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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]

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]

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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]

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.

Approximately 2% of adolescents and young adults display symptoms indicating a high risk for psychotic disorders. Apart from a risk of 20-35% of developing a psychotic disorder, these individuals show high rates of persisting mental health problems and functional impairment, even in the absence of a psychotic transition. Treatment in specialized centers can improve outcomes in these patients, but the need to provide timely access to care needs to be balanced against the risks of premature psychiatrization, stigmatization and unnecessary medication treatment. The transcantonal project PsyYoung aims to optimize early detection in young people, while at the same time minimizing unnecessary psychiatrization. This will be achieved through improved networking across the entire care chain and a stepped-care intervention approach., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

In this review of recent therapeutic developments in psychiatry, we will report on three domains where new strategies have been proposed. First we will discuss the concept of neuroprotection in patients at "ultra high risk" to develop psychosis and the encouraging results of a randomised controlled trial comparing the effect of placebo and fish oil. We will then present the impact of metacognition programs which aim at adding some flexibility to thought processes used by patients with psychosis in order to reduce psychotic symptoms. We finally will report on a program of supported employment which was developed in order to help patients find an active place in society.