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Abstract Background Borderline personality disorder (BPD) is often characterized by severe functional impairment, even after a decrease in symptoms. A comprehensive understanding of psychosocial functioning in BPD is necessary to tailor treatment offer, which should address relevant aspects of daily life. The aims of the present study are to (1) conduct a cross-sectional comparison of functioning of a group with BPD and a non-BPD clinical comparison group at service entry, and to (2) assess the relationship between intensity of BPD symptom domains and psychosocial functioning. Methods The sample consists of N = 65 participants with BPD and N = 57 participants from the clinical comparison group without BPD (non-BPD group). The Revised Borderline Follow-up Interview (BFI-R) was used to evaluate psychosocial functioning and the Revised Diagnostic Interview for Borderlines (DIB-R) to assess BPD symptoms. Linear, logistic, and multinomial regression models were run separately for each aspect of functioning as a function of BPD status or BPD symptom domains. Results Only 23% of participants in the BPD group fulfilled criteria for good overall psychosocial functioning, compared to 53% in the non-BPD group. Furthermore, participants in the BPD group were less likely to have completed a high number of years of education, to work consistently, to be financially independent, to be in a cohabiting relationship and have a good relationship with parents. In addition, various links were identified between BPD symptom domains and functional impairments. Conclusions Consistent with prior research, the main impairments in functioning in the BPD group are found in the educational and vocational domains. Though some domains show impairment, others, like friendships, may act as potential resources. Further investigation on the relationships with symptom domains is required.

Abstract Given the unpredictable rapid onset and ubiquitous consequences of weight gain induced by antipsychotics, there is a pressing need to get insights into the underlying processes at the brain system level that will allow stratification of “at risk” patients. The pathophysiological hypothesis at hand is focused on brain networks governing impulsivity that are modulated by neuro-inflammatory processes. To this aim, we investigated brain anatomy and functional connectivity in patients with early psychosis (median age: 23 years, IQR = 21–27) using anthropometric data and magnetic resonance imaging acquired one month to one year after initiation of AP medication. Our analyses included 19 patients with high and rapid weight gain (i.e., ≥5% from baseline weight after one month) and 23 patients with low weight gain (i.e.,

Abstract Background Metabolic side effects of psychotropic medications are a major drawback to patients’ successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip. Results A global methylation increase was noted after the first month of treatment, which was more pronounced (p

Abstract Adolescence is marked by the maturation of systems involved in emotional regulation and by an increased risk for internalizing disorders (anxiety/depression), especially in females. Hypothalamic-pituitary-adrenal (HPA)-axis function and redox homeostasis (balance between reactive oxygen species and antioxidants) have both been associated with internalizing disorders and may represent critical factors for the development of brain networks of emotional regulation. However, sex-specific interactions between these factors and internalizing symptoms and their link with brain maturation remain unexplored. We investigated in a cohort of adolescents aged 13–15 from the general population (n = 69) whether sex-differences in internalizing symptoms were associated with the glutathione (GSH)-redox cycle homeostasis and HPA-axis function and if these parameters were associated with brain white matter microstructure development. Female adolescents displayed higher levels of internalizing symptoms, GSH-peroxidase (GPx) activity and cortisol/11-deoxycortisol ratio than males. There was a strong correlation between GPx and GSH-reductase (Gred) activities in females only. The cortisol/11-deoxycortisol ratio, related to the HPA-axis activity, was associated with internalizing symptoms in both sexes, whereas GPx activity was associated with internalizing symptoms in females specifically. The cortisol/11-deoxycortisol ratio mediated sex-differences in internalizing symptoms and the association between anxiety and GPx activity in females specifically. In females, GPx activity was positively associated with generalized fractional anisotropy in widespread white matter brain regions. We found that higher levels of internalizing symptoms in female adolescents than in males relate to sex-differences in HPA-axis function. In females, our results suggest an important interplay between HPA-axis function and GSH-homeostasis, a parameter strongly associated with brain white matter microstructure.

Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles.Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment.Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03–1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02–1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04–1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04–1.55, p = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment.Conclusion: PRSresponse defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.

BackgroundPsychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission.MethodsBetween 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances.ResultsA total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission.ConclusionThe observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk.

