Insomnia in neurological disorders: Prevalence, mechanisms, impact and treatment approaches.

Insomnia is more prevalent in neurological disorders compared to the general population, with rates ranging from 11 to 74.2% in neurodegenerative disorders, 20 to 37% in vascular diseases, 13.3 to 50% in inflammatory diseases, 28.9 to 74.4% in epilepsy, and nearly 70% in migraines. Insomnia in neurological disorders stems from a variety of factors, encompassing physical and neuropsychiatric factors, behavioral patterns, and disruptions in the biological clock and circadian rhythm. There are bidirectional connections between neurological disorders and insomnia. Insomnia in neurological disorders worsens symptoms, resulting in heightened depressive symptoms, elevated mortality rates, reduced quality of life, and intensified acute symptoms. Managing comorbid sleep disorders, especially in the presence of psychiatric comorbidities, is crucial. Cognitive behavioral therapy for insomnia (CBT-I) is the first-line recommendation for insomnia management in neurological disorders. Other treatments are second-line strategies. Melatonin may demonstrate effectiveness in addressing insomnia, with soporific and chronobiotic effects. Furthermore, it has the potential to alleviate "sundowning" and behavioral disturbances, while generally being well-tolerated. Other treatment options that may be of interest include morning bright light therapy, sedative antidepressants, new orexin dual antagonists and levodopa specifically indicated for Parkinson's disease. Benzodiazepines and z-drugs can be used primarily during acute phases to prevent pharmacotolerance and minimize side effects. However, they should be avoided in patients with neurological disorders and not used in patients over 75 years old due to the risk of falls and confusion. In neurological disorders, insomnia has a profound impact on daytime functioning, making its management crucial. Effective treatment can result in improved outcomes, and additional research is necessary to investigate alternative therapeutic options and enhance patient care.

Comparison between pre-mortem and post-mortem cadaveric images for use with augmented reality headsets during dissection.

PURPOSE: Medical training has undergone many transformations to incorporate diagnostic imaging along side anatomical education. Post-mortem computed tomography (CT) scanning of body donors prior to dissection has been proposed. However, it poses challenges secondary to the embalming process and other post-mortem physiological changes that significantly alter the imaging quality. The purposes of this study were to compare the accuracy of pathology identification on pre- and post-mortem CT scans of body donors and to assess the integration of those scans in a dissection-based course, where these images were overlaid onto body donors using augmented reality (AR). METHODS: Participants in this study included 35 fourth year medical students, 5 radiology residents and 3 radiologists. A convergent, parallel mixed methods design was employed with quantitative measures that included statistical analyses of a double-blinded comparison of pathological lesions recognition, on both image sets, the group responses to a study participant survey and the login access data from imaging repository. The study also included qualitative analysis of post-elective structured interviews. RESULTS: The double-blinded comparison revealed that staff radiologists can only identify, on post-mortem images, 54.8% of the pathologies that they were able to detect on the pre-mortem scans. Analyses of the surveys and login access data reveal that 60% of radiology residents and 56% of students preferred pre-mortem scans and used those scans more often than post-mortem scans (67 access vs 36, respectively). However, post-mortem scans were significantly preferred when used to overlay onto body donors using AR (p = 0.0047). CONCLUSION: These results show that post-mortem imaging can be valuable alongside pre-mortem imaging, as they represent the most concordance between the anatomical structures and pathologies seen on the images and what is being dissected.

Sleep quality of medical students and relationships with academic performances.

OBJECTIVE: Sleep health is a major public health concern because of its correlation with physical and mental health, and it may be particularly altered in medical students. This study aims: i) to examine the sleep characteristics of French medical students and their knowledge about basic sleep hygiene rules and; ii) to examine the correlations between sleep quality and academic performances, as well as between sleep quality and sleep knowledge. METHODS: Students from 4th, 5th and 6th years of medicine, of the Faculty of Paris Diderot, voluntarily responded to an online questionnaire including PSQI and multiple-choice quizzes (MCQ) about basic sleep hygiene rules. RESULTS: From the 177 participants, 49.7% had a poor sleep (PSQI>5). Regarding sleep latency, 44.6% needed>30min to fall asleep at least once a week, 26.5% slept 6 hours or less by night, 42.4% of them qualified their sleep quality as bad or very bad. A serious lack of knowledge about basic sleep hygiene rules was observed, with an average score at the MCQ of 6.61/10, and only 31% of medical students were aware of basic good sleep habits. Significant correlations were observed between sleep efficiency and all academic mean scores (both regarding the morning, afternoon, and pooled mean scores), and between sleep disturbances and the morning mean score. CONCLUSIONS: French medical students have a poor sleep quality, correlating with academic performances, and present a poor knowledge of basic sleep rules. These findings are a call to improve medical training schedules and to develop prevention and training programs.

