero electroporation of a plasmid encoding for fluorescently tagged gephyrin into the precursors of pyramidal cells along with ionotophoretic injection of Lucifer Yellow can reliably and specifically detect GABAergic synapses on the dendritic arbour of single pyramidal neurons. Using this technique and focusing on the basal dendritic arbour of layer 2/3 pyramidal cells of the medial prefrontal cortex, we demonstrate an intense development of GABAergic inputs onto these cells between postnatal days 10 and 20. While the spatial distribution of gephyrin clusters was not affected by the distance from the cell body at postnatal day 10, we found that distal dendritic segments appeared to have a higher gephyrin density at later developmental stages. We also show a transient increase around postnatal day 20 in the percentage of spines that are carrying a gephyrin cluster, indicative of innervation by a GABAergic terminal. Since the precise spatial arrangement of synaptic inputs is an important determinant of neuronal responses, we believe that the method described in this work may allow a better understanding of how inhibition settles together with excitation, and serve as basics for further modelling studies focusing on the geometry of dendritic inhibition during development.

[Adults with intellectual disability : actual concepts and clinical challenges]. / Le handicap intellectuel chez l'adulte : concepts actuels et défis dans l'approche clinique.

The condition of the adult with intellectual disability (AWID) includes the largely autonomous, integrated person but also the one in need of constant support, with grossly altered communication abilities, frequently affected by somatic and mental comorbidities and non-adapted behaviors. Their prevalence is about 1 % of the adult population. They should benefit from particular attention of health care professionals, including in mental health. However, their access to health care is often limited and their quality of life and life expectancy are diminished. Recent advances in the field of ID include modified diagnostic criteria, as well as individualized care in a multidisciplinary approach in partnership with relatives and professionals from the community/service providers. These approaches allow to better address special needs of AWID.

La condition de l'adulte porteur d'un diagnostic de handicap intellectuel (ADHI) va de la personne largement autonome et intégrée dans la communauté à celle nécessitant une surveillance constante, avec des difficultés de communication, des comorbidités somatiques et mentales et des comportements non adaptés. Leur prévalence est d'environ 1 % de la population adulte. Elles devraient bénéficier d'une attention particulière de la part des professionnels de la santé, y compris mentale. Cependant, l'accès aux soins et leur qualité sont souvent limités. L'espérance et la qualité de vie des ADHI sont diminuées. Des évolutions dans le domaine du handicap intellectuel concernent le diagnostic et les approches de soins individualisés et intégrés en partenariat avec les proches et le réseau. Elles permettent de mieux répondre aux spécificités de l'ADHI.

Predicting Mood Changes in Bipolar Disorder through Heartbeat Nonlinear Dynamics.

Bipolar Disorder (BD) is characterized by an alternation of mood states from depression to (hypo)mania. Mixed states, i.e., a combination of depression and mania symptoms at the same time, can also be present. The diagnosis of this disorder in the current clinical practice is based only on subjective interviews and questionnaires, while no reliable objective psychophysiological markers are available. Furthermore, there are no biological markers predicting BD outcomes, or providing information about the future clinical course of the phenomenon. To overcome this limitation, here we propose a methodology predicting mood changes in BD using heartbeat nonlinear dynamics exclusively, derived from the ECG. Mood changes are here intended as transitioning between two mental states: euthymic state (EUT), i.e., the good affective balance, and non-euthymic (non-EUT) states. Heart Rate Variability (HRV) series from 14 bipolar spectrum patients (age: 33.439.76, age range: 23-54; 6 females) involved in the European project PSYCHE, undergoing whole night ECG monitoring were analyzed. Data were gathered from a wearable system comprised of a comfortable t-shirt with integrated fabric electrodes and sensors able to acquire ECGs. Each patient was monitored twice a week, for 14 weeks, being able to perform normal (unstructured) activities. From each acquisition, the longest artifact-free segment of heartbeat dynamics was selected for further analyses. Sub-segments of 5 minutes of this segment were used to estimate trends of HRV linear and nonlinear dynamics. Considering data from a current observation at day t0, and past observations at days (t􀀀1, t􀀀2,...,), personalized prediction accuracies in forecasting a mood state (EUT/non-EUT) at day t+1 were 69% on average, reaching values as high as 83.3%. This approach opens to the possibility of predicting mood states in bipolar patients through heartbeat nonlinear dynamics exclusively.