Background There is a lack of standardised psychometric data in electronic health record (EHR)-based research. Proxy measures of symptom severity based on patients' clinical records may be useful surrogates in mental health EHR research. Aims This study aimed to validate proxy tools for the short versions of the Positive and Negative Syndrome Scale (PANSS-6), Young Mania Rating Scale (YMRS-6) and Montgomery–Åsberg Depression Rating Scale (MADRS-6). Method A cross-sectional, multicentre study was conducted in a sample of 116 patients with first-episode psychosis from 12 public hospitals in Spain. Concordance between PANSS-6, YMRS-6 and MADRS-6 scores and their respective proxies was evaluated based on information from EHR clinical notes, using a variety of statistical procedures, including multivariate tests to adjust for potential confounders. Bootstrapping techniques were used for internal validation, and an independent cohort from the Treatment and Early Intervention in Psychosis Program (TIPP-Lausanne, Switzerland) for external validation. Results The proxy versions correlated strongly with their respective standardised scales (partial correlations ranged from 0.75 to 0.84) and had good accuracy and discriminatory power in distinguishing between patients in and not in remission (percentage of patients correctly classified ranged from 83.9 to 91.4% and bootstrapped optimism-corrected area under the receiver operating characteristic curve ranged from 0.76 to 0.89), with high interrater reliability (intraclass correlation coefficient of 0.81). The findings remained robust in the external validation data-set. Conclusions The proxy instruments proposed for assessing psychotic and affective symptoms by reviewing EHR provide a feasible and reliable alternative to traditional structured psychometric procedures, and a promising methodology for real-world practice settings.

IntroductionStudies on the integration of peer mental health practitioners (PMHP) in hospitals are sparse, despite significant benefits being reported for patients and professionals. The integration of PMHP requires the consideration of several parameters and a change in the culture of care. This study aims to understand the impact of the integration of a PMHP in a hospital unit caring for patients with psychiatric disorders.MethodsA qualitative content analysis of three focus groups with the interdisciplinarity team were conducted. A consulting PMHP was integrated into the entire research process.ResultsData analysis revealed five main themes: the importance of integration, benefits for patients linked to the identification process, benefits for the team and institution, potentials risks, and perspectives.DiscussionThe study was conducted in a hospital setting with patients suffering from severe psychiatric disorders associated with behavioral disturbances. The benefits reported in the results outline the feasibility of PMHP integration in an acute psychiatric care setting. Nevertheless, further formalization of the PMHP role is required to minimize possible areas of tension between respective fields of activity of each professional.

Abstract Traumatic events during childhood/early adolescence can cause long-lasting physiological and behavioral changes with increasing risk for psychiatric conditions including psychosis. Genetic factors and trauma (and their type, degree of repetition, time of occurrence) are believed to influence how traumatic experiences affect an individual. Here, we compared long-lasting behavioral effects of repeated social defeat stress (SD) applied during either peripuberty or late adolescence in adult male WT and Gclm-KO mice, a model of redox dysregulation relevant to schizophrenia. As SD disrupts redox homeostasis and causes oxidative stress, we hypothesized that KO mice would be particularly vulnerable to such stress. We first found that peripubertal and late adolescent SD led to different behavioral outcomes. Peripubertal SD induced anxiety-like behavior in anxiogenic environments, potentiated startle reflex, and increased sensitivity to the NMDA-receptor antagonist, MK-801. In contrast, late adolescent SD led to increased exploration in novel environments. Second, the long-lasting impact of peripubertal but not late adolescent SD differed in KO and WT mice. Peripubertal SD increased anxiety-like behavior in anxiogenic environments and MK-801-sensitivity mostly in KO mice, while it increased startle reflex in WT mice. These suggest that a redox dysregulation during peripuberty interacts with SD to remodel the trajectory of brain maturation, but does not play a significant role during later SD. As peripubertal SD induced persisting anxiety- and fear-related behaviors in male mice, we then investigated anxiety in a cohort of 89 early psychosis male patients for whom we had information about past abuse and clinical assessment during the first year of psychosis. We found that a first exposure to physical/sexual abuse (analogous to SD) before age 12, but not after, was associated with higher anxiety at 6–12 months after psychosis onset. This supports that childhood/peripuberty is a vulnerable period during which physical/sexual abuse in males has wide and long-lasting consequences.

Abstract 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.

