Transgender is an umbrella term that refers to individuals whose gender identity does not align with their birth-assigned sex. Comprehensive psychological assessment is essential to evaluate psychological functioning in this population, such as stress control, cognition, affect, self-perception, and interpersonal perception. However, there is a lack of consensus on the most appropriate assessment procedures. Moreover, commonly used self-report measures may be affected by biases and limitations. This exploratory study aimed to investigate, using the Rorschach test, the psychological functioning of a sample of 28 Italian trans individuals hormone naive compared to a homogeneous group of 29 trans individuals under gender-affirming hormone therapy (GAHT) for at least 3 months. All participants were at least 18 years old, had a diagnosis of gender dysphoria according to DSM-5, were on a waiting list for gender-affirming surgery, and could provide informed consent. Individuals diagnosed with schizophrenia, other psychotic disorders, or moderate to severe intellectual disability were excluded. Hormone-naïve participants tended to show higher levels of coping deficits, impulsivity, and a predilection for escapist fantasies. Conversely, individuals undergoing GAHT showed higher human detail responses, more total human content, better emotional and cognitive resources for coping with daily stressors, and a significant tendency toward activity in interpersonal behaviors. At the same time, their responses suggested a form of cognitive rigidity, which may be associated with a transitional phase of psychological consolidation and defensive stabilization. Both groups showed a general tendency to avoid emotional stimuli, with particularly low affective engagement in the hormone-naïve group. These exploratory findings suggest that the Rorschach test may be a valuable tool for assessing psychological functioning during different phases of gender affirmation.

Facial emotion recognition (FER) and the jumping to conclusions (JTC) biases are well-documented in psychotic disorders and have been proposed as an intermediate phenotype for the disorder. However, their relationship with subclinical psychotic features and their longitudinal course remains unclear. This study aimed to investigate the association of FER and the JTC with psychosis vulnerability in a sample of healthy individuals, with an eight-year follow-up in a subgroup to assess long-term changes. A total of 100 healthy participants were recruited at baseline. FER and JTC were assessed at baseline using the Degraded Facial Affect Recognition (DFAR) task and the Beads task. Psychotic-like experiences (PLEs) and schizotypal traits were measured at baseline and follow-up using the Community Assessment of Psychic Experiences (CAPE) and the Structured Interview for Schizotypy-Revised (SIS-R), respectively. Longitudinal analyses were conducted in a subgroup of 17 participants after 8 years. At baseline, poorer FER and the presence of JTC were associated with a higher SIS-R positive score. Longitudinal analyses showed that baseline JTC and DFAR anger and fear were associated with an increase in negative PLEs and schizotypal traits over time. These findings support the role of facial negative emotion recognition deficits and the JTC as a potential endophenotypic marker for psychosis vulnerability. The results highlight the importance of metacognition and social cognition impairments in the development and persistence of schizotypal traits. Future research should investigate the neurobiological and environmental mechanisms underlying these associations to inform early intervention strategies.

The increasing prevalence of suicidal ideation among university students, especially those enrolled in medical and healthcare courses, necessitates innovative approaches for early detection and prevention. The southern part of Italy presents a distinct cultural, social, and economic context and is under-represented in research. This study leverages the capabilities of machine learning methods and explainable artificial intelligence (XAI) to address this challenge, developing a predictive model for suicidal thoughts within a large sample of university students in Sicily, the southernmost and largest Italian region. The XGBoost algorithm was implemented for model training on survey data from 3278 students, including sociodemographic factors, academic performance metrics, and mental health indicators such as the Depression, Anxiety, and Stress Scale short version (DASS-21) and the Eating Attitude Test short version (EAT-26). The optimized XGBoost achieved promising performance, with AUROC ranging from 0.719 to 0.808 and balanced accuracy between 0.666 and 0.780 across internal and external test sets. Probability calibration was generally reasonable (Brier 0.151–0.185; ECE 0.035–0.120), supporting the reliability of predicted risk estimates. Performance in general varied by degree program, suggesting cohort-specific characteristics. Our findings underscore the potential of machine learning models to identify at-risk students and XAI for understating model prediction, emphasizing the importance of early intervention and targeted mental health support in university settings. The model's performance and explainability highlight the potential in developing a student-centric and self-assessment framework while helping to mitigate potential ethical concerns associated with predictive mental health tools.

