Identification of four novel loci associated with psychotropic drug-induced weight gain in a Swiss psychiatric longitudinal study: A GWAS analysis.

Patients suffering from mental disorders are at high risk of developing cardiovascular diseases, leading to a reduction in life expectancy. Genetic variants can display greater influence on cardiometabolic features in psychiatric cohorts compared to the general population. The difference is possibly due to an intricate interaction between the mental disorder or the medications used to treat it and metabolic regulations. Previous genome wide association studies (GWAS) on antipsychotic-induced weight gain included a low number of participants and/or were restricted to patients taking one specific antipsychotic. We conducted a GWAS of the evolution of body mass index (BMI) during early (i.e., ≤ 6) months of treatment with psychotropic medications inducing metabolic disturbances (i.e., antipsychotics, mood stabilizers and some antidepressants) in 1135 patients from the PsyMetab cohort. Six highly correlated BMI phenotypes (i.e., BMI change and BMI slope after distinct durations of psychotropic treatment) were considered in the analyses. Our results showed that four novel loci were associated with altered BMI upon treatment at genome-wide significance (p < 5 × 10-8): rs7736552 (near MAN2A1), rs11074029 (in SLCO3A1), rs117496040 (near DEFB1) and rs7647863 (in IQSEC1). Associations between the four loci and alternative BMI-change phenotypes showed consistent effects. Replication analyses in 1622 UK Biobank participants under psychotropic treatment showed a consistent association between rs7736552 and BMI slope (p = 0.017). These findings provide new insights into metabolic side effects induced by psychotropic drugs and underline the need for future studies to replicate these associations in larger cohorts.

Therapeutic Drug Monitoring of Olanzapine: Effects of Clinical Factors on Plasma Concentrations in Psychiatric Patients.

BACKGROUND: Therapeutic drug monitoring (TDM) is strongly recommended for olanzapine due to its high pharmacokinetic variability. This study aimed to investigate the impact of various clinical factors on olanzapine plasma concentrations in patients with psychiatric disorders. METHODS: The study used TDM data from the PsyMetab cohort, including 547 daily dose-normalized, steady-state, olanzapine plasma concentrations (C:D ratios) from 248 patients. Both intrinsic factors (eg, sex, age, body weight) and extrinsic factors (eg, smoking status, comedications, hospitalization) were examined. Univariate and multivariable, linear, mixed-effects models were employed, with a stepwise selection procedure based on Akaike information criterion to identify the relevant covariates. RESULTS: In the multivariable model (based on 440 observations with a complete data set), several significant findings emerged. Olanzapine C:D ratios were significantly lower in smokers (ß = -0.65, P < 0.001), valproate users (ß = -0.53, P = 0.002), and inpatients (ß = -0.20, P = 0.025). Furthermore, the C:D ratios decreased significantly as the time since the last dose increased (ß = -0.040, P < 0.001). The male sex had a significant main effect on olanzapine C:D ratios (ß = -2.80, P < 0.001), with significant interactions with age (ß = 0.025, P < 0.001) and body weight (ß = 0.017, P = 0.011). The selected covariates explained 30.3% of the variation in C:D ratios, with smoking status accounting for 7.7% and sex contributing 6.9%. The overall variation explained by both the fixed and random parts of the model was 67.4%. The model facilitated the prediction of olanzapine C:D ratios based on sex, age, and body weight. CONCLUSIONS: The clinical factors examined in this study, including sex, age, body weight, smoking status, and valproate comedication, remarkably influence olanzapine C:D ratios. Considering these factors, in addition to TDM and the clinical situation, could be important for dose adjustment.

Self-reported caffeine consumption miss-matched consumption measured by plasma levels of caffeine and its metabolites: results from two population-based studies.

