Risk For Psychosis Research Articles

Synaptic Density in Early Stages of Psychosis and Clinical High Risk.

Synaptic dysfunction is involved in schizophrenia pathophysiology. However, whether in vivo synaptic density is reduced in early stages of psychosis, including its high-risk states, remains unclear. To investigate whether synaptic density (synaptic vesicle glycoprotein 2A [SV2A] binding potential) is reduced in first-episode psychosis (FEP) and in clinical high risk (CHR) and investigate the effect of cannabis use on synaptic density and examine its relationship with psychotic symptoms and gray matter microstructure across groups. This cross-sectional study was performed in a tertiary care psychiatric hospital from July 2021 to October 2023. Participants were patients with antipsychotic-free or minimally exposed FEP or CHR and healthy controls with a clean urine drug screen (except cannabis). Synaptic density was quantified with dynamic 90-minute [18F]SynVesT-1 positron emission tomography (PET) scans across prioritized brain regions of interest (ROIs) delineated in individual magnetic resonance images (MRIs). Cannabis use was confirmed with urine drug screens. Gray matter microstructure was assessed using diffusion-weighted MRI to estimate neurite density. A total of 49 participants were included, including 16 patients with FEP (mean [SD] age, 26.1 [4.6] years; 9 males and 7 females), 17 patients at CHR (mean [SD] age, 21.2 [3.5] years; 8 males and 9 females), and 16 healthy controls (mean [SD] age, 23.4 [3.6] years; 7 males and 9 females). Synaptic density was significantly different between groups (F2,273 = 4.02, P = .02, Cohen F = 0.17; ROI: F5,273 = 360.18, P < .01, Cohen F = 2.55) with a group × ROI interaction (F10,273 = 2.67, P < .01, Cohen F = 0.32). Synaptic density was lower in cannabis users (F1,272 = 5.31, P = .02, Cohen F = 0.14). Lower synaptic density across groups was associated with more negative symptoms (Positive and Negative Syndrome Scale negative scores: F1,81 = 4.31, P = .04, Cohen F = 0.23; Scale of Psychosis-Risk Symptoms negative scores: F1,90 = 4.12, P = .04, Cohen F = 0.21). SV2A binding potential was significantly associated with neurite density index (F1,138 = 6.76, P = .01, Cohen F = 0.22). This study found that synaptic density reductions were present during the early stages of psychosis and its risk states and associated with negative symptoms. The implications of SV2A for negative symptoms in psychosis and CHR warrant further investigation. Future studies should investigate the impact of cannabis use on synaptic density in CHR longitudinally.

Emergency Department Visits Involving Hallucinogen Use and Risk of Schizophrenia Spectrum Disorder.

Interest in and use of hallucinogens has been increasing rapidly. While a frequently raised concern is that hallucinogens may be associated with an increased risk of psychosis, there are limited data on this association. To examine whether individuals with an emergency department (ED) visit involving hallucinogen use have an increased risk of developing a schizophrenia spectrum disorder (SSD). This population-based, retrospective cohort study (January 2008 to December 2021) included all individuals aged 14 to 65 years in Ontario, Canada, with no history of psychosis (SSD or substance induced). Data were analyzed from May to August 2024. An incident ED visit involving hallucinogen use. Diagnosis of SSD using a medical record-validated algorithm. Associations between ED visits involving hallucinogens and SSD were estimated using cause-specific adjusted hazard models. Individuals with an incident ED visit involving hallucinogens were compared with members of the general population (primary analysis) or individuals with ED visits involving alcohol or cannabis (secondary analysis). The study included 9 244 292 individuals (mean [SD] age, 40.4 [14.7] years; 50.2% female) without a history of psychosis, with a median follow-up of 5.1 years (IQR, 2.3-8.6 years); 5217 (0.1%) had an incident ED visit involving hallucinogen use. Annual rates of incident ED visits involving hallucinogens were stable between 2008 and 2012 and then increased by 86.4% between 2013 and 2021 (3.4 vs 6.4 per 100 000 individuals). Individuals with ED visits involving hallucinogens had a greater risk of being diagnosed with an SSD within 3 years compared with the general population (age- and sex-adjusted hazard ratio [HR], 21.32 [95% CI, 18.58-24.47]; absolute proportion with SSD at 3 years, 208 of 5217 with hallucinogen use [3.99%] vs 13 639 of 9 239 075 in the general population [0.15%]). After adjustment for comorbid substance use and mental health conditions, individuals with hallucinogen ED visits had a greater risk of SSD compared with the general population (HR, 3.53; 95% CI, 3.05-4.09). Emergency department visits involving hallucinogens were associated with an increased risk of SSD within 3 years compared with ED visits involving alcohol (HR, 4.66; 95% CI, 3.82-5.68) and cannabis (HR, 1.47; 95% CI, 1.21-1.80) in the fully adjusted model. In this cohort study, individuals with an ED visit involving hallucinogen use had a greater risk of developing an SSD compared with both the general population and with individuals with ED visits for other types of substances. These findings have important clinical and policy implications given the increasing use of hallucinogens and associated ED visits.