Background and Hypothesis Using data from the EU-GEI Work Package 2 (EU-GEI WP2) programme, we sought to test several hypotheses related to gaps in our knowledge of associations between childhood adversities and psychosis.Study Design EU-GEI WP2 comprises incidence and case-control studies of first-episode psychosis conducted in 17 sites in 6 countries. In each site, over 2-year periods, we identified and collected relevant data from individuals aged 18-64 with a first-episode psychosis and with no history of psychosis. Missing data were imputed. We used multi-level logistic regression to test our hypotheses.Study Results In total, 1071 cases and 1497 controls were included. We found variations in the prevalence and the magnitude of associations between any adversity and psychosis by place (eg, odds ratios ranged from 0.4 [Cuenca, Spain] to 12.1 [Madrid, Spain]). The weighted percentages reporting adversities in control samples were associated with site incidence rates (eg, 3+ adversities: Spearman's rho 0.56, P .025). We found variations in the magnitude of associations by sex (eg, effect of physical and sexual abuse stronger among women), by age of exposure, and by severity and frequency of adversities (eg, largest odds ratios for adversities involving hostility, threat, and violence).Conclusions Variations across populations in prevalence and effects of adversities may contribute to variations in rates of psychosis. Variations in effects by sex and age of onset may point to sex-specific mechanisms and to developmentally sensitive periods. Adversities involving severe threat, hostility, and violence may have the largest effects on risk of psychosis.

Background: Feeding and eating disorders (FEDs) are increasingly prevalent among university students, due to the combined effects of at risk age, academic stress, performance pressure, and societal expectations regarding body image. The SMS‑ME (Sicilian Medical Students’ Mental Health) project aimed to assess the prevalence and predictors of disordered eating behaviors, as well as preferred mental‑health support strategies, in an underrepresented group in the literature: Sicilian university students enrolled in healthcare degree programs Methods: A cross-sectional web-based survey was conducted between 2022 and 2024 across multiple Sicilian universities. The questionnaire included sociodemographic data, the EAT-26 scale, DASS-21, and behavioral items assessing binge eating, vomiting, laxative use, and suicidal ideation. Stepwise regression analysis was used to identify predictors of disordered eating. Results: We collected 3,278 participants. Despite most students having a normal BMI, many reported significant body dissatisfaction and unhealthy weight control behaviors. 14.1% scored above the EAT-26 threshold, indicating risk for FEDs, and 38.2% met criteria for specialist referral. Key predictors included vomiting episodes, psychological distress, lifetime weight fluctuation, laxative use, weight dissatisfaction, binge eating, female sex, younger age, and suicidal ideation. The model explained 32% of the variance in EAT-26 scores. Conclusions: Healthcare students in Sicily exhibited high levels of psychological distress and disordered eating behaviors, underscoring the need for targeted mental health interventions. Universities should prioritize early detection, stigma-free psychological support, and the integration of mental health resources, such as mentoring programs and self-monitoring tools, within academic environments to support student well-being.

Objective: Psychotic disorders are heterogeneous in their clinical presentation and outcome. While early research focused on poor prognoses in schizophrenia, recent longitudinal studies tracking first-episode psychosis (FEP) have identified more favourable outcome trajectories. This study investigates the stability and predictive value of metacognitive and social cognitive impairments-Jumping to Conclusions (JTC) bias and Facial Emotion Recognition (FER) deficits-as intermediate phenotypes of psychosis over a 5-year follow-up period. Method: A total of 134 FEP patients and 105 population-based controls from the GAP and EU-GEI follow-up study in London were reassessed after an average of 4.8 years. JTC was measured using the 60:40 Beads task, while FER was assessed through the Degraded Facial Affect Recognition (DFAR) task Clinical, functional, and social outcomes-including hospital admissions, symptom severity, and employment status-were evaluated. Mixed models and regression modeling examined the stability of these cognitive traits and their association with long-term outcomes. Results: JTC and FER impairments remain stable over time, supporting their classification as intermediate phenotypes. However, neither JTC nor FER was associated with clinical outcomes (hospitalization rates, symptom severity) or social functioning (employment, independent living, relationships). A weak correlation was found between global FER impairment and negative symptoms at follow-up, but no associations emerged with real-world functional measures. Additionally, while patients demonstrated greater impairments than controls, the differences were more quantitative than qualitative, aligning with the psychosis continuum hypothesis. Conclusions: These findings demonstrate that JTC and FER are stable in people with psychosis and controls. Therefore, they may serve as important treatment targets for early intervention in psychosis. Future research should integrate the potential role of environmental factors as well as genetic influence to deepen our understanding of cognitive impairments in psychotic disorders.

