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To examine the metabolic profile of adolescents at baseline and to determine the potential predictive power of a 1-month weight gain (WG) on weight changes during longer term second-generation antipsychotic (SGA) treatment. A retrospective chart review study, including patients between 13 and 18 years of age and treated with SGA, was conducted. Available data at baseline, 1, 3, and 12 months of treatment were recorded. Four hundred fifty-six patients were included, with a median age of 15 years. Ten percent of the patients were obese (>95th percentile) and abdominal obesity (>90th percentile) was observed in 12% of patients. In a subgroup of 42 patients with both baseline, 1, and 3-month weight data available, WG >4.5% after 1 month was found to be the best predictor (sensitivity: 100; specificity: 66; area under the curve: 83) for a WG >15% after 3 months. After adjusting for potential confounders, a threshold of WG >4% was found as being the best predictor. A worrisome prevalence of metabolic disorders was observed in an adolescent psychiatric cohort. In such patients, a WG >4% during the first month of treatment should raise concerns about weight controlling strategies. Further research is needed to confirm the present results and to determine the impact of a 1-month WG on a 1-year weight change.

Resume Les programmes specialises pour les psychoses emergentes se sont largement developpes dans le monde. La plupart de ces programmes incluent des elements de suivi intensif dans le milieu (assertive community treatment). Il existe deux modeles. Dans le premier, le suivi intensif dans le milieu est propose a tous les patients et constitue le cœur de l’intervention. Dans le second, un programme de case management standard est propose a tous les patients et un case management intensif a un sous-groupe de patients difficiles a engager dans les soins. Le programme TIPP a Lausanne fait partie de cette deuxieme categorie. Le but de cet article est d’examiner dans un programme specialise pour les psychoses emergentes (TIPP) les caracteristiques et l’evolution de patients qui necessitent ou non un suivi intensif dans le milieu, et de l’illustrer par des exemples cliniques. Il s’agit d’une etude prospective portant sur 229 patients inclus dans le programme TIPP de maniere consecutive pendant trois ans. Environ un quart de ces patients ont necessite un case management intensif. Au debut du suivi TIPP, ces patients presentent une adhesion au traitement, un fonctionnement academique et un insight plus faibles, et ont des antecedents de consommation d’alcool et de cannabis. Apres 18 mois, le niveau d’adhesion au traitement est semblable dans les deux groupes. Toutefois, les patients qui necessitent un case management intensif continuent a presenter un niveau de fonctionnement plus faible, et davantage de symptomes psychotiques apres trois ans de suivi.

Sensory impairments constitute core dysfunctions in schizophrenia. In the auditory modality, impaired mismatch negativity (MMN) has been observed in chronic schizophrenia and may reflect N-methyl-d-aspartate (NMDA) hypo-function, consistent with models of schizophrenia based on oxidative stress. Moreover, a recent study demonstrated deficits in the N100 component of the auditory evoked potential (AEP) in early psychosis patients. Previous work has shown that add-on administration of the glutathione precursor N-acetyl-cysteine (NAC) improves the MMN and clinical symptoms in chronic schizophrenia. To date, it remains unknown whether NAC also improves general low-level auditory processing and if its efficacy would extend to early-phase psychosis. We addressed these issues with a randomized, double-blind study of a small sample (N=15) of early psychosis (EP) patients and 18 healthy controls from whom AEPs were recorded during an active, auditory oddball task. Patients were recorded twice: once prior to NAC/placebo administration and once after six months of treatment. The N100 component was significantly smaller in patients before NAC administration versus controls. Critically, NAC administration improved this AEP deficit. Source estimations revealed increased activity in the left temporo-parietal lobe in patients after NAC administration. Overall, the data from this pilot study, which call for replication in a larger sample, indicate that NAC improves low-level auditory processing in early psychosis.

Background Premorbid characteristics may help predict the highly variable functional and illness outcomes of young people with early stage Bipolar Disorder (BD). We sought to examine the relationships between premorbid adjustment and short to medium-term outcomes after a first treated episode of mania. Methods We examined the baseline and 18-month follow-up characteristics of 117 participants with first episode of mania, treated at two tertiary early intervention services in Melbourne, Australia. The baseline demographic, family history, diagnoses, comorbidity and clinical features were determined using unstructured questionnaires and structured diagnostic interviews. Premorbid adjustment was determined using the Premorbid Adjustment Scale (PAS), the components of which were identified using a principal component analysis. Eighteen-month follow-up outcome measures included the Clinical Global Impressions scale, Social and Occupational Functioning Assessment Scale and the Heinrichs’ Quality of Life Scale (QLS). Correlations and linear regressions were utilised to examine the relationships between component scores and outcomes, while controlling for baseline and follow-up confounders. Results The social adjustment component of the PAS correlated with the interpersonal relations ( r s = −0.46, p r s =−0.39, p = 0.004). Premorbid adjustment did not predict illness severity or objective functioning. Limitations Lack of information on cognition, personality factors and prodromal symptoms limited the assessment of their impact on outcomes. Conclusions Impairments in domains of premorbid adjustment may be early markers of persistent difficulties in social and vocational functioning and may benefit from targeted interventions.

Objectives Community Treatment Order (CTO) is a legal regime that obliges patients suffering mental disorder to adhere to treatment in the community and allows for a swift admission to hospital if necessary. Study aims were to: (i) determine CTO frequency in a large representative sample of first episode psychosis (FEP) patients; (ii) compare the characteristics of patients with or without CTO before entry, during treatment and at discharge from an early psychosis program. Methods Information on 660 patients treated at the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1998 and 2000 was collected from medical files. Results 19.2% of patients were under CTO at least once during treatment and they differed on most pre-treatment, baseline, treatment and service discharge variables. They were less educated, more likely to have a history of offending behavior, had lower pre-morbid functioning, longer duration of untreated psychosis, increased prevalence and more persistent substance use disorders, greater severity of symptoms, lower functioning, poorer insight at any time during treatment and were more likely to be admitted to hospital. Conclusions CTO frequency was high, likely related to the representativeness of the cohort. Characteristics of patients on CTO are comparable to those with serious and persistent mental illness. Considering the absence of solid evidence regarding the effectiveness of this form of compulsion, it is crucial to study the use of CTO in FEP patients in order to explore its impact and identify patients for whom it may be beneficial.

