Search

Cristina Domenech,1,2 Adriana Pastore,3 A Carlo Altamura,4 Corrado Bernasconi,5 Ricardo Corral,6 Helio Elkis,7 Jonathan Evans,8 Ashok Malla,9 Francesco Margari,3 Marie-Odile Krebs,10 Anna-Lena Nordstroem,5 Mathias Zink,11 Josep Maria Haro1,2 1Universitat de Barcelona, Barcelona, Spain; 2Parc Sanitari Sant Joan de Déu, CIBERSAM, Institut de Recerca Sant Joan de Déu, Barcelona, Spain; 3Department of Basic Medical Science, Neuroscience and Sense Organs, ‘Policlinico’ Hospital, University of Bari ‘Aldo Moro’, Bari, Italy; 4University of Milan, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy; 5F. Hoffmann-La Roche Ltd, Basel, Switzerland; 6Fundación para el Estudio y Tratamiento de las Enfermedades Mentales (FETEM), Buenos Aires, Argentina; 7Departamento e Instituto de Psiquiatria – FMUSP, Sao Paulo, Brazil; 8Centre for Academic Mental Health, University of Bristol, Bristol, UK; 9Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada; 10Service Hospitalo Universitaire, Laboratoire de Physiopathologie des Maladies Psychiatriques, Inserm, Université Paris Descartes, Hôpital Sainte-Anne, Paris, France; 11Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany and Regional Clinical Centre, Ansbach, GermanyCorrespondence: Josep Maria HaroParc Sanitari Sant Joan de Déu - Antoni Pujadas, 42 - 08830 Sant Boi de Llobregat, Barcelona, SpainTel +34 93 600 26 85Email jmharo@pssjd.orgBackground: Generic health-related quality of life (HRQoL) scales are increasingly being used to assess the effects of new treatments in schizophrenia. The objective of this study is to better understand the usefulness of generic and condition specific HRQoL scales in schizophrenia by analyzing their correlates.Methods: Data formed part of the Pattern study, an international observational study among 1379 outpatients with schizophrenia. Patients were evaluated with the Mini International Neuropsychiatric Inventory, the Clinical Global Impression-Schizophrenia (CGI-SCH) Scale and the Positive and Negative Syndrome Scale (PANSS) and reported their HRQoL using the Schizophrenia Quality of Life Scale (SQLS), the Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D). The two summary values of the SF-36 (the Mental Component Score and the Physical Component Score, SF-36 MCS and SF-36 PCS) were calculated.Results: Higher PANSS positive dimension ratings were associated with worse HRQoL for the SQLS, EQ-5D VAS, SF-36 MCS, and SF-36 PCS. Higher PANSS negative dimension ratings were associated with worse HRQoL for the EQ-5D VAS, SF-36 MCS, and SF-36 PCS, but not for the SQLS or the EQ-5D tariff. PANSS depression ratings were associated with lower HRQoL in all the scales. There was a high correlation between the HRQoL scales. However, in patients with more severe cognitive/disorganized PANSS symptoms, the SQLS score was relatively higher than the EQ-5D tariff and SF-36 PCS scores.Conclusion: This study has shown substantial agreement between three HRQoL scales, being either generic or condition specific. This supports the use of generic HRQoL measures in schizophrenia.Clinicaltrials.gov identifier: NCT01634542 (July 6, 2012, retrospectively registered).Keywords: schizophrenia, health-related quality of life, epidemiology, persistent symptoms

Background: Treatment resistance is a major challenge in psychiatric disorders. Early detection of potential future resistance would improve prognosis by reducing the delay to appropriate treatment adjustment and recovery. Here, we sought to determine whether neurodevelopmental markers can predict therapeutic response., Methods: Healthy controls ( N = 236), patients with schizophrenia ( N = 280) or bipolar disorder ( N = 78) with a known therapeutic outcome, were retrospectively included. Age, sex, education, early developmental abnormalities (obstetric complications, height, weight, and head circumference at birth, hyperactivity, dyslexia, epilepsy, enuresis, encopresis), neurological soft signs (NSS), and ages at first subjective impairment, clinical symptoms, treatment, and hospitalization, were recorded. A supervised algorithm leveraged NSS and age at first clinical signs to classify between resistance and response in schizophrenia., Results: Developmental abnormalities were more frequent in schizophrenia and bipolar disorder than in controls. NSS significantly differed between controls, responsive, and resistant participants with schizophrenia (5.5 ± 3.0, 7.0 ± 4.0, 15.0 ± 6.0 respectively, p = 3 × 10 -10 ) and bipolar disorder (5.5 ± 3.0, 8.3 ± 3.0, 12.5 ± 6.0 respectively, p < 1 × 10 -10 ). In schizophrenia, but not in bipolar disorder, age at first subjective impairment was three years lower, and age at first clinical signs two years lower, in resistant than responsive subjects ( p = 2 × 10 -4 and p = 9 × 10 -3 , respectively). Age at first clinical signs and NSS accurately predicted treatment response in schizophrenia (area-under-curve: 77 ± 8%, p = 1 × 10 -14 )., Conclusions: Neurodevelopmental features such as NSS and age of clinical onset provide a means to identify patients who may require rapid treatment adaptation.