IMPORTANCE AND OBJECTIVE: Self-reported caffeine consumption has been widely used in research while it may be subject to bias. We sought to investigate the associations between self-reported caffeine consumption and plasma levels of caffeine and its two main metabolites (paraxanthine and theophylline) in the community. METHODS: Data from two population-based studies (SKIPOGH1 and 2 (N = 1246) and CoLaus|PsyCoLaus (N = 4461)) conducted in Switzerland were used. Self-reported caffeine consumption was assessed using questionnaires. Plasma levels of caffeine and its metabolites were quantified by ultra-high performance liquid chromatography coupled to a tandem quadrupole mass spectrometer. RESULTS: In both studies, mean log plasma levels of caffeine and its two metabolites were over 6.48 (plasma levels = 652 ng/ml) when no caffeine consumption was reported. Subsequently, nonlinear associations between log plasma levels and self-reported caffeine consumption were observed in SKIPOGH, with a change of the slope at 3-5 cups of espresso per day in SKIPOGH1 but not SKIPOGH2. In CoLaus|PsyCoLaus, increased daily consumption of caffeinated beverages was associated with increased log plasma levels with a change of the slope at 3 cups. In both studies, declared caffeine consumption higher than 3-5 cups per day was not associated with higher plasma levels of caffeine and its metabolites. CONCLUSION: Self-reports of no or low caffeine consumption and consumption of more than 3-5 cups of coffee should be interpreted with caution, with possible under- or over-estimation. Quantifying plasma levels of caffeine and its metabolites may contribute to a better estimation of caffeine intake.

[Antihistamines : An ongoing narrative]. / Antihistaminiques : une histoire sans fin.

Histamine is responsible for many processes mediated by different receptors expressed on a variety of cells. The discovery of the first H1 antihistamines in the 1940s led to the development of numerous H1 and H2 antagonists with a broad application in many indications. The recent identification of two new histamine receptors (H3, H4) in the 1980s and 2000s led to the market authorization in Switzerland of new drugs since 2018. The purpose of this review is to provide a brief overview of the physiology of histamine, the recent development of new compounds in this field, antihistamine drug indications and relevant side effects.

L'histamine possède de nombreuses propriétés physiologiques, tant centrales que périphériques, via son action sur différents récepteurs. La découverte des premiers antihistaminiques H1 dans les années 1940 stimula le développement de nombreux autres antagonistes H1, puis H2, utilisés dans diverses spécialités médicales. L'identification plus récente de deux récepteurs à l'histamine (H3, H4) dans les années 1980 et 2000 relança le développement de nouveaux composés avec, en Suisse, une première autorisation de mise sur le marché en 2018. L'objectif de cet article de revue est de présenter brièvement la physiologie de l'histamine, l'histoire du développement des antihistaminiques, leurs utilisations actuelles, ainsi que leurs effets indésirables notables.

[Antipsychotic prescribing in adults : what to watch out for ?] / Prescription d'antipsychotiques chez les adultes : à quoi faut-il être attentif ?

Antipsychotics are known to produce frequent and/or potentially serious adverse effects, including neurological, cardiovascular, metabolic and endocrine effects. The side-effects of antipsychotics vary according to their affinity for different central and peripheral receptors, and individual vulnerabilities. Some of these side-effects are dose-dependent, while others are little or not ; thus, management strategies need to be adapted. Good management of adverse events is important to encourage patients' medication adherence and to reduce the cardiovascular morbidity and mortality of side effects. Good collaboration between psychiatrists and general practitioners or specialists is essential.

Les antipsychotiques sont connus pour engendrer des effets indésirables fréquents et/ou potentiellement graves, notamment neurologiques, cardiovasculaires, métaboliques et endocriniens. Les effets secondaires des antipsychotiques varient selon leur profil d'affinités pour les différents récepteurs cérébraux et périphériques et selon les vulnérabilités individuelles. Certains d'entre eux sont dose-dépendants, d'autres peu ou pas ; les stratégies de prise en charge sont donc à adapter. Une bonne gestion des effets indésirables est importante pour favoriser l'adhésion médicamenteuse des patients et atténuer leur impact en termes de morbimortalité. Une bonne collaboration entre médecins psychiatres et généralistes ou spécialistes est nécessaire.