Objectifs:Une proportion importante de patients présentant un premier épisode psychotique commettent des actes violents hétéro-agressifs. L’objectif de cette étude est d’explorer l’association entre insight et comportement violent (CV) et l’évolution de l’insight durant la période de suivi.Méthode:L’étude est conduite sur une cohorte prospective de 265 patients recrutés au sein du programme de traitement et d’intervention précoce dans les troubles psychotiques et suivis sur une période de 3 ans. L’évaluation de l’insight est basée sur une échelle d’insight en 3 points et l’item de l’insight à la Positive and Negative Syndrome Scale (PANSS). Les CV ont été évalués par les case-managers, par les informations provenant des services forensiques et par l’intermédiaire d’un relevé des CV en cours d’hospitalisation. Des analyses de régression logistique uni-variées et multi-variées, des tests-t et des corrélations ont été réalisés.Résultats:L’effet significatif de l’insight comme facteur associé aux CV trouvé dans les analyses uni-variées disparaît après avoir contrôlé l’effet des symptômes positifs, du diagnostic de dépendance aux substances, de l’impulsivité et de l’adhésion au traitement.Conclusion:Si la prise de conscience des patients à l’égard de leur maladie évolue positivement au cours du traitement, nos résultats suggèrent que le risque de survenue de CV n’est pas influencé par le degré d’insight. Il est par contre significativement lié à l’abus de substances et à l’impulsivité, impliquant de cibler ces deux dimensions dans les stratégies préventives. L’impact de l’insight sur le CV doit être l’objet d’analyses prospectives plus précises.

Nous présentons d’abord brièvement le programme TIPP et les concepts généraux de la prise en charge précoce dans la psychose débutante. Un des objectifs de l’intervention dans la phase précoce des troubles psychotiques est notamment de proposer des soins spécifiques adaptés à cette phase de la maladie. En début de prise en charge, l’équipe de soins et en particulier le gestionnaire de cas (case manager), chef d’orchestre de la prise en charge, sont confrontés à une quantité importante d’information dont il faut dégager les lignes de forces pour mettre en place une prise en charge adaptée. Cet article propose un modèle qui peut constituer un outil de travail précieux pour les équipes travaillant dans l’intervention précoce pour faire émerger une formulation de cas et synthétiser les situations cliniques des patients, en extraire une histoire qui fasse sens et ainsi faciliter la mise en place d’un projet thérapeutique.

Most patients with first episode psychosis (FEP) are neither studying nor employed (have a poor functional status) when first accessing care. Knowledge of the characteristics of patients with poor functioning and the features influencing functional status over time may pave the way to better treatment. A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics on 661 FEP patients who consecutively attended the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, between 1998 and 2000. Functional status was ascertained using the modified vocational status index and was rated at baseline (poor or good) and according to its evolution over the treatment period (stable good, stable poor, deteriorating or improved functional status). 52.0% of patients had a poor functional status at service entry. They were more likely to be male with a non-affective psychosis. They also had lower levels of premorbid global functioning and education, and were more likely to have self-reported histories of learning disability, forensic issues, traumatic experiences and substance use. At service entry, they had more severe symptoms and poorer global functioning. 37% of these patients maintained a poor functional status at discharge, and 18% of those with a good functional status at service entry experienced a decline. Although psychosocial interventions might assist a young person with FEP with working towards functional goals, for some, the impact of factors such as ongoing substance use and forensic issues on functional status needs to be addressed.

Background The ability to recognize whether sensory consequences have been self-generated or externally produced is an important element of motor control and self-monitoring. Deficits in self-monitoring have been proposed to cause abnormal bodily experiences and psychotic symptoms such as hallucinations. A recent study designed a robotic system that applies sensorimotor stimulation in healthy subjects and safely induces mild presence hallucinations (PH) and passivity experiences (Blanke et al., 2014). PH are defined as the sensation that someone is close by when actually no one is present and passivity experiences are characterized by perceptions or beliefs that an external agent is controlling one’s actions, perceptions, and/or thoughts. Although, both symptoms occur in schizophrenia and Parkinson’s disease, their neural mechanisms are unknown. Methods Here, we first investigated the neural mechanisms of PH and passivity experiences in 25 healthy subjects. We developed a new MR-compatible robotic system able to generate the aforementioned sensorimotor conflicts, while recording subjects’ brain activity using fMRI. In addition, we applied lesion network mapping to 11 neurological patients with symptomatic PH and compared both populations to find a common PH network. In a final step, we investigated the relevance of the PH network by analyzing the connectivity of the PH network in resting state fMRI data from 58 psychotic patients. Results We first evaluated the regions associated with the general sensorimotor conflict, which revealed the left sensorimotor area, the left putamen, the right inferior parietal lobule and the right cerebellum. Then, we analyzed the regions that were more activated during the condition eliciting PH and passivity experiences and found the inferior frontal gyrus (IFG), the insula, the superior medial gyrus and the middle temporal gyrus (MTG). Comparison of these two networks with the symptomatic PH network in neurological patients highlighted the IFG, the MTG and the vPMc. The resting state analysis within those regions in psychotic patients revealed no global differences between the groups but a functional connectivity decrease between MTG and IFG (bilaterally) specific for psychotic patients experiencing passivity experiences. Discussion Collectively, we showed that through the use of a robotic system generating sensorimotor conflicts, the neural correlates of induced-PH and passivity experiences can be studied in healthy subjects in a controlled manner. In addition, we found two networks associated with induced-PH and passivity experience. Of these regions, three were also recruited in patients with PH of neurological origin, forming the PH network. MTG-IFG connectivity in the PH network was altered selectively in psychotic patients with passivity experiences, revealing the relevance of the neural mechanisms of PH and passivity experiences in psychosis.

Over the past 50 years, deinstitutionalization changed the face of psychiatry. However, outpatient treatment in the community does not always fit the needs of those who left institutions and sometimes leads to frequent re-hospitalizations, a mechanism known as the “revolving door” phenomenon. The study aim was to identify different typologies of hospitalization trajectories. Records of 892 inpatients from the Department of Psychiatry of Lausanne University Hospital were analyzed over a 3-year period with discrete sequential-state analysis. Trajectories could be split between atypical users (4.9% of patients totalling 30.6% of hospital days) and regular users. Within the atypical users group, three categories were identified: “Permanent stays” (3 patients totalling 6.3% of hospital days), “long stays” (1.7% patients/8.6% hospital days) and “revolving door” stays (2.9% patients/15.8% hospital days). The remaining 95.1% of the patients were classified into “unique episodes” (70.0% patients/24.5% hospital days) and “repeated episodes” (25.0% patients/44.9% hospital days). Diagnoses of schizophrenia were overrepresented among heavy users. Most patients went through a unique or low number of brief hospital admissions over the 3 years of the study. While the shift of previously institutionalized individuals towards high users of psychiatric hospital seems limited, this phenomenon should not be neglected since 4.9% of patients use about a third of hospital beds. Early identification of problematic profiles could allow the implementation of relapse prevention strategies and facilitate the development of alternatives to hospitalization such as assertive community treatment or housing first programs.