Introduction Evidence suggests that childhood maltreatment affects cognitive performance in both patients with psychosis and community controls. However, the interplay between childhood maltreatment, post-traumatic stress symptoms (PTSS), and intelligence has not been investigated. This study investigated the relationship between childhood maltreatment, subclinical PTSS, and intelligence among patients with first-episode psychosis (FEP) and community controls.Methods Patients with FEP (N = 602) and controls (N = 853) from the EU-GEI study were assessed for childhood maltreatment, PTSS, and intelligence quotient (IQ).Results PTSS were associated with lower IQ among community controls but not among patients with FEP. In the FEP group, an interaction (p = 0.044) between PTSS and childhood maltreatment on IQ was found, such that the association between PTSS and lower IQ was only present among those exposed to childhood maltreatment. No interaction was evident in controls (p = 0.826).Conclusions The findings suggest the relevance of cognitive rehabilitation for FEP patients with childhood maltreatment and PTSS.

BACKGROUND:Previous studies identified clusters of first-episode psychosis (FEP) patients based on cognition and premorbid adjustment. This study examined a range of socio-environmental risk factors associated with clusters of FEP, aiming a) to compare clusters of FEP and community controls using the Maudsley Environmental Risk Score for psychosis (ERS), a weighted sum of the following risks: paternal age, childhood adversities, cannabis use, and ethnic minority membership; b) to explore the putative differences in specific environmental risk factors in distinguishing within patient clusters and from controls. METHODS:A univariable general linear model (GLS) compared the ERS between 1,263 community controls and clusters derived from 802 FEP patients, namely, low (n = 223) and high-cognitive-functioning (n = 205), intermediate (n = 224) and deteriorating (n = 150), from the EU-GEI study. A multivariable GLS compared clusters and controls by different exposures included in the ERS. RESULTS:The ERS was higher in all clusters compared to controls, mostly in the deteriorating (β=2.8, 95% CI 2.3 3.4, η2 = 0.049) and the low-cognitive-functioning cluster (β=2.4, 95% CI 1.9 2.8, η2 = 0.049) and distinguished them from the cluster with high-cognitive-functioning. The deteriorating cluster had higher cannabis exposure (meandifference = 0.48, 95% CI 0.49 0.91) than the intermediate having identical IQ, and more people from an ethnic minority (meandifference = 0.77, 95% CI 0.24 1.29) compared to the high-cognitive-functioning cluster. CONCLUSIONS:High exposure to environmental risk factors might result in cognitive impairment and lower-than-expected functioning in individuals at the onset of psychosis. Some patients' trajectories involved risk factors that could be modified by tailored interventions.

Objectives: To establish whether the risk of psychotic disorders in cannabis users changes with time following cannabis cessation using data from the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI) case-control study. Methods: The EU-GEI case-control study collected data from first episode psychosis patients and population controls across sites in Europe and Brazil between May 2010 and April 2015. Adjusted logistic regressions were applied to examine whether the odd of psychosis case status changed: (1) with time following cannabis cessation and (2) across different cannabis use groups. Results: Psychosis risk declined following cessation of cannabis use (beta = -0.002; 95% CI -0.004 to 0.000; P = 0.067). When accounting for duration of use, this effect remained (beta = -0.003; 95% CI -0.005 to -0.001; P = 0.013). However, in models adjusting for frequency and potency of use the result was not significant. Analysis of different cannabis use groups indicated that ex-users who stopped 1 to 4 weeks previously had the highest risk for psychotic disorder compared to never users (OR = 6.89; 95% CI 3.91-12.14; P < 0.001); risk declined for those who stopped 5 to 12 weeks previously (OR = 2.70; 95% CI 1.73-4.21; P < 0.001) and 13 to 36 weeks previously (OR = 1.53; 95% CI 1.00-2.33; P = 0.050). Ex-users who stopped 37 to 96 weeks (OR = 1.01; 95% CI 0.66-1.57; P = 0.949), 97 to 180 weeks (OR = 0.73; 95% CI 0.45-1.19; P = 0.204), and 181 weeks previously or more (OR = 1.18; 95% CI 0.76-1.83; P = 0.456) had similar psychosis risk to those who had never-used cannabis. Conclusion: Risk of psychotic disorder appears to decline with time following cannabis cessation, receding to that of those who have never used cannabis after 37 weeks or more of abstinence. Although, preliminary results suggest that frequent users of high potency types of cannabis might maintain an elevated risk compared to never users even when abstaining for longer than 181 weeks.

