Centre for Youth Mental Health - Research Publications

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    Dynamics between insight and medication adherence in first-episode psychosis: Study of 3-year trajectories.
    Elowe, J ; Ramain, J ; Solida, A ; Conus, P ; Golay, P (Royal College of Psychiatrists, 2022-08-15)
    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.
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    Time of exposure to social defeat stress during childhood and adolescence and redox dysregulation on long-lasting behavioral changes, a translational study.
    Schnider, M ; Jenni, R ; Ramain, J ; Camporesi, S ; Golay, P ; Alameda, L ; Conus, P ; Do, KQ ; Steullet, P (Springer Science and Business Media LLC, 2022-09-26)
    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.
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    Gene set enrichment analysis of pathophysiological pathways highlights oxidative stress in psychosis.
    Pistis, G ; Vázquez-Bourgon, J ; Fournier, M ; Jenni, R ; Cleusix, M ; Papiol, S ; Smart, SE ; Pardiñas, AF ; Walters, JTR ; MacCabe, JH ; Kutalik, Z ; Conus, P ; Crespo-Facorro, B ; Q Do, K (Springer Science and Business Media LLC, 2022-12)
    Polygenic risk prediction remains an important aim of genetic association studies. Currently, the predictive power of schizophrenia polygenic risk scores (PRSs) is not large enough to allow highly accurate discrimination between cases and controls and thus is not adequate for clinical integration. Since PRSs are rarely used to reveal biological functions or to validate candidate pathways, to fill this gap, we investigated whether their predictive ability could be improved by building genome-wide (GW-PRSs) and pathway-specific PRSs, using distance- or expression quantitative trait loci (eQTLs)- based mapping between genetic variants and genes. We focused on five pathways (glutamate, oxidative stress, GABA/interneurons, neuroimmune/neuroinflammation and myelin) which belong to a critical hub of schizophrenia pathophysiology, centred on redox dysregulation/oxidative stress. Analyses were first performed in the Lausanne Treatment and Early Intervention in Psychosis Program (TIPP) study (n = 340, cases/controls: 208/132), a sample of first-episode of psychosis patients and matched controls, and then validated in an independent study, the epidemiological and longitudinal intervention program of First-Episode Psychosis in Cantabria (PAFIP) (n = 352, 224/128). Our results highlighted two main findings. First, GW-PRSs for schizophrenia were significantly associated with early psychosis status. Second, oxidative stress was the only significantly associated pathway that showed an enrichment in both the TIPP (p = 0.03) and PAFIP samples (p = 0.002), and exclusively when gene-variant linking was done using eQTLs. The results suggest that the predictive accuracy of polygenic risk scores could be improved with the inclusion of information from functional annotations, and through a focus on specific pathways, emphasizing the need to build and study functionally informed risk scores.
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    Effects of psychotropic switches on weight change: a prospective cohort study
    Piras, M ; Ranjbar, S ; Dubath, C ; Laaboub, N ; Grosu, C ; Gamma, F ; Von Plessen, K ; Von Gunten, A ; Conus, P ; Eap, C (Royal College of Psychiatrists, 2022-06)
    Introduction Many psychotropic drugs can induce weight gain with differences in their metabolic risk profiles (i.e. high, medium or low-risk). Objectives To compare the weight evolution of patients switching versus patients keeping their psychotropic drugs with different risk-profiles. Methods Data for patients switching or keeping the same drug were obtained from the Psyclin (from 2007 to 2015) and Psymetab (2007- 2019) cohort studies, conducted at the Lausanne University Hospital, Switzerland. Patients either switched from a high to a low-risk, a high to a medium-risk, a medium to a low-risk drug, or for a drug with the same risk category. Patients not switching either kept a high, medium or low-risk drug. The evolution of weight is currently being analyzed using a linear mixed-effect model. Results Preliminary results showed that switching from a high to low-risk molecule had the strongest impact on weight changes. The analysis being ongoing, the quantitative results will be presented at the congress. Conclusions Switching from a high-risk to a low-risk molecule is likely to have the strongest impact on weight changes. Disclosure No significant relationships.
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    The psychosis metabolic risk calculator (PsyMetRiC) for young people with psychosis: International external validation and site-specific recalibration in two independent European samples.
    Perry, BI ; Vandenberghe, F ; Garrido-Torres, N ; Osimo, EF ; Piras, M ; Vazquez-Bourgon, J ; Upthegrove, R ; Grosu, C ; De La Foz, VO-G ; Jones, PB ; Laaboub, N ; Ruiz-Veguilla, M ; Stochl, J ; Dubath, C ; Canal-Rivero, M ; Mallikarjun, P ; Delacrétaz, A ; Ansermot, N ; Fernandez-Egea, E ; Crettol, S ; Gamma, F ; Plessen, KJ ; Conus, P ; Khandaker, GM ; Murray, GK ; Eap, CB ; Crespo-Facorro, B (Elsevier BV, 2022-11)
    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.
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    Publisher Correction: Insomnia disorders are associated with increased cardiometabolic disturbances and death risks from cardiovascular diseases in psychiatric patients treated with weight-gain-inducing psychotropic drugs: results from a Swiss cohort.
    Laaboub, N ; Dubath, C ; Ranjbar, S ; Sibailly, G ; Grosu, C ; Piras, M ; Délessert, D ; Richard-Lepouriel, H ; Ansermot, N ; Crettol, S ; Vandenberghe, F ; Grandjean, C ; Delacrétaz, A ; Gamma, F ; Plessen, KJ ; von Gunten, A ; Conus, P ; Eap, CB (Springer Science and Business Media LLC, 2022-07-08)
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    Insomnia disorders are associated with increased cardiometabolic disturbances and death risks from cardiovascular diseases in psychiatric patients treated with weight-gain-inducing psychotropic drugs: results from a Swiss cohort.