Background: Dermatoglyphic pattern deviances have been associated with schizophrenia-spectrum disorders (SSD) and are considered neurodevelopment vulnerability markers based on the shared ectodermal origin of the epidermis and the central nervous system. The endocannabinoid system participates in epidermal differentiation, is sensitive to prenatal insults and is associated with SSD. Objective: We aimed to investigate whether the Cannabinoid Receptor 1 gene ( CNR1 ) modulates the dermatoglyphics-SSD association. Methods: In a sample of 112 controls and 97 patients with SSD, three dermatoglyphic markers were assessed: the total palmar a-b ridge count (TABRC), the a-b ridge count fluctuating asymmetry (ABRC-FA), and the pattern intensity index (PII). Two CNR1 polymorphisms were genotyped: rs2023239-T/C and rs806379-A/T. We tested: (i) the CNR1 association with SSD and dermatoglyphic variability within groups; and (ii) the CNR1 × dermatoglyphic measures interaction on SSD susceptibility. Results: Both polymorphisms were associated with SSD. The polymorphism rs2023239 modulated the relationship between PII and SSD: a high PII score was associated with a lower SSD risk within C-allele carriers and a higher SSD risk within TT-homozygotes. This result indicates an inverse relationship between the PII and the SSD predicted probability conditional to the rs2023239 genotype. Conclusions: These novel findings suggest the endocannabinoid system's role in the development and variability of dermatoglyphic patterns. The identified interaction encourages combining genetic and dermatoglyphics to assess neurodevelopmental alterations predisposing to SSD in future studies.

There is no multi-country/multi-language study testing a-priori multivariable associations between non-modifiable/modifiable factors and validated wellbeing/multidimensional mental health outcomes before/during the COVID-19 pandemic. Moreover, studies during COVID-19 pandemic generally do not report on representative/weighted non-probability samples. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is a multi-country/multi-language survey conducting multivariable/LASSO-regularized regression models and network analyses to identify modifiable/non-modifiable factors associated with wellbeing (WHO-5)/composite psychopathology (P-score) change. It enrolled general population-representative/weighted-non-probability samples (26/04/2020-19/06/2022). Participants included 121,066 adults (age=42±15.9 years, females=64 %, representative sample=29 %) WHO-5/P-score worsened (SMD=0.53/SMD=0.74), especially initially during the pandemic. We identified 15 modifiable/nine non-modifiable risk and 13 modifiable/three non-modifiable protective factors for WHO-5, 16 modifiable/11 non-modifiable risk and 10 modifiable/six non-modifiable protective factors for P-score. The 12 shared risk/protective factors with highest centrality (network-analysis) were, for non-modifiable factors, country income, ethnicity, age, gender, education, mental disorder history, COVID-19-related restrictions, urbanicity, physical disorder history, household room numbers and green space, and socioeconomic status. For modifiable factors, we identified medications, learning, internet, pet-ownership, working and religion as coping strategies, plus pre-pandemic levels of stress, fear, TV, social media or reading time, and COVID-19 information. In multivariable models, for WHO-5, additional non-modifiable factors with |B|>1 were income loss, COVID-19 deaths. For modifiable factors we identified pre-pandemic levels of social functioning, hobbies, frustration and loneliness, and social interactions as coping strategy. For P-scores, additional non-modifiable/modifiable factors were income loss, pre-pandemic infection fear, and social interactions as coping strategy. COH-FIT identified vulnerable sub-populations and actionable individual/environmental factors to protect well-being/mental health during crisis times. Results inform public health policies, and clinical practice., Competing Interests: Conflict of interest Conflict of interest statements of all authors are detailed in eTable 12., (Copyright © 2024. Published by Elsevier B.V.)