Ruminative thinking mediates the effects of exposure to adverse life events on psychotic-like experiences

Introduction:A growing literature has shown that exposure to adverse life events during childhood or adolescence is associated with the presence of psychotic-like experiences (PLEs), which is in turn associated with the risk of psychotic outcomes. Ruminative thinking, i.e., the tendency to dwell on particular issues or ideas, may affect the perceived aversiveness and ability to cope with adverse life events. However, the role that rumination plays in the relationship between adverse life events and the presence of PLEs remains unclear. The purpose of this study is to assess the association between adverse life events and PLEs in a longitudinal sample of young adults and adolescents, and to investigate whether this relationship is mediated by ruminative thinking.MethodsWe used a longitudinal naturalistic sample of 706 volunteers assessed at ages 18 and 22 years, within the Imagen consortium. Lifetime occurrence of adverse life events (i.e., events perceived as strongly negative by participants) was investigated using the Life Events Questionnaire. The Community Assessment of Psychic Experience (CAPE-42) served to assess the presence of PLEs, while ruminative thinking was investigated through the Ruminative Response Scale.ResultsResults showed that both frequency of PLEs and their persistence over time were associated with greater adverse life events exposure (r = 0.32, p &amp;lt; 0.001 and F1 = 9.8; p &amp;lt; 0.001, respectively) and greater ruminative response (r = 0.66, p &amp;lt; 0.001 and F1 = 94.9; p &amp;lt; 0.001, respectively). Mediation analyses showed that relationship between adverse life events and PLEs frequency was partially mediated by rumination (direct effect Z: 5.4, p &amp;lt; 0.001; indirect effect Z: 6.9, p &amp;lt; 0.001; total effect Z: 5.9, p &amp;lt; 0.001). Considering changes between the two assessment timepoints, relationship between PLEs variation between 18 and 22 years and adverse life events occurred during the same period was partially mediated by changes in rumination (direct effect Z: 2.8, p &amp;lt; 0.005; indirect effect Z: 4.3, p &amp;lt; 0.001; total effect Z: 4.3; p &amp;lt; 0.001).DiscussionOverall, our findings confirm that the presence of adverse life events may increase the risk of experiencing PLEs in healthy individuals and suggest that dysfunctional coping strategies, such as ruminative thinking, may be related to psychosis proneness. Results do not disentangle whether individuals with greater risk for psychosis tend to ruminate more or whether rumination exacerbates psychosis risk.

Psychotic-like Experiences and Underlying Mechanisms: An Integrative Model of ADHD Symptoms, Rumination, Negative Affect, and Trauma Experience