Amisulpride is an antipsychotic used in a wide range of doses. One of the major adverse events of amisulpride is hyperprolactinemia, and the drug might also induce body weight gain. The aims of this work were to characterize the pharmacokinetics of amisulpride in order to suggest optimal dosage regimens to achieve the reference range of trough concentrations at steady-state (C min,ss ) and to describe the relationship between drug pharmacokinetics and prolactin and body weight data. The influence of clinical and genetic characteristics on amisulpride pharmacokinetics was quantified using a population approach. The final model was used to simulate C min,ss under several dosage regimens, and was combined with a direct E max model to describe the prolactin data. The effect of model-based average amisulpride concentrations over 24 h (C av ) on weight was estimated using a linear model. A one-compartment model with first-order absorption and elimination best fitted the 513 concentrations provided by 242 patients. Amisulpride clearance significantly decreased with age and increased with lean body weight (LBW). C min,ss was higher than the reference range in 65% of the patients aged 60 years receiving 400 mg twice daily, and in 82% of the patients aged > 75 years with a LBW of 30 kg receiving 200 mg twice daily. The pharmacokinetic/pharmacodynamic model included 101 prolactin measurements from 68 patients. The E max parameter was 53% lower in males compared with females. Model-predicted prolactin levels were above the normal values for C min,ss within the reference range. Weight gain did not depend on C av . Amisulpride treatment might be optimized when considering age and body weight. Hyperprolactinemia and weight gain do not depend on amisulpride concentrations. Modification of the amisulpride dosage regimen is not appropriate to reduce prolactin concentrations and alternative treatment should be considered.

In psychiatry, alternatives to hospitalisation have been developed further to deinstitutionalisation. With the decrease in the number of psychiatric beds and the emergence of new representations regarding the possibility of recovery for people with mental disorder, hospitalisations have been limited to crisis periods. Sheltered housing has been created for vulnerable people. New models of care such « assertive » community treatment » allow to following people with severe mental disorders in the community, whilst avoiding precariousness and isolation. This article aims to present alternatives to psychiatric hospitalisation in a vision of care that answers patients' needs in a proportional and efficient way, that offers a good collaboration with other care providers and that is well-balanced between community care and hospitalisations.En psychiatrie, les alternatives à l’hospitalisation ont été développées suite au virage communautaire. La réduction du nombre de lits et la prise de conscience des possibilités de rétablissement des troubles psychiques ont conduit à réserver les hospitalisations aux périodes de crise. Actuellement, de nouvelles structures d’accueil et d’hébergement et des modèles de soins tels que l’

Aim Impulsive behaviours, which are frequent in young people suffering from psychosis have been linked to risky and violent behaviours and participate to the burden of psychotic illness. Given that morphological brain correlates of impulsivity in schizophrenia have been poorly investigated especially in young adults, the aim of this study was to investigate the relationship between impulsivity and cortical thickness in early psychosis (EP) patients. Method A total of 17 male subjects in the early phase of psychosis were recruited. Impulsivity was assessed with the Lecrubier Impulsivity Rating Scale. Mean cortical thickness was extracted from magnetic resonance imaging brain scans, using surface-based methods. Results Mean cortical thickness in the frontal lobe correlated positively with mean impulsivity in EP male patients. Conclusion Our results suggest that psychotic subjects exhibiting higher impulsivity have larger frontal cortical thickness, which may pave the way towards the identification of patients with a higher risk to display impulsive behaviours.

Urban living is a major risk factor for psychosis. Considering worldwide increasing rates of urbanization, new approaches are needed to enhance patients’ wellbeing in cities. Recent data suggest that once psychosis has emerged, patients struggle to adapt to urban milieu and that they lose access to city centers, which contributes to isolation and reduced social contacts. While it is acknowledged that there are promising initiatives to improve mental health in cities, concrete therapeutic strategies to help patients with psychosis to better handle urban stress are lacking. We believe that we should no longer wait to develop and test new therapeutic approaches. In this review, we first focus on the role of urban planning, policies, and design, and second on possible novel therapeutic strategies at the individual level. We review how patients with psychosis may experience stress in the urban environment. We then review and describe a set of possible strategies, which could be proposed to patients with the first-episode psychosis. We propose to group these strategies under the umbrella term of ‘urban remediation’ and discuss how this novel approach could help patients to recover from their first psychotic episode. The concepts developed in this paper are speculative and a lot of work remains to be done before it can be usefully proposed to patients. However, considering the high prevalence of social withdrawal and its detrimental impact on the recovery process, we strongly believe that researchers should invest this new domain to help patients regain access to city centers.

The objective of this study is to explore, within a sample of early psychosis patients (EPP), if subgroups regarding rate of violent behaviour (VB) against others can be identified on the basis of dynamic risk factors (treatment modifiable characteristics). In a sample of 265 EPP, treated at the Treatment and Early Intervention in Psychosis Program in Lausanne, we conducted a latent-class analysis on the basis of the main dynamic VB risk factors (substance use disorder [SUD], positive symptoms, insight, and impulsivity). VB were restricted to "serious violence" and were assessed through patients self-report, interview with relatives or forensic services and with a standardized instrument. The analysis confirmed the heterogeneity of the sample regarding rate of VB. Patients could be stratified within 4 subgroups, 3 of which were at increased risk of VB. The two groups with the highest rates of VB displayed specific clinical profiles. The first one was characterized by high levels of impulsivity, hostility, positive symptoms and SUD, and the second, by low level of insight and low social functioning. These patterns suggest that significant difficulties in social interaction may contribute to the emergence of aggressive reactions against others. Identification of EPP at increased risk of VB seems possible on the basis of dynamic risk factors. If confirmed prospectively, this could pave the way to the development of preventive strategies and specific interventions.

Early psychosis programs treat high ratios of migrants, given they display higher rates of psychosis. Studies on this topic are limited and less is known about outcomes. The aim of this study was to compare the premorbid, baseline and outcome profile of patients according to migration (M) and migration in psychosocial adversity (MA) in order to explore if there were differences suggesting particular needs in terms of treatment. 257 early psychosis patients aged 18-35 years old were followed-up over 36 months. MA (29.6%) and M (17.9%) were compared to patients who were born in Switzerland (NM). At entry to the program, MA patients had poorer functional levels and higher symptom intensity. MA patients were more likely to report past exposure to trauma. While M patients have similar outcome compared to NM patients, MA patients were less likely to reach symptom remission, displayed lower functioning and were more likely to relapse. Results suggests that migration in adversity is a potential determinant of functional impairment in early psychosis. While patients who migrated in other contexts have a better outcome, patients who experienced migration in adversity have specific needs considering they are less integrated and more likely to have been exposed to trauma.

Lipid disturbances following treatment with second-generation antipsychotics (SGAs) represent a major health concern. A previous study determined that early changes of plasma lipid levels ≥ 5% during the first month of treatment with SGAs predicts further lipid worsening and development of dyslipidemia. This current study aimed to determine the proportion of adolescents with early lipid changes ≥ 5% and who develop dyslipidemia during SGA treatment. Data were obtained from a 1-year longitudinal study ongoing since 2007 including 53 adolescent psychiatric (ICD-10) patients (median age 16.5 years; interquartile range [IQR], 14.8-17.5 years) whose metabolic parameters were monitored prospectively during treatment. Plasma lipid levels (total, low-density lipoprotein, high-density lipoprotein [HDL-C], and non-high-density lipoprotein cholesterol and fasting triglycerides ) were measured at baseline and after 1, 3, and/or 12 months of SGA treatment. Half (n = 26; 49%) the adolescents had an early increase of total cholesterol levels by 5% or more during the first month of treatment, and one-third (n = 8/24; 33%) developed new-onset hypercholesterolemia during the first year of treatment. Hypercholesterolemia developed more frequently in female patients (P = .01) and in patients with an early increase of total cholesterol ≥ 5% (P = .02). Finally, patients whose HDL-C levels decreased by ≥ 5% during the first month of treatment had a larger HDL-C worsening after 3 months of treatment as compared with patients with early decrease of HDL-C by < 5% (P = .02). This study underlines the importance of prospectively monitoring metabolic parameters in adolescents after the introduction of SGAs.

