Philippe Conus

Brain network alterations preceding first-episode psychosis often escape connectomic approaches based on conventional neuroimaging, such as diffusion or functional magnetic resonance imaging (MRI). Whole-brain magnetic resonance spectroscopic imaging (MRSI) offers a potentially more sensitive alternative: by mapping neurometabolites across the brain, it enables the construction of metabolic connectomes that may capture very early and subtle disruptions of brain network properties. We combined whole-brain proton MRSI, diffusion MRI, and resting-state functional MRI in a sample of 29 individuals meeting DSM-5 criteria for Attenuated Psychosis Syndrome (APS) or Schizotypal Personality Disorder (SCZT), pooled into a single High Risk for Psychosis (HR) group, and 30 healthy controls (HC) to construct metabolic, structural, and functional connectomes. Network-based statistics identified a significant metabolic connectivity subnetwork with higher connectivity in HR than in HC, whereas no corresponding structural or functional connectivity differences were detected. Nodes of this subnetwork had modestly higher structural strength but were not consistently enriched among structural hubs, and no significant regional abnormalities in individual metabolite concentrations were detected. Eigenmode analysis of metabolic connectivity revealed a low-dimensional organization spanning a posterior unimodal-to-transmodal axis and a transmodal-to-limbic axis. Path analysis revealed higher bilateral energy in HR, indicating reduced coherence along a metabolic gradient that parallels the neurodevelopmental sensorimotor- to-association axis. These findings identify whole-brain metabolic network organization derived from MRSI as a systems-level phenotype of psychosis risk and raise the possibility that it captures altered development of large-scale cortical organization.

Background: Switzerland’s mental health workforce heavily relies on foreign-trained psychiatrists. Unlike many European training systems, Swiss postgraduate psychiatry integrates formal psychotherapy training that leads to a dual psychiatrist-psychotherapist qualification. However, the role of this training model in shaping international trainee mobility has not been systematically studied. Methods: We conducted a cross-sectional online survey among physicians who obtained their medical degrees outside Switzerland and had been recruited into psychiatry training at Lausanne University Hospital between 2006 and 2022. The questionnaire combined items adapted from the European Federation of Psychiatric Trainees Brain Drain study with additional items addressing training pathways, migration motivations, and perceptions of psychotherapy training. Responses were analysed using descriptive statistics and seven post hoc exploratory comparisons with two-sided Fisher’s exact tests and Holm adjustment. Results: Of the 203 physicians contacted for the survey, 130 were included in the analysis (64.0%). Academic opportunities were the most frequently assigned rank-1 category in the general push and pull questions. Psychotherapy training received independent importance ratings of 1–3 from 78/118 respondents (66.1%), compared with 73/118 (61.9%) for training quality and 69/118 (58.5%) for the combined qualification. None of the seven exploratory comparisons reached statistical significance after adjustment for multiple testing. Conclusions: In this single-centre sample, participants frequently attributed importance to psychotherapy training when recalling their reasons for coming to Switzerland. Its integration represents a potentially modifiable educational feature within a broader set of structural and personal considerations. These findings describe perceived relevance rather than establish causal effects on migration or subsequent retention.

Although transport infrastructures are increasingly recognised as determinants of urban wellbeing, their role in trajectories of becoming well and becoming ill has received little empirical and theoretical attention, particularly in serious mental ill‐health. This paper examines how bus infrastructures function as everyday resources and obstacles for people living with psychosis. Drawing on qualitative research with young people recovering from early psychosis in Lausanne, Switzerland, we examine the socio‐material and affective dimensions of bus mobility through relational geographical perspectives on health and place, mobility studies and work on infrastructures of care. We show how buses can function as affective lifelines, anchors of autonomy and independence and gateways to formal and informal resources for wellbeing, supporting recovery and re‐engagement with the city. Buses can also entail sensory overstimulation, proximity to others, perceived surveillance, anxiety and financial constraints. Our analysis highlights how mobility capacities are relationally constituted through encounters with urban infrastructures: buses can cultivate or undermine capacities to engage with the city. We argue that buses should therefore be understood not simply as transport services or conduits to therapeutic resources, but as ordinary infrastructures of care and enabling places through which recovery is enacted in urban life.