Abstract Objectives Small area analysis is a health services research technique that facilitates geographical comparison of services supply and utilization rates between health service areas (HSAs). HSAs are functionally relevant regions around medical facilities within which most residents undergo treatment. We aimed to identify HSAs for psychiatric outpatient care (HSA‐PSY) in Switzerland. Methods We used HSAr, a new and automated methodological approach, and comprehensive psychiatric service use data from insurances to identify HSA‐PSY based on travel patterns between patients' residences and service sites. Resulting HSA‐PSY were compared geographically, demographically and regarding the use of inpatient and outpatient psychiatric services. Results We identified 68 HSA‐PSY, which were reviewed and validated by local mental health services experts. The population‐based rate of inpatient and outpatient service utilization varied considerably between HSA‐PSY. Utilization of inpatient and outpatient services tended to be positively associated across HSA‐PSY. Conclusions Wide variation of service use between HSA‐PSY can hardly be fully explained by underlying differences in the prevalence or incidence of disorders. Whether other factors such as the amount of services supply did add to the high variation should be addressed in further studies, for which our functional mapping on a small‐scale regional level provides a good analytical framework.

IntroductionRecent efforts have been made to apply machine learning and deep learning approaches to the automated classification of schizophrenia using structural magnetic resonance imaging (sMRI) at the individual level. However, these approaches are less accurate on early psychosis (EP) since there are mild structural brain changes at early stage. As cognitive impairments is one main feature in psychosis, in this study we apply a multi-task deep learning framework using sMRI with inclusion of cognitive assessment to facilitate the classification of patients with EP from healthy individuals.MethodUnlike previous studies, we used sMRI as the direct input to perform EP classifications and cognitive estimations. The proposed deep learning model does not require time-consuming volumetric or surface based analysis and can provide additionally cognition predictions. Experiments were conducted on an in-house data set with 77 subjects and a public ABCD HCP-EP data set with 164 subjects.ResultsWe achieved 74.9 ± 4.3% five-fold cross-validated accuracy and an area under the curve of 71.1 ± 4.1% on EP classification with the inclusion of cognitive estimations.DiscussionWe reveal the feasibility of automated cognitive estimation using sMRI by deep learning models, and also demonstrate the implicit adoption of cognitive measures as additional information to facilitate EP classifications from healthy controls.

Aims: Psychotic disorders are one of the main causes of chronic disability in young people. An at-risk mental state (ARMS) is represented by subclinical symptoms that precede the first episode of psychosis (FEP). The PsyYoung project aims to optimize the detection of an ARMS while reducing unnecessary psychiatric treatments. It investigates the effects of service changes on the referrals and outcomes of young people with ARMS or a FEP. Methods: Six psychiatric outpatient clinics in three cantons (Basel-Stadt, Vaud, and Geneva) participated in the project. They passed through an implementation phase including service changes and the adaptation of a standardized stepped care model for diagnosis and assessment, in addition to measures for increasing the awareness, networking and training of local professionals. Preliminary results: All participating cantons had entered the implementation phase. By March 2023, there were 619 referrals to participating sites. A total of 163 patients (37% FEP and 31% ARMS) and 15 close relatives had participated in individual longitudinal assessments, and 26 patients participated in qualitative interviews. Conclusion: This national collaborative project addresses the issue of early intervention for emerging psychoses, and creates spaces for fruitful reflections and collaboration in Switzerland. The ultimate aim of PsyYoung is to harmonize clinical practices in early intervention of psychosis on a national level.

Abstract Psychotropic drugs can induce strong metabolic adverse effects, potentially increasing morbidity and/or mortality of patients. Metabolomic profiling, by studying the levels of numerous metabolic intermediates and products in the blood, allows a more detailed examination of metabolism dysfunctions. We aimed to identify blood metabolomic markers associated with weight gain in psychiatric patients. Sixty‐two patients starting a treatment known to induce weight gain were recruited. Two hundred and six selected metabolites implicated in various pathways were analyzed in plasma, at baseline and after 1 month of treatment. Additionally, 15 metabolites of the kynurenine pathway were quantified. This latter analysis was repeated in a confirmatory cohort of 24 patients. Among the 206 metabolites, a plasma metabolomic fingerprint after 1 month of treatment embedded 19 compounds from different chemical classes (amino acids, acylcarnitines, carboxylic acids, catecholamines, nucleosides, pyridine, and tetrapyrrole) potentially involved in metabolic disruption and inflammation processes. The predictive potential of such early metabolite changes on 3 months of weight evolution was then explored using a linear mixed‐effects model. Of these 19 metabolites, short‐term modifications of kynurenine, hexanoylcarnitine, and biliverdin, as well as kynurenine/tryptophan ratio at 1 month, were associated with 3 months weight evolution. Alterations of the kynurenine pathway were confirmed by quantification, in both exploratory and confirmatory cohorts. Our metabolomic study suggests a specific metabolic dysregulation after 1 month of treatment with psychotropic drugs known to induce weight gain. The identified metabolomic signature could contribute in the future to the prediction of weight gain in patients treated with psychotropic drugs.