Background Psychosis is often depicted as a disruption of the self-model. Patients suffering from psychosis report many symptoms relating to deficiencies in the minimal self, including loss of the sense of control over their actions (Sense of Agency) as well as numerous disturbances of body representation (e.g. Body Ownership). Positive symptoms of psychosis such as passivity symptoms and auditory hallucinations (termed first-rank symptoms) are characterized by a diminished demarcation of self-other boundaries, causing misattribution of self-generated actions to external sources. It has been suggested that this deficiency in self-monitoring in schizophrenia is due to abnormal sensorimotor prediction mechanisms, causing a loss of agency for actions and thoughts. While the neurobiological underpinnings of schizophrenia are yet unclear, many studies have reported aberrant neural connectivity in schizophrenia patients which may impact sensorimotor prediction and integration. Methods Recently, we have shown that introducing sensorimotor conflict (SMC) can induce psychosis like symptoms in healthy patients. Employing a master-slave robotic system we induced a conflict by introducing a delay between the participants’ movements and the haptic feedback. The SMC caused a feeling of a Presence (FoP) which is a first rank symptom of psychosis. The FoP is also found in neurological patients with lesions in cortical regions of the temporoparietal cortex, insular cortex and fronto-parietal cortex related to abnormal bodily self-representation. Here, we tested if SMC may cause misattribution of auditory stimuli and if this is related to neural connectivity. We tested first episode psychosis patients (N=31) with and without first rank symptoms (related to the sense of control over actions and thoughts) as well as healthy participants (N=20) on an auditory attribution task while inducing conflict with the master-slave robot. Results We found that when a SMC was introduced patients with first rank symptoms showed a decrease in their ability to judge if the auditory stimuli were in their own voice or the voice of another person. Resting state functional connectivity analysis indicated that the first rank patients had reduced connectivity in the network related to the SMC, but not in other control regions. Furthermore, the reduced functional connectivity correlated with the rates of auditory misattribution. Conclusions Our results show that induction of SMC can cause auditory misattributions, and that this is related to reduced cortical communication in regions related to sensorimotor body representation. These findings connect two influential theories of psychosis linking cognitive theories of sensorimotor prediction error in schizophrenia with systems level theories of neural disconnectivity. Understanding these neurocognitive mechanisms underlying the disruption of the self-model in psychosis may allow novel approaches in early diagnosis and treatment of these conditions.

Background Specialist early intervention (SEI) service models are designed to treat symptoms, promote social and vocational recovery, prevent relapse, and resource and up skill patients and their families. While the immediate benefits of SEI are clear, and have been demonstrated, the long-term impact of SEI on illness course is less clear. The First Episode Outcome Study involves the long-term follow-up of a representative sample of first episode psychosis patients who were first treated at the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1998 and 2000. In this presentation the preliminary data on physical health outcomes are reported. Methods Between January 1998 and December 2000, 661 patients between the ages of 15–29 years were treated at the Early Psychosis Prevention and Intervention Centre, Melbourne Australia. The 18-month treatment characteristics of this cohort have been extensively examined in the First Episode Psychosis Outcome Study (FEPOS). The long-term outcomes of this cohort are now being examined in a new study (known as FEPOS15). Results The rates of self-report physical health problems in 100 participants 15 years after being treated for a first episode psychosis were significant for high cholesterol (41%), asthma (33.7%), chronic pain (25.3%), allergies (19.3%), respiratory problems (16.9%) anemia (12.2%), arthritis (12.0%), hepatitis C (10.8%) and diabetes (6.3%). Cardiovascular problems were also noted including heart attack (2.4%), other heart problems (8.4%), and stroke (3.6%). Sexual health problems are explored. Physical health findings pertaining to Coroners’ findings on those who had died will be also used to describe the long-term impacts of psychotic disorder. Discussion This follow-up study is one of the longest, largest and most comprehensive studies of the multidimensional outcomes of a SEI service for psychosis. The physical health outcomes of individuals 15-years after the first episode psychosis are poor. The importance of monitoring and managing physical health problems in those with psychotic disorder is highlighted.

Psychiatric patients are known to be at high risk of developing cardiovascular diseases (CVDs), leading to an increased mortality rate. To assess the CVD risk (presence of metabolic syndrome [MetS] and calculated 10-year CVD risk) in a Swiss psychiatric cohort taking weight gain-inducing psychotropic drugs, compare the findings to a Swiss population-based cohort, and evaluate the prevalence of participants treated for metabolic disruptions in both cohorts. Data for 1,216 psychiatric patients (of whom 634 were aged 35-75 years) were obtained between 2007 and 2017 from a study with metabolic parameters monitored during psychotropic treatment and between 2003 and 2006 for 6,733 participants from the population-based CoLaus|PsyCoLaus study. MetS as defined by the International Diabetes Federation (IDF) was identified in 33% of the psychiatric participants and 24.7% of the population-based subjects. Specifically, prevalence per the IDF definition was more than 3 times higher in the psychiatric cohort among women aged 35 to 49 years (25.6% vs 8.0%; P < 10-4). The psychiatric and population-based cohorts, respectively, had comparable predicted CVD risk (10-year risk of CVD event > 20%: 0% vs 0.1% in women and 0.3% vs 1.8% [P = .01] in men; 10-year risk of CVD death > 5%: 8.5% vs 8.4% [P = .58] in women and 13.4% vs 16.6% [P = .42] in men). No difference was observed among the proportion of participants with MetS treated for metabolic disturbances in the two cohorts, with the exception of women aged 35-49 years, for whom those in the psychiatric cohort were half as likely to receive treatment compared to participants in CoLaus|PsyCoLaus (17.8% vs 38.8% per the IDF definition; P = .0004). These findings emphasize the concern that psychiatric patients present an altered metabolic profile and that they do not receive adequate treatment for metabolic disruptions. Presence of metabolic disturbances should be routinely assessed, and adequate follow-up is needed to intervene early after illness onset.

The treatment of psychiatric disorders has been subject of numerous research, which are at the basis of international guidelines and recommendations. The Swiss Society for Psychiatry and Psychotherapy has decided to mandate various expert groups to develop Swiss recommendations. Such recommendations are now available for the main psychiatric disorders and this paper summarizes their main features in order to make them more visible.La prise en charge des troubles psychiatriques a fait l’objet de nombreux travaux de recherche qui sont à la base de guidelines et recommandations internationales. La Société suisse de psychiatrie et psychothérapie a décidé de mettre à disposition des recommandations suisses et d’en confier la rédaction à des groupes d’experts. Elles existent maintenant pour les grandes pathologies psychiatriques et cet article en résume les points principaux afin de les rendre visibles.

