The Covid-19 infection: An opportunity to develop systematic vitamin D supplementation in psychiatry.

Psychiatric patients are at risk of hypovitaminosis D and Covid-19-related mortality. In addition to the mental health benefits, vitamin D supplementation may be potentially effective in preventing severe forms of Covid-19 infections. Vitamin D supplementation is not necessary and is not reimbursed in France for this indication. A monthly supplementation of 50,000 IU may be sufficient in most cases. Double the dose is recommended for obese patients. The risk of renal lithiasis is not increased at these doses, even when supplemented in a patient without vitamin D deficiency. The Covid-19 crisis is an opportunity to disseminate vitamin D supplementation in psychiatric patients, as it has been shown to be effective in other respiratory diseases such as mild upper respiratory tract infections and influenza.

Increase of precuneus metabolism correlates with reduction of PTSD symptoms after EMDR therapy in military veterans: an 18F-FDG PET study during virtual reality exposure to war.

PURPOSE: The prevalence of posttraumatic stress disorder (PTSD) is higher among veterans, and can lead to disastrous consequences such as suicide. Eye movement desensitization and reprocessing (EMDR) is recommended in first-line psychotherapies for PTSD. Virtual reality exposure (VRE) coupled with 18F-FDG PET imaging can highlight the activated brain regions during stress exposure. The objective of this study is to identify, after EMDR therapy, the regions of brain metabolism that evolve during the stress exposure of a war scene with symptomatic remission in a group of military veterans suffering from PTSD, and to secondarily search for predictive metabolic features. METHODS: We recruited 15 military veterans suffering from PTSD who performed an 18F-FDG PET sensitized by the exposure to a virtual war scene, before (T0) and after (T1) EMDR therapy. Statistical parametric mapping was used to compare brain metabolism before and after treatment and to study correlations between metabolism and evolution scores on PTSD clinical scales (PTSD Checklist Scale, PCLS; Clinician-Administered PTSD Scale, CAPS). RESULTS: The metabolic activity of the precuneus was increased after EMDR therapy (p < 0.005 uncorrected, k > 180) and correlated with clinical improvement with the CAPS scale (r = -0.73 and p < 0.001). Moreover, the precuneus metabolic value before therapy predicted the clinical improvement on the PCLS scale (T1-T0) after EMDR (r = -0.667 and p < 0.006). CONCLUSION: The clinical improvement in military patients with PTSD after EMDR is related to increased precuneus metabolism upon VR stress exposure.

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

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

Hypovitaminosis D is associated with depression and anxiety in schizophrenia: Results from the national FACE-SZ cohort.

OBJECTIVE: Hypovitaminosis D has been associated with respectively major depressive disorder, schizophrenia (SZ) and cognitive disorders in the general population, and with positive and negative symptoms and metabolic syndrome in schizophrenia. The objectives were (i) to determine the prevalence of hypovitaminosis D and associated factors (with a focus on depression and cognition) in a national non-selected multicentric sample of community-dwelling SZ subjects (ii) to determine the rate of SZ patients being administered vitamin D supplementation and associated factors. METHODS: A comprehensive 2 daylong clinical and neuropsychological battery was administered in 140 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Hypovitaminosis D was defined by blood vitamin D level <25 nM. Depressive symptoms were assessed by the Positive and Negative Syndrome Scale depressive subscore and current anxiety disorder by the Structured Clinical Interview for Mental Disorders. RESULTS: Hypovitaminosis D has been found in 21.4% of the subjects and none of them had received vitamin D supplementation in the previous 12 months. In multivariate analysis, hypovitaminosis D has been significantly associated with respectively higher depressive symptoms (aOR = 1.18 [1.03-1.35], p = 0.02) and current anxiety disorder (aOR = 6.18 [2.15-17.75], p = 0.001), independently of age and gender. No association of hypovitaminosis D with respectively positive and negative symptoms, cognitive scores or other biological variables has been found (all p > 0.05), however, a trend toward significance has been found for metabolic syndrome (p = 0.06). Vitamin D supplementation has been administered during the previous 12 months in only 8.5% of the subjects but was associated with lower depressive symptoms (aOR = 0.67 [0.46-0.98], p = 0.04) and lower rate of current anxiety disorder (aOR = 0.06 [0.01-0.66], p = 0.02) compared to patients with hypovitaminosis D. CONCLUSION: Hypovitaminosis D is frequent and associated with depressive symptoms and anxiety disorders in schizophrenia. Vitamin D supplementation is associated with lower depressive and anxiety symptoms, however patients with hypovitaminosis D remain insufficiently treated.