Background: Psychotic-like experiences (PLEs) are low-intensity subclinical phenomena, often transient in nature. The etiology of PLEs primarily involves neurodevelopmental changes, trauma exposure, and maladaptive coping styles. Attention-Deficit/Hyperactivity Disorder (ADHD) is considered to be one of the factors that increase the risk of future psychosis. Furthermore, ADHD symptoms predict a heightened incidence of traumatic experiences, ruminative thoughts, and negative affect (NA). This present study examines whether rumination and NA mediate the relationship between ADHD symptoms and PLEs and whether trauma experiences moderate these pathways. Methods: A total of 188 participants (72% female) aged 18–35 completed questionnaires assessing ADHD symptoms and traumatic experiences and took part in a seven-day experience sampling method (ESM) procedure, completing ratings of PLEs experiences, the intensity of ruminations, and NA. Results: Correlation analysis showed significant relationships between all tested variables. Serial mediation analysis revealed a significant indirect effect of rumination and NA in the link between ADHD symptoms and PLEs. There was no significant impact of trauma experience in this relationship. Conclusions: Our study underscores the important role of rumination and NA in the co-development of ADHD symptoms and PLEs. Future research should consider investigating the intra-individual dynamics of ADHD and trauma using ecologically valid research methods in the context of PLEs to better understand these complex relationships.

Psychosis Spectrum Symptoms Before and After Adolescent Cannabis Use Initiation

Adolescent cannabis use has been consistently posited to contribute to the onset and progression of psychosis. However, alternative causal models may account for observed associations between cannabis use and psychosis risk, including shared vulnerability for both cannabis use and psychosis or efforts to self-medicate distress from psychosis spectrum symptomology. To test 3 hypotheses that may explain cannabis-psychosis risk associations by modeling psychosis spectrum symptom trajectories prior to and after cannabis initiation across adolescent development (approximately 10-15 years of age). This cohort study used data from 5 waves across 4 years of follow-up from the Adolescent Brain Cognitive Development (ABCD) Study. The ABCD study is an ongoing large-scale, longitudinal study of brain development and mental and physical health of children in the US launched in June 2016. Data are collected from 21 research sites. The study included data from 11 868 adolescents aged 9 to 10 years at baseline. Three participants were excluded from the present analysis owing to missing data. Data analysis was performed from September 2023 to July 2024. Discontinuous growth curve modeling was used to assess trajectories of psychosis spectrum symptoms before and after cannabis initiation. Control variables considered for this investigation were age, sex, internalizing and externalizing symptoms, socioeconomic status, parental mental health, and other substance use. Among the 11 858 participants at wave 1, the mean (SD) age was 9.5 (0.5) years; 6182 (52%) participants were male. Consistent with a shared vulnerability hypothesis, adolescents who used cannabis at any point during the study period reported a greater number of psychosis spectrum symptoms (B, 0.86; 95% CI, 0.68-1.04) and more distress (B, 1.17; 95% CI, 0.96-1.39) from psychosis spectrum symptoms relative to those who never used cannabis. Additionally, consistent with a self-medication hypothesis, the number of psychosis spectrum symptoms (B, 0.16; 95% CI, 0.12-0.20) and distress (B, 0.23; 95% CI, 0.21-0.26) from psychosis spectrum symptoms increased in the time leading up to cannabis initiation. We observed mixed evidence for an increase in psychosis symptoms after cannabis initiation (ie, contributing risk hypothesis). The findings underscore the importance of accounting for shared vulnerability and self-medication effects when modeling cannabis-psychosis risk associations.

Attention Deficit Hyperactivity Disorder among Youth at Clinical High Risk of Psychosis

Abstract Background Attention Deficit Hyperactivity Disorder (ADHD) affects a significant proportion of the population and is associated with numerous adverse outcomes including lower educational attainment, occupational challenges, increased substance use, and various mental health issues including psychosis. This study examined the demographic, clinical, cognitive, social cognitive and functional differences between youth at clinical high-risk (CHR) for psychosis with and without co-morbid ADHD. Method Data was drawn from the North American Prodrome Longitudinal Studies (NAPLS2 and NAPLS3), which included 764 and 710 CHR individuals, respectively. After applying exclusion criteria, the sample consisted of 271 CHR participants with ADHD and 1118 without ADHD. All data was examined cross-sectionally. Results Compared to the non-ADHD group, the ADHD group was younger, had more difficulties with role functioning, premorbid functioning, social cognition, were more likely to have a co-morbid learning disorder and reported less depression symptoms. There were no significant differences between the groups on positive or negative psychotic symptoms, transition rates, adverse events, or other co-morbid disorders including substance use and depression. Discussion Co-morbid ADHD is likely not a significant predictor of transition to psychosis among CHR youth, however those CHR with ADHD may experience symptoms at a younger age than those without and present with a distinct clinical profile.

