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Background: Frequently associated with early psychosis, depressive and manic dimensions may play an important role in its course and outcome. While manic and depressive symptoms can alternate and co-occur, most of the studies in early intervention investigated these symptoms independently. The aim of this study was therefore to explore the co-occurrence of manic and depressive dimensions, their evolution and impact on outcomes. Methods: We prospectively studied first-episode psychosis patients (N = 313) within an early intervention program over 3 years. Based on latent transition analysis, we identified sub-groups of patients with different mood profiles considering both manic and depressive dimensions, and studied their outcomes. Results: Our results revealed six different mood profiles at program entry and after 1.5 years follow-up (absence of mood disturbance, co-occurrence, mild depressive, severe depressive, manic and hypomanic), and four after 3 years (absence of mood disturbance, co-occurrence, mild depressive and hypomanic). Patients with absence of mood disturbance at discharge had better outcomes. All patients with co-occurring symptoms at program entry remained symptomatic at discharge. Patients with mild depressive symptoms were less likely to return to premorbid functional level at discharge than the other subgroups. Patients displaying a depressive component had poorer quality of physical and psychological health at discharge. Conclusions: Our results confirm the major role played by mood dimensions in early psychosis, and show that profiles with co-occurring manic and depressive dimensions are at risk of poorer outcome. An accurate assessment and treatment of these dimensions in people with early psychosis is crucial. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Aim: Reduction of duration of untreated psychosis (DUP) remains a key goal of early intervention programs. While a significant body of literature suggests that a short DUP has a positive impact on outcome, little is known regarding the threshold above which various dimensions of outcome are impaired. In this study, we explore the DUP threshold that best discriminates subgroups with poorer outcome regarding global functioning and quality of life after 3 years of treatment. Method: A total of 432 patients were followed‐up prospectively over 3 years. Several hypothetical cut‐off points for DUP were tested in order to maximize differences in effect size for quality of life and general functioning. Results: While a DUP cut‐off of 86 weeks defined two subpopulations with a difference of greatest effect size in quality of life after 3 years, it is already at a cut‐off of 3 weeks of DUP that two subpopulations with a difference in global functioning of the greatest effect size was reached. Conclusion: DUP seems to have a differential impact on the various components of outcome, and in particular on quality of life and global functioning. Our data suggest that aiming at very short DUP is justified, but that DUP over 3 weeks are still compatible with good quality of life after 3 years of treatment. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Introduction The atypical antipsychotic quetiapine is known to induce weight gain and other metabolic complications. The underlying mechanisms are multifactorial and poorly understood with almost no information on the effect of dosage. Concerns were thus raised with the rise in low-dose quetiapine off-label prescription (i. e.,<150 mg/day). Methods In this study, we evaluated the influence of quetiapine dose for 474 patients included in PsyMetab and PsyClin studies on weight and metabolic parameter evolution. Weight, blood pressure, lipid, and glucose profiles were evaluated during a follow-up period of 3 months after treatment initiation. Results Significant dose-dependent metabolic alterations were observed. The daily dose was found to influence weight gain and increase the risk of undergoing clinically relevant weight gain (≥7% from baseline). It was also associated with a change in plasma levels of cholesterol (total cholesterol, LDL cholesterol, and HDL cholesterol) as well as with increased odds of developing hypertriglyceridemia, as well as total and LDL hypercholesterolemia. No impact of a dose increase on blood pressure and plasma glucose level was observed. Discussion The dose-dependent effect highlighted for weight gain and lipid alterations emphasizes the importance of prescribing the minimal effective dose. However, as the effect size of a dose increase on metabolic worsening is low, the potential harm of low-dose quetiapine should not be dismissed. Prescriptions must be carefully evaluated and regularly questioned in light of side effect onset. [ABSTRACT FROM AUTHOR]