Insomnia disorders are associated with increased cardiometabolic disturbances and death risks from cardiovascular diseases in psychiatric patients treated with weight-gain-inducing psychotropic drugs: results from a Swiss cohort.

STUDY OBJECTIVES: Insomnia disorders as well as cardiometabolic disorders are highly prevalent in the psychiatric population compared to the general population. We aimed to investigate their association and evolution over time in a Swiss psychiatric cohort. METHODS: Data for 2861 patients (8954 observations) were obtained from two prospective cohorts (PsyMetab and PsyClin) with metabolic parameters monitored routinely during psychotropic treatment. Insomnia disorders were based on the presence of ICD-10 "F51.0" diagnosis (non-organic insomnia), the prescription of sedatives before bedtime or the discharge letter. Metabolic syndrome was defined using the International Diabetes Federation definition, while the 10-year risk of cardiovascular event or death was assessed using the Framingham Risk Score and the Systematic Coronary Risk Estimation, respectively. RESULTS: Insomnia disorders were observed in 30% of the cohort, who were older, predominantly female, used more psychotropic drugs carrying risk of high weight gain (olanzapine, clozapine, valproate) and were more prone to suffer from schizoaffective or bipolar disorders. Multivariate analyses showed that patients with high body mass index (OR = 2.02, 95%CI [1.51-2.72] for each ten-kg/m2 increase), central obesity (OR = 2.20, [1.63-2.96]), hypertension (OR = 1.86, [1.23-2.81]), hyperglycemia (OR = 3.70, [2.16-6.33]), high density lipoprotein hypocholesterolemia in women (OR = 1.51, [1.17-1.95]), metabolic syndrome (OR = 1.84, [1.16-2.92]) and higher 10-year risk of death from cardiovascular diseases (OR = 1.34, [1.17-1.53]) were more likely to have insomnia disorders. Time and insomnia disorders were associated with a deterioration of cardiometabolic parameters. CONCLUSIONS: Insomnia disorders are significantly associated with metabolic worsening and risk of death from cardiovascular diseases in psychiatric patients.

[Does liraglutide have a place in psychiatry ?] / Le liraglutide a-t-il sa place en psychiatrie ?

The relative risk of developing MetS is higher in patients with severe mental illness (SMI) than in the general population. Similarly, the risk of developing obesity or type 2 diabetes (T2DM) is also higher in patients with SMI. GLP-1 receptor agonists, such as liraglutide, have been shown to be effective in the treatment of T2DM and, more recently, in obesity or overweight associated with at least one metabolic disease. Their psychiatric adverse effect profiles seem to be reassuring, thus not represent a limitation for prescribing in psy chiatry. We aimed to explore the therapeutic usefulness of liraglutide in patients with psychiatric disorders associated with somatic comorbidities such as obesity, T2DM or MetS.

Le risque relatif de développer un syndrome métabolique (SMet) est plus élevé chez les patients connus pour une maladie psychiatrique sévère (MPS) que dans la population générale. De même, le risque de développer une obésité ou un diabète de type 2 (DT2) est également plus important chez les patients souffrant de MPS. Les analogues du GLP-1 (Glucagon-Like Peptide 1), tels que le liraglutide, ont fait leurs preuves pour le traitement du DT2 et, plus récemment, de l'obésité ou de la surcharge pondérale associée à une maladie métabolique. Leurs profils d'effets indésirables sur la santé mentale semblent rassurants, ne représentant ainsi pas de limitation à leur prescription en psychiatrie. Nous questionnons ici l'intérêt du liraglutide chez les patients souffrant de troubles psychiques associés à des comorbidités somatiques telles que l'obésité, le DT2 ou le SMet.