Background: Psychiatric disorders often emerge during adolescence or young adulthood, leading to significant disability among youth. The transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) is critical for individuals experiencing emerging psychopathology, with delayed access to care negatively impacting long-term outcomes. Accessing mental health services for adolescents and young adults is often complex and delayed due to challenges in service visibility, accessibility and appropriateness., Methods: This study examines the care trajectories of individuals consecutively accessing the early detection and intervention (EDI) centre C'JAAD (Evaluation Centre for Young Adults and Adolescents) in Paris (France) over the year 2021. The main goal was to clarify the role of this EDI centre in the continuity of care and transition to AMHS. Data about their history of care, hospitalisations and referral sources were collected retrospectively., Results: The sample comprised 194 individuals, with 57.2% males and a median age of 20 years. Most patients (67.5%) were ≥18 years old upon arrival, with 31% in a situation of not being in education, employment, or training (NEET). Over one-third (35.2%) had prior psychiatric hospitalisations. Patients were mainly referred to our EDI centre from other hospital departments (42.3%). Regarding care in CAMHS, 50.3% of the total sample had medical follow-up during childhood, of whom 41.9% had discontinued care upon arrival at the EDI centre. The median onset age of care in CAMHS was 14, with a median duration of 12 months. Adult patients experienced an approximately 3-year gap between the end of CAMHS care and assessment at the EDI centre., Discussion: The sample's characteristics resemble those of other EDI centres, but concerns persist regarding referral timing and the NEET status of many youths. Lack of prior medical follow-up and challenges in transitioning to AMHS underscore the need to enhance care continuity and address difficulties in accessing care during the transition to adulthood., (© 2024 The Author(s). Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Individuals with schizophrenia generally show difficulties in interpersonal communication. Linguistic analyses shed new light on speech atypicalities in schizophrenia. However, very little is known about conversational interaction management by these individuals. Moreover, the relationship between linguistic features, psychopathology, and patients' subjectivity has received limited attention to date. We used a novel methodology to explore dyadic conversations involving 58 participants (29 individuals with schizophrenia and 29 control persons) and medical doctors. High-quality stereo recordings were obtained and used to quantify turn-taking patterns. We investigated psychopathological dimensions and subjective experiences using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Examination of Anomalous Self Experience scale (EASE), the Autism Rating Scale (ARS) and the Abnormal Bodily Phenomena questionnaire (ABPq). Different turn-taking patterns of both patients and interviewers characterised conversations involving individuals with schizophrenia. We observed higher levels of overlap and mutual silence in dialogues with the patients compared to dialogues with control persons. Mutual silence was associated with negative symptom severity; no dialogical feature was correlated with anomalous subjective experiences. Our findings suggest that individuals with schizophrenia display peculiar turn-taking behaviour, thereby enhancing our understanding of interactional coordination in schizophrenia., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Detecting patients with a high-risk profile for treatment-resistant schizophrenia (TRS) can be beneficial for implementing individually adapted therapeutic strategies and better understanding the TRS etiology. The aim of this study was to explore, with machine learning methods, the impact of demographic and clinical patient characteristics on TRS prediction, for already established risk factors and unexplored ones. This was a retrospective study of 500 patients admitted during 2020 to the University Hospital Group for Paris Psychiatry. We hypothesized potential TRS risk factors. The selected features were coded into structured variables in a new dataset, by processing patients discharge summaries and medical narratives with natural-language processing methods. We compared three machine learning models (XGBoost, logistic elastic net regression, logistic regression without regularization) for predicting TRS outcome. We analysed feature impact on the models, suggesting the following factors as markers of a high-risk TRS profile: early age at first contact with psychiatry, antipsychotic treatment interruptions due to non-adherence, absence of positive symptoms at baseline, educational problems and adolescence mental disorders in the personal psychiatric history. Specifically, we found a significant association with TRS outcome for age at first contact with psychiatry and medication non-adherence. Our findings on TRS risk factors are consistent with the review of the literature and suggest potential in using early pathophysiologic features for TRS prediction. Results were encouraging with the use of natural-langage processing techniques to leverage raw data provided by discharge summaries, combined with machine leaning models. These findings are a promising step for helping clinicians adapt their guidelines to early detection of TRS., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Hypothesis: Cognition has been associated with socio-occupational functioning in individuals at Clinical High Risk for Psychosis (CHR-P). The present study hypothesized that clustering CHR-P participants based on cognitive data could reveal clinically