Validation of a data collection set for the psychiatric, addiction, sleep and chronobiological assessments of patients with depression: A Delphi study for the SoPsy-depression French national cohort.

OBJECTIVES: Despite international efforts to identify biomarkers of depression, none has been transferred to clinical practice, neither for diagnosis, evolution, nor therapeutic response. This led us to build a French national cohort (through the clinical and research network named SoPsy within the French biological psychiatry society (AFPBN) and sleep society (SFRMS)), to better identify markers of sleep and biological rhythms and validate more homogeneous subgroups of patients, but also to specify the manifestations and pathogeneses of depressive disorders. Before inclusions, we sought to provide a predefined, standardized, and robust set of data to be collected in all centers. METHODS: A Delphi process was performed to achieve consensus through the independent rating of invited experts, the SoPsy-depression co-investigators (n=34). The initial set open for vote included 94 questionnaires targeting adult and child psychiatry, sleep and addiction. RESULTS: Two questionnaire rounds were completed with 94% participation in the first round and 100% participation in the second round. The results of the Delphi survey incorporated the consensus opinion of the 32 members who completed both rounds. Nineteen of the 94 questionnaires achieved consensus at the first round and seventy of 75 at the second round. The five remaining questionnaires were submitted to three experts involved in the steering committee during a dedicated meeting. At the end, 24 questionnaires were retained in the mandatory and 26 in the optional questionnaire set. CONCLUSIONS: A validated data collection set of questionnaires is now available to assess psychiatry, addiction, sleep and chronobiology dimensions of depressive disorders.

Simplified Monopalmitoyl Toll-like Receptor 2 Ligand Mini-UPam for Self-Adjuvanting Neoantigen-Based Synthetic Cancer Vaccines.

Synthetic vaccines, based on antigenic peptides that comprise MHC-I and MHC-II T-cell epitopes expressed by tumors, show great promise for the immunotherapy of cancer. For optimal immunogenicity, the synthetic peptides (SPs) should be adjuvanted with suitable immunostimulatory additives. Previously, we have shown that improved immunogenicity in vivo is obtained with vaccine modalities in which an SP is covalently connected to an adjuvanting moiety, typically a ligand to Toll-like receptor 2 (TLR2). SPs were covalently attached to UPam, which is a derivative of the classic TLR2 ligand Pam3 CysSK4 . A disadvantage of the triply palmitoylated UPam is its high lipophilicity, which precludes universal adoption of this adjuvant for covalent modification of various antigenic peptides as it renders the synthetic vaccine insoluble in several cases. Here, we report a novel conjugatable TLR2 ligand, mini-UPam, which contains only one palmitoyl chain, rather than three, and therefore has less impact on the solubility and other physicochemical properties of a synthetic peptide. In this study, we used SPs that contain the clinically relevant neoepitopes identified in a melanoma patient who completely recovered after T-cell therapy. Homogeneous mini-UPam-SP conjugates have been prepared in good yields by stepwise solid-phase synthesis that employed a mini-UPam building block pre-prepared in solution and the standard set of Fmoc-amino acids. The immunogenicity of the novel mini-UPam-SP conjugates was demonstrated by using the cancer patient's T-cells.

Use of immediate release melatonin in psychiatry: BMI impacts the daily-dose.

OBJECTIVE: There is a growing interest in psychiatry regarding melatonin use both for its soporific and chronobiotic effects. This study aimed to evaluate factors impacting the daily-dose. METHODS: In a university department of psychiatry in Paris (France), we conducted a posteriori naturalistic observational study from April 03, 2017 to January 31, 2018. We assessed links between sociodemographic and clinical characteristics and daily dose of melatonin (the daily-dose of melatonin initiation and the daily-dose at Hospital discharge). A survey of drug interactions was performed regarding metabolic inducers and inhibitors of the cytochrome P450 1A2. RESULTS: Forty patients were included and treated with immediate-release melatonin. For patients with no history of melatonin use, the initiation dose of was 2 or 4mg, with no effects of age, weight, BMI, melatonin indication, cause of hospitalization. We found that higher discharge dose was associated with higher BMI (P=0.036) and more reevaluations of melatonin dose (P=0.00019). All patients with a moderate inducer (n=3, here lansoprazole) were significantly more associated with the discontinuation melatonin group (P=0.002). CONCLUSION: The BMI and the number of reevaluations impact the daily dose of melatonin. Two mechanisms may explain that BMI may need higher doses: (i) melatonin diffuses into the fat mass, (ii) the variant 24E on melatonin receptor MT2, more frequent in obese patients, leads to a decrease of the receptor signal.