[Comparison of medical and economic benefits of antipsychotics in the treatment of schizophrenia in France]. / Comparaison des bénéfices médico-économiques des antipsychotiques dans la prise en charge de la schizophrénie en France.

INTRODUCTION: The course of schizophrenia can vary widely, and patients experience remission phases alternating with relapse episodes, which generally lead to hospitalisation and have a significant impact on the burden of disease. The prevalence of schizophrenia in France is estimated to be approximately 600,000 people, with an incidence of 10,000 new patients per year. Patients with schizophrenia represent the largest group of hospitalised patients in French public institutions and specialised centres, and the French authorities recognise that the management of schizophrenia is a major public health concern. The Haute Autorité de Santé (HAS) and most of the evidence-based guidelines for the maintenance treatment of schizophrenia recommend long-acting injectable (LAI) antipsychotics to be used predominantly in the prevention of relapse for non-compliant patients; however, in clinical practice, the use of LAIs remains low. OBJECTIVE: This analysis aimed to estimate and to compare the cost-effectiveness of the most common antipsychotic strategies in France in the management of schizophrenia. METHODS: A Markov model was developed to simulate the progression of a cohort of patients with schizophrenia through four health states (stable treated, stable non-treated, relapse and death) and considered up to three lines of treatment to account for changes in treatment management. Antipsychotics including aripiprazole LAI (ALAI), olanzapine LAI (OLAI), paliperidone LAI (PLAI), risperidone LAI (RLAI), haloperidol decanoate (HD) and oral olanzapine (OO) were compared in terms of costs and clinical outcomes. Thus, costs, quality-adjusted life-years (QALYs) and number of relapses were assessed over five years based on three-month cycles from a French health insurance perspective with a discount rate of 4 %. Patients were considered to be stabilised after clinical decompensation and would enter the model at an initiation phase, followed by a prevention of relapse phase if successful. Data (e.g. relapse or discontinuation rates) for the initiation phase came from randomised clinical trials, whereas relapse rates in the prevention phase were derived from hospitalisation risks based on French real-life data in order to capture adherence effects. Safety and utility data were derived from international publications. Additionally costs were retrieved from French health insurance databases and publications. Robustness of results was assessed through deterministic and probabilistic sensitivity analyses. RESULTS: First and second generations of LAIs were found to have similar costs over five years; i.e. approximately € 55,000, except for PLAI which was associated with a discounted cost of € 50,880. Oral antipsychotics were found to be less costly (i.e. OO cost € 50,379 after five years) but associated with a lower number of QALYs gained and relapse avoided. PLAI and RLAI were associated with the greatest number of QALYs gained; i.e. PLAI dominated ALAI, OLAI and HD and was associated with an incremental costs-effectiveness ratio (ICER) of € 2411 per QALY gained versus OO. Finally, PLAI and OLAI were associated with the lowest number of relapses; i.e. PLAI dominated RLAI, ALAI and HLAI and was associated with an ICER of € 1782 per avoided relapse compared to OO. OO and HD were found to have led to the highest number of relapses. CONCLUSION: This analysis, to the best of our knowledge, is the first of its kind to assess the cost-effectiveness of antipsychotics based on French observational data. PLAI was associated with the highest probability of being the optimal treatment from the French health insurance perspective.

[Reflection on the psychiatric financial allocation in France]. / Réflexion sur la péréquation financière de psychiatrie en France.

For 25years work has been underway in France for the implementation of an alternative to public financing of health care. In the absence of progress, some regional health agencies are engaged in work related to the reallocation of public finances between psychiatric institutions. We propose a reflection with suggestion on the method proposed by the Provence Alpes Côte d'Azur Regional Health Agency. Without questioning the need for a reallocation of resources between psychiatric institutions, the method proposed here needs to evolve further to be applied in a legitimate and appropriate manner. There is a kind of urgency for a reallocation of resources between psychiatric institutions in France, but it implies a collective thinking and especially the definition of evaluation procedures for the selected models. These conditions are necessary to guarantee the quality of French psychiatry and equity in access to psychiatric care.