Summary: Background: Cardiometabolic dysfunction is common in young people with psychosis. Recently, the Psychosis Metabolic Risk Calculator (PsyMetRiC) was developed and externally validated in the UK, predicting up-to six-year risk of metabolic syndrome (MetS) from routinely collected data. The full-model includes age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations; the partial-model excludes biochemical predictors. Methods: To move toward a future internationally-useful tool, we externally validated PsyMetRiC in two independent European samples. We used data from the PsyMetab (Lausanne, Switzerland) and PAFIP (Cantabria, Spain) cohorts, including participants aged 16–35y without MetS at baseline who had 1–6y follow-up. Predictive performance was assessed primarily via discrimination (C-statistic), calibration (calibration plots), and decision curve analysis. Site-specific recalibration was considered. Findings: We included 1024 participants (PsyMetab n=558, male=62%, outcome prevalence=19%, mean follow-up=2.48y; PAFIP n=466, male=65%, outcome prevalence=14%, mean follow-up=2.59y). Discrimination was better in the full- compared with partial-model (PsyMetab=full-model C=0.73, 95% C.I., 0.68–0.79, partial-model C=0.68, 95% C.I., 0.62–0.74; PAFIP=full-model C=0.72, 95% C.I., 0.66–0.78; partial-model C=0.66, 95% C.I., 0.60–0.71). As expected, calibration plots revealed varying degrees of miscalibration, which recovered following site-specific recalibration. PsyMetRiC showed net benefit in both new cohorts, more so after recalibration. Interpretation: The study provides evidence of PsyMetRiC's generalizability in Western Europe, although further local and international validation studies are required. In future, PsyMetRiC could help clinicians internationally to identify young people with psychosis who are at higher cardiometabolic risk, so interventions can be directed effectively to reduce long-term morbidity and mortality. Funding: NIHR Cambridge Biomedical Research Centre (BRC-1215-20014); The Wellcome Trust (201486/Z/16/Z); Swiss National Research Foundation (320030-120686, 324730- 144064, and 320030-173211); The Carlos III Health Institute (CM20/00015, FIS00/3095, PI020499, PI050427, and PI060507); IDIVAL (INT/A21/10 and INT/A20/04); The Andalusian Regional Government (A1-0055-2020 and A1-0005-2021); SENY Fundacion Research (2005-0308007); Fundacion Marques de Valdecilla (A/02/07, API07/011); Ministry of Economy and Competitiveness and the European Fund for Regional Development (SAF2016-76046-R and SAF2013-46292-R).For the Spanish and French translation of the abstract see Supplementary Materials section.

Abstract Weight gain and metabolic complications are major adverse effects of many psychotropic drugs. We aimed to understand how socio-economic status (SES), defined as the Swiss socio-economic position (SSEP), is associated with cardiometabolic parameters after initiation of psychotropic medications known to induce weight gain. Cardiometabolic parameters were collected in two Swiss cohorts following the prescription of psychotropic medications. The SSEP integrated neighborhood-based income, education, occupation, and housing condition. The results were then validated in an independent replication sample (UKBiobank), using educational attainment (EA) as a proxy for SES. Adult patients with a low SSEP had a higher risk of developing metabolic syndrome over one year versus patients with a high SSEP (Hazard ratio (95% CI) = 3.1 (1.5–6.5), n = 366). During the first 6 months of follow-up, a significant negative association between SSEP and body mass index (BMI), weight change, and waist circumference change was observed (25 ≤ age