Evaluating the integration of pre-mortem body donor imaging into a dissection-based medical anatomy course.

BACKGROUND: Medical faculties are currently embracing a modernistic approach to anatomical education that integrates diagnostic imaging largely through post-mortem computed tomography scanning of body donors. Post-mortem imaging, however, poses a multitude of challenges. The purpose of this study was to assess the implementation of pre-mortem donor-specific diagnostic imaging on student learning and dissection experience in addition to understanding the potential impact on students' preparation for clinical practice. METHODS: Students in a fourth-year medicine elective course were divided into groups; group 1 received pre-mortem donor-specific diagnostic imaging, while group 2 received pathology-specific diagnostic imaging, a collection of images relating to the type(s) of pathologies the donors exhibited, though not specific to the donors themselves. Both groups also received a donor-specific case vignette. A convergent, parallel mixed methods design was employed. This included integrating data from group responses to a study participant survey and students' academic assessment scores analyzed quantitatively through statistical analyses with data from focus group sessions investigating the psychosocial aspects of the student dissection experience and perceptions of the imaging use in the course analyzed qualitatively. RESULTS: As compared to students receiving pathology-specific diagnostic imaging, the quantitative results demonstrated that students receiving pre-mortem donor-specific diagnostic imaging more positively supported the relevancy of diagnostic imaging to their understanding of anatomy, valued the integration for future practice, and suggested an earlier integration within their medical curriculum. Qualitatively, two main themes were observed: the influence of diagnostic imaging integration on dissection experience and on professional mindset. Although both student groups received imaging corresponding to their body donor, consideration towards the humanistic nature of the body donor as a patient with a history was limited to student feedback from the donor- specific diagnostic imaging group. CONCLUSION: Overall the integration of pre-mortem donor-specific diagnostic imaging into anatomical dissection provided students with practical skill development, an enhanced dissection experience, and reinforced personal qualities critical for future practice.

Flammability and combustion hazard of preserved human tissues.

Preservation techniques have evolved over the years to respond to the need of longer dissection periods, with formaldehyde being widely used for this purpose. In recent years, efforts have been focusing on reducing the health hazards of this fixative and the rigidity of the tissues embalmed with it. With every embalming technique that they are either developing or resurrecting from various protocols, institutions need to assess the fire and health hazards of all the chemicals being used. Compliance with the storage and handling safeguards listed in the Material Safety Data Sheet of each chemical, needs to be accompanied by infrastructure changes. To reduce the health hazards of formaldehyde, institutions are taking appropriate countermeasures directed at the source itself, by using substitutes or injecting formaldehyde chelating agents, and are adopting high performance air extraction systems to protect the users. However, little is known about the flammability risk of embalmed human bodies. During a recent visit to McGill University morgue by architects and safety inspectors to expand it, we were asked about the flammability risk of the embalmed specimens, so we carried out a flashpoint test to evaluate the flammability potential of specimens embalmed with each of our three embalming techniques: formaldehyde-based, Thiel, and phenol-based. With the phenol-based embalming showing the most risks, attention should be drawn to all institutions who are experimenting with various embalming techniques to evaluate the flammability potential of their embalmed specimens.

[Psychopathological consequences of confinement]. / Conséquences psychopathologiques du confinement.

The psychological effects of isolation have already been described in the literature (polar expeditions, submarines, prison). Nevertheless, the scale of confinement implemented during the COVID-19 pandemic is unprecedented. In addition to reviewing the published studies, we need to anticipate the psychological problems that could arise during or at a distance from confinement. We have gone beyond the COVID-19 literature in order to examine the implications of the known consequences of confinement, like boredom, social isolation, stress, or sleep deprivation. Anxiety, post-traumatic stress disorder, depression, suicidal or addictive behaviours, domestic violence are described effects of confinement, but the mechanisms of emergence of these disorders and their interrelationships remain to be studied. For example, what are the mechanisms of emergence of post-traumatic stress disorders in the context of confinement? We also remind the reader of points of vigilance to be kept in mind with regard to eating disorders and hallucinations. Hallucinations are curiously ignored in the literature on confinement, whereas a vast literature links social isolation and hallucinations. Due to the broad psychopathological consequences, we have to look for these various symptoms to manage them. We quickly summarize the diagnostic and therapeutic approaches already in place, such as telemedicine, which is undergoing rapid development during the COVID-19 crisis.