Cognitive impairment is a common feature of schizophrenia, particularly affecting attention, memory, and executive functions. Early identification and remediation of cognitive impairments can enhance outcomes and well-being. This study investigates the efficacy and specificity of a novel training program based on a Virtual Reality environment aimed at remediating visuospatial memory, focused and sustained attention, working memory, and reasoning skills. Twenty-eight individuals diagnosed with schizophrenia were enrolled in a randomized controlled trial and allocated to either an experimental group and a control group. Pre- and post-intervention assessments measured cognitive performance. Results suggest that VR-based cognitive training offers a promising, immersive approach to cognitive rehabilitation.

INTRODUCTION:Suicidal ideation is common among individuals with first episode psychosis (FEP), with prevalence estimates up to 56.5 %. Despite its high prevalence, relatively little is known about how sociodemographic, clinical and/or developmental characteristics contribute to the experience of suicidal ideation in individuals with FEP. METHODS:In this cross-sectional study (FEP n = 551 and controls n = 857), univariate logistic regression analyses were performed to study the associations of sociodemographic, clinical, and developmental factors with suicidal ideation in individuals with FEP as well as controls. Suicidal ideation was assessed using the Community Assessment of Psychic Experiences (CAPE). In addition, multivariate logistic regression analyses were conducted based on a stepwise approach. RESULTS:In FEP, only depressive symptoms remained significantly associated with suicidal ideation when all correlates were integrated into one model. In the multivariate model in controls, depressive symptoms, positive symptoms, and traumatic childhood experiences were significantly associated with suicidal ideation. CONCLUSIONS:This study showed that depressive symptoms are an important factor relating to suicidal ideation in individuals with FEP, over and above other clinical, sociodemographic, and developmental factors. This underscores the relevance of screening for suicidal ideation in individuals with FEP, and highlights the need for a better understanding of the diagnostic uncertainty and course of mood symptoms in early psychosis. LIMITATIONS:Cross-sectional study design, self-reported questionnaires.

Background We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.Methods We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.Results The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53).Conclusions The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Introduction: Several studies have investigated the specific neural correlates of trans people, highlighting mixed results. This study aimed to compare the presence of specific functional connectivity and differences in cognitive profile and hormone levels in trans men diagnosed with gender dysphoria (GD), and a homogeneous group of cisgender men and cisgender women. Methods: A total of 42 participants (19 trans men, 11 cisgender men, and 12 cisgender women) underwent a resting state fMRI and were measured for blood levels of testosterone, estradiol, and progesterone. A neuropsychological battery evaluated executive functions, attention, visual-perceptual ability, verbal fluency, manual preference, and general intelligence. Results: Trans men showed weaker functional connectivity in the precentral gyrus, subcallosal cortex, paracingulate gyrus, temporal pole, and cingulate gyrus than cisgender men (p < 0.01). Trans men performed worse than cisgender men in verbal and visuospatial working memory but similarly to cisgender women (p < 0.05). In trans men, functional connectivity of the precentral gyrus correlated positively with testosterone (r = 0.459, p = 0.064) and negatively with estradiol (r = -0.654, p = 0.004) and progesterone blood levels (r = -0.475, p = 0.054). The cluster involving the subcallosal cortex showed a positive correlation with testosterone (r = 0.718, p = 0.001), and a negative correlation with estradiol (r = -0.602, p = 0.011). The functional connectivity from a cluster involving the paracingulate gyrus showed a positive correlation with testosterone (r = 0.592, p = 0.012). Conclusions: This study highlights the importance of overpassing the binary model by underlining the presence of neural pathways that could represent the peculiarity of the neural profile of people with GD.

Background Multiple genetic and environmental risk factors play a role in the development of both schizophrenia-spectrum disorders and affective psychoses. How they act in combination is yet to be clarified.Methods We analyzed 573 first episode psychosis cases and 1005 controls, of European ancestry. Firstly, we tested whether the association of polygenic risk scores for schizophrenia, bipolar disorder, and depression (PRS-SZ, PRS-BD, and PRS-D) with schizophrenia-spectrum disorder and affective psychosis differed when participants were stratified by exposure to specific environmental factors. Secondly, regression models including each PRS and polyenvironmental measures, including migration, paternal age, childhood adversity and frequent cannabis use, were run to test potential polygenic by polyenvironment interactions.Results In schizophrenia-spectrum disorder vs controls comparison, PRS-SZ was the strongest genetic predictor, having a nominally larger effect in nonexposed to strong environmental factors such as frequent cannabis use (unexposed vs exposed OR 2.43 and 1.35, respectively) and childhood adversity (3.04 vs 1.74). In affective psychosis vs controls, the relative contribution of PRS-D appeared to be stronger in those exposed to environmental risk. No evidence of interaction was found between any PRS with polyenvironmental score.Conclusions Our study supports an independent role of genetic liability and polyenvironmental risk for psychosis, consistent with the liability threshold model. Whereas schizophrenia-spectrum disorders seem to be mostly associated with polygenic risk for schizophrenia, having an additive effect with well-replicated environmental factors, affective psychosis seems to be a product of cumulative environmental insults alongside a higher genetic liability for affective disorders.

