[Impact of social determinants on mental disorders in adolescents and young adults]. / Impact des déterminants sociaux sur les troubles psychiques des adolescents et jeunes adultes.

The impact of social determinants on mental disorders of adolescents and young adults has been amplified by the Covid-19 pandemic and its consequences. To raise clinicians' awareness of these effects in practice, this article examines two particularly well-studied areas: the effects of socioeconomic disadvantages on emerging psychotic disorders and the impact of gender on depression. In clinical practice it is crucial to consider social stress factors, confronting young people in an unequal manner, as they contribute to the emergence or relapse of mental disorders. Two illustrations of the potential impacts of social determinants on the mental health of adolescents and young adults are presented, as well as intervention strategies for practitioners.

L'impact des déterminants sociaux sur les troubles psychiques des adolescents et des jeunes adultes a été amplifié par la pandémie de Covid-19 et ses conséquences économiques et sociales. Afin de sensibiliser les cliniciens à leurs effets dans la pratique, cet article présente deux domaines particulièrement étudiés : les effets des désavantages socioéconomiques sur l'émergence des troubles psychotiques et ceux du genre sur la dépression. Dans la pratique clinique, il est crucial de prendre en compte ces facteurs de stress sociaux, auxquels les jeunes sont confrontés de manière inégale, car ils contribuent à l'émergence ou à la rechute de leurs troubles psychiques. Deux illustrations de l'impact potentiel des déterminants sociaux sur la santé mentale des adolescents et des jeunes adultes sont proposées, ainsi que des pistes d'interventions pour les praticiens.

[Detection and management of patients with clinical high risk for psychosis]. / Détection et prise en charge des patients avec états mentaux à risque de psychose.

This article explores best practices for managing patients with Clinical High Risk for psychosis with a particular focus on the role of general practitioners and pediatricians. It offers clear guidelines for the assessment and monitoring of these patients, highlighting early warning signs, screening tools, and appropriate interventions. Additionally, the article lists local resources available for healthcare professionals to ensure optimal and coordinated care. By providing this information, this article aims to equip general practitioners and pediatricians with the necessary knowledge to effectively identify and manage this patient profile, while connecting them to the appropriate available resources.

Cet article explore les meilleures pratiques pour la prise en charge des états mentaux à risque de psychose avec un accent particulier sur le rôle des généralistes et des pédiatres. Il propose des directives claires pour l'évaluation et le suivi de ces patients, en mettant en lumière les premiers signes avant-coureurs, les outils de dépistage et les interventions appropriées. En outre, l'article recense les ressources locales disponibles pour les professionnels de santé, afin d'assurer une prise en charge optimale et coordonnée. En fournissant ces informations, il vise à mieux armer les généralistes et pédiatres des connaissances nécessaires pour identifier et gérer efficacement ces patients, tout en les connectant aux ressources adéquates disponibles.

[Diagnostic of a first psychotic episode : role of the general practitioner]. / Diagnostic d'un premier épisode psychotique : le rôle clé du médecin généraliste.

As psychoses can have a long-term impact, they need to be diagnosed as quickly as possible in order to provide appropriate care and avoid the onset of comorbid complications. As general practitioners are often the first to be approached, it is important that they think about this diagnosis in young patients, even if the manifestations are often atypical or if patients are reluctant to talk about it. Specialized programs have sprung up all over the world, staffed by mobile teams and professionals specialized in this type of treatment, with far superior results at a lower overall cost than the usual treatments. In the absence of a clear national policy in this area, Switzerland remains poorly equipped, although successful programs do exist in some regions.

Les psychoses pouvant avoir un impact à long terme, les diagnostiquer aussi rapidement que possible permet d'offrir des soins adaptés aux patients et d'éviter la survenue de complications comorbides. Les médecins généralistes étant souvent sollicités en premier, il est important qu'ils pensent à ce diagnostic chez des patients jeunes, même si les manifestations sont souvent atypiques ou les patients réticents à en parler. Des programmes spécialisés se sont développés dans le monde entier, dotés d'équipes mobiles et de professionnels spécialisés dans ce type de traitements, avec des résultats nettement supérieurs à un coût global moindre que ceux habituels. En l'absence d'une politique nationale claire à cet égard, la Suisse reste mal dotée dans ce domaine bien que des programmes performants existent dans quelques régions.