Which actigraphic variables optimally characterize the sleep-wake cycle of individuals with bipolar disorders?

OBJECTIVE: To examine which combination of objectively measured actigraphy parameters best characterizes the sleep-wake cycle of euthymic individuals with bipolar disorder (BD) compared with healthy controls (HC). METHODS: Sixty-one BD cases and 61 matched HC undertook 21 consecutive days of actigraphy. Groups were compared using discriminant function analyses (DFA) that explored dimensions derived from mean values of sleep parameters (Model 1); variability of sleep parameters (2); daytime activity (3); and combined sleep and activity parameters (4). Exploratory within-group analyses examined characteristics associated with misclassification. RESULTS: After controlling for depressive symptoms, the combined model (4) correctly classified 75% cases, while the sleep models (1 and 2) correctly classified 87% controls. The area under the curve favored the combined model (0.86). Age was significantly associated with misclassification among HC, while a diagnosis of BD-II was associated with an increased risk of misclassifications of cases. CONCLUSION: Including sleep variability and activity parameters alongside measures of sleep quantity improves the characterization of cases of euthymic BD and helps distinguish them from HC. If replicated, the findings indicate that traditional approaches to actigraphy (examining mean values for the standard set of sleep parameters) may represent a suboptimal approach to understanding sleep-wake cycles in BD.

Peptides conjugated to 2-alkoxy-8-oxo-adenine as potential synthetic vaccines triggering TLR7.

Covalent linking of immunogenic oligopeptides with synthetic Toll-like receptor ligands is a useful approach to develop self-adjuvanting vaccines. In particular, small-molecule based agonists of Toll-like receptor 7 (TLR7) that are derived from 8-oxo-adenine core are potentially promising because these chemically robust TLR7 ligands can be connected to peptide T-cell epitopes via straightforward solid-phase peptide synthesis. In this contribution we present the synthesis of a Boc-protected 9-benzyl-2-alkoxy-8-oxo-adenine building block and its application in the online solid phase synthesis of three peptide conjugates that differ in the position of the TLR7 ligand within the peptide. The conjugates are able to induce dendritic cell maturation and T cell proliferation while the position of the ligand impacts T cell proliferation potency.

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.

Metabolic syndrome and actigraphy measures of sleep and circadian rhythms in bipolar disorders during remission.

OBJECTIVE: This study explored the correlations between sleep and circadian rhythm measures and the metabolic syndrome (MetS) components in remitted patients with bipolar disorder (BD). METHOD: Euthymic patients with BD (n = 67) were recorded by 3 weeks with actigraphy. We used nonparametric correlations to study the links between the MetS parameters, atherogenic index of plasma (AIP), sleep efficacy, sleep latency, fragmentation index, and phase and amplitude of rhythms. We performed multivariable analyses to take into account potential confounding factors such as sleep apnea risk, antipsychotics use, and smoker status. RESULTS: We found correlations between lower sleep efficiency and higher triglyceride levels (P = 0.002), lower M10 onset (beginning of the 10 most active hours during the 24-h cycle) and higher systolic blood pressure (P = 0.03), higher fragmentation index and higher systolic blood pressure (P = 0.009), lower sleep efficiency, higher fragmentation index, and higher AIP (respectively P = 0.02 and P = 0.04). These correlations mostly remained significant when adjusting for confounders, with the exception of M10 onset and systolic blood pressure. CONCLUSION: Sleep efficiency and fragmentation index might contribute to the cardiovascular risk of patients with BD independently of major confounding factors. Although these associations did not imply causality, proposing interventions on sleep quality and circadian rhythm regularity might contribute to reduce cardiovascular risk in patients with BD.

Childhood trauma and mixed episodes are associated with poor response to lithium in bipolar disorders.