Using venlafaxine to treat behavioral disorders in patients with autism spectrum disorder.

OBJECTIVE: To test the efficacy of venlafaxine at a dose of 18.75 mg/day on the reduction of behavioral problems such as irritability and hyperactivity/noncompliance in patients with intellectual disabilities and autism spectrum disorder (ASD). Our secondary hypothesis was that the usual doses of zuclopenthixol and/or clonazepam would decrease in the venlafaxine-treated group. METHODS: In a randomized double-blind study, we compared six patients who received venlafaxine along with their usual treatment (zuclopenthixol and/or clonazepam) with seven patients who received placebo plus usual care. Irritability, hyperactivity/noncompliance, and overall clinical improvement were measured after 2 and 8 weeks, using validated clinical scales. RESULTS: Univariate analyses showed that the symptom of irritability improved in the entire sample (p = 0.023 after 2 weeks, p = 0.061 at study endpoint), although no difference was observed between the venlafaxine and placebo groups. No significant decrease in hyperactivity/noncompliance was observed during the study. At the end of the study, global improvement was observed in 33% of participants treated with venlafaxine and in 71% of participants in the placebo group (p = 0.29). The study found that decreased cumulative doses of clonazepam and zuclopenthixol were required for the venlafaxine group. Multivariate analyses (principal component analyses) with at least three combinations of variables showed that the two populations could be clearly separated (p b 0.05). Moreover, in all cases, the venlafaxine population had lower values for the Aberrant Behavior Checklist (ABC), Behavior Problems Inventory (BPI), and levels of urea with respect to the placebo group. In one case, a reduction in the dosage of clonazepam was also suggested. For an additional set of variables (ABC factor 2, BPI frequency of aggressive behaviors, hematic ammonia at Day 28, and zuclopenthixol and clonazepam intake), the separation between the two samples was statistically significant as was the Bartlett's test, but the Kaiser­Meyer­Olkin Measure of Sampling Adequacy was below the accepted threshold. This set of variables showed a reduction in the cumulative intake of both zuclopenthixol and clonazepam. CONCLUSION: Despite the small sample sizes, this study documented a statistically significant effect of venlafaxine. Moreover, we showed that lower doses of zuclopenthixol and clonazepam were needed in the venlafaxine group, although this difference was not statistically significant. This was confirmed by multivariate analyses, where this difference reached statistical significance when using a combination of variables involving zuclopenthixol. Larger-scale studies are recommended to better investigate the effectiveness of venlafaxine treatment in patients with intellectual disabilities and ASD.

Telemonitoring with respect to mood disorders and information and communication technologies: overview and presentation of the PSYCHE project.

This paper reviews what we know about prediction in relation to mood disorders from the perspective of clinical, biological, and physiological markers. It then also presents how information and communication technologies have developed in the field of mood disorders, from the first steps, for example, the transition from paper and pencil to more sophisticated methods, to the development of ecological momentary assessment methods and, more recently, wearable systems. These recent developments have paved the way for the use of integrative approaches capable of assessing multiple variables. The PSYCHE project stands for Personalised monitoring SYstems for Care in mental HEalth.

[Treatment resistant depression: therapy and novel neuromodulatory treatments]. / Dépression résistant au traitement: enjeux, thérapie et place des nouvelles approches de neurostimulation.

Unipolar depression is among the leading cause of invalidity and disability-adjusted life-years. Many depressed patients do not respond to several antidepressant treatments. Several treatments have been investigated in resistant depression using electrical or magnetic stimulation of the brain. In this field, electroconvulsivotherapy remains to date the only treatment validated for efficacy and security. Novel neuromodulatory treatments used in neurological conditions are currently under investigation. Vagus nerve stimulation and deep brain stimulation may offer long-term efficacy and therefore justify expensive and highly specialized treatment programs.