Medication and aggressiveness in real-world schizophrenia. Results from the FACE-SZ dataset.

INTRODUCTION: The primary objective of this study was to determine if second-generation antipsychotic (SGA) administration was associated with lower aggressiveness scores compared to first-generation (FGA) in schizophrenia (SZ). The secondary objective was to determine if antidepressants, mood stabilizers, and benzodiazepines administration were respectively associated with lower aggressiveness scores compared to patients who were not administered these medications. METHODS: Three hundred thirty-one patients with schizophrenia (N = 255) or schizoaffective disorder (N = 76) (mean age = 32.5 years, 75.5 % male gender) were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with the structured clinical interview for DSM-IV Axis I disorders and validated scales for psychotic symptomatology, insight, and compliance. Aggressiveness was measured by the Buss-Perry Aggression Questionnaire (BPAQ) score. Ongoing psychotropic treatment was recorded. RESULTS: Patients who received SGA had lower BPAQ scores than patients who did not (p = 0.01). More specifically, these patients had lower physical and verbal aggression scores. On the contrary, patients who received benzodiazepines had higher BPAQ scores than patients who did not (p = 0.04). No significant difference was found between BPAQ scores of patients respectively being administered mood stabilizers (including valproate), antidepressant, and the patients who were not. These results were found independently of socio-demographical variables, psychotic symptomatology, insight, compliance into treatment, daily-administered antipsychotic dose, the way of antipsychotic administration (oral vs long acting), current alcohol disorder, and daily cannabis consumption. CONCLUSION: The results of the present study are in favor of the choice of SGA in SZ patients with aggressiveness, but these results need further investigation in longitudinal studies. Given the potent side effects of benzodiazepines (especially dependency and cognitive impairment) and the results of the present study, their long-term prescription is not recommended in patients with schizophrenia and aggressive behavior.

[Interactive rTMS protocols in psychiatry]. / Protocoles de rTMS interactives en psychiatrie.

BACKGROUND: The efficiency of repetitive transcranial magnetic stimulation (rTMS) in the treatment of psychiatric disorders is robust for major depressive episode (MDE) while results are encouraging for schizophrenia. However, rTMS protocols need to be optimized. Basic researches in TMS led to the concept of "state dependency TMS". This concept suggests that the neural circuits' activation states, before and during the stimulation, influence the pulse effect. Indeed, TMS effect must be seen, not simply as a stimulus, but also as the result of an interaction between a stimulus and a level of brain activity. Those data suggest that rTMS efficiency could be increased in psychiatric disorders by triggering patients' neurocognitive activities during stimulation. Thus "interactive rTMS protocols" have been submitted. OBJECTIVES: This article provides a review and a classification of different interactive protocols implemented in the treatment of MDE and schizophrenia. Protocols' interactions with cognitive activities and brain electrical activities will be discussed. LITERATURE FINDINGS: Interactive rTMS protocols that manipulate cognitive activities have been developed for MDE treatments. They aim at regulating emotional states of depressed patients during the stimulation. The patients perform emotional tasks in order to activate cortical networks involving the left dorsolateral prefrontal cortex (DLPFC) into a state that may be more sensitive to the rTMS pulse effect. Simultaneous cognitive behavioral therapy ("CBT rTMS") and cognitive-emotional reactivation ("affective rTMS") have thus been tested during left DLPFC rTMS in MDE. Interactive rTMS protocols that manipulate brain electrical activities have been developed for MDE and schizophrenia treatments. Two categories of protocols should be identified. In the first set, personalized brain activity has been analyzed to determine the parameters of stimulation (i.e. frequency of stimulation) matching the patient ("personalized rTMS"). Personalized rTMS protocols can be made "online" or "offline" depending on whether the EEG activity is measured during or prior to rTMS. Online protocol is called "contingent rTMS": it consists in stimulating the brain only when a specific EEG pattern involving the intensity of alpha rhythm is recorded and recognized. Offline protocol is called "alpha rTMS", and relies on ascertaining frequency of stimulation in accordance with personalized alpha peak frequency prior to rTMS. In the second set, electrical brain activity is modulated before or during rTMS in order to stimulate the DLPFC in optimal conditions. Brain activity modulation may be obtained by transcranial direct current stimulation ("tDCS rTMS") or EEG-biofeedack ("EEG-biofeedback rTMS"). CONCLUSION: Interactive rTMS studies have various limitations, notably their exploratory character on a small sample of patients. Furthermore, their theoretical neurocognitive framework justification remains unclear. Nonetheless, interactive rTMS protocols allow us to consider a new field of rTMS, where cognitive and cerebral activities would no longer be considered as simple neural noise, leading to a kind of "first person rTMS", and certainly to innovative therapy in psychiatry.