Protective Factors Predict Resilient Outcomes in Clinical High-Risk Youth with the Highest Individualized Psychosis Risk Scores.

Studying individuals at Clinical High Risk (CHR) for psychosis provides an opportunity to examine protective factors that predict resilient outcomes. Here, we present a model for the study of protective factors in CHR participants at the very highest risk for psychotic conversion based on the Psychosis Risk Calculator. CHR participants (N = 572) from NAPLS3 were assessed on the Risk Calculator. Those who scored in the top half of the distribution and had 2 years of follow-up (N = 136) were divided into those who did not convert to psychosis (resilient, N = 90) and those who did (nonresilient, N = 46). Groups were compared based on candidate protective factors that were not part of the Risk Calculator. Better functional outcome was also examined as an outcome measure of resiliency. Study Results: Exploratory analyses suggest that Hispanic heritage, social engagement, desirable life experiences, premorbid functioning and IQ are all potential protective factors that predict resilient outcomes. Reduced startle reactivity, brain area and volume were also associated with greater resilience. The primary focus of CHR research has been the risk and prediction of psychosis, while less is known about protective factors. Clearly, a supportive childhood environment, positive experiences, and educational enrichment may contribute to better premorbid functioning and brain development, which in turn contribute to more resilient outcomes. Therapies focused on enhancing protective factors in the CHR population are logical preventive interventions that may benefit this vulnerable population. Future CHR research might use similar models to develop a "protective index" to predict resilient outcomes.

Regulatory Landscape of Cannabis Warning Labels in US States with Legal Retail Nonmedical Cannabis, 2024.

Objectives. To characterize regulatory practices related to nonmedical cannabis warning labels in states across the United States that have legalized retail nonmedical cannabis. Methods. In March 2024, we conducted a content analysis of regulations for nonmedical cannabis warning labels required on product packages in 20 states where, as of March 2024, adults could legally purchase nonmedical cannabis in retail environments. For each state, we examined requirements related to warning label content and characteristics. Results. Required warning label content and characteristics varied widely across states. Only 2 states required a warning about mental health risks (10%) and 2 states required a warning for high potency products on risk of psychosis (10%). No states required front-of-package warning placement, only 2 states required rotating warnings (10%), and 4 states required contrasting colors (20%). Warnings were often verbose (mean = 57 words), vague, and had small or no minimum font size. Conclusions. Opportunities exist for states to improve the alignment of their nonmedical cannabis warning label regulations with evidence that has been generated so far in cannabis effects, cannabis warning efficacy, and warning label design. (Am J Public Health. 2024;114(S8):S681-S684. https://doi.org/10.2105/AJPH.2024.307722).

Recent Insights in the Treatment for Clinical High Risk for Psychosis and Recent Onset Psychosis

Objectives: This study aims to assess the effectiveness of early interventions in preventing psychosis transition, promoting remission, and reducing hospitalization rates in individuals at high risk for psychosis and those with recent onset psychosis (ROP).Methods: A systematic review and meta-analysis were conducted, comparing early intervention strategies such as cognitive-behavioral therapy and psychosocial support to no intervention. The study focused on outcomes related to psychosis transition, remission rates, and prevention of psychiatric hospitalization.Results: Although only a subset of clinical high risk (CHR) individuals transition to full psychosis, non-pharmacological treatments like cognitive-behavioral therapy are generally recommended as a first-line approach. In ROP patients, early pharmacological treatment reduces relapse rates, while psychosocial interventions aim to improve various functional outcomes. The meta-analysis results of this study did not show a significant reduction in psychosis transition rates with specialized interventions for CHR patients. For ROP patients, early interventions initially reduced hospitalization rates, but this effect was not sustained in mid-term follow-up results.Conclusion: While early interventions offer short-term benefits in reducing psychosis transition and hospitalization, additional research is needed to determine their long-term effectiveness in functional recovery and overall patient outcomes.

Personality changes during adolescence predict young adult psychosis proneness and mediate gene-environment interplays of schizophrenia risk.