[Benzodiazepines, addiction and cantonal authorization : legal framework and clinical implications.] / Benzodiazépines, addiction et autorisation cantonale : cadre juridique et implications cliniques.

Use of benzodiazepine and Z-drug is common in Switzerland, also for prolonged periods of time. Physical dependence, psychological dependence and a syndrome of dependence may ensue. Related to a lack of well-established medical guidelines, current clinical practices are subject to debate. Also controversial is the need to request an authorization from the cantonal health authorities before starting treatment with these controlled substances. The present article describes the limited circumstances in which such prior authorization is required.

La prescription de benzodiazépines et de Z-drugs (zolpidem, zopiclone, zaléplone) est fréquente en Suisse, y compris en traitement de longue durée. Il peut s'ensuivre une dépendance physique ou psychologique, et plus rarement un syndrome de dépendance. En l'absence de directives reposant sur des évidences scientifiques consolidées, les pratiques effectives des professionnels de la santé sont sujettes à débat. L'est également l'obligation d'obtenir une autorisation cantonale préalable à la mise en place d'un traitement contenant ces substances soumises à contrôle. Le présent article décrit les conditions dans lesquelles une telle autorisation est requise ou non.

[Treatment of insomnia, with what to start ?] / Traitement de l'insomnie, par quoi commencer ?

Confronted with a complaint of insomnia, several points must be considered before prescribing a specific treatment. In particular, it is necessary to optimize the management of somatic and psychiatric comorbidities that can affect sleep and to review the intake of sleep-disrupting substances and drugs. The current guidelines for insomnia rank treatment options based on the quality of the evidence. They all agree to recommend cognitive behavioural therapy for insomnia as first-line treatment. Pharmacological treatment should only be considered if this therapy fails. We then propose to start with the drugs presenting the best safety profile before prescribing, if necessary, those having better effectiveness evidence but carrying a greater risk of side effects.

Face à une plainte d'insomnie, plusieurs points sont à prendre en compte avant d'envisager un traitement spécifique, notamment l'optimisation de la prise en charge des comorbidités somatiques et psychiatriques pouvant péjorer le sommeil et la revue de la prise de substances et médicaments le perturbant. Les recommandations sur l'insomnie classent les options thérapeutiques selon la qualité des études à disposition. Elles s'accordent toutes à recommander la thérapie cognitivo-comportementale spécifique pour l'insomnie en première intention. Un traitement pharmacologique ne devrait être envisagé qu'en cas d'échec de cette thérapie. Nous proposons alors de débuter avec les molécules présentant le meilleur profil de sécurité avant de passer, si nécessaire, à celles ayant mieux démontré leur efficacité mais comportant un plus grand risque d'effets secondaires.

[Recommendations for management of misuses and addictions to benzodiazepines]. / Recommandations de prise en charge des mésusages et addictions aux benzodiazepines.

The management of patients who have become dependent on benzodiazepines and analogues is a problem frequently encountered in both somatic and psychiatric medicine. No pharmacological treatment is currently recognized as effective in the management of these addictions, apart from a gradual reduction of doses. We propose practical strategies for the implementation of gradual dose reduction and choice of molecules while promoting individual adaptation to the withdrawal symptoms presented by the patient.

La prise en charge de patients ayant développé une dépendance aux benzodiazépines et analogues est une problématique rencontrée fréquemment tant en médecine somatique que psychiatrique. Aucun traitement pharmacologique n'est actuellement reconnu comme efficace dans la prise en charge de ces dépendances, en dehors d'une réduction progressive des doses. Nous proposons des stratégies pratiques de mise en œuvre de réduction progressive des doses et de choix de molécules tout en favorisant une adaptation individuelle aux symptômes de sevrage présentés par le patient.

[Psychiatry]. / Psychiatrie.