[Impact of the Covid-19 pandemic on psychological disorders in adolescents and young adults]. / Impact de la pandémie de Covid-19 sur les troubles psychiques des adolescents et jeunes adultes.

The current pandemic and its economic and social consequences increase the stress of young people and their families. For the most vulnerable young people, this situation of increased or cumulative stress may be a risk factor for the emergence or relapse of psychological disorders. In this article, we propose a brief literature review of the research published on this issue since the emergence of the crisis put in perspective of local observations and possible interventions for practitioners.

La pandémie que nous traversons ainsi que ses conséquences économiques et sociales augmentent le stress des jeunes et de leurs familles. Pour les jeunes les plus vulnérables, cette situation de stress accru ou cumulé peut être un facteur de risque pour l'émergence ou la rechute de troubles psychiques. Nous proposons dans cet article une brève revue de littérature des recherches publiées sur cette question depuis l'émergence de la crise mise dans la perspective d'observations locales et des pistes d'interventions pour les praticiens.

[PsyYoung: A transcantonal project for facilitating access to care for young people at risk for psychotic disorders]. / PsyYoung†: un projet pluri-cantonal pour faciliter l'accès aux soins des jeunes à risque de développer une psychose.

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.

Près de 2 % des adolescents et jeunes adultes présentent des symptômes indiquant un risque élevé de développer une psychose. Outre ce risque se situant entre 20 et 35 %, ces individus présenteront des taux élevés d'autres troubles psychiques et déficits fonctionnels, même en l'absence de transition vers la psychose. Le traitement dans des centres spécialisés peut améliorer l'évolution de ces patients mais les besoins de fournir un accès rapide aux soins doivent être mis en perspective des risques de psychiatrisation prématurée, stigmatisation, et médication inutile. Le projet pluri-cantonal PsyYoung vise à optimiser la détection précoce pour les jeunes, tout en minimisant la psychiatrisation inutile. Ceci sera atteint en améliorant le réseautage de l'ensemble de la chaîne de soins et la mise en œuvre d'un modèle de soins par étapes.

Differences of temporal dynamics and signal complexity of gamma band oscillations in first-episode psychosis during a working memory task.

Gamma band oscillations participate in the temporal binding needed to synchronize cortical networks, involved in early sensory and short term memory processes. In earlier studies, alterations of these neurophysiological parameters have been found in psychotic disorders. To date no study has explored the temporal dynamics and signal complexity of gamma band oscillations in first episode psychosis (FEP). To address this issue, gamma band analysis was performed in 15 FEP patients and 18 healthy controls who successfully performed an adapted 2-back working memory task. Multiple linear and logistic regression models were computed to explore the relationship between the cognitive status and gamma oscillation changes over time. Based on regression model results, phase diagrams were constructed and their complexity was estimated using fractal dimension, a mathematical tool that describes shapes as numeric values. When adjusted for gamma values at time lags -3 to -4 ms and -15 to -16 ms, FEP patients displayed significantly higher time-dependent changes than controls, independently of the nature of the task. The present results are consistent with a discoordination of the activity of cortical generators engaged by the stimulus apparition in FEP patients, leading to a global binding deficit. In addition, fractal analysis showing higher complexity of gamma signal, confirmed this deficit. Our results provide evidence for recruitment of supplementary cortical generators as compensating mechanisms and yield further understanding for the pathophysiology cognitive impairments in FEP.

[Early intervention for emerging mental illness in young adults : the Geneva model]. / Prise en charge des troubles psychiques débutants chez le jeune adulte, modèle genevois.