Psychotic symptoms in adolescence are associated with social adversity and genetic risk for schizophrenia. This gene-environment interplay may be mediated by personality, which also develops during adolescence. We hypothesized that (i) personality development predicts later Psychosis Proneness Signs (PPS), and (ii) personality traits mediate the association between genetic risk for schizophrenia, social adversities, and psychosis. A total of 784 individuals were selected within the IMAGEN cohort (Discovery Sample-DS: 526; Validation Sample-VS: 258); personality was assessed at baseline (13-15 years), follow-up-1 (FU1, 16-17 years), and FU2 (18-20 years). Latent growth curve models served to compute coefficients of individual change across 14 personality variables. A support vector machine algorithm employed these coefficients to predict PPS at FU3 (21-24 years). We computed mediation analyses, including personality-based predictions and self-reported bullying victimization as serial mediators along the pathway between polygenic risk score (PRS) for schizophrenia and FU3 PPS. We replicated the main findings also on 1132 adolescents recruited within the TRAILS cohort. Growth scores in neuroticism and openness predicted PPS with 65.6% balanced accuracy in the DS, and 69.5% in the VS Mediations revealed a significant positive direct effect of PRS on PPS (confidence interval [CI] 0.01-0.15), and an indirect effect, serially mediated by personality-based predictions and victimization (CI 0.006-0.01), replicated in the TRAILS cohort (CI 0.0004-0.004). Adolescent personality changes may predate future experiences associated with psychosis susceptibility. PPS personality-based predictions mediate the relationship between PRS and victimization toward adult PPS, suggesting that gene-environment correlations proposed for psychosis are partly mediated by personality.

Effectiveness of Omega-3 Fatty Acids Versus Placebo in Subjects at Ultra-High Risk for Psychosis: The PURPOSE Randomized Clinical Trial.

In the past 2 decades, substantial effort has been put into research on therapeutic options for people at ultra-high risk (UHR) for developing a first episode of psychosis (FEP), focusing on omega-3 polyunsaturated fatty acids (PUFAs) in preventing transition to psychosis. Despite an initial positive finding, subsequent studies failed to find a beneficial effect. The current study aimed to further investigate the effect of omega-3 PUFAs in UHR, to determine whether this line of research is worth pursuing. A double-blind, randomized, placebo-controlled study testing the efficacy of 6-month treatment with omega-3 PUFAs in 135 subjects at UHR for FEP, aged 13 to 20 years on the prevention of a transition to psychosis, followed up for 18 months post-treatment. The trial was conducted at 16 general hospitals and psychiatric specialty centers located in 8 European countries and Israel. There was no beneficial effect of treatment with omega-3 PUFAs compared to placebo; the rate of transition over 2 years did not differ between treatment arms nor was there a difference in change in symptom severity after 6-month treatment. Dropout rates and serious adverse events were similar across the groups. This is the third study that fails to replicate the original finding on the protective effect of omega-3 PUFAs in UHR subjects for transition to psychosis. The accumulating evidence therefore suggests that omega-3 PUFAs do not reduce transition rates to psychosis in those at increased risk at 2 years follow-up. This trial is registered with ClinicalTrials.gov (NCT02597439; Study Details | Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe | ClinicalTrials.gov).

Suicidal thinking and behavior in young people at Clinical High Risk for Psychosis: Psychopathological considerations and treatment response across a 2-year follow-up study.

Suicidal ideation has high rates among individuals at Clinical High Risk for Psychosis (CHR-P). CHR-P mental states are currently defined as attenuated psychotic symptoms, brief intermittent psychotic symptoms, or genetic risk and functioning deterioration syndrome. However, the relationship between psychotic experiences and suicidality in CHR-P subjects is still not fully understood. Research emphasizes the need to address suicidality in CHR-P individuals due to its incidence and severe socio-economic impact. This study aimed to assess the baseline prevalence and 2-year incidence rates of suicidal thinking and behaviors in an Italian CHR-P sample, investigate the stability of suicidal ideation over 2 years, and examine its associations with treatment outcomes, sociodemographic characteristics, and clinical factors. CHR-P participants were treated in an "Early Intervention in Psychosis" program and completed the PANSS and the GAF scale at baseline and every 12 months. 180 CHR-P individuals were enrolled (92 with suicidal ideation [SI+]). SI+ subjects had a higher baseline prevalence of past suicide attempts. Over 2 years, a decrease in suicidal ideation severity was observed in the total group. Longitudinal improvement in disorganized symptoms was a key predictor of the decrease in suicidal ideation. Participants with a history of suicide attempts were more likely to attempt again. Addressing disorganization is crucial for suicide prevention in the CHR-P population. Continuous risk monitoring and preventive actions are needed for those with past suicide attempts.