Abstract Background While specialized early intervention programs represent the gold standard in terms of optimal management of first-episode psychosis (FEP), poor medication adherence remains a predominant unmet need in the treatment of psychosis. In this regard, an interaction between insight and adherence in FEP patients has been hypothesized but has been challenged by multiple pitfalls. Methods Latent profile analysis and trajectory modeling techniques were used to evaluate insight and adherence of 331 FEP patients engaged at the beginning, middle, and end of a 3-year specialized early psychosis program. A Bayesian model comparison approach was used to compare scores of clinical, functional, and socioeconomic outcomes at the end point of the study. Results Nearly one-third of the patients maintain a high level of insight and adherence during the entire program. At the end of the 3-year follow-up, more than three-quarters of patients are considered adherent to their medication. Patients with low levels of insight and adherence at the beginning of the program improve first in terms of adherence and then of insight. Furthermore, patients with high levels of insight and adherence are most likely to reach functional recovery and to experience an increase in environmental quality of life. Conclusions Latent FEP subpopulations can be identified based on insight and adherence. Medication adherence was the first variable to improve, but a gain in insight possibly plays a role in the reinforcement of adherence.

Abstract Background Borderline personality disorder (BPD) is one of the most frequent, most debilitating and lethal mental conditions and is associated with a serious burden of disease. Treatment for patients with BPD involves structured psychotherapy, and may involve brief psychiatric treatment as first-line intervention. No controlled study has assessed the effectiveness of such brief intervention. Whereas most psychotherapy studies in patients with BPD focus on the effectiveness of the intervention, we still lack an understanding of how and why these effects are produced from a patient process perspective. It is therefore of utmost importance to study the treatment-underlying mechanisms of change. The present study plans to apply novel measurement methods for assessing change in two central psychobiological processes in BPD: emotion and socio-cognitive processing. The study uses theory-driven and ecologically valid experimental tasks, which take the patient’s individual experience as the anchor, by integrating methodology from psychotherapy process and neurofunctional imagery research. Methods The aim of this two-arm, randomized controlled study is to test the effects (i.e., symptom reduction) and the underlying mechanisms of change associated with a brief psychiatric treatment (10 sessions over 4 months), compared with treatment as usual. Participants (N = 80 patients with BPD) undergo assessments at four points (intake, 2 months, discharge, and 12-month follow up). In addition to symptom measures, individuals undergo a 2-step assessment for the potential mechanisms of change (i.e., emotion and socio-cognitive processing): (1) behavioral and (2) (for a sub-sample) neurofunctional. We hypothesize that change in the mechanisms explains the treatment effects. Discussion This study uses an easy-to-implement treatment of BPD, and a sophisticated assessment procedure to demonstrate the critical role of psychobiological change in emotion and socio-cognitive processing in brief treatments. It will help increase the effectiveness of brief treatment for BPD and help diminish the societal burden of disease related to BPD, in these early stages of treatment. Trial registration {2} ClinicalTrials.gov: NCT03717818 . Registered on 24 October 2018). Protocol version {3} number 2 from 9 February 2018.

Objective: We first sought to examine the relationship between plasma levels of methylxanthines (caffeine and its metabolites) and sleep disorders, and secondarily between polygenic risk scores (PRS) of caffeine consumption or sleep duration with methylxanthine plasma levels and/or sleep disorders in a psychiatric cohort.Methods: Plasma levels of methylxanthines were quantified by ultra-high performance liquid chromatography/tandem mass spectrometry. In inpatients, sleep disorder diagnosis was defined using ICD-10 “F51.0,” sedative drug intake before bedtime, or hospital discharge letters, while a subgroup of sedative drugs was used for outpatients. The PRS of coffee consumption and sleep duration were constructed using publicly available GWAS results from the UKBiobank.Results: 1,747 observations (1,060 patients) were included (50.3% of observations with sleep disorders). Multivariate analyses adjusted for age, sex, body mass index, setting of care and psychiatric diagnoses showed that patients in the highest decile of plasma levels of methylxanthines had more than double the risk for sleep disorders compared to the lowest decile (OR = 2.13, p = 0.004). PRS of caffeine consumption was associated with plasma levels of caffeine, paraxanthine, theophylline and with their sum (β = 0.1; 0.11; 0.09; and 0.1, pcorrected = 0.01; 0.02; 0.02; and 0.01, respectively) but not with sleep disorders. A trend was found between the PRS of sleep duration and paraxanthine levels (β = 0.13, pcorrected = 0.09).Discussion: Very high caffeine consumption is associated with sleep disorders in psychiatric in- and outpatients. Future prospective studies should aim to determine the benefit of reducing caffeine consumption in high caffeine-consuming patients suffering from sleep disorders.