OBJECTIVES: Reliable predictors of response to lithium are still lacking in bipolar disorders (BDs). However, childhood trauma has been hypothesized to be associated with poor response to lithium. METHODS: We included 148 patients with BD, euthymic when retrospectively and clinically assessed for response to lithium and childhood trauma using reliable scales. RESULTS: According to the 'Alda scale', the sample consisted in 20.3% of excellent responders, 49.3% of partial responders and 30.4% of non-responders to lithium. A higher level of physical abuse significantly correlated with a lower level of response to lithium (P = 0.009). As compared to patients not exposed to any abuse, patients with at least two trauma abuses (emotional, physical or sexual) were more at risk of belonging to the non-responders group (OR = 4.91 95% CI (1.01-27.02)). Among investigated clinical variables, lifetime presence of mixed episodes and alcohol misuse were associated with non-response to lithium. Multivariate analyses demonstrated that physical abuse and mixed episodes were independently associated with poor response to lithium (P = 0.005 and P = 0.013 respectively). CONCLUSIONS: Childhood physical abuse might be involved in a poor future response to lithium prophylaxis, this effect being independent of the association between clinical expression of BD and poor response to lithium.

[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.

Course of residual symptoms according to the duration of euthymia in remitted bipolar patients.

OBJECTIVE: Although many studies showed the negative impact of residual symptoms on the course of bipolar disorder (BD), there is a need to examine potential differences in residual symptoms according to the duration of euthymia in remitted BD patients. METHOD: This was a large cross-sectional study of 525 euthymic BD out-patients. A multivariate analysis of covariance was conducted to compare depressive and manic residual symptoms, sleep disturbances and cognitive complaints among three patient groups on the basis of duration of euthymia (A. 6 months to <1 year; B. 1 year to <3 years; C. 3 years to ≤5 years). RESULTS: A significant difference between the three groups was found in residual symptoms [Pillai's Trace: F(8942) = 4.659, P < 0.001]. Tukey post hoc analysis indicated that patients from Group C presented lower residual depressive symptoms, higher sleep quality and better perceived cognitive performance compared with Group A. Group B also presented better sleep and cognitive outcomes than Group A. In addition, Group C showed the lowest incidence of functional impairment. CONCLUSION: This study suggests that the intensity of residual symptoms and functional impairment in remitted BD patients is negatively related to the duration of euthymia.

Synthesis and evaluation of fluorescent Pam3Cys peptide conjugates.

Chirally pure R- and S-epimers of TLR2 ligand Pam3CysSK4 were prepared and separately conjugated to an OVA model epitope, in which lysine was replaced by azidonorleucine. The azide function in the conjugate permitted labelling with different fluorophores by use of strain-promoted 3+2 cycloaddition. The R-epimer of the labelled conjugates induced TLR2-dependent DC maturation, while S-epimer proved to be inactive. Combining the lipophilicity of Pam3CysSK4 ligand with fluorophores influenced the solubility of the resulting conjugates in an unpredictable way and only the conjugates labelled with Cy-5 were suitable for confocal fluorescence microscopy experiments. It was shown that both epimers of the Cy-5 labelled lipopeptides were internalized equally well, indicating TLR2-independent cellular uptake. The presented results demonstrate the usefulness of strain-promoted azide-alkyne cycloaddition in the labelling of highly lipophilic lipopeptides without disturbing the in vitro activity of these conjugates with respect to activation of TLR-2.

Lithium and suicide prevention in bipolar disorder.

INTRODUCTION: Bipolar disorder (BD) is a severe and recurrent psychiatric disorder. The severity of prognosis in BD is mainly linked to the high rate of suicide in this population. Indeed, patients with BD commit suicide 20 to 30 times more frequently than the general population, and half of the BD population with an early age of onset have a history of suicide attempt. International therapeutic guidelines recommend lithium (Li) as the first-line treatment in BD for its prophylactic action on depressive or manic episodes. In addition, Li is the only mood stabilizer that has demonstrated efficacy in suicide prevention. This effect of Li is unfortunately often unknown to psychiatrists. Thus, this review aims to highlight evidence about the preventive action of Li on suicide in BD populations. METHODS: We conducted a literature search between April 1968 and August 2014 in PubMed database using the following terms: "lithium" AND "suicide" OR "suicidality" OR "suicide attempt". RESULTS: As confirmed by a recent meta-analysis, many studies show that Li has a significant effect on the reduction of suicide attempts and deaths by suicide in comparison to antidepressants or other mood-stabilisers in BD populations. Studies have demonstrated that long-term treatment with Li reduces suicide attempts by about 10% and deaths by suicide by about 20%. The combination of Li and an antidepressant could reduce suicidal behaviours by reducing suicidal ideation prior to depressive symptoms. It appears crucial for Li efficacy in suicide prevention to maintain the Li blood concentrations in the efficient therapeutic zone and to instate long-term Li treatment. The "impulsive-aggressive" endophenotype is associated with suicide in BD. The specific action of Li on the 5-HT serotoninergic system could explain the specific anti-suicidal effects of Li via the modulation of impulsiveness and aggressiveness. Furthermore, genetic variants of the glycogen synthase kinase 3α/ß (GSK3α and ß; proteins inhibited by Li) seem to be associated with more impulsiveness in BD populations. CONCLUSION: The anti-suicidal effect of Li has been very well demonstrated. By its specific action on the serotoninergic system, treatment with Li significantly reduces "impulsive-aggressive" behaviour which is a vulnerability factor common to suicide and BD. Long-term appropriately modulated treatment with Li seems to have considerable impact on the reduction of suicidal behaviours, suicidal ideation and death by suicide in the BD population.