Background: It 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. Methods: 113 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. Results: Late-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. Conclusions: Exposition 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. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim In a survey conducted in the Lausanne catchment area in 2000, we could estimate on the basis of file assessment that first-episode psychosis ( FEP) patients had psychotic symptoms for more than 2 years before treatment and that 50% did not attend any outpatient appointment after discharge from hospital. In this paper, we describe the implementation of a specialized programme aimed at improving engagement and quality of treatment for early psychosis patients in the Lausanne catchment area in Switzerland. Method The Treatment and Early Intervention in Psychosis Program- Lausanne is a comprehensive 3-year programme composed of (i) an outpatient clinic based on assertive case management; (ii) a specialized inpatient unit; and (iii) an intensive mobile team, connected for research to the Center for Psychiatric Neuroscience. Results Eight years after implementation, the programme has included 350 patients with a disengagement rate of 9% over 3 years of treatment. All patients have been assessed prospectively and 90 participated in neurobiological research. Based on this experience, the Health Department funded the implementation of similar programmes in other parts of the state, covering a total population of 540 000 people. Conclusion Programmes for early intervention in psychosis have a major impact on patients' engagement into treatment. While development of mobile teams and assertive case management with specific training are crucial, they do not necessitate massive financial support to be started. Inclusion of a research component is important as well, in terms of service planning and improvement of both quality of care and impact of early intervention strategies. [ABSTRACT FROM AUTHOR]

In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex- and age- matched healthy controls (p=0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p=0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.Neuropsychopharmacology (2008) 33, 2187–2199; doi:10.1038/sj.npp.1301624; published online 14 November 2007 [ABSTRACT FROM AUTHOR]

Background: In general, MR spectroscopy (MRS) studies report alterations of both glutamatergic indices and NAA not only in first episode psychosis and established schizophrenia but also in high risk populations, suggesting that altered excitatory neurotransmission and loss of neuronal integrity are early pathophysiological processes. However, interpretation of these findings is limited by the region-of-interest approach of current MRS techniques, limiting the measurement of metabolites to delimited cerebral volumes, selected by a priori hypotheses. In that context, we developed and implemented a new technique including specific MR sequence and data reconstruction that allows for whole brain high-resolution MRS imaging (MRSI) in two or three dimensions. The results enable the mapping of main metabolites in all brain regions (cortex, white matter, deep grey matter) of youths at clinical high risk for psychosis (CHR-P). Methods: An FID-MRSI (Henning et al. NMR Biomed 2009) sequence with a 3D phase encoding accelerated by compressed-sensing was implemented on a 3T Prisma fit MRI (Siemens, Erlangen, Germany). The echo time (TE) was 0.65 ms, repetition time (TR) was 355 ms and the flip angle 35 degree. FID was acquired with 4 kHz bandwidth. The size of the excited Volume of Interest (VOI) was (A/P-R/L-H/F) 210 mm by 160 mm by 95 mm with a matrix of 42 x 32 x 20 resulting in 5 mm isotropic resolution. After reconstruction (Klauser A et al. Magn Reson Med. 2018), 3D MRSI data were quantified with LCModel to produce 3D metabolite maps. Concentration for total N-acetyl aspartate (tNAA), total creatinine (tCre), choline-containing compounds (Cho), myo-inositol (Ins), glutamate and glutamine (Glx) were calculated in every single voxel. A T1-weighted MPRAGE anatomical scan was acquired for positioning of the 3D MRSI and for the segmentation of the brain. For each participant, brain tissue was segmented into gray and white matter. Cerebral lobes and deep grey mater structures were also delineated using Freesurfer software package. CHR-P individuals were recruited in the service of child and adolescent psychiatry and in the service of general psychiatry, department of psychiatry at Lausanne university hospital. They were help-seeking adolescents and young adults aged between 14 and 35, who presented a psychosisrisk syndrome or basic symptoms as assessed by the Structured Interview for Psychosis-Risk Syndromes (SIPS) and the Schizophrenia Proneness Instrument, Adult (SPI-A) or Child & Youth version (SPI-CY). Healthy controls matched for age and sex were recruited in the general population. Results: Three-dimension MRSI provides spatial specificity by allowing main metabolites (i.e., tNAA, tCre, Cho, Ins and Glx) to be reliably mapped in the volume of the entire brain. The resulting contrast allows the recognition of brain compartments and subcortical structures. Individual brain segments, cerebral lobes and subcortical structures were registered to 3D MRSI data and the mean concentration in each structure was computed to allow group comparisons between CHR-P and HC. Discussion: In general, there is a strong need to develop new tools for the identification and stratification of CHR-P populations. Alterations of gross brain anatomy are relatively late events but early and subtle neurochemical changes and especially those reflecting oxidative stress and concomitant synaptic remodeling are promising candidates. This pilot study illustrates the potential of three-dimension MRSI to detect such alterations in the whole brain and with a good spatial resolution. [ABSTRACT FROM AUTHOR]

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 helpseekers 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 PsychosisRisk 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). [ABSTRACT FROM AUTHOR]