meaningful subtypes., Study Design: A cohort of 291 CHR-P subjects was recruited through the multicentre EU-GEI high-risk study. We explored whether an underlying cluster structure was present in the cognition data. Clustering of cognition data was performed using k-means clustering and density-based spatial clustering of applications with noise. Cognitive subtypes were validated by comparing differences in functioning, psychosis symptoms, transition outcome, and grey matter volume between clusters. Network analysis was used to further examine relationships between cognition scores and clinical symptoms., Study Results: No underlying cluster structure was found in the cognitive data. K-means clustering produced "spared" and "impaired" cognition clusters similar to those reported in previous studies. However, these clusters were not associated with differences in functioning, symptomatology, outcome, or grey matter volume. Network analysis identified cognition and symptoms/functioning measures that formed separate subnetworks of associations., Conclusions: Stratifying patients according to cognitive performance has the potential to inform clinical care. However, we did not find evidence of cognitive clusters in this CHR-P sample. We suggest that care needs to be taken in inferring the existence of distinct cognitive subtypes from unsupervised learning studies. Future research in CHR-P samples could explore the existence of cognitive subtypes across a wider range of cognitive domains., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Relatives of ADHD probands are known to be at increased risk of schizophrenia and bipolar disorder, suggesting shared genetic factors. In this study, we aim to identify shared common risk variants (i.e., Single-Nucleotide Polymorphisms, SNPs) between ADHD and schizophrenia, and between ADHD and bipolar disorder., Methods: With the summary data from three GWAS, one on ADHD (20,183 cases with ADHD and 35,191 controls), another on schizophrenia (76,755 cases with schizophrenia and 243,649 controls) and another on bipolar disorder (41,917 cases with bipolar disorder and 371,549 controls), we used colocalization analysis to identify SNPs shared by ADHD and schizophrenia, and SNPs shared by ADHD and bipolar disorder. Functional genomic analyses were then conducted on these two sets of shared common genetic variants., Results: We found that three of the 12 SNPs associated with ADHD colocalized with schizophrenia SNPs and one of the 12 SNPs associated with ADHD colocalized with bipolar disorder. Only 0.4% of the SNPs associated with schizophrenia (2 out of 431) and 2.3% of the SNPs associated with bipolar disorder (2 out of 86), colocalized with ADHD SNPs. Some genes mapped to these shared genetic variants (SCN2A and UNC5D) are involved in the development of the nervous system., Conclusions: Using colocalization analysis, the present study uncovers shared genetic variants associated with ADHD and schizophrenia as well as ADHD and bipolar disorder, and may at least partially explain the increased risk of schizophrenia and bipolar disorder in relatives of ADHD probands., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score, and their associations with COVID-19 deaths/restrictions, 12 a-priori defined risk individual/cumulative factors, and coping strategies during COVID-19 pandemic (26/04/2020-26/06/2022) in 30 languages (representative, weighted non-representative, adults). T-test, χ 2 , penalized cubic splines, linear regression, correlation analyses were conducted. Analyzing 121,066/142,364 initiated surveys, WHO-5/P-score worsened intra-pandemic by 11.1±21.1/13.2±17.9 points (effect size d=0.50/0.60) (comparable results in representative/weighted non-probability samples). Persons with WHO-5 scores indicative of depression screening (<50, 13% to 32%) and major depression (<29, 3% to 12%) significantly increased. WHO-5 worsened from those with mental disorders, female sex, COVID-19-related loss, low-income country location, physical disorders, healthcare worker occupations, large city location, COVID-19 infection, unemployment, first-generation immigration, to age=18-29 with a cumulative effect. Similar findings emerged for P-score. Changes were significantly but minimally related to COVID-19 deaths, returning to near-pre-pandemic values after >2 years. The most subjectively effective coping strategies were exercise and walking, internet use, social contacts. Identified risk groups, coping strategies and outcome trajectories can inform global public health strategies., Competing Interests: Declaration of competing interest Conflict of interest statements of all authors are detailed in eTable 8., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Hypothesis: The emergence of psychosis in ultra-high-risk subjects (UHR) is influenced by gene-environment interactions that rely on epigenetic mechanisms such as microRNAs. However, whether they can be relevant pathophysiological biomarkers of psychosis' onset remains unknown., Study Design: We present a longitudinal study of microRNA expression, measured in plasma by high-throughput sequencing at baseline and follow-up, in a prospective cohort of 81 UHR, 35 of whom developed psychosis at follow-up (converters). We combined supervised machine learning and differential graph analysis to assess the relative weighted contribution of each microRNA variation to the difference in outcome and identify outcome-specific networks. We then applied univariate models to the resulting microRNA variations common to both strategies, to interpret them as a function of demographic and clinical covariates., Study Results: We identified 207 microRNA variations that significantly contributed to the classification. The differential network analysis found 276 network-specific correlations of microRNA variations. The