The Covid-19 pandemic has a major impact on psychiatry by its social consequences and possible direct effect of certain forms of Covid-19 on mental health. During this crisis, the accessibility of technology meets a state of necessity, which has propelled telepsychiatry from the shadows into the light. The contribution of several technologies (i.e. virtual reality, actigraphy, computational psychiatry) combining clinical data and neuroscience underlines the great neurobehavioural variability even within the same diagnostic category, calling for greater precision in therapeutic offers as suggested e.g. by developments in neurofeedback. The place of intranasal esketamin in the panoply of antidepressent drug treatments for resistant depression has not yet been defined.

La pandémie de Covid-19 bouleverse la psychiatrie par ses conséquences sociales et par de possibles séquelles psychiatriques. La crise actuelle révèle l'accessibilité de technologies digitales telles que la télépsychiatrie. Des technologies comme la réalité virtuelle, l'actigraphie, la psychiatrie computationnelle combinées aux données cliniques et aux neurosciences révèlent une importante variabilité neurocomportementale même au sein d'une catégorie diagnostique donnée, invitant à une plus grande précision des traitements comme suggéré par les recherches en neurofeedback. La place de l'eskétamine intranasale dans la panoplie thérapeutique médicamenteuse de la dépression résistante doit encore être définie.

[Gabapentinoids : misuses and addictions]. / Gabapentinoïdes : mésusages et addictions.

Cases of addictions and misuses on gabapentinoids are increasingly reported. But the underlying pharmacological mechanism is not completely understood. Here is an uptodate of the current knowledges on this dependence and its management.

Des cas de mésusages et d'addictions aux gabapentinoïdes sont de plus en plus fréquemment rapportés, sans que le mécanisme pharmacologique sous-jacent ne soit complètement compris. Nous faisons un état des lieux des connaissances sur cette dépendance et sa prise en charge.

[Rapid tranquilisation in adults†: algorithm proposed for psychopharmacological treatment]. / Agitation aiguë chez l'adulte†: proposition d'un algorithme de traitement psychopharmacologique.

Acute treatment of agitation in psychiatry is one of the urgent situations for which management recommendations are needed. Various existing international recommendations have been evaluated and adapted to our clinical practice and to the drugs available in Switzerland in order to propose a uniform management strategy in our hospital. This strategy includes a treatment choice algorithm with different options depending on the clinical situation and the possible route of administration. Dose recommendations for the oral and intramuscular routes, certain pharmacokinetic parameters, as well as risks of interactions and important warnings are also included in this clinical recommendation.

Le traitement aigu de l'agitation en psychiatrie fait partie des situations urgentes pour lesquelles des recommandations de prise en charge sont nécessaires. Diverses recommandations internationales existantes ont été évaluées et adaptées à notre pratique clinique ainsi qu'aux médicaments disponibles en Suisse afin de proposer une stratégie de prise en charge uniformisée au sein de notre hôpital. Cette stratégie inclut un algorithme de choix de traitement avec différentes options selon la situation clinique et la voie d'administration possible. Des recommandations de doses pour les voies orale et intramusculaire, certains paramètres pharmacocinétiques, ainsi que les risques d'interactions et des mises en garde importantes figurent également dans cette recommandation clinique.

Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients.

New-onset diabetes mellitus after transplantation (NODAT) is a complication following solid organ transplantation (SOT) and may be related to immune or inflammatory responses. We investigated whether single nucleotide polymorphisms (SNPs) within 158 immune- or inflammation-related genes contribute to NODAT in SOT recipients. The association between 263 SNPs and NODAT was investigated in a discovery sample of SOT recipients from the Swiss Transplant Cohort Study (STCS, n1  = 696). Positive results were tested in a first STCS replication sample (n2  = 489) and SNPs remaining significant after multiple test corrections were tested in a second SOT replication sample (n3  = 156). Associations with diabetic traits were further tested in several large general population-based samples (n > 480 000). Only SP110 rs2114592C>T remained associated with NODAT in the STCS replication sample. Carriers of rs2114592-TT had 9.9 times (95% confidence interval [CI]: 3.22-30.5, P = .00006) higher risk for NODAT in the combined STCS samples (n = 1184). rs2114592C>T was further associated with NODAT in the second SOT sample (odds ratio: 4.8, 95% CI: 1.55-14.6, P = .006). On the other hand, SP110 rs2114592C>T was not associated with diabetic traits in population-based samples, suggesting a specific gene-environment interaction, possibly due to the use of specific medications (ie, immunosuppressants) in transplant patients and/or to the illness that may unmask the gene effect.