AbstractBackground:Although evidence from psychosis patients demonstrates the adverse effects of cannabis use (CU) at a young age and that the rate of CU is high in subgroups of young violent patients with psychotic disorders, little is known about the possible effect of the age of onset of CU on later violent behaviors (VB). So, we aimed to explore the impact of age at onset of CU on the risk of displaying VB in a cohort of early psychosis patients.Method:Data were collected prospectively over a 36-month period in the context of an early psychosis cohort study. A total of 265 patients, aged 18–35 years, were included in the study. Logistic regression was performed to assess the link between age of onset of substance use and VB.Results:Among the 265 patients, 72 had displayed VB and 193 had not. While violent patients began using cannabis on average at age 15.29 (0.45), nonviolent patients had started on average at age 16.97 (0.35) (p = 0.004). Early-onset CU (up to age 15) was a risk factor for VB (odds ratio = 4.47, confidence interval [CI]: 1.13–20.06) when the model was adjusted for age group, other types of substance use, being a user or a nonuser and various violence risk factors and covariates. History of violence and early CU (until 15) were the two main risk factors for VB.Conclusions:Our results suggest that early-onset CU may play a role in the emergence of VB in early psychosis.

BackgroundIt has been suggested that exposure to Childhood Trauma [CT] may play a role in the risk of obesity in Early Psychosis [EP] patients; however, whether this is independently of age at exposure to CT and the medication profile has yet to be investigated.Methods113 EP-patients aged 18-35 were recruited from the Treatment and Early Intervention in Psychosis Program [TIPP-Lausanne]. Body Mass Index [BMI], Weight Gain [WG] and Waist Circumference [WC] were measured prospectively at baseline and after 1, 2, 3, 6 and 12 months of weight gain inducing psychotropic treatment. Patients were classified as Early-Trauma and Late-Trauma if the exposure had occurred before age 12 or between ages 12 and 16 respectively. Generalized Linear Mixed-Models were adjusted for age, sex, socioeconomic status, baseline BMI, medication and for diagnosis of depression.ResultsLate-Trauma patients, when compared to Non-Trauma patients showed greater WCs during the follow-up [p = 0.013]. No differences were found in any of the other follow-up measures.ConclusionsExposition to CT during adolescence in EP-patients treated with psychotropic medication is associated with greater WC during the early phase of the disease. Further investigation exploring mechanisms underlying the interactions between peripubertal stress, corticoids responsiveness and a subsequent increase of abdominal adiposity is warranted.

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.

Background: Psychiatric patients are at risk of cardiovascular diseases, and many psychotropic drugs can prolong QTc interval. Requirements for electrocardiogram (ECG) monitoring have been set up in our psychiatric university hospital. The objective of this study was to determine the proportion of adult patients who had an ECG during their hospitalization, the prevalence of ECG abnormalities, the evolution of the QTc after admission, and the risk factors for QTc prolongation. Methods: Retrospective analysis of ECGs and clinical data of all patients with a complete hospitalization in 2015. Assessment of the influence of covariates on QTc using linear mixed-effects models. Results: At least one ECG ( n = 600) was performed during 37.6% of the stays ( n = 1198) and in 45.5% of the patients ( n = 871). Among the patients with an ECG, 17.9% had significant ECG abnormalities, including 7.6% with a prolonged QTc. QTc measured at admission and during hospitalization did not change significantly ( n = 46, 419.4 ± 29.7 ms, 417.2 ± 27.6 ms, p = 0.71). In the multivariate model (292 patients, 357 ECGs), the covariates significantly associated with the QTc were gender (+15.9 ms if female, p