combination of both strategies identified 25 microRNAs, whose gene targets were overrepresented in cognition and schizophrenia genome-wide association studies findings. Interpretable univariate models further supported the relevance of miR-150-5p and miR-3191-5p variations in psychosis onset, independent of age, sex, cannabis use, and medication., Conclusions: In this first longitudinal study of microRNA variation during conversion to psychosis, we combined 2 methodologically independent data-driven strategies to identify a dynamic epigenetic signature of the emergence of psychosis that is pathophysiologically relevant., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The aim of this study was to develop and evaluate a French version of the Barriers to Access to Care Evaluation (BACE-3) scale that is tailored to the socio-cultural and language setting of the study., Methods: The translation of the BACE-3 into French and its validation were the two key components of this psychometric investigation. An online survey was created and circulated to French-speaking participants who volunteered to participate in the study., Results: For all translated questions, the reliability analysis key results (Cronbach's alpha and McDonald's Omega) were both>0.95, which is an excellent reliability value. The BACE-3 items were shown to be positively related to one another, implying excellent validity. Results of exploratory and confirmatory factor analyses showed that all stigma-related items were loaded under the same factor., Conclusions: The BACE-3 has been validated in French, and its psychometric qualities have been thoroughly evaluated and found to be excellent., (Copyright © 2024 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Aim: Social and role functioning impairments characterize patients along the schizophrenia spectrum, but the existing evaluations tools do not specifically address younger population issues. The Global Functioning Social (GF:S) and Global Functioning Role (GF:R) scales have been specifically designed for that purpose. The aim of this study is to establish the reliability and concurrent validity of the French version of GF:S and GF:R scales., Methods: The two scales GF: Social (GF:S) and Role (GF:R) have first been translated into French and independently back translated and validated by the original authors. Between March 2021 and March 2022, we enrolled 51 participants (20.3 ± 3.7 years old; female = 22/51) amongst help-seekers referring to two different early mental health services in the Île-de-France. In an ecological design, participants met different diagnoses, 7 (13.7%) met the criteria for Ultra-High Risk of psychosis (UHR) using CAARMS criteria., Results: Inter-rater reliability was excellent for scores related to the past month and to the higher levels of functioning over the past year. Both scales showed good to excellent concurrent validity as measured by correlation with the Social and Occupational Functioning Assessment Scale (SOFAS) and the Personal and Social Performance Scale (PSP)., Conclusion: Overall, this study confirms the reliability and validity of the French version of the GF:S and GF:R scales. The use of these scales may improve the evaluation of social and occupational functioning in French-speaking young help-seekers, in a transdiagnostic approach, both in clinical and research settings., (© 2023 John Wiley & Sons Australia, Ltd.)

Background: Quantitative electroencephalography (EEG) analysis offers the opportunity to study high-level cognitive processes across psychiatric disorders. In particular, EEG microstates translate the temporal dynamics of neuronal networks throughout the brain. Their alteration may reflect transdiagnostic anomalies in neurophysiological functions that are impaired in mood, psychosis, and autism spectrum disorders, such as sensorimotor integration, speech, sleep, and sense of self. The main questions this study aims to answer are as follows: 1) Are EEG microstate anomalies associated with clinical and functional prognosis, both in resting conditions and during sleep, across psychiatric disorders? 2) Are EEG microstate anomalies associated with differences in sensorimotor integration, speech, sense of self, and sleep? 3) Can the dynamic of EEG microstates be modulated by a non-drug intervention such as light hypnosis?, Methods: This prospective cohort will include a population of adolescents and young adults, aged 15 to 30 years old, with ultra-high-risk of psychosis (UHR), first-episode psychosis (FEP), schizophrenia (SCZ), autism spectrum disorder (ASD), and major depressive disorder (MDD), as well as healthy controls (CTRL) (N = 21 × 6), who will be assessed at baseline and after one year of follow-up. Participants will undergo deep phenotyping based on psychopathology, neuropsychological assessments, 64-channel EEG recordings, and biological sampling at the two timepoints. At baseline, the EEG recording will also be coupled to a sensorimotor task and a recording of the characteristics of their speech (prosody and turn-taking), a one-night polysomnography, a self-reference effect task in virtual reality (only in UHR, FEP, and CTRL). An interventional ancillary study will involve only healthy controls, in order to assess whether light hypnosis can modify the EEG microstate architecture in a direction opposite to what is seen in disease., Discussion: This transdiagnostic longitudinal case-control study will provide a multimodal neurophysiological assessment of clinical dimensions (sensorimotor integration, speech, sleep, and sense of self) that are disrupted across mood, psychosis, and autism spectrum disorders. It will further test the relevance of EEG microstates as dimensional functional biomarkers., Trial Registration: ClinicalTrials.gov Identifier NCT06045897., (© 2023. The Author(s).)