Mental illness often emerges in young adulthood, usually before the age of 25 years. Early detection and intervention have a positive impact on the evolution of mental illness and quality of life. Specific interventions for this age group are recommended with a focus on ease of access to health care, adaptation to problems facing the young adult, using an integrated medical psycho-social approach. Furthermore, for this population, determination of a specific medical diagnosis does not seem essential, the concept of early stages of mental illness with less specific symptoms often being more useful. The Young Adult Psychiatry Unit in Geneva is built around these concepts and aims to offer, for the young adult with emerging mental illness, a large range of mental health services that are easily accessible.

Les troubles psychiques émergent fréquemment à l'âge du jeune adulte, souvent avant 25 ans. Une détection et une intervention précoces ont un impact positif sur l'évolution des troubles et la qualité de vie. Il est recommandé une prise en charge spécifique à cette tranche d'âge mettant le focus sur la facilité d'accès aux soins, l'adaptation aux problématiques du jeune adulte, avec approches médicale et psychosociale intégrées. En même temps, pour cette population, la détermination d'un diagnostic médical précis ne semble pas essentielle, avec un concept de stade précoce de troubles psychiques sans grande spécificité symptomatique souvent plus adapté. L'Unité de psychiatrie du jeune adulte à Genève s'inspire de ces concepts en visant à proposer aux jeunes adultes présentant des troubles psychiques débutants un large éventail de services, facilement accessibles.

Pathways to care in youth and young adults at clinical high risk for psychosis in Switzerland: Current situation and clinical implementation of the PsyYoung project.

AIM: We aim to give an insight into the current situation in Switzerland concerning the pathways to care of young people with clinical high risk of psychosis. In a second step we propose a procedure of optimizing pathways to care developed within the project PsyYoung. METHODS: A qualitative survey derived and adapted from Kotlicka-Antczak et al. (2020) was conducted in large early detection services of three Swiss cantons (Geneva, Basel-Stadt, Vaud) focusing on pathways to care. More specifically, using questionnaires delivered to the heads of participating services, information was collected on referral sources, on activities to implement outreach campaigns and on the use of a pre-screening tool. RESULTS: Main results on referral source indicated that sources were variable but seemed to come primarily from the medical sector and more so from the psychiatric sector. Very few referrals came from non-medical sectors. Outreach activities included the contact to other clinics as well as through brochures and posters. All services but one used the Prodromal Questionnaire - 16 as pre-screening tool. CONCLUSIONS: All in all, the results indicate a referral and care pathway system implemented mostly within the medical and particularly mental health sector. Accordingly, the PsyYoung project proposes a procedure for pathways to care which could help overcome the obstacle of referrals being restrained to a narrow field of mental health and to harmonize the referral process within services dedicated to the same aim of helping young people at high risk of developing a psychosis.

Individualized pretest risk estimates to guide treatment decisions in patients with clinical high risk for psychotic disorders.

INTRODUCTION: Clinical High Risk for Psychosis (CHR) states are associated with an increased risk of transition to psychosis. However, the predictive value of CHR screening interviews is dependent on pretest risk enrichment in referred patients. This poses a major obstacle to CHR outreach campaigns since they invariably lead to risk dilution through enhanced awareness. A potential compensatory strategy is to use estimates of individual pretest risk as a 'gatekeeper' for specialized assessment. We aimed to test a risk stratification model previously developed in London, UK (OASIS) and to train a new predictive model for the Swiss population. METHOD: The sample was composed of 513 individuals referred for CHR assessment from six Swiss early psychosis detection services. Sociodemographic variables available at referral were used as predictors whereas the outcome variable was transition to psychosis. RESULTS: Replication of the risk stratification model developed in OASIS resulted in poor performance (Harrel's c = 0.51). Retraining resulted in moderate discrimination (Harrel's c = 0.67) which significantly differentiated between different risk groups. The lowest risk group had a cumulative transition incidence of 6.4% (CI: 0% - 23.1%) over two years. CONCLUSION: Failure to replicate the OASIS risk stratification model might reflect differences in the public health care systems and referral structures between Switzerland and London. Retraining resulted in a model with adequate discrimination performance. The developed model in combination with CHR assessment result, might be useful for identifying individuals with high pretest risk, who might benefit most from specialized intervention.

Combined grey matter VBM and white matter TBSS analysis in young first episode psychosis patients with and without cannabis consumption.