Background: Numerous studies have investigated prognostic and preoperative factors associated with the outcomes of bariatric surgery in terms of weight loss. Nonetheless, postoperative factors influencing weight loss are less clear. Therefore, this work aims to provide a comprehensive overview of the literature on postoperative behavioural and psychological predictors of weight loss outcomes following bariatric surgery. Methods: The scoping review was conducted following the Arksey and O’Malley framework. Searches were conducted on PubMed, Springer, Google Scholar, Science Direct, and Cochrane Library for data between January 2010 and December 2020. The focus was on postoperative predictors of weight loss and regain one year after bariatric surgery. Results: The literature search yielded 462 unique records, with 220 articles eliminated based on irrelevant titles and/or abstracts. A total of 242 full-text articles were reviewed, and ultimately, 28 articles were included in this scoping review. Three major postoperative areas emerged: eating behaviour, adherence to professional recommendations, and psychological disorders. Conclusions: Follow-up strategies after bariatric surgery should include assessing the patient's strengths and weaknesses to offer tailored behavioural recommendations. Additionally, encouraging the search for proper formal support when needed is crucial for long-term success.

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1 gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localised in the MCU gene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure.

BACKGROUND:The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis. METHODS:Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use. RESULTS:In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08-8.43, p = 3.21 × 10-10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use. CONCLUSIONS:Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.

We examined the feasibility of using the neofunctional deep breathing (NDB) technique to reduce the allostatic load following the Trier Social Stress Test (TSST). Forty-four healthy subjects were randomised into experimental and control groups. Following the TSST procedure, participants underwent either a single session of NDB or an attention control intervention. The Procomp Infinity Biofeedback system measured breath per minute (BPM), respiratory amplitude, HRV linear domains, skin conductance, and trapezius muscle electromyographic activity. Cortisol and cytokine salivary concentrations, perceived stress, and anxiety levels were also assessed. These parameters were combined into an allostatic load index (ALI) to measure the intervention's effect. This pilot RCT demonstrated the feasibility of the study design and practicality of the intervention. The NDB group showed reduced ALI, increased respiratory abdominal amplitude, decreased BPM, increased HRV indicating parasympathetic activation, and decreased cortisol and inflammatory cytokines. This study highlighted the feasibility of testing the NDB technique in reducing allostatic load through a neurobiological and anti-inflammatory response after exposure to psychosocial stress. This protocol can represent a non-invasive therapeutic adjutant in disorders related to a dysregulation of the HPA axis or to an inflammatory state. Trial Registration: NCT04102813We examined the feasibility of using the neofunctional deep breathing (NDB) technique to reduce the allostatic load following the Trier Social Stress Test (TSST). Forty-four healthy subjects were randomised into experimental and control groups. Following the TSST procedure, participants underwent either a single session of NDB or an attention control intervention. The Procomp Infinity Biofeedback system measured breath per minute (BPM), respiratory amplitude, HRV linear domains, skin conductance, and trapezius muscle electromyographic activity. Cortisol and cytokine salivary concentrations, perceived stress, and anxiety levels were also assessed. These parameters were combined into an allostatic load index (ALI) to measure the intervention's effect. This pilot RCT demonstrated the feasibility of the study design and practicality of the intervention. The NDB group showed reduced ALI, increased respiratory abdominal amplitude, decreased BPM, increased HRV indicating parasympathetic activation, and decreased cortisol and inflammatory cytokines. This study highlighted the feasibility of testing the NDB technique in reducing allostatic load through a neurobiological and anti-inflammatory response after exposure to psychosocial stress. This protocol can represent a non-invasive therapeutic adjutant in disorders related to a dysregulation of the HPA axis or to an inflammatory state. Trial Registration: NCT04102813

Background Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP.Methods We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately.Results Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia.Conclusions Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.

Background. Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls. Methods. We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables. Results. FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123-2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368-0.997 and OR = 0.646, CI 0.457-0.913 respectively) and JTC bias (OR = 0.625, CI 0.422-0.925 and OR = 0.602, CI 0.460-0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297-2.578, FRP deficits (OR = 1.393, CI 1.031-1.882, and JTC (OR = 1.661, CI 1.271-2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups. Conclusions. Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.