“Ask” or “Inquire”: operationalizing speech formality in psychosis and its risk states using etymology

Many individuals with psychotic symptoms have less complex language than healthy individuals. Word etymology is a lexical feature that has not yet been studied in clinical populations, but among healthy individuals, words of Old French origin are chosen over Germanic-origin words to convey formality (e.g. “inquire” vs. “ask”). Differences in language complexity among individuals with psychotic symptoms may relate to differences in etymological content in speech. Here, we determined the proportion of Germanic-origin word use and Old-French-origin word use in a large cohort of individuals with recent-onset psychosis or at clinically high risk for psychosis, hypothesizing that individuals with recent onset psychosis would have increased use of Germanic-origin words and decreased use of Old-French-origin words. This hypothesis was borne out, even after adjusting for sex, age, recruitment site, education, racial identity, and for a subset, IQ. Etymology proportions were associated with role but not social functioning in individuals with psychotic symptoms, consistent with the premise that they reflect speech formality. Understanding speech differences in the psychosis spectrum through the lens of etymology may lead to new interventions to improve role functioning.

Exploring the Interactions Between Psychotic Symptoms, Cognition, and Environmental Risk Factors: A Bayesian Analysis of Networks.

Psychotic disorders (PDs) have huge personal and societal impact, and efforts to improve outcomes in patients are continuously needed. Environmental risk factors (ERFs), especially modifiable risk factors, are important to study because they pose a target for intervention and prevention. No studies have investigated ERFs, cognition, and psychotic symptoms together in a network approach. We explored interactions between 3 important ERFs (tobacco smoking, cannabis use, and childhood trauma), 6 cognitive domains, and 3 dimensions of symptoms in psychosis. From the Genetic Risk and Outcome of Psychosis (GROUP) cohort, we used data from patients, siblings, and healthy controls to construct networks using Bayesian analyses of all 12 variables. We constructed networks of the combined sample and of patients and siblings separately. We found that tobacco smoking was directly associated with cognition and psychotic symptoms. The cognitive variable processing speed was the most central node, connecting clusters of psychotic symptoms and substance use through the variables of positive symptoms and tobacco smoking. Comparing the networks of patients and siblings, we found that networks were relatively similar between patients and siblings. Our results support a potential central role of processing speed deficits in PDs. Findings highlight the importance of integrating tobacco smoking as potential ERFs in the context of PDs and to broaden the perspective from cannabis discontinuation to smoking cessation programs in patients or people at risk of PDs.

Defining Urbanicity in the Context of Psychosis Research: A Qualitative Systematic Literature Review.

Numerous studies have found that being born or raised in urban environments increases the odds of developing psychosis in Northern and Western Europe. However, available research from Southern Europe, Latin America, and Asia has reported null results. A limitation in most studies to date is the inadequate characterization of urban and rural life components that may contribute to varying psychosis risk across regions. To deepen our understanding of the different concepts and measures of urbanicity and related factors in psychosis research, we conducted a qualitative systematic literature review extracting information from studies published between 2000 and 2024. Sixty-one articles met the inclusion and exclusion criteria and were used in the thematic analysis. The analysis revealed that urbanicity lacked a single, coherent definition across studies and regions. Three major categories of themes were developed from the analysis: (1) Urbanicity comprises several interconnected constructs, (2) Urbanicity measurements vary between countries from the Global North and the Global South, and (3) Urbanicity operates through key neighborhood-level mechanisms. Future research on urbanicity and psychosis should consider the potential limitations of urbanicity's conceptualization and operationalization and aim to address these limitations by focusing on contextual, historical, and community-level factors, utilizing locally validated measures, and employing mixed-method designs.