[Bariatric surgery and psychotropic drugs†: where are we now†?] / Chirurgie bariatrique et psychotropes: où en sommes-nous?

Bariatric surgery is considered an effective treatment against obesity. This intervention and the subsequent weight loss can affect several pharmacokinetic parameters leading to a possible need of dosing adjustment. Despite an increasing number of bariatric interventions, clinical recommendations are often based on theoretical principles and expert opinions. Because reliable clinical and biological parameters for adjusting psychotropic drug are not available, the use of therapeutic drug monitoring needs to be advised as a useful approach. However, it is not currently possible to predict the effect of bariatric surgery on psychotropic blood levels, and due to their important inter-individual variability, preoperative medication blood levels should be measured to ensure an adequate postoperative dosing adaptation.

La chirurgie bariatrique est un traitement efficace de l'obésité. Cette intervention, ainsi que la perte de poids consécutive, peuvent affecter différents paramètres pharmacocinétiques, justifiant une adaptation posologique du traitement. Malgré l'essor de cette chirurgie, les recommandations cliniques restent basées sur des concepts théoriques et des avis d'experts. En raison du manque de paramètres cliniques et biologiques permettant d'adapter les traitements psychotropes, l'usage des dosages plasmatiques des médicaments peut être justifié. Cependant, ne pouvant prédire l'effet d'une intervention bariatrique sur les concentrations plasmatiques du médicament et de par la grande variabilité interindividuelle, un dosage plasmatique préopératoire devrait être effectué afin d'assurer une adaptation correcte des posologies postopératoires.

Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs.

OBJECTIVES: Dyslipidemia represents a major health issue in psychiatry. We determined whether weighted polygenic risk scores (wPRSs) combining multiple single-nucleotide polymorphisms (SNPs) associated with lipid levels in the general population are associated with lipid levels [high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides] and/or dyslipidemia in patients receiving weight gain-inducing psychotropic drugs. We also determined whether genetics improve the predictive power of dyslipidemia. PATIENTS AND METHODS: The influence of wPRS on lipid levels was firstly assessed in a discovery psychiatric sample (n=332) and was then tested for replication in an independent psychiatric sample (n=140). The contribution of genetic markers to predict dyslipidemia was evaluated in the combined psychiatric sample. RESULTS: wPRSs were significantly associated with the four lipid traits in the discovery (P≤0.02) and in the replication sample (P≤0.03). Patients whose wPRS was higher than the median wPRS had significantly higher LDL, TC, and triglyceride levels (0.20, 0.32 and 0.26 mmol/l, respectively; P≤0.004) and significantly lower HDL levels (0.13 mmol/l; P<0.0001) compared with others. Adding wPRS to clinical data significantly improved dyslipidemia prediction of HDL (P=0.03) and a trend for improvement was observed for the prediction of TC dyslipidemia (P=0.08). CONCLUSION: Population-based wPRSs have thus significant effects on lipid levels in the psychiatric population. As genetics improved the predictive power of dyslipidemia development, only 24 patients need to be genotyped to prevent the development of one case of HDL hypocholesterolemia. If confirmed by further prospective investigations, the present results could be used for individualizing psychotropic treatment.

Association of genetic risk scores with body mass index in Swiss psychiatric cohorts.