Cannabis consumption is temporally associated with the development of first episode psychosis (FEP). Whether or not the chronic use of this substance induces structural brain changes that may be responsible for the cognitive and psychological disturbances in this disorder is still matter of debate. To address this issue, we compared the magnetic resonance imaging (MRI)-assessed grey (GM) and white matter (WM) changes in young FEP patients between users versus non-users of cannabis. This prospective study included 50 consecutive FEP subjects: 33 users (22.7 ± 4.1 years, 4 women) and 17 non-users (23.9 ± 4.2 years, 10 women). Users were further divided into 15 heavy (23.3 ± 4.5 years, 2 women) and 18 light users (22.2 ± 3.8 years, 2 women) according to their lifetime cannabis use. Voxel-based-morphometry (VBM) analysis of GM and tract-based-spatial-statistics (TBSS) analysis of WM were performed. Age and gender were used as non-explanatory co-regressors. There were no supra-threshold differences between user and non-user groups for both GM and WM parameters. This was also the case when only heavy users were compared to non-users. Multivariate models controlling for age and gender confirmed these findings. We found no evidence for cannabis consumption related alterations in GM or WM in FEP subjects. Due to the strict correction for multiple comparisons and sample size, we cannot formally exclude subtle morphometric changes associated with cannabis consumption. However, even if present, such potential alterations would be of low magnitude.

Improving Pathways to Care for Patients at High Psychosis Risk in Switzerland: PsyYoung Study Protocol.

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.

Magnetic resonance imaging correlates of first-episode psychosis in young adult male patients: combined analysis of grey and white matter.

BACKGROUND: Several patterns of grey and white matter changes have been separately described in young adults with first-episode psychosis. Concomitant investigation of grey and white matter densities in patients with first-episode psychosis without other psychiatric comorbidities that include all relevant imaging markers could provide clues to the neurodevelopmental hypothesis in schizophrenia. METHODS: We recruited patients with first-episode psychosis diagnosed according to the DSM-IV-TR and matched controls. All participants underwent magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis and mean diffusivity voxel-based analysis (VBA) were used for grey matter data. Fractional anisotropy and axial, radial and mean diffusivity were analyzed using tract-based spatial statistics (TBSS) for white matter data. RESULTS: We included 15 patients and 16 controls. The mean diffusivity VBA showed significantly greater mean diffusivity in the first-episode psychosis than in the control group in the lingual gyrus bilaterally, the occipital fusiform gyrus bilaterally, the right lateral occipital gyrus and the right inferior temporal gyrus. Moreover, the TBSS analysis revealed a lower fractional anisotropy in the first-episode psychosis than in the control group in the genu of the corpus callosum, minor forceps, corticospinal tract, right superior longitudinal fasciculus, left middle cerebellar peduncle, left inferior longitudinal fasciculus and the posterior part of the fronto-occipital fasciculus. This analysis also revealed greater radial diffusivity in the first-episode psychosis than in the control group in the right corticospinal tract, right superior longitudinal fasciculus and left middle cerebellar peduncle. LIMITATIONS: The modest sample size and the absence of women in our series could limit the impact of our results. CONCLUSION: Our results highlight the structural vulnerability of grey matter in posterior areas of the brain among young adult male patients with first-episode psychosis. Moreover, the concomitant greater radial diffusivity within several regions already revealed by the fractional anisotropy analysis supports the idea of a late myelination in patients with first-episode psychosis.

Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis.

BACKGROUND: Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance. METHODS: We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-backworking memory tasks as well as oddball detection and passive fixation tasks. RESULTS: We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory-related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls. LIMITATIONS: Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out. CONCLUSION: The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.

Viewer and object mental rotation in young adults with psychotic disorders.