Aim: Neuroimaging-based machine-learning predictions of psychosis onset rely on the hypothesis that structural brain anomalies may reflect the underlying pathophysiology. Yet, current predictors remain difficult to interpret in light of brain structure. Here, we combined an advanced interpretable supervised algorithm and a model of neuroanatomical age to identify the level of brain maturation of the regions most predictive of psychosis., Methods: We used the voxel-based morphometry of a healthy control dataset (N = 2024) and a prospective longitudinal UHR cohort (N = 82), of which 27 developed psychosis after one year. In UHR, psychosis was predicted at one year using Elastic-Net-Total-Variation (Enet-TV) penalties within a five-fold cross-validation, providing an interpretable map of distinct predictive regions. Using both the whole brain and each predictive region separately, a brain age predictor was then built and validated in 1605 controls, externally tested in 419 controls from an independent cohort, and applied in UHR. Brain age gaps were computed as the difference between chronological and predicted age, providing a proxy of whole-brain and regional brain maturation., Results: Psychosis prediction was performant with 80 ± 4% of area-under-curve and 69 ± 5% of balanced accuracy (P < 0.001), and mainly leveraged volumetric increases in the ventromedial prefrontal cortex and decreases in the left precentral gyrus and the right orbitofrontal cortex. These regions were predicted to have delayed and accelerated maturational patterns, respectively., Conclusion: By combining an interpretable supervised model of conversion to psychosis with a brain age predictor, we showed that inter-regional asynchronous brain maturation underlines the predictive signature of psychosis., (© 2023 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Aims: Evidence for case-control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome., Methods: Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale., Results: During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome., Conclusions: These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder., (© 2023 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: We performed a pilot study on whether tablet-based measures of manual dexterity can provide behavioral markers for detection of first-episode psychosis (FEP), and whether cortical excitability/inhibition was altered in FEP., Methods: Behavioral and neurophysiological testing was undertaken in persons diagnosed with FEP ( N  = 20), schizophrenia (SCZ, N  = 20), autism spectrum disorder (ASD, N  = 20), and in healthy control subjects ( N  = 20). Five tablet tasks assessed different motor and cognitive functions: Finger Recognition for effector (finger) selection and mental rotation, Rhythm Tapping for temporal control, Sequence Tapping for control/memorization of motor sequences, Multi Finger Tapping for finger individuation, and Line Tracking for visuomotor control. Discrimination of FEP (from other groups) based on tablet-based measures was compared to discrimination through clinical neurological soft signs (NSS). Cortical excitability/inhibition, and cerebellar brain inhibition were assessed with transcranial magnetic stimulation., Results: Compared to controls, FEP patients showed slower reaction times and higher errors in Finger Recognition, and more variability in Rhythm Tapping. Variability in Rhythm Tapping showed highest specificity for the identification of FEP patients compared to all other groups (FEP vs. ASD/SCZ/Controls; 75% sensitivity, 90% specificity, AUC = 0.83) compared to clinical NSS (95% sensitivity, 22% specificity, AUC = 0.49). Random Forest analysis confirmed FEP discrimination vs. other groups based on dexterity variables (100% sensitivity, 85% specificity, balanced accuracy = 92%). The FEP group had reduced short-latency intra-cortical inhibition (but similar excitability) compared to controls, SCZ, and ASD. Cerebellar inhibition showed a non-significant tendency to be weaker in FEP., Conclusion: FEP patients show a distinctive pattern of dexterity impairments and weaker cortical inhibition. Easy-to-use tablet-based measures of manual dexterity capture neurological deficits in FEP and are promising markers for detection of FEP in clinical practice., Competing Interests: MT and PL own shares in Dextrain company (www.dextrain.com) which develops and commercializes solutions for measurement and rehabilitation of manual dexterity. MT, MM, and PL have a patent on the DexTrain manipulandum (WO2020070305A1) and method for evaluating manual dexterity (WO2016184935A2). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Le Boterff, Rabah, Carment, Bendjemaa, Térémetz, Alouit, Levy, Tanguy, Morin, Amado, Cuenca, Turc, Maier, Krebs and Lindberg.)