Aim: Protective factors and resources to recovery in urban milieus remain poorly understood, calling for user‐led initiatives to develop relevant interventions embedded in patients' daily‐life environments. Experience‐based co‐design is key to need‐based interventions in real‐life settings and calls for novel methodologies. Observation: This multi‐stakeholder (service users, psychiatrists, geographers, community actors and public authorities) initiative aims to identify key elements of an ‘urban recovery milieu for psychosis’ in Lausanne, Switzerland based on a Living Lab approach. Beyond questions of usage, feasibility and acceptability, we will identify which types of interventions are more useful for which group of patients. This pilot phase may pave the way towards a future randomized control trial and the definition of the most appropriate sample size for it. Results: Qualitative data are collected through field notes, audio‐recorded walk‐alongs, workshops and focus groups with care teams and participants. The quantitative analysis is based on observational and correlational study design. We will assess how 55 patients of two psychosis‐specialized cohorts use the urban interventions in their day‐to‐day practices and monitor psychometric variables before and after the experimentation. The data stems from tailor‐made questionnaires (City avoidance questionnaire, Urban remediation questionnaire, etc.), clinical rating scales (ASI, RAS, TEPS, ISMI and CRDPS) and routine follow‐up procedures (SOFAS, GAF, CGI, WHOQOL and PAS). Discussion: Additionally, insights from this study will inform mental health plan on municipal level and be upscaled for broader public benefits.

Introduction: Suicidal ideation and behaviors (SIB) are common among individuals at clinical high risk for psychosis (CHR‐P), but their relationship with the overall clinical profile remains unclear. This study aimed to identify sociodemographic/clinical factors associated with SIB in CHR‐P individuals and to examine whether subthreshold psychotic symptom severity increases with suicidal risk. Methods: Data from the AMP SCZ initiative included 1443 CHR‐P participants aged 12–30 years. SIB were assessed using the Columbia Suicide Severity Rating Scale (C‐SSRS). Three Elastic Net regression models examined associations between suicidal ideation severity, intensity, and behaviors using 54 variables spanning sociodemographics, general psychopathology, subthreshold psychotic symptoms, and socio‐occupational functioning. Moreover, ANCOVA compared overall psychotic symptom severity across five groups defined by increasing severity on the C‐SSRS. Results: Sixty‐eight percent of participants reported lifetime suicidal ideation, and 26% reported previous suicidal behaviors. Model performance was modest but significant (cross‐validated ideation severity: R ² = 0.161, RMSE = 0.916; ideation intensity: R ² = 0.193, RMSE = 0.898; suicidal behavior: accuracy = 0.685; AUC = 0.675; p < 0.001). Across all models, concurrent depressive symptoms, present/past diagnosis of depression, female sex at birth, cannabis use, visual/gustatory abnormalities, guilt, and lower role functioning were the most consistent correlates of SIB. Ideation was associated with lower disorganized communication expression and lower negative symptoms, whereas behaviors were associated with schizotypal personality disorder. Other core CHR‐P symptoms, including Unusual Thoughts and Experiences, did not contribute to any model. ANCOVA ( p < 0.001, partial η ² = 0.041) indicated increasing overall subthreshold psychotic symptoms across the SIB spectrum. Conclusion: SIB in CHR‐P individuals reflects a multidimensional clinical profile primarily outside of core psychosis‐risk symptoms. Trial Registration: ClinicalTrials.gov identifier: NCT05905003