OBJECTIVE: Weight gain is associated with psychiatric disorders and/or with psychotropic drug treatments. We analyzed in three psychiatric cohorts under psychotropic treatment the association of weighted genetic risk scores (w-GRSs) with BMI by integrating BMI-related polymorphisms from the candidate-gene approach and Genome-Wide Association Studies (GWAS). MATERIALS AND METHODS: w-GRS of 32 polymorphisms associated previously with BMI in general population GWAS and 20 polymorphisms associated with antipsychotics-induced weight gain were investigated in three independent psychiatric samples. RESULTS: w-GRS of 32 polymorphisms were significantly associated with BMI in the psychiatric sample 1 (n=425) and were replicated in another sample (n=177). Those at the percentile 95 (p95) of the score had 2.26 and 2.99 kg/m(2) higher predicted BMI compared with individuals at the percentile 5 (p5) in sample 1 and in sample 3 (P=0.009 and 0.04, respectively). When combining all samples together (n=750), a significant difference of 1.89 kg/m(2) predicted BMI was found between p95 and p5 individuals at 12 months of treatment. Stronger associations were found among men (difference: 2.91 kg/m(2) of predicted BMI between p95 and p5, P=0.0002), whereas no association was found among women. w-GRS of 20 polymorphisms was not associated with BMI. The w-GRS of 52 polymorphisms and the clinical variables (age, sex, treatment) explained 1.99 and 3.15%, respectively, of BMI variability. CONCLUSION: The present study replicated in psychiatric cohorts previously identified BMI risk variants obtained in GWAS analyses from population-based samples. Sex-specific analysis should be considered in further analysis.

Prediction of early weight gain during psychotropic treatment using a combinatorial model with clinical and genetic markers.

BACKGROUND: Psychotropic drugs can induce significant (>5%) weight gain (WG) already after 1 month of treatment, which is a good predictor for major WG at 3 and 12 months. The large interindividual variability of drug-induced WG can be explained in part by genetic and clinical factors. AIM: The aim of this study was to determine whether extensive analysis of genes, in addition to clinical factors, can improve prediction of patients at risk for more than 5% WG at 1 month of treatment. METHODS: Data were obtained from a 1-year naturalistic longitudinal study, with weight monitoring during weight-inducing psychotropic treatment. A total of 248 Caucasian psychiatric patients, with at least baseline and 1-month weight measures, and with compliance ascertained were included. Results were tested for replication in a second cohort including 32 patients. RESULTS: Age and baseline BMI were associated significantly with strong WG. The area under the curve (AUC) of the final model including genetic (18 genes) and clinical variables was significantly greater than that of the model including clinical variables only (AUCfinal: 0.92, AUCclinical: 0.75, P<0.0001). Predicted accuracy increased by 17% with genetic markers (Accuracyfinal: 87%), indicating that six patients must be genotyped to avoid one misclassified patient. The validity of the final model was confirmed in a replication cohort. Patients predicted before treatment as having more than 5% WG after 1 month of treatment had 4.4% more WG over 1 year than patients predicted to have up to 5% WG (P≤0.0001). CONCLUSION: These results may help to implement genetic testing before starting psychotropic drug treatment to identify patients at risk of important WG.

[New developments in psychiatry]. / Psychiatrie.

Three issues are discussed: i) While number of psychiatric beds has been reduced in most countries and although treatments proposed in psychiatric hospitals have evolved, they continue to be viewed as asylums implementing constraints. Considering this prevents their adequate use and leads to patients' stigmatisation, promotion of a better knowledge of contemporary hospital treatments is needed. 2) In addition, most psychiatric disorders emerging during adolescence and early adulthood, it is important to develop accessible care on university campuses. 3) While risk of weight gain and metabolic syndrome under neuroleptics or mood stabilisers is known, there is a need for the development of <> that are easy to identify. A 5% increase in weight during the first month of treatment indicates the risk for important later weight gain.