Caring for a relative with a severe mental disorder puts family caregivers to a great risk of depression. While overall caregiving burden is a strong predictor of depression, the contribution of the various dimensions of burden to caregivers' depression as well as their relationships with depressive symptoms has received little attention. 384 family caregivers completed a cross-sectional online survey including the Center for Epidemiological Studies Depression (CES-D) scale, the Zarit Burden Interview (ZBI), and the Brief Experience of Caregiving Inventory (BECI), measuring caregiving burden and experience. We estimated the structure of the relationships between caregiving experiences (i.e., ZBI and BECI subscales) and CES-D symptoms using a network approach. Negative Emotion/Consequences, (lack of) Positive Personal Experience, and Stigma/Effects on Family were the most connected caregiving dimensions to depression. To untangle the role of the Negative Emotion/Consequences component (by far the most central node in estimated networks), a secondary analysis incorporating its composing items was estimated. Losing control over life, feeling strained around the relative and impaired self-perceived health emerged as central nodes. Interestingly, these caregiving-related dimensions or experiences were differentially connected to depressive symptoms. We discuss how these findings might help future research and inform tailored psychoeducational interventions for family caregivers of people with a severe mental disorder., (© 2022. The Author(s).)

Background: Electroencephalography (EEG) microstates translate resting-state temporal dynamics of neuronal networks throughout the brain and could constitute possible markers of psychiatric disorders. We tested the hypothesis of an increased imbalance between a predominant self-referential mode (microstate C) and a decreased attentional mode (microstate D) in psychosis, mood, and autism spectrum disorders., Methods: We retrospectively included 135 subjects from an early psychosis outpatient unit, with available eyes-closed resting-state 19 electrodes EEG. Individual-level then group-level modified K -means clustering in controls provided four microstate maps that were then backfitted to all groups. Differences between microstate parameters (occurrence, coverage, and mean duration) were computed between controls and each group, and between disease groups., Results: Microstate class D parameters were systematically decreased in disease groups compared with controls, with an effect size increasing along the psychosis spectrum, but also in autism. There was no difference in class C. C/D ratios of mean duration were increased only in SCZ compared with controls., Conclusions: The decrease in microstate class D may be a marker of stage of psychosis, but it is not specific to it and may rather reflect a shared dimension along the schizophrenia-autism spectrum. C/D microstate imbalance may be more specific to schizophrenia.

The use of eCRFs is now commonplace in clinical research studies. We propose here an ontological model of these forms allowing to describe them, to express their granularity and to link them to the relevant entities of the study in which they are used. It has been developed in a psychiatry project but its generality may allow a wider application.

Alterations in membrane lipids are reported in schizophrenia. However, no conclusion can be drawn regarding the extended and predictive value of these alterations in persons at ultra-high risk of psychosis (UHR). Recent studies suggested that sterols' impact on psychiatric disorders was underestimated. Here, we simultaneously explored sterols, fatty acids (FA), and phospholipids (PL) in UHR persons for the first time. We analysed erythrocyte membrane lipids in 61 UHR persons, including 29 who later converted to psychosis (UHR-C) and 32 who did not (UHC-NC). We used gas chromatography for FA and liquid chromatography tandem with mass spectrometry for sterols and phospholipids. Among UHR individuals, elevated baseline membrane linoleic acid level was associated with conversion to psychosis (26.1% vs. 60.5%, p = 0.02). Combining sterols, FA, and PL membrane composition improved the prediction of psychosis onset (AUC = 0.73). This is the first report showing that membrane sterol participates, with other membrane lipids, in modulating the risk of psychosis. It suggests that membrane lipids could be used as biomarkers for personalised medicine in UHR patients.