Background: The main objective of this project is to create a research and intervention model to promote large-scale implementation and evaluations of generic very brief interventions for children of parents with mental disorders (COPMI). Feasible interventions for COPMI aged 0–18 years are highly needed, as this is a large high-risk group in society. Reducing behavioral problems and enhancing wellbeing for families with parents affected by any mental disorder are important preventive initiatives. One key prevention strategy is to reduce the risk and expression of psychopathology in children and to promote wellbeing. The present model protocol offers an intervention for children of parents with mental disorders internationally based on a model already implemented in the Netherlands and Norway.Methods: Participants will be parents receiving treatment in mental health services in participating countries and their minor children aged 6–18 years. Participants should be randomized into an intervention group or control group. Data should be retrieved from electronic patient journals (demographics, DSM 5/ICD-10, SCID, MINI) as well as from assessment measures administered at baseline and follow-up, including the KIDSCREEN-27, Strengths and Difficulties Questionnaire (SDQ), Parents’ Evaluations of Developmental Status (PEDS), Parenting Sense of Competence (PSOC), Resilience Scale for Adolescence (READ), Guilt and Shame Questionnaire for Adolescents of Parents with Mental Illness (GSQ-APMI), Mental Health Literacy Scale, and Parent–Child Communication Scale.Results: The hypothesis is that there will be improvements of child behavioral and emotional problems, and outcomes in the project will be reported in terms of parent´s diagnosis, child behavioral and emotional problems, child wellbeing, family communication and functioning, as well as participants’ satisfaction.Discussion: This multi-site international protocol will focus the attention of European scientific and policy makers toward COPMI. This young segment of the population is presently almost completely neglected in most European health policies, despite having a large burden of disability and being at risk of transgenerational transmission of psychopathology. We will further discuss the feasibility of a very brief intervention aiming at preventing mental disorders in young people.

Background: A considerable amount of research has explored the link between living in an urban environment during childhood and the increased risk to develop psychosis. However, the urban milieu is more than a risk factor as it is also a place for socialization and enrichment. The aims of the current study were to explore, in a large sample of early psychosis (EP) patients, their pattern of use of the city, their perception when exposed to various critical stressors, and their sensitivity to diverse forms of stimuli.Methods: We sent a questionnaire (based on previous work conducted in a group of patients, including video-recorded walk-along in the city and a literature review) to 305 EP patients and to 220 medical students.Results: Response rate in patients was low (38%). City avoidance and negative perceptions towards the urban environment increased in patients after onset of psychosis. Patients’ tendency to avoid city center correlates with both problematic social interactions and stimuli perceived as unpleasant. Patients seemed less likely to enjoy urban spaces considered as relaxing, suggesting a lower capacity to benefit from positive aspects of this environment.Conclusions: The development of psychosis influences the way EP patients perceive the city and their capacity to feel at ease in the urban environment, leading to a high rate of city avoidance. Considering the possible influence of city avoidance on social relations and the recovery process, the development of strategies to help patients in this regard may have a significant effect on their recovery process.

Importance: Multiple studies conducted in the general population identified an association between self-reported coffee consumption and plasma lipid levels. To date, no study assessed whether and which plasma methylxanthines (caffeine and/or its metabolites, i.e., paraxanthine, theophylline, and theobromine) are associated with plasma lipids. In psychiatric patients, an important coffee consumption is often reported and many psychotropic drugs can induce a rapid and substantial increase of plasma lipid levels.Objective: To determine whether plasma methylxanthines are associated with metabolic parameters in psychiatric patients receiving treatments known to induce metabolic disturbances.Design, Setting, and Participants: Data were obtained from a prospective study including 630 patients with metabolic parameters [i.e., body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and fasting triglycerides (TG)] monitored routinely during psychotropic treatment.Exposures: Plasma methylxanthines levels.Main Outcomes and Measures: Metabolic variables including BMI and plasma lipid levels.Results: Multivariate analyses indicated that BMI, TC, HDL-C, and non-HDL-C increased significantly with increasing total methylxanthines (pcorrected ≤ 0.05). In addition, compared to patients with plasma caffeine concentration in the lowest quartile, those with caffeine concentration in the highest quartile were twice more prone to suffer from non-HDL hypercholesterolemia (pcorrected = 0.05), five times more likely to suffer from hypertriglyceridemia (pcorrected = 0.01) and four times more susceptible to be overweight (pcorrected = 0.01).Conclusions and Relevance: This study showed that plasma caffeine and other methylxanthines are associated with worsening of metabolic parameters in patients receiving psychotropic treatments known to induce metabolic disturbances. It emphasizes that important caffeine consumption could be considered as an additional environmental risk factor for metabolic worsening in patients receiving such treatments.