A generalisability theory approach to quantifying changes in psychopathology among ultra-high-risk individuals for psychosis

Distinguishing stable and fluctuating psychopathological features in young individuals at Ultra High Risk (UHR) for psychosis is challenging, but critical for building robust, accurate, early clinical detection and prevention capabilities. Over a 24-month period, 159 UHR individuals were assessed using the Positive and Negative Symptom Scale (PANSS). Generalisability Theory was used to validate the PANSS with this population and to investigate stable and fluctuating features, by estimating the reliability and generalisability of three factor (Positive, Negative, and General) and five factor (Positive, Negative, Cognitive, Depression, and Hostility) symptom models. Acceptable reliability and generalisability of scores across occasions and sample population were demonstrated by the total PANSS scale (Gr = 0.85). Fluctuating symptoms (delusions, hallucinatory behaviour, lack of spontaneity, flow in conversation, emotional withdrawal, and somatic concern) showed high variability over time, with 50–68% of the variance explained by individual transient states. In contrast, more stable symptoms included excitement, poor rapport, anxiety, guilt feeling, uncooperativeness, and poor impulse control. The 3-factor model of PANSS and its subscales showed robust reliability and generalisability of their assessment scores across the UHR population and evaluation periods (G = 0.77–0.93), offering a suitable means to assess psychosis risk. Certain subscales within the 5-factor PANSS model showed comparatively lower reliability and generalisability (G = 0.33–0.66). The identified and investigated fluctuating symptoms in UHR individuals are more amendable by means of intervention, which could have significant implications for preventing and addressing psychosis. Prioritising the treatment of fluctuating symptoms could enhance intervention efficacy, offering a sharper focus in clinical trials. At the same time, using more reliable total scale and 3 subscales can contribute to more accurate assessment of enduring psychosis patterns in clinical and experimental settings.

Exploring the role of TNF-α, TGF-β, and IL-6 serum levels in categorical and noncategorical models of mood and psychosis

Psychotic and mood disorders are discussed as part of the same continuum. The potential role of immune dysregulation in defining their clinical presentations, however, remains unclear. Differences in TNF-α, IL-6 and TGF-β levels were investigated in 143 patients with schizophrenia (SCH = 63) and bipolar disorder (BD = 80), in remission. Cytokines were evaluated against the dimensional assessment of psychosis and affective symptoms using the schizo-bipolar scale, together with the severity of the same symptom domains measured by the brief psychiatric rating scale (BPRS). Lower TGF-β was associated with more lifetime episodes, family risk for psychosis, and more severe mood and psychotic symptoms in all patients. BPRS Affect symptoms domain correlated with lower TGF-β levels in BD, and higher TGF-β levels in SCH patients. Using moderated mediation analysis, TGF-β was a relevant predictor only in the setting of non-categorical symptom distribution, with familial risk for psychosis confirmed as a significant moderator. Severity of BPRS Affect symptoms domain was an independent predictor of inclination towards the psychosis spectrum. The underlying immune dysregulation may be shared by the disorders, rather than a unique characteristic of each, having significant implications for our understanding of the continuum vs. categorical approach to psychosis and mood disorders.

A Systematic Review of Resilience in At-Risk Youth for Psychotic Disorders: An Analysis of Protective and Risk Factors from Recent Literature.

Psychotic disorders in youth pose significant challenges for mental health services, necessitating a detailed understanding of the interplay between risk factors and resilience. This systematic review aimed to assess how resilience factors might buffer the adverse effects of risk factors on the development of psychosis among youth, thereby informing targeted interventions. Studies were selected based on criteria including a focus on individuals aged up to 25 years old at risk for psychosis, the examination of both risk factors and resilience, and the use of validated instruments for measuring outcomes. Literature searches were conducted across several databases, such as PubMed, Scopus, and Web of Science. Data extraction emphasized odds ratios (ORs) and hazard ratios (HRs) for risk factors, including familial, developmental, and socio-environmental influences. The review included and analyzed nine studies, encompassing a diverse sample of 140,972 participants. Significant findings indicate that highly supportive familial and community environments significantly reduce the risk of psychosis onset. For instance, children with strong family support and engagement in structured activities demonstrated a 40% lower incidence of developing psychotic symptoms [p < 0.05]. Furthermore, the presence of neurobehavioral deficits, such as impaired verbal memory and attention, emerged as significant predictors of psychosis, with these children exhibiting a threefold increase in risk compared to their peers [OR = 3.2, 95% CI: 2.1-4.8, p < 0.01]. Resilience factors play a critical role in mitigating the impact of psychosocial and neurobiological risks in the development of psychosis among youths. Interventions enhancing resilience could potentially alter the trajectory of psychosis development, emphasizing the need for early and targeted psychosocial interventions to support at-risk populations. This study underscores the importance of fostering resilience through both individual-focused and community-based strategies to prevent the onset of psychotic disorders in vulnerable young populations.