[Mitochondrial Neuro-Gastro-Intestinal Encephalopathy (MNGIE): When and how to suspect it in front of an atypical anorexia nervosa?] / Encéphalopathie mitochondriale neuro-gastro-intestinale (MNGIE) : quand et comment l'évoquer devant une anorexie mentale atypique ?

INTRODUCTION: The Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) disease is an extremely underrated syndrome beginning around the age of eighteen years. Because of its severity, this diagnosis should be considered when a patient presents an atypical anorexia nervosa. MNGIE disease is inherited in an autosomal recessive manner and related to mutations of the TYMP gene (ch22q13.32-qter), encoding the thymidine phosphorylase. The MNGIE is often misdiagnosed and is associated with a time to diagnostic of about 12 years after first symptoms. Thus this critical review aims to help clinicians better identify symptoms and paraclinical markers of the MNGIE as a differential diagnosis of atypical anorexia nervosa. METHODS: A literature search was performed using PubMed and Google Scholar databases. RESULTS: The clinical diagnosis of the MNGIE disease should be based on the association of severe loss of weight and some additional symptoms: (1) severe gastrointestinal dysmotility (nausea, vomiting, intestinal pseudo-obstruction), (2) ptosis or external ophtalmoplegia and (3) peripheral sensorimotor neuropathy. When MNGIE disease is clinically suspected, paraclinical testing can help to validate the MNGIE diagnostic: (1) Arterial blood test reveals lactic acidemia (e.g. an increased serum concentration of lactate without pH modifications), and (2) Brain MRI indicates leukoencephalopathy, usually asymptomatic. Direct evidence of MNGIE disease is based on specific testing of: (1) the thymidine phopshorylase enzyme activity in leukocytes is less than 10% of the control, (2) the increase of plasmatic thymidine (>3µmol/L) and the increase of plamatic deoxyuridine (>5µmol/L), (3) the evidence of mutations of the TYMP gene by molecular genetic testing. CONCLUSION: The MNGIE disease is a severe trouble with multisystemic complications. The thymidine phopshorylase enzyme activity in leukocytes should be measured as soon as possible when a patient presents atypical anorexia nervosa.

[Psychiatry in elderly prisoners]. / Psychiatrie du sujet âgé en milieu pénitentiaire.

CONTEXT: The high prevalence of psychiatric disorders in prison and the aging of inmates should lead to the consideration of gerontopsychiatry in the prison environment. OBJECTIVE: This review aims to emphasize the clinical characteristics and associated comorbidities of elderly prisoners with psychiatric disorders. We examined the international literature in September 2013 and performed the literature search with PubMed electronic database using the following Mesh headings: "prisons", "prisoners", "geriatric psychiatry", "geriatric assessment", "geriatric nursing". RESULTS: Fourteen studies were retained by the literature search strategy and were included in the qualitative analysis. More than one out of two elderly prisoners (>60 year-old) suffer from a psychiatric disorder. Major depressive disorder (MDD) is the first psychiatric disorder diagnosed among elderly prisoners, affecting 30 to 50% of them. Personality disorders are also very common demonstrating a prevalence of about 30%. Psychotic disorders concern 5% of the elderly prisoners and thus largely exceed the prevalence in the general population. Furthermore, stress events are frequent in prison and might precipitate or worsen psychiatric disorders. This review highlights the difficulties and complexities of care plans and management for the elderly in prison. CONCLUSION: The situation of elderly prisoners with psychiatric disorders is extremely worrying. In addition, both the aging of the population and the lengthening of incarcerations increase the number of elderly prisoners, widely exposed to psychiatric disorders, and thus will probably worsen these issues in the future.