Background: A high level of insight in first episode psychosis (FEP) is positively correlated to important prognostic factors such as medication adherence and functional outcome but is associated with increased depression level and suicidal behavior. This is the first study questioning the potential moderating role of cannabis use in the relationship between insight and depression one year after a FEP. Methods: In this prospective observational study, we enrolled 214 FEP patients who had been referred to a specialized early psychosis program and followed for 36 months. A series of multivariate regression models were used. Baseline insight, medication adherence and cannabis use (level of use on a continuum) were entered as independent variables while the PANSS positive score, PANSS negative score, the MADRS score and the GAF score after one year were alternately selected as the dependent variable. Outcomes: We found a three-way interaction term between cannabis use, insight and medication adherence on depression level one year after the entry into the program. A high level of insight was significantly associated with higher MADRS scores in patients with high cannabis use, while depression decreased in high-insight patients with low cannabis use. Interpretation: Cannabis use continuation during the year following a first episode psychosis may play a significant role in the development or the maintenance of post-psychotic depression in patients who present with high level of insight and adherence to medication, stressing the need for specific therapeutic strategies in this subgroup of patients. Funding Statement: The authors declare: "No funding." Declaration of Interests: The authors have no conflicts of interest to disclose and have not been paid for this article. Ethics Approval Statement: The Research and Ethics Committee of the Faculty of Biology and Medicine of Lausanne University granted permission to access all clinical data for research purposes, and all patients who enter the program do so on a voluntary basis and are automatically included in the study if they meet the clinical inclusion criteria.

Objective: This study aims to determine whether it is possible to identify clinical profiles at risk of violent behaviors (VB) in the early phase of psychotic disorders, on the basis of the main dynamic psychopathological risk factors and describe characteristics of the groups with highest levels of violent behaviors. Method: A total of 265 patients, aged 18 to 35, treated at the Treatment and early Intervention in Psychosis Program (TIPP - Lausanne), a specialized early psychosis program, were included in this study. We conducted a latent-class analysis and a discriminative analysis on the basis of the main dynamic VB risk factors: substance use disorder, impulsivity, positive symptoms, insight, aggression, hostility, anger, emotional instability and adherence to treatment. These factors were evaluated by specialized scales and on the basis of the Positive and Negative Syndrome Scale (PANSS). VB were restricted to physical aggression against people, defined as “serious violence”. They were assessed on the basis of a questionnaire listing violent offenses (Swiss Criminal Code) and VB such as assault and battery; information through the forensic psychiatric services and on the basis of the Staff Observation Aggression Scale (SOAS-R scale) during inpatient treatment phase. Results: Four heterogeneous subgroups were identified with respect to the studied clinical characteristics, including two groups with high rates of VB. The first group, comprising 46% of patients with VB, is distinguished by the prevalence of a range of dimensions related to hostility, impulsivity and emotional instability, associated with high levels of substance abuse and positive symptoms. These clinical dimensions are very significant at the statistical level, since they explain 70% of the construction of subgroups (discriminant analysis). The second group with 37% of patients with VB, is characterized by a lack of insight, lack of adherence to treatment and substance use. These two clinical profiles could increase the impairment of cognitive, functional and relational abilities and contribute to the development of VB in this early phase of psychosis. The third subgroup, with a violent behaviors rate of 28.6%, is distinguished by its high proportion of diagnoses of substance abuse (100%) and women (54%). A last subgroup of patients, the largest quantitatively, has a low proportion of VB (15%) and the lowest levels on the studied factors, suggesting that the majority of patients with this profile commit few VB. Conclusion: Our results show that it is possible to identify groups at risk of violent behaviors during the early phase of psychosis, on the basis of clinical characteristics that may evolve and therefore be the focus of preventive care. These results highlight the need to target substance use, impulsivity and lack of insight at follow-up in order to prevent VB.

Changes in emotional processing (EP) and in theory of mind (TOM) are central across treatment approaches for patients with borderline personality disorder (BPD). Although the assessment of EP relies on the observation of a patient's self-criticism in a two-chair dialogue, an individual's TOM assessments is made based on responses to humorous stimuli based on false beliefs. For this pilot study, we assessed eight patients with BPD before and after a 3-month-long psychiatric treatment, using functional magnetic resonance imaging and behavioral tasks. We observed arousal increase within the session of the two-chair dialogue (d = 0.36), paralleled by arousal decrease between sessions (d = 0.80). We found treatment-associated trends for neural activity reduction in brain areas central for EP and TOM. Our exploratory findings using an integrative assessment procedure of changes in EP and TOM point toward evidence for treatment effects at the brain systems level related to behavioral modulation.

Primarily on the basis of epidemiological studies, recent research in psychiatry has established a robust link between urban living and psychosis. This paper argues first, that an experienced-based approach, moving beyond epidemiology, is needed in order to enable more fine-grained understandings of the city/psychosis nexus. The second part of the paper presents preliminary fieldwork results based on video-elicitation sessions with first-episode patients with psychotic disorders. These results lead to the generation of a series of hypotheses for further research on the role of density, sensory overload and social interaction as factors in the onset of non-affective psychoses. The conclusion discusses the insights gained from viewing the city as an experiential milieu rather than as a set of substances. We argue that such insights enable, on the one hand, observation of the role of specific places and situations - and thus to unpack 'the city'; and, on the other, to envisage the urban milieu as a nexus of possible sites of recovery.

Objective To examine the potential differential impact of childhood trauma, according to the age at the time of exposure, on the psychopathological profile of patients with early psychosis treated in a specialized 3-year program during the early phase of the disease. Methods 196 subjects with early psychosis aged 18-35 years were followed up prospectively over 36 months of treatment between 2004 and 2010. Patients who had faced at least 1 experience of abuse (physical, sexual, or emotional) or neglect (physical or emotional) were classified according to age at the time of the first exposure (early trauma: before 12 years of age; late trauma: from age 12 through 16 years) and then compared with unexposed patients (nontrauma). The level of symptoms was assessed using the Positive and Negative Syndrome Scale, the Young Mania Rating Scale, and the Montgomery-Asberg Depression Rating Scale. Results Exposure to 1 or more forms of trauma before 16 years of age was present in 31.63% of patients. Comparisons over the 3 years of treatment with the nontrauma patients revealed that (1) patients with early trauma showed consistently higher levels of positive (P = .006), depressive (P = .001), manic (P = .006), and negative (P = .029) symptoms and (2) patients with late trauma showed only more negative symptoms (P = .029). Conclusions These results suggest that the age at the time of exposure to trauma has a modulating effect on symptoms in patients with early psychosis. Various biological and psychological hypotheses can be proposed to explain this observation, and they need to be investigated in an experimental setting in order to develop therapeutic avenues.