Age-at-migration, ethnicity and psychosis risk: Findings from the EU-GEI case-control study

Several studies have highlighted increased psychosis risk in migrant and minority ethnic populations. Migration before age 18 appears to increase risk, but further evidence is required. We investigated this issue in a European case-control study. We hypothesized that migration during two key socio-developmental periods, childhood and adolescence, would be most strongly associated with increased odds of psychosis, and that this would be more pronounced for racialised minorities. We used data from five countries in the EUropean network of national schizophrenia networks studying Gene-Environment Interactions [EU-GEI] study. We examined the association between migration in infancy (0–4 years), childhood (5–10 years), adolescence (11–17 years) or adulthood (18+ years) and first episode psychotic disorder. We fitted unadjusted and adjusted logistic regression models to estimate odds ratios [OR] and 95% confidence intervals [95%CI] for associations between age-at-migration and psychosis. In stratified models, we also examined whether these associations varied by ethnicity. The sample consisted of 937 cases and 1,195 controls. Migration at all ages, including infancy (OR: 2.03, 95%CI: 1.01–4.10), childhood (OR: 2.07, 95%CI: 1.04–4.14), adolescence (OR: 3.26, 95%CI: 1.89–5.63) and adulthood (OR: 1.71, 95%CI: 1.21–2.41), was associated with increased odds of psychosis compared with the white majority non-migrant group, after adjustment for all confounders except ethnoracial identity. After additional adjustment for ethnoracial identity, only migration during adolescence remained associated with psychosis (OR 1.94, 95%CI: 1.11–3.36). In stratified analyses, migration during adolescence was associated with increased odds of psychosis in Black (OR: 6.52, 95%CI: 3.00–14.20) and North African (OR: 16.43, 95%CI: 1.88–143.51) groups.Migration during adolescence increased psychosis risk, particularly in racially minoritised young people. This suggests that development of interventions for minoritised young migrants that alleviate stressors associated with migration and acculturation are warranted.

Risk of Incident Psychosis and Mania With Prescription Amphetamines.

Amphetamine prescribing has increased in the United States in recent years. Previous research identified an increased risk of incident psychosis with prescription amphetamines. The purpose of this study was to examine the impact of dose levels of prescription amphetamines on the risk of this rare but serious adverse outcome. A case-control study using electronic health records was conducted to compare the odds of incident psychosis or mania with past-month exposure to prescription amphetamines. Case subjects were patients ages 16-35 hospitalized at McLean Hospital for incident psychosis or mania between 2005 and 2019. Control subjects were patients with an initial psychiatric hospitalization for other reasons, most commonly depression and/or anxiety. Amphetamine doses were converted to dextroamphetamine equivalents and divided into terciles. Secondary analyses evaluated the odds of psychosis or mania with methylphenidate use. Among 1,374 case subjects and 2,748 control subjects, the odds of psychosis and mania were increased for individuals with past-month prescription amphetamine use compared with no use (adjusted odds ratio=2.68, 95% CI=1.90-3.77). A dose-response relationship was observed; high doses of amphetamines (>30 mg dextroamphetamine equivalents) were associated with 5.28-fold increased odds of psychosis or mania. Past-month methylphenidate use was not associated with increased odds of psychosis or mania compared with no use (adjusted odds ratio=0.91, 95% CI=0.54-1.55). Although use of hospitalized control subjects excludes individuals with less severe disease, leading to selection bias, the study results suggest that caution should be exercised when prescribing high doses of amphetamines, with regular screening for symptoms of psychosis or mania.