Schizophrenia patients have difficulty with processing visuo-spatial information, which may explain their deficits with considering other people's point-of-view. Processing visuo-spatial information operates on egocentric and allocentric frames of reference. Here, we tested the ability of individuals at different stages of psychotic disorders, specifically ultra-high-risk for psychosis individuals, as well as first-episode psychosis, and chronic schizophrenia patients, to perform a viewer mental rotation task and an object mental rotation task. The two tasks were differentiated only by the instruction given. Healthy individuals and patients with a diagnosis of anxiety/depressive mood disorder served as non-patient and patient controls, respectively. The results show that first-episode psychosis and chronic schizophrenia patients, but not ultra-high-risk individuals, had more errors and longer response times with both mental rotation tasks than the two control groups. In addition, chronic schizophrenia patients had additional difficulty with the object rotation task. The difference in performance between groups and tasks remained significant even after controlling for age, IQ, and antipsychotic medication dose. The results indicate that patients with psychotic disorders have a deficit of mental spatial imagery that include both egocentric and allocentric representations. This deficit may explain the difficulty of these patients with perspective-taking, and inferring other people's point of view, thoughts or intentions which is at the core of the pathogenesis of schizophrenia.

Mapping Child and Adolescent Mental Health Services and the Interface During Transition to Adult Services in Six Swiss Cantons.

Rationale: Transition in psychiatry refers to the period where young people transit from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS). Discontinuity of care during this period is well-documented but little is known about provisions and transition characteristics and policies across Switzerland. The aim of this article is to describe the architecture of public mental health providers in Switzerland and compare it to EU countries. Method: Two mapping surveys, developed previously for European countries, were adapted and sent to cantonal experts: the adapted European CAMHS Mapping Questionnaire (ECM-Q) assessing the architecture and functioning of CAMHS and the adapted Standardized Assessment Tool for Mental Health Transition (SATMeHT) to map CAMHS-AMHS interface. Results: Data were gathered from six cantons. Activity data and transition policies were comparable between Swiss regions and European countries. The percentage of young people below 19 years who were in care was above 2% in every responding canton with a higher proportion of boys than girls for patients <12 years of age. The transition occurred at the age of 18 years, civil majority, in each canton, and between 0 and 24% (3/7) and 25% and 49% (4/7) of young people were expected to transition. One canton (1/7) benefitted from written guidelines, at the CAMHS level only, regarding transition but none had guidelines for mapping CAMHS/AMHS interface even at the regional level. Conclusion: Despite the availability of resources and even if the possibilities of access to care are on average higher than in many European countries, issues regarding transition remain comparable in six Swiss cantons when compared to Europe. Meaning that beyond resources, it is the coordination between services that needs to be worked on. Importantly, implementing those changes would not require investing financial resources but rather working on the coordination between existing teams.

Working memory impairments in first-episode psychosis and chronic schizophrenia.

Working memory (WM) impairments are core cognitive deficits in patients with schizophrenia linked to prefrontal cortical dysfunctions. Determining the differences between early phases of illness allows a better understanding of its course and constitutes an important guide for treatment. The present cross-sectional study examined differences of working memory functions between 33 first-episode and 29 chronic schizophrenic patients, as well as 64 healthy controls. On the basis of a two-back visual-verbal computerized working memory task, reaction time was slower and accuracy was worse in both patient groups than in controls. Test variables, however, were not significantly different between the patient groups, suggesting stability of the deficits over time. Effect size accuracy variables nevertheless showed larger deficits in chronic patients.

Practical Guidance on the Use of Lurasidone for the Treatment of Adults with Schizophrenia.

INTRODUCTION: Lurasidone is an atypical antipsychotic that was approved in Europe in 2014 for the treatment of schizophrenia in adults aged ≥ 18 years. Clinical experience with lurasidone in Europe is currently limited, and there is therefore a need to provide practical guidance on using lurasidone for the treatment of adults with schizophrenia. METHODS: A panel of European psychiatrists with extensive experience of prescribing lurasidone was convened to provide recommendations on using lurasidone to treat adults with schizophrenia. RESULTS: Extensive evidence from clinical trials and the panel's clinical experience suggest that lurasidone is as effective as other atypical agents, with the possible exception of clozapine. Lurasidone is associated with a lower propensity for metabolic side effects (in particular, weight gain) and hyperprolactinaemia than most other atypical antipsychotics and has a relatively benign neurocognitive side effect profile. Patients switching to lurasidone from another antipsychotic may experience weight reduction and/or improvements in the ability to focus/concentrate. Most side effects with lurasidone (such as somnolence) are transitory, easily managed and/or ameliorated by dose adjustment. Akathisia and extrapyramidal symptoms may occur in a minority of patients, but these can be managed effectively with dose adjustment, adjunctive therapy and/or psychosocial intervention. CONCLUSIONS: Given the crucial importance of addressing the physical as well as mental healthcare needs of patients, lurasidone is a rational therapeutic choice for adults with schizophrenia, both in the acute setting and over the long term. FUNDING: Sunovion Pharmaceuticals Europe Ltd.