Most specialized Early Psychosis (EP) programs include assertive outreach (AO) principles, either for all patients or as an intensive case management (ICM) subprogram in selected situations. The objective of this study is to examine prevalence, characteristics and outcomes of patients who needed additional ICM in a specialized EP program.In a 3-year prospective naturalistic study of 229 consecutive EP patients treated at TIPP-Lausanne we compared characteristics of those who needed ICM and those who did not.60 (26.2%) TIPP patients needed ICM. At baseline, ICM-patients showed a poorer academic premorbid functioning (p=0.019); lower level of insight (p0.001); had a previous history of alcohol (p=0.043) and cannabis (p=0.040) use. ICM-patients were less likely to be adherent to medication during the early phase of treatment but differences disappeared during follow-up. ICM-patients showed globally a poorer functional level and higher level of positive and negative symptoms during the follow-up.About one quarter of EP patients needed a combination of ICM and assertive outreach. Despite the high treatment adherence in both groups, psychotic symptoms remained higher in ICM-patients. In a real live setting with limited resources, combination of ICM and AO in selected situations seems a valid solution.

Background Pharmacological, neurochemical and electrophysiological studies provide compelling evidence that N-methyl-D-aspartate-receptor (NMDAR) hypofunction is a pathologic feature of schizophrenia (SZ). GWAS studies highlighted risk genes such as Serine Racemase (SRR), which synthesizes D-Serine (D-Ser), the co-agonist of glycine site at NMDARs, and Serine Hydroxymethyltransferase (SHMT1) which synthesizes L-Serine (L-Ser), the substrate of SRR. Around 30% of patients do not respond to dopamine modulation and are considered to suffer from treatment resistant SZ (TRS). While the exact cause of TRS remains unclear, multiple lines of evidence suggest the involvement of a dysregulation of the Glutamate (Glu) neurotransmission. To test the hypothesis whether Glu system dysregulation mediated by NMDAR hypofunction is an underlying mechanism of TRS, we investigate the Glu and D-Ser pathways in TRS and treatment responder (RESP) early psychosis patients (EPP). Methods From a total of 621 EPP aged 18 to 35, included in the TIPP (early Intervention Program in Lausanne, Baumann & al., 2013), 225 EPP were classified as TRS (n=33) or RESP (n=192) according to the strict Treatment Response and Resistance in Psychosis (TRRIP) criteria (Howes & al., 2017), with compliance ascertained by antipsychotic plasma levels. A matched healthy control (HC) group (N=114) was also recruited (DIGS criteria). No patient was taking clozapine at baseline. Clinical data was collected over a 3-year period. At baseline, following systems were assessed: 1) D-Ser pathway: plasmatic D-Ser, L-Ser and Glycine by HPLC (Hashimoto & al., 2016), protein levels of SRR and SHMT1 by ELISA; 2) Glu pathway: Glu and glutamine in plasma (HPLC) and prefrontal cortex (magnetic resonance spectroscopy, Xin & al., 2016). Results D-Ser pathway: in TRS, SRR levels were decreased by 56% as compared to RESP. Interestingly, we observed a positive correlation between plasma levels of D-Ser (SRR metabolite) and L-Ser (SRR substrate) in the TRS (r= 0.58; p =0.0015) but not in the RESP group, suggesting that SRR dysregulation might be a limiting factor in TRS patients. Moreover, in TRS patients, SHMT1 levels were decreased by 15% as compared to RESP, with a positive correlation between the substrate and metabolite of SHMT1, glycine and L-Ser (r =0.48; p =0.011). Dysregulation of SHMT1 might thus be a limiting factor in the TRS group. As compared to HC, L-Ser and D-Ser were significantly increased in patients (p Glu pathway: comparing TRS with RESP patients, plasma Glu levels were increased in the TRS group (p Global Assessment of Functioning (GAF): at baseline, TRS and RESP displayed the same range of GAF. After a 3-year follow-up, TRS patients had poorer functioning as compared to RESP group (p Discussion Taken together, our results suggest that the TRS group, in which the levels of SRR and SHMT1 were lower and Glu plasma levels were higher, display a different regulation of the synthesis, degradation and/or accumulation of D-Ser and Glu as compared to the RESP group. However, replication in larger groups is needed. Moreover, our findings highlighted a dysregulation of D-Ser and Glu pathways in TRS patients in their early phase of psychosis. On the clinical side, our results confirm the significantly poorer functioning outcome in TRS patients.

Background The Clinical High Risk state (CHR) concept was implemented to promote the early detection of young help-seeking patients with higher risk of psychotic transition. This category is based on specific clinical criteria (EPA, 2015) and require narrow frequency/duration ratings of subclinical positive psychotic symptoms to allow its definition. Prevalence of CHR “category” appears nevertheless rare in help-seeking young people and the rate of psychotic transition of CHR state is lower than predicted by early studies. Therefore, the binary outcome of transition to psychosis proposed by the “CHR model” actually fails to be an efficient marker to stratify, in neurobiological studies, people with different psychopathological trajectories, notably those who develop psychosis from those who do not. In order to rely on a vulnerability model for schizophrenic psychosis more sensitive to psychosocial functioning and negative dimension, we study prospectively with three years of follow-up a population of help-seekers addressed for clinical suspicion of prodromal state of psychosis. We aimed here to identify subgroups of patients in a sample of subclinical psychotic states using psychological and cognitive outcomes as profiling criteria, focusing not only on transition but also on psychosocial functioning as main outcome. Methods A total of 32 help-seeking adolescents and young adults aged 14 to 35 were referred by health care providers for a specialized evaluation in case of suspicion of a prodromal psychotic state and/or detected by the French version of the Prodromal Questionnaire (PQ-16; cut-off 6/16). Their CHR status was assessed by the Structured Interview for Psychosis-Risk Syndromes (SIPS) and the Schizophrenia Proneness Instrument, Adult (SPI-A). Individuals included in the study presented either a CHR status, a subclinical CHR status or negative symptomatology. All subjects performed an additional neuropsychological battery and blood test for redox markers (Glutathione Peroxidase (GPx) and Glutathione Reductase (GR) activities) (Xin et al, 2016). Based on their clinical profile, we made a stratification of the patients using a Principal Component Analysis. Results Cognitive and psychological outcome stratification of all help-seekers revealed two subgroups (called group1 and group2) of patients with distinct profiles. Individuals in group1 (n=18) had greater levels of basic symptoms and general symptomatology. On the other hand, in group2 (n=14), individuals showed a weaker self-esteem and a lower rate of “living independently”. Cognitive scores for speed processing, attention, verbal learning and social cognition were significantly lower in group2 compared to group1. In addition, these cognitive outcomes were negatively correlated with negative symptoms only in group2. Analysis of redox markers revealed a positive correlation between GPx and GR activities in group1, a correlation disrupted in group2. Discussion Stratification of a cohort of young help-seekers with suspicion of prodromal psychosis, regardless of their CHR status, allowed us to distinguish two subgroups with different clinical profiles: group1 with higher levels of basic symptoms and general symptomatology, and group2 with weaker self-esteem, less autonomy and poorer neurocognition. In addition, analysis of redox markers revealed a redox dysregulation in patients with poorer cognitive profile. Considering the impact of neurocognitive impairment on functioning, special focus to patients of group2 is needed, mostly in clinical practice. Moreover, they might benefit of supplementation with antioxidant compounds such as NAC, which may improve cognitive deficits (Conus et al, 2018).