Adolescence is marked by coordinated endocrine and brain maturation, yet how blood circulating steroid hormones relate to neurochemical change in the brain remains largely unknown. We combined longitudinal data from a novel fast whole-brain, high-resolution three-dimensional proton magnetic resonance spectroscopic imaging technique with repeated measurements of sexual hormones and adrenal steroids in the serum of 42 healthy adolescents (13-15 years; 24 females) totalizing 100 scan-visits. Longitudinal voxel-wise models separated within-individual changes from stable between-individual differences and controlled the false discovery rate across whole-brain tests. In the whole sample, increasing age was associated with higher N-acetylaspartate plus N-acetylaspartylglutamate within individuals, whereas age was positively associated with higher glutamate plus glutamine between individuals. We then observed a hormone-metabolite coupling that differed by sex and steroids. In males, within-individual increases in testosterone tracked frontal increases in glutamate plus glutamine and disseminated increases in total N-acetylaspartate. In females, higher mean estradiol between individuals was associated with higher frontal choline-containing compounds. Within-individual changes in cortisone were associated with myo-inositol and choline-containing compounds in a widespread sex-interaction effect, with positive coupling in males and negative in females. The cortisone/cortisol ratio showed a similar sex-interaction for choline-containing compounds. These findings reveal spatially distributed, sex-dependent links between steroid maturation and adolescent brain neurochemical composition and underscore the importance of differentiating within- and between-individual associations. These observational data extend predominantly structural descriptions of pubertal brain development by identifying distinct coupling of gonadal hormones with neuronal-metabolic markers and glucocorticoid interconversion with glia-weighted metabolites.

Background: Somatic and psychiatric illnesses and multimorbidities increase stress-vulnerability and decrease well-being. Objective: We aimed to identify high-risk disorder profiles for lower well-being and well-being decline under stress, modelling COVID-19 as a natural experiment. Methods: The global Collaborative Outcomes Study on Health and Functioning during Infection Times survey assessed the World Health Organization-Five Well-being Index (WHO-5) (0–100) retrospectively pre-pandemic and intra-pandemically. Mixed-effects models, controlling for demographic/pandemic-related covariates, examined coprimary outcomes: total pre-pandemic WHO-5 and pre-to-intra-pandemic change (estimating β); pre-pandemic WHO-5 pre-pandemic: autism-spectrum disorder (β=−7.00±2.93/OR=1.27–2.65), schizophrenia/schizoaffective disorder (β=−5.39±3.42/OR=1.09–2.64); pre-to-intra-pandemic: major depressive disorder (β=−2.45±0.89/OR=1.25–1.55), post-traumatic stress disorder (β=−1.98±1.42/OR=1.19–1.67)) versus somatic disorders ( pre-pandemic: diarrhoea (β=−3.29±2.49/OR=1.11–2.15), chronic skin disease (CSD) (β=−2.53±1.44/OR=1.11–1.65); pre-to-intra-pandemic: CSD (β=−2.31±1.47/OR=1.23–1.75), injury (β=−2.22±0.99/OR=1.11–1.40)). Multimorbidities were associated with non-linear/supra-additive adverse outcomes beyond single disorders ( pre-pandemic: anorexia nervosa+schizophrenia/schizoaffective disorder (β=−27.58±12.71/OR=1.41–19.94), inflammatory bowel disease+psychosis (β=−24.89±10.59/OR=2.68–24.25), stroke+osteoarthritis (β=−13.68±7.33/OR=1.23–6.48); pre-to-intra-pandemic: haemorrhoids+obsessive-compulsive disorder (β=−8.86±6.54/OR=1.22–5.21), binge-eating disorder/bulimia nervosa+social anxiety disorder (β=−6.87±5.49/OR=0.78–2.85), back pain+retinopathy (β=−6.55±6.54/OR=1.04–4.69)). Dose–response relationships were observed between the number of disorders and poorer well-being ( pre-pandemic per diagnosis: psychiatric (β=−1.22±0.23/OR=1.11–1.17), somatic (β=−0.21±0.13/OR=1.02–1.05); pre-to-intra-pandemic per diagnosis: psychiatric (β=−0.37±0.24/OR=1.04–1.10)). Conclusions: Poor well-being and further decline under stress were observed particularly with psychiatric illnesses and complex psychiatric and mixed psychiatric-somatic multimorbidity. Clinical implications: The finding of supra-additive multimorbidity burden highlights a need for targeted care models, beyond individual conditions. Vulnerable groups require support during crises, beyond COVID-19.