    Laaboub, N ; Dubath, C ; Ranjbar, S ; Sibailly, G ; Grosu, C ; Piras, M ; Délessert, D ; Richard-Lepouriel, H ; Ansermot, N ; Crettol, S ; Vandenberghe, F ; Grandjean, C ; Delacrétaz, A ; Gamma, F ; Plessen, KJ ; von Gunten, A ; Conus, P ; Eap, CB (Springer Science and Business Media LLC, 2022-05-17)
    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.
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    [Strength in Numbers: Launching a National and International French-Speaking Movement for the Implementation of Early Intervention Services].
    Bertulies-Esposito, B ; Abdel-Baki, A ; Conus, P ; Krebs, M-O (Consortium Erudit, 2021)
    Objective To describe the implementation of early intervention for psychosis in 3 French-speaking countries, the challenges encountered and potential facilitators for successful implementation. Methods Narrative synthesis of the scientific and grey literature on early intervention for psychosis programs implementation in the French-speaking world. Results Compared to other countries (Australia, United Kingdom, etc.), early intervention program implementation in the French-speaking world has been delayed and faces various challenges, making its widespread implementation still very heterogeneous. Although a large proportion of the population has access to early intervention services (EIS) in Quebec (Canada), adherence with certain essential components of the model still poses challenges. However, various facilitators, including government involvement through the publication of a provincial framework standardizing practices, dedicated funding, and clinical support for program implementation and continuous improvement through the National Centre of Excellence in Mental Health (a provincial organization) and a provincial community of practice, the Association québécoise des programmes pour premiers épisodes psychotiques (AQPPEP), which offers mentoring and continuing education, have been identified. In France, although the implementation has been more heterogenous, several centers already offer EIS, and there is growing interest in this model, as expressed by several teams, giving hope for the implementation of a network of EIS throughout the country. Since 2007, the "Réseau transition" has been organizing scientific meetings, specialized training, validation of tools and is working on publishing a reference tool adapted to the French system to standardize EIS. In French-speaking Switzerland, although programs were implemented relatively early (in 2000 in Geneva, and in 2004 in Lausanne), they remained associated to individual initiatives and local choices. This is largely due to the complete autonomy of each of the 26 cantons in the organization of the healthcare system and the absence of a national mental health policy. However, a French-speaking Swiss group has been set up in 2020, to support the implementation of 5 programs in 5 cantons. Several specificities of the organization of mental health care in each country may have an impact on implementation. These include the relative autonomy of different catchment areas, and the separation of child and adolescent psychiatry from adult services. Furthermore, it seems that poor involvement in quality assurance activities and the lack of monitoring of adherence to expert recommendations on essential components of the EIS model may impact program implementation. Conclusion In addition to continuing national efforts, a francophone branch of the International Early Psychosis Association (IEPA) founded by Swiss, French and Quebec leaders to join forces on a larger scale seeks to promote networking as well as tool and expertise sharing through an annual international francophone conference focused on early intervention in first-episode psychosis.
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    [Early Detection and Intervention for Psychosis: Why and How?].
    Bertulies-Esposito, B ; Sicotte, R ; Iyer, SN ; Delfosse, C ; Girard, N ; Nolin, M ; Villeneuve, M ; Conus, P ; Abdel-Baki, A (Consortium Erudit, 2021)
    Objectives This article aims to synthesize the critical stages in the development of early detection and intervention services (EIS) for psychosis over the past 30 years, and to review key literature on the essential components and effectiveness of these programs. Method We conducted a narrative review of the literature on the international development of EIS leading to its endorsement as a service delivery model for young people with first-episode psychosis (FEP). We also reviewed various international and Canadian guidelines to identify consensus about the essential components of EIS for psychosis and their effectiveness. Challenges to the implementation of these different essential components are presented, along with practical solutions to addressing them. A particular emphasis is placed on implementing EIS in the Quebec context. Results Based on a model developed in the early 1990s, EIS for psychosis have now been disseminated worldwide and are deployed on a large scale in some regions, such as the United Kingdom and Quebec. The model's gradual expansion has been facilitated by efforts to identify its main objectives and the components essential to achieve them, and by several studies demonstrating its effectiveness. Along with an important philosophical shift to optimism and hope, EIS have typically focused on the twin aims of reducing treatment delay (or the duration of untreated psychosis) and enhancing engagement in specialized, phase-specific, developmentally appropriate treatment. A meta-analysis (published in 2018) demonstrated the superiority of EIS for psychosis compared to standard treatment on several outcomes including hospitalizations, relapse of symptoms, treatment discontinuation, and vocational and social functioning. Based on these studies and expert consensus, many jurisdictions around the world have developed guidelines to ensure compliance with essential components that are associated with the effectiveness of EIS, while accounting for their contextual realities. The components that have been prioritized include outreach to enable early identification and referral; rapid access to care and youth-friendly services; a range of biopsychosocial interventions (pharmacotherapy, cognitive behavioral therapy, psychoeducation, family interventions, integrated substance use interventions, employment and educational support); a shared-decision making approach; and the intensive case management approach adapted to FEP, which are all delivered by an interdisciplinary team. There is also increasing acknowledgement of the value of continuous evaluation that informs treatment decision-making and quality improvement. Conclusion EIS for psychosis have developed gradually and research has demonstrated its effectiveness. Disseminating the model in ways that ensure fidelity to its core values and the implementation of its essential components is needed to ensure effectiveness; and instill hope for recovery and improve the quality of lives of young people with psychosis and their families.