Highlights • Stability of biomarker selection for predicting schizophrenia in the human connectome • Multi-modal connectome provides the best stability and classification accuracy. • The affected core in schizophrenia is identified through a feature selection process. • We find affected cores for different modalities and parcellations including subcortical regions., Schizophrenia, as a psychiatric disorder, has recognized brain alterations both at the structural and at the functional magnetic resonance imaging level. The developing field of connectomics has attracted much attention as it allows researchers to take advantage of powerful tools of network analysis in order to study structural and functional connectivity abnormalities in schizophrenia. Many methods have been proposed to identify biomarkers in schizophrenia, focusing mainly on improving the classification performance or performing statistical comparisons between groups. However, the stability of biomarkers selection has been for long overlooked in the connectomics field. In this study, we follow a machine learning approach where the identification of biomarkers is addressed as a feature selection problem for a classification task. We perform a recursive feature elimination and support vector machines (RFE-SVM) approach to identify the most meaningful biomarkers from the structural, functional, and multi-modal connectomes of healthy controls and patients. Furthermore, the stability of the retrieved biomarkers is assessed across different subsamplings of the dataset, allowing us to identify the affected core of the pathology. Considering our technique altogether, it demonstrates a principled way to achieve both accurate and stable biomarkers while highlighting the importance of multi-modal approaches to brain pathology as they tend to reveal complementary information.

Early in the course of psychosis, alterations in brain connectivity accompany the emergence of psychiatric symptoms and cognitive impairments, including processing speed. The clinical-staging model is a refined form of diagnosis that places the patient along a continuum of illness conditions, which allows stage-specific interventions with the potential of improving patient care and outcome. This cross-sectional study investigates brain connectivity features that characterize the clinical stages following a first psychotic episode. Structural brain networks were derived from diffusion-weighted MRI for 71 early-psychosis patients and 76 healthy controls. Patients were classified into stage II (first-episode), IIIa (incomplete remission), IIIb (one relapse), and IIIc (two or more relapses), according to the course of the illness until the time of scanning. Brain connectivity measures and diffusion parameters (fractional anisotropy, apparent diffusion coefficient) were investigated using general linear models and sparse linear discriminant analysis (sLDA), studying distinct subgroups of patients who were at specific stages of early psychosis. We found that brain connectivity impairments were more severe in clinical stages following the first-psychosis episode (stages IIIa, IIIb, IIIc) than in first-episode psychosis (stage II) patients. These alterations were spatially diffuse but converged on a set of vulnerable regions, whose inter-connectivity selectively correlated with processing speed in patients and controls. The sLDA suggested that relapsing-remitting (stages IIIb, IIIc) and non-remitting (stage IIIa) patients are characterized by distinct dysconnectivity profiles. Our results indicate that neuroimaging markers of brain dysconnectivity in early psychosis may reflect the heterogeneity of the illness and provide a connectomics signature of the clinical-staging model.

Aim Selection bias could be an important limiting factor in psychiatric neurobiological research. The study aim was to compare, within an early psychosis program, patients who agreed to participate to neurobiological research with patients who refused. Methods 284 patients with early psychosis were assessed at baseline on a large set of socio-demographic and clinical variables and were followed-up over 36 months. Results There were no differences between groups, except regarding forensic/psychiatric history, lifetime substance abuse and social-occupational level during follow-up. Conclusions While patients participating to neurobiological research seem representative of our clinical cohort, the few differences identified may deserve attention.

Mechanism-based treatments for schizophrenia are needed, and increasing evidence suggests that oxidative stress may be a target. Previous research has shown that N-acetylcysteine (NAC), an antioxidant and glutathione (GSH) precursor almost devoid of side effects, improved negative symptoms, decreased the side effects of antipsychotics, and improved mismatch negativity and local neural synchronization in chronic schizophrenia. In a recent double-blind randomized placebo-controlled trial by Conus et al., early psychosis patients received NAC add-on therapy (2700 mg/day) for 6 months. Compared with placebo-treated controls, NAC patients showed significant improvements in neurocognition (processing speed) and a reduction of positive symptoms among patients with high peripheral oxidative status. NAC also led to a 23% increase in GSH levels in the medial prefrontal cortex (GSHmPFC) as measured by 1H magnetic resonance spectroscopy. A subgroup of the patients in this study were also scanned with multimodal MR imaging (spectroscopy, diffusion, and structural) at baseline (prior to NAC/placebo) and after 6 months of add-on treatment. Based on prior translational research, we hypothesized that NAC would protect white matter integrity in the fornix. A group × time interaction indicated a difference in the 6-month evolution of white matter integrity (as measured by generalized fractional anisotropy, gFA) in favor of the NAC group, which showed an 11% increase. The increase in gFA correlated with an increase in GSHmPFC over the same 6-month period. In this secondary study, we suggest that NAC add-on treatment may be a safe and effective way to protect white matter integrity in early psychosis patients.

Psychiatric treatments often involve numerous partners. The organization of coordination meetings during in-patient admissions is necessary in order to harmonize interventions. The expectations of each partner during such meetings may however differ and some issues that may seem important to some of them may be neglected. In this paper, we report the results of a survey conducted among the various partners involved in psychiatric patient's treatment in order to identify their expectations, the challenges they may have faced and the solutions they would propose. If perfection ca not be warrantied in all situations, taking these elements into account may improve these meetings and allow to better respect the role of each actor while giving to the patient the central role that they should play when defining their treatment.Les traitements psychiatriques impliquent souvent plusieurs partenaires et nécessitent une coordination des interventions à travers des réunions de réseau, en particulier en cas d’hospitalisation. Les attentes à l’égard de ce genre de réunion sont différentes pour chacun des acteurs impliqués et les besoins de certains partenaires sont parfois négligés. Dans cet article, nous rapportons les avis de plusieurs de ces acteurs sur les attentes qu’ils ont à l’égard de ces rencontres, les difficultés qu’ils y rencontrent et les solutions qu’ils proposent. Si la perfection ne peut pas être garantie à chaque fois, la prise en compte de ces éléments permettrait d’améliorer le déroulement des entretiens de réseau, de mieux respecter la place de chacun et de laisser au patient le rôle central qu’il doit jouer dans l’élaboration de sa prise en charge.

BACKGROUND: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure.METHODS: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV.RESULTS: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion < control; Cohen's d < -1), and the caudate and hippocampus (control > duplication; -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results.CONCLUSIONS: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.

Dans cette version courte, la Societe Suisse de Psychiatrie et de Psychotherapie presente des elements centraux des recommandations therapeutiques a l’intention des medecins de toutes les specialites.

Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC’s impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase activity [GPxBC]). No changes in negative or positive symptoms or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on neurocognition (processing speed). NAC also led to increases of GSHmPFC by 23% (P = .005) and GSHBC by 19% (P = .05). In patients with high-baseline GPxBC compared to low-baseline GPxBC, subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC. In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest baseline levels. However, NAC led to some neurocognitive improvements and an increase in brain GSH levels, indicating good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help identify a subgroup of patients who improve their positive symptoms with NAC. Thus, future trials with antioxidants in EP should consider biomarker-guided treatment.

Children of patients with psychiatric disorders are at higher risk to develop a psychiatric illness. In addition, phases of crisis and hospitalization of the parent are often traumatizing to the children, especially during childhood. Although a specific offer to face these issues is compulsory in some countries, such is not the case in Switzerland. In this paper we describe the implementation of a special offer for children of parents with mental illness (Famille +) in the service of general psychiatry at the Department of psychiatry of the Lausanne University hospital in Switzerland. We will also discuss the development and implementation of the Joint Crisis Plan, a collaborative tool where psychiatric patients and clinicians define the strategies that should be applied in case of crisis, which strengthens the empowerment of patients and their participation to decisions about their treatment.Les enfants de patients souffrant d’un trouble psychiatrique ont un risque accru de développer eux-mêmes des troubles psychiatriques au cours de leur vie. De plus, les phases de crise et les hospitalisations de parents sont souvent vécues de manière traumatisante par leurs enfants. Bien qu’une offre spécialisée pour les enfants de patients psychiatriques soit obligatoire dans certains pays nordiques, tel n’est pas le cas en Suisse. Le développement d’un tel programme est décrit dans cet article. Il y sera aussi question du développement et de l’implantation du plan de crise conjoint, un outil partenarial entre patients et soignants qui définit les interventions et les modalités de prise en charge en cas de crise et permet ainsi de renforcer l’autodétermination des patients et leur participation aux décisions qui les concernent.

Patients diagnosed with schizophrenia often present with low-level sensory deficits. It is an open question whether there is a functional link between these deficits and the pathophysiology of the disease, e.g. oxidative stress and glutathione (GSH) metabolism dysregulation. Auditory evoked potentials (AEPs) were recorded from 21 psychosis disorder patients and 30 healthy controls performing an active, auditory oddball task. AEPs to standard sounds were analyzed within an electrical neuroimaging framework. A peripheral measure of participants' redox balance, the ratio of glutathione peroxidase and glutathione reductase activities (GPx/GR), was correlated with the AEP data. Patients displayed significantly decreased AEPs over the time window of the P50/N100 complex resulting from significantly weaker responses in the left temporo-parietal lobe. The GPx/GR ratio significantly correlated with patients' brain activity during the time window of the P50/N100 in the medial frontal lobe. We show for the first time a direct coupling between electrophysiological indices of AEPs and peripheral redox dysregulation in psychosis patients. This coupling is limited to stages of auditory processing that are impaired relative to healthy controls and suggests a link between biochemical and sensory dysfunction. The data highlight the potential of low-level sensory processing as a trait-marker of psychosis.

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. 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. 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

Background Metabolic syndrome (MetS) associated with psychiatric disorders and psychotropic treatments represents a major health issue. 11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is an enzyme that catalyzes tissue regeneration of active cortisol from cortisone. Elevated enzymatic activity of 11 beta-HSD1 may lead to the development of MetS. Methods We investigated the association between seven HSD11B1 gene (encoding 11 beta-HSD1) polymorphisms and BMI and MetS components in a psychiatric sample treated with potential weight gain-inducing psychotropic drugs (n = 478). The polymorphisms that survived Bonferroni correction were analyzed in two independent psychiatric samples (n(R1) = 168, n(R2) = 188) and in several large population-based samples (n(1) = 5338; n(2) = 123 865; n(3) > 100 000). Results HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele carriers were found to be associated with lower BMI, waist circumference, and diastolic blood pressure compared with the reference genotype (P-corrected < 0.05). These associations were exclusively detected in women (n = 257) with more than 3.1 kg/m(2), 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele carriers compared with noncarriers (P-corrected < 0.05). Conversely, carriers of the rs846906-T allele had significantly higher waist circumference and triglycerides and lower high-density lipoprotein-cholesterol exclusively in men (P-corrected = 0.028). The rs846906-T allele was also associated with a higher risk of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53-7.17, P-corrected = 0.014). No association was observed between HSD11B1 polymorphisms and BMI and MetS components in the population-based samples. Conclusions Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not play a significant role in the general population. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

Objectives Previous literature suggests that early psychosis (EP) patients with a history of offending behavior (HOB) have specific clinical needs. The aims of this study were to assess: (1) the prevalence of HOB in a representative sample of EP; (2) the premorbid and baseline characteristics of patients with HOB, and (3) the potential differences in short-term outcome of such patients when compared to patients without HOB. Methods The Early Psychosis Prevention and Intervention Centre (EPPIC) admitted 786 EP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. Data of 647 patients could be analyzed. Results HOB patients (29% of the sample) were more likely to be male with lower level of premorbid functioning and education, have used illicit substances and have attempted suicide. They presented with a more complex clinical picture and had poorer 18-month outcome. Most importantly, they had a significantly longer duration of untreated psychosis. Conclusions On the basis of the high prevalence and specific features of EP patients with HOB, our study confirms a need for additional research in this domain and for the development of specific treatment strategies. Most importantly, it suggests a need for the promotion of early detection strategies among the populations of young offenders, considering that some of them may be going through the early phases of a psychotic disorder and that reduction of treatment delay and provision of well adapted interventions may have a significant impact at numerous levels in such patients.

Starting from the early descriptions of Kraepelin and Bleuler, the construct of schizotypy was developed from observations of aberrations in nonpsychotic family members of schizophrenia patients. In contemporary diagnostic manuals, the positive symptoms of schizotypal personality disorder were included in the ultra high-risk (UHR) criteria 20 years ago, and nowadays are broadly employed in clinical early detection of psychosis. The schizotypy construct, now dissociated from strict familial risk, also informed research on the liability to develop any psychotic disorder, and in particular schizophrenia-spectrum disorders, even outside clinical settings. Against the historical background of schizotypy it is surprising that evidence from longitudinal studies linking schizotypy, UHR, and conversion to psychosis has only recently emerged; and it still remains unclear how schizotypy may be positioned in high-risk research. Following a comprehensive literature search, we review 18 prospective studies on 15 samples examining the evidence for a link between trait schizotypy and conversion to psychosis in 4 different types of samples: general population, clinical risk samples according to UHR and/or basic symptom criteria, genetic (familial) risk, and clinical samples at-risk for a nonpsychotic schizophrenia-spectrum diagnosis. These prospective studies underline the value of schizotypy in high-risk research, but also point to the lack of evidence needed to better define the position of the construct of schizotypy within a developmental psychopathology perspective of emerging psychosis and schizophrenia-spectrum disorders.