Individuals at clinical high risk (CHR) for psychosis have been found to have altered cytokine levels, but whether these changes are related to clinical outcomes remains unclear. We addressed this issue by measuring serum levels of 20 immune markers in 325 participants (n = 269 CHR, n = 56 healthy controls) using multiplex immunoassays, and then followed up the CHR sample to determine their clinical outcomes. Among 269 CHR individuals, 50 (18.6 %) developed psychosis by two years. Univariate and machine learning techniques were used to compare levels of inflammatory markers in CHR subjects and healthy controls, and in CHR subjects who had (CHR-t), or had not (CHR-nt) transitioned to psychosis. An ANCOVA identified significant group differences (CHR-t, CHR-nt and controls) and post-hoc tests indicated that VEGF levels and the IL-10/IL-6 ratio were significantly higher in CHR-t than CHR-nt, after adjusting for multiple comparisons. Using a penalised logistic regression classifier, CHR participants were distinguished from controls with an area-under the curve (AUC) of 0.82, with IL-6 and IL-4 levels the most important discriminating features. Transition to psychosis was predicted with an AUC of 0.57, with higher VEGF level and IL-10/IL-6 ratio the most important discriminating features. These data suggest that alterations in the levels of peripheral immune markers are associated with the subsequent onset of psychosis. The association with increased VEGF levels could reflect altered blood-brain-barrier (BBB) permeability, while the link with an elevated IL-10/IL-6 ratio points to an imbalance between anti- and pro-inflammatory cytokines., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: VM has received research funding from Johnson & Johnson as part of a research program on depression and inflammation, but this is unrelated to the work presented in this study. The remaining authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score"., Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed., Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex., Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health., Competing Interests: Conflict of interest Conflict of interest statements of all authors are detailed in Supplementary Table 7., (Copyright © 2022 Elsevier B.V. All rights reserved.)

On June 2022, the 2nd Webinar "Neurodevelopmental Disorders (NDD) without boundaries took place at the Imagine Institute in Paris and was broadcasted live and in replay. The aim of this webinar is to address NDD in a dimensional rather than in a categorical approach. Several speakers were invited to present their researches on the subject. Classifications in NDD were discussed: irritability in NDD, involvement of the immune system in neurodevelopment, nutrition and gut microbiota modulate brain inflammation and neurodevelopment, co-occurring conditions in autistic adolescents and adults without intellectual disability. Classifications in psychiatric disorders were asked: mapping the effect of genes on cognition and autism risk, epigenetics and symptomatic trajectory in neurodevelopmental disorders, the autism-schizophrenia continuum in two examples: minor neurological signs and EEG microstates, the cerebellum in schizophrenia and autism: from imaging to intervention perspectives. Both genetic and environmental factors, along with clinical and imaging features, argue toward a continnum between NDD but also with adult psychiatric presentations. This new paradigm could modify the therapeutic strategy, with the development of large-spectrum treatments or new psychotherapies addressing co-occuring symptoms. The complexity and the heterogeneity of NDD apply well to the next scientific and political challenges: developing international convergence to push back the frontiers of our knowledge. This article is a summary of the 2nd webinar "Neurodevelopmental Disorders (NDD) without boundaries: research and interventions beyond classifications" sponsored by the French National Academy of Medicine, the autism and neurodevelopmental disorders scientific interest group (GIS), the International Research Network Dev-O-Psy and the French Institute of Psychiatry (GDR3557). Oral presentations are available as a replay on the following website (in French): https://autisme-neurodev.org/evenements/2022/04/12/tnd-sans-frontieres-la-recherche-et-les-interventions-au-dela-des-classifications/ ., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Down syndrome (DS) is one of the most frequent genetic disorders and represents the first cause of intellectual disability of genetic origin. While the majority of patients with DS follow a harmonious evolution, an unusual neurodevelopmental regression may occur, distinct from that described in the context of autism spectrum disorders, called down syndrome regression disorder (DSRD). Based on four patients, two males and two females, with age range between 20 and 24, treated at the Reference Center for Rare Psychiatric Disorders of the GHU Paris Psychiatry and Neurosciences [Pôle hospitalo-universitaire d'Évaluation Prévention et Innovation Thérapeutique (PEPIT)], we describe this syndrome, discuss its etiologies and propose therapeutic strategies. DSRD often occurs in late adolescence. There is a sudden onset of language disorders, loss of autonomy and daily living skills, as well as behavioral symptoms such as depression, psychosis, or catatonia. These symptoms are non-specific and lead to an overlap with other diagnostic categories, thus complicating diagnosis. The etiologies of the syndrome are not clearly identified but certain predispositions of patients with trisomy 21 have suggested an underlying immune-mediated mechanism. Symptomatic therapeutic approaches (serotonergic antidepressants, atypical antipsychotics, benzodiazepines) were not effective, and generally associated with poor tolerance. Etiological treatments, including anti-inflammatory drugs and corticosteroids, led to partial or good recovery in the four cases. Early recognition of regressive symptoms and rapid implementation of adapted treatments are required to improve the quality of life of patients and their families., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bonne, Iftimovici, Mircher, Conte, Louveau, Legrand, Danset-Alexandre, Cannarsa, Debril, Consoli, Krebs, Ellul and Chaumette.)