[Psychometric properties of the Activities Daily Life Scale (ADL)]. / Caractéristiques psychométriques de l'échelle des activités de la vie quotidienne (AVQ).

OBJECTIVE: Deficits in social functioning are an important core feature of mental health. Recently in France, the Activities Daily Life (ADL) scale has been proposed by the French authorities to assess social functioning for all hospitalized patients in a psychiatric ward. The perspective is to use this scale in the financing and organization of mental health services in France. The ADL scale is a 6-item (dressing/undressing, walking/mobility, eating/drinking, using toilets, behaviour, relationships/communication) heteroquestionnaire completed by a health care professional at the beginning of each hospitalization, assessing functioning of patients suffering from mental health diseases. However, limited consensus exists on this scale. The psychometric properties of the ADL scale have not been assessed. There is a pressing need for detailed examination of its performance. The aim of this study was to explore ADL psychometric properties in a sample of hospitalized patients in a psychiatric ward. METHOD: We retrospectively analyzed data for all episodes of care delivered to hospitalized patients in a psychiatric ward in our French Public Hospital from January 1, 2008 to June 30, 2008. The study involved retrospective review of administrative and medical databases. The following data were collected: age, gender, diagnoses based on the International Classification of Diseases - 10th version, ADL scale and Assessment of Social Self-Sufficiency scale (ASSS). The psychometric properties were examined using construct validity, reliability, external validity, reproducibility and sensitivity to change. Data analysis was performed using SPSS 15.0 and WINSTEP software. RESULTS: A total of 1066 patients completed the ADL scale. Among them, 49.7% were male, mean age was 36.5 ± 10.8, and 83.5% were single. Schizophrenia, schizotypal and delusional disorders (40.0%), mood disorders (27.9%) and mental and behavioural disorders due to psychoactive substance use (12%) were the most common diagnoses. Factor analysis with varimax rotation identified a 2-factor structure accounting for 82% of the total variance. The first dimension (ADL 1) comprised four items and represented personal care activities. The second dimension (ADL 2) comprised two items and represented social functioning. A floor effect was reported for ADL 1 and its unidimensionality was not satisfactory: two items showed an INFIT statistic outside the acceptable range. Internal consistency was satisfactory for the two dimensions: each item achieved the 0.40 standard for item-internal consistency. The correlation of each item with its contributory dimension was higher than with the other (item discriminant validity). Cronbach's alpha coefficients ranged over 0.70 in the whole sample. Concerning external validity, positive correlations were not systematically found between ADL and ASSS dimensions. The score of ADL 1 had medium to high correlations with four dimensions scores of the ASSS, while the score of ADL 2 were not at all or weakly correlated with ASSS dimension scores. Globally, ADL did not cover sentimental life and social relationships. There were statistical associations between ADL and age or gender: women and subjects older than 60 had a higher level of dependency. We didn't find any association with marital status or diagnoses. The ADL scale presented a good reproducibility but was not sensitive to change. CONCLUSION: The psychometric properties of the ADL scale were not sufficient for several parameters such as validity or sensitivity to change, contrary to other available French scales. The use of a heteroquestionnaire rather than a self-administered questionnaire should be discussed by professionals and the French authorities. These results should be taken into account in the use of the ADL scale for the economic and administrative management of psychiatry. Further research should be conducted to confirm these results.