Background: Previous literature suggests that prevalence of cannabis use in the early phase of psychosis is high, and that early psychosis patients are at high-risk for violent behavior. However, the link between cannabis use and violent behavior in early psychosis patients is unclear. We carried out a study on a sample of early psychosis patients, in order to explore the impact of cannabis use on the risk of violent behavior (VB), while taking into account (1) potential confounding factors and, (2) interactions with other dynamic risk factors of VB.Method: In a sample of 265 early psychosis patients, treated at the Treatment and Early Intervention in Psychosis Program (TIPP) in Lausanne, we used logistic regression models to explore the link between various dynamic risk factors of VB [positive symptoms, substance use disorder (drugs including cannabis, alcohol and others drugs), insight, impulsivity, affective instability, and treatment adherence], and VB occurring during treatment. In order to understand hierarchical effects attributable to the combinations of risk factors on VB we conducted a Classification and Regression Tree (CART).Results: Our results show that cannabis use disorder is a risk factor for VB. The associations among risk factors suggest the presence of two patient profiles with an increased rate of VB: the first is composed of patients with cannabis use disorder and impulsivity, and the second of patients combining cannabis use disorder, absence of insight and non-adherence to treatment. The results also show the moderating role of insight and adherence to treatment on the rate of VB in patients with cannabis use disorder.Conclusion: This study suggests that cannabis use disorder is a significant risk factor for VB amongst early psychosis patients, particularly when combined with either impulsivity, lack of insight and non-adherence to treatment. These results suggest that preventive strategies could be developed on the basis of such patient profiles.

The Health of the Nation Outcome Scales (HoNOS) is a widely used measure of health and social functioning of people with mental illness. The goals of this study were to verify the internal validity of the one factor and several four-factor scoring structures and to evaluate the predictive validity of HoNOS items with regards to duration of hospitalization, probability of readmission in the following year and time before readmission. 6175 hospital stays at the department of psychiatry of Lausanne University Hospital were screened and the first HoNOS of each patient was taken into account (N = 2722). Data were analyzed through Confirmatory Factor Analysis (CFA) and the predictive validity of HoNOS items was evaluated with two approaches: item level regressions and latent class analysis (LCA). CFA indicated that the suggested factor structures were not supported by the data. Predictive validity of the 12 items was weak but LCA revealed five distinct and meaningful profiles that were related to length of stay or readmission. HoNOS may be more adapted to the evaluation of patients case-mix rather than to the individual level and concepts such as predictive validity may be more appropriate than internal validity to guide its use.

Obesity development during psychotropic treatments represents a major health issue in psychiatry. Melanin-concentrating hormone receptor 2 (MCHR2) is a central receptor involved in energy homeostasis. MCHR2 shares its promoter region with MCHR2-AS1, a long antisense non-coding RNA. The aim of this study was to determine whether tagging single nucleotide polymorphisms (tSNPs) of MCHR2 and MCHR2-AS1 are associated with the body mass index (BMI) in the psychiatric and in the general population. The influence of MCHR2 and MCHR2-AS1 tSNPs on BMI was firstly investigated in a discovery psychiatric sample (n1 = 474). Positive results were tested for replication in two other psychiatric samples (n2 = 164, n3 = 178) and in two population-based samples (CoLaus, n4 = 5409; GIANT, n5 = 113809). In the discovery sample, TT carriers of rs7754794C>T had 1.08 kg/m2 (p = 0.04) lower BMI as compared to C-allele carriers. This observation was replicated in an independent psychiatric sample (-2.18 kg/m2; p = 0.009). The association of rs7754794C>T and BMI seemed stronger in subjects younger than 45 years (median of age). In the population-based sample, a moderate association was observed (-0.17 kg/m2; p = 0.02) among younger individuals (

There exist many case reports and studies on the antipsychotic augmentation by aripirazole in partial responders to clozapine, the most seem to be finding a slight difference in the PANSS and CGI scores after the aripirazole addition. The results of our report are compatible with those of other studies but, we have found a considerable antianxiety action in both of the cases. The 5HT1A agonism of aripirazole could be hypothesized as mechanism contributing to this effect.