Sex differences in brain disorders span age at onset, symptom profiles, disease course and treatment response, and may partly reflect underlying differences in cellular metabolism. Indeed, in vivo evidence of sex-related neurometabolic variation remains sparse, with heterogenous and conflicting findings. Using fast high-resolution whole-brain three-dimensional magnetic resonance spectroscopic imaging, we mapped five brain metabolites in three independent cohorts of healthy participants (total n = 114). In a discovery sample of adolescents scanned at 3 Tesla (3T) (n = 61), males showed higher total N-acetylaspartate (tNAA) across widespread gray matter regions. Regional analyses further revealed opposing sex patterns with a complementary higher total creatine (tCr) observed in females, motivating examination of their ratio as an integrative metabolic index. The tNAA/tCr ratio was consistently higher in males in the discovery sample and this finding was replicated across two independent young-adult samples (3T, n = 26; 7T, n = 27), with a widespread gray and white matter distribution. This tNAA/tCr ratio may link neuronal mitochondrial metabolism with cellular energy buffering, positioning it as a potential index of bioenergetic balance relevant for conditions showing both sex differences and altered neurometabolism, notably multiple sclerosis, Alzheimer disease, and psychosis. Together, these findings reveal a reproducible, distributed metabolic sexual dimorphism in the human brain, and underscore the importance of accounting for sex-specific neurometabolic profiles in studies of brain health and disease.

Introduction: Return to studies or employment, a major element of recovery after a first episode of psychosis (FEP), is out of reach of a significant proportion of patients. Specific programs such as Individual Placement Support (IPS) have been proposed to overcome this hurdle. While some early intervention programs include IPS, others must rely on IPS programs that are open to a wider range of patients. The aim of this paper was to explore the accessibility of IPS for FEP patients treated in such a context. Methods: One hundred and eighty nine patients of an ongoing FEP cohort study who were treated at our program in the period where the IPS program was available and for whom sufficient data was available were included in the study. We assessed reasons for non‐referral to RESSORT and compared baseline and outcome characteristics of patients who did or did not enter the program. Results: A small minority of patients had access to RESSORT. Patients who entered RESSORT had better premorbid functioning and a higher degree of insight at baseline than the ones who did not enter the program. Patients who entered RESSORT had a significantly higher rate of return to premorbid PAS score, without significant difference on other dimensions of functioning. Conclusions: When IPS programs are not embedded in early intervention programs, FEP patients have limited chances to access them. Integrating supported employment skills within the role of case managers may be a solution in programs where resources are lacking to develop an IPS program specifically dedicated to FEP patients.

Advances in three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI) allow for the high-resolution mapping of multiple neurometabolites throughout the entire brain in vivo and within clinically compatible time frames. Leveraging this capability, we created a voxel-based pipeline that corrects and spatially normalizes whole-brain maps of total N-acetylaspartate (tNAA), myo-inositol (Ins), choline compounds (Cho), glutamate + glutamine (Glx) and creatine + phosphocreatine (tCr). We examined 2 different 3D-MRSI dataset: first, a clinical sample of adolescents and young adults at risk for psychosis (n = 21) meeting DSM-5 criteria for Attenuated Psychosis Syndrome (APS) or Schizotypal Personality Disorder (SCZT), and age-/sex-matched healthy controls (n = 13); and second, a non-clinical sample of adolescents (n = 61) scanned on a different site. The objective of the study was threefold: first, to assess the reproducibility of 3D-MRSI measures across datasets and scanning sites; second, to validate the feasibility of whole-brain, voxel-based analyses on 3D-MRSI data; and third, to test the sensitivity of this approach. Metabolite distributions showed reproducible regional variation in standard space between the two independent samples and scanning sites (r ranging from 0.82 to 0.99). Relative to controls, at-risk participants exhibited higher tNAA levels in frontal grey matter; the SCZT subgroup additionally displayed widespread cortical and subcortical elevations of Ins levels compared with both APS and controls. Voxel-based analyses of structural (i.e., gray and white matter volumes or densities) and diffusion (i.e., generalized fractional anisotropy) parameters yielded no significant differences between patients and controls. These preliminary findings suggest that high-resolution 3D-MRSI may be sensitive enough to detect subtle neurometabolic alterations at the group level in the early stages of psychotic disorders when structural or diffusion measures show no difference. High-resolution whole-brain metabolic mapping may have the potential to help with early identification of young people at risk for psychosis or other mental disorders.