Psychosis Risk Syndrome: What Now?

BACKGROUND: Schizophrenia is a chronic psychiatric disorder that generally begins in late adolescence or early adulthood. This early onset is often linked with a devastating lifelong impact on both the social network and work capacities of the affected subjects. Beginning in the mid-1990s, several sets of diagnostic criteria aiming to identify "high-risk" patients were developed and applied in clinical studies. Short-term rates of onset of psychosis in this subgroup of subjects ranged from 20% to 40%. However, 20 years later, the proposal to introduce "psychosis risk syndrome" as a coded diagnostic category in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders remained controversial and was finally rejected. Instead, "attenuated psychosis syndrome" was included in section III of the newly published manual as a condition for further studies. OBJECTIVE: The goal of this article is to review the extant literature concerning the advantages and risks of early assessment of psychotic symptoms ("prodrome" and "psychosis-risk syndrome") and concerning available therapeutic options, both psychosocial and pharmacological. CONCLUSIONS: "Attenuated psychosis syndrome" is a clinically useful concept. It identifies help-seeking individuals with mental health problems who need an intervention and who, if no treatment strategy is proposed, present a higher likelihood of developing a psychosis spectrum disorder in the years following their first contact with a mental health facility. In parallel with the clinical utility of this concept, additional research focused on this group of patients is warranted to further understand the emerging phase of psychotic disorders and to develop effective and efficient evidence-based prevention strategies.

Impact of early life stress on the pathogenesis of mental disorders: relation to brain oxidative stress.

Stress is an inevitable part of human life and it is experienced even before birth. Stress to some extent could be considered normal and even necessary for the survival and the regular psychological development during childhood or adolescence. However, exposure to prolonged stress could become harmful and strongly impact mental health increasing the risk of developing psychiatric disorders. Recent studies have attempted to clarify how the human central nervous system (CNS) reacts to early life stress, focusing mainly on neurobiological modifications. Oxidative stress, defined as a disequilibrium between the oxidant generation and the antioxidant response, has been recently described as a candidate for most of the observed modifications. In this review, we will discuss how prolonged stressful events during childhood or adolescence (such as early maternal separation, parental divorce, physical violence, sexual or psychological abuses, or exposure to war events) can lead to increased oxidative stress in the CNS and enhance the risk to develop psychiatric diseases such as anxiety, depression, drug abuse or psychosis. Defining the sources of oxidative stress following exposure to early life stress might open new beneficial insights in therapeutic approaches to these mental disorders.

Exome sequencing in 53 sporadic cases of schizophrenia identifies 18 putative candidate genes.

Schizophrenia (SCZ) is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs) to SCZ, we sequenced the exomes of 53 individuals with sporadic SCZ and of their non-affected parents. We identified 49 DNVs, 18 of which were predicted to alter gene function, including 13 damaging missense mutations, 2 conserved splice site mutations, 2 nonsense mutations, and 1 frameshift deletion. The average number of exonic DNV per proband was 0.88, which corresponds to an exonic point mutation rate of 1.7×10(-8) per nucleotide per generation. The non-synonymous-to-synonymous mutation ratio of 2.06 did not differ from neutral expectations. Overall, this study provides a list of 18 putative candidate genes for sporadic SCZ, and when combined with the results of similar reports, identifies a second proband carrying a non-synonymous DNV in the RGS12 gene.