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Aim: Schizophrenia is a leading cause of disability worldwide; early detection and intervention are critical. Early in their illness, individuals at clinical high‐risk (CHR) for psychosis have subthreshold psychotic symptoms that are often derogatory and self‐directed. We hypothesized that CHR participants with negative self‐reference (NSR) as a component of subthreshold psychosis would also have higher levels of social anxiety and depression, lower self‐esteem and lower social/role/global functioning as compared with CHR participants without NSR. Methods: One hundred and sixty‐eight participants from the National Institute of Mental Health (NIMH) funded Regroup Cognitive Behavioural Social Skills Training (CBSST) study were included. Clinical vignettes that included the Scale of Psychosis‐Risk Symptoms were coded categorically to indicate whether NSR was present. t‐tests were used to determine the association between NSR, symptom, and functional measures. Results: Participants with NSR demonstrated significantly more social interaction anxiety (p <.001), negative beliefs about the self (p ≤.001), defeatist beliefs (p <.05), depressive symptoms (p <.05) and positive symptoms (p <.005). There were no significant differences in social self‐efficacy, positive or negative beliefs about others, positive beliefs about the self or psychosocial functioning between the two groups. Conclusions: Clinically significant differences were found between CHR participants with and without NSR, suggesting that this may be a useful factor to identify and address. Follow‐up studies are needed to determine whether NSR responds to CBSST and whether or not its resolution would be associated with improvement in other symptom domains. [ABSTRACT FROM AUTHOR]

• Negative symptoms impact quality of life and functioning. • Complement regulators and coagulation regulators are prognostic factors of negative symptoms. • Their prognostic value is independent of clinical and demographic prognostic factors. • These results may aid early intervention for negative symptoms of psychosis. Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (β: 0.501, 95 % CI: 0.160, 0.842; β: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (β: 0.501, 95 % CI: −0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (β: 0.442, 95 % CI: 0.127, 0.757). The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that clinical high risk for psychosis (CHR-P) is highly specific for psychotic disorders other than pluripotential to various serious mental illnesses. However, not all CHR-P develop psychotic disorder only, and psychosis can occur in non-psychotic disorders as well. Our prospective cohort study aims to investigate the characteristics and clinical outcomes of a pluripotent high-risk group with the potential to develop a diverse range of psychiatric disorders. The SPRIM study is a prospective naturalistic cohort program that focuses on the early detection of those at risk of developing serious mental illness, including psychosis (CHR-P), bipolar (CHR-B), and depressive disorder (CHR-D), as well as undifferentiated risk participants (UCHR). Our study has a longitudinal design with a baseline assessment and eight follow-up evaluations at 6, 12, 18, 24, 30, 36, 42, and 48 months to determine whether participants have transitioned to psychosis or mood disorders. The SPRIM sample consisted of 90 CHR participants. The total cumulative incidence rate of transition was 53.3% (95% CI 32.5–77.2). CHR-P, CHR-B, CHR-D, and UCHR had cumulative incidence rates of 13.7% (95% CI 3.4–46.4), 52.4% (95% CI 28.1–81.1), 66.7% (95% CI 24.6–98.6) and 54.3% (95% CI 20.5–93.1), respectively. The cumulative incidence of psychosis, bipolar, and depressive disorder among all participants was 3.3% (95% CI 0.8–11.5), 45.7% (95% CI 24.4–73.6), and 11.2% (95% CI 3.1–36.2), respectively. Our study suggests that the concept of pluripotent high-risk for a diverse range of psychiatric disorders is an integrative approach to examining transdiagnostic interactions between illnesses with a high transition rate and minimizing stigma. • Characteristics and clinical outcomes of pluripotent high-risk group; potential for diverse psychiatric disorders. • The total cumulative incidence rate of transition was 53.3% (95% CI 32.5–77.2). • The cummulative incidence of psychosis, bipolar, and depressive disorder among all participants was 3.3%, 45.7%, and 11.2%. [ABSTRACT FROM AUTHOR]

Background: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. Methods: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. Results: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. Conclusions: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development. [ABSTRACT FROM AUTHOR]

Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n = 41) and ESZ (n = 70) relative to healthy controls (HC; n = 74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (ps

BACKGROUND AND HYPOTHESIS: While individuals at clinical high-risk (CHR) for psychosis experience higher levels of discrimination than healthy controls, it is unclear how these experiences contribute to the etiology of attenuated positive symptoms. The present study examined the association of perceived discrimination with positive symptoms in a cohort from the North American Prodrome Longitudinal Study (NAPLS2). It predicted that CHR individuals will report higher levels of lifetime and past year perceived discrimination related to their race and ethnicity (ethnoracial discrimination) and that this form of discrimination will be significantly associated with baseline positive symptoms. STUDY DESIGN: Participants included 686 CHR and 252 healthy controls. The present study examined data from the perceived discrimination (PD) scale, the Brief Core Schema Scale, and the Scale for the Psychosis-Risk Symptoms. Structural equation modeling was employed to examine whether negative schema of self and others mediated the relation of past year ethnoracial PD to baseline suspiciousness symptoms. RESULTS: CHR individuals report higher levels of past year and lifetime PD compared to healthy controls. Lifetime ethnoracial PD was associated with suspiciousness and total positive symptoms. Negative schema of self and others scores partially mediated the relation of past year ethnoracial PD to suspiciousness, one of five positive symptom criteria for CHR. CONCLUSIONS: For CHR individuals, past year ethnoracial discrimination was associated with negative beliefs about themselves and others, which was associated with suspiciousness. These findings contribute to an emerging literature characterizing the mechanisms by which discrimination contributes to the positive symptoms characterizing the CHR syndrome.

BackgroundSince its inception, research in the clinical high-risk (CHR) phase of psychosis has included identifying and exploring the impact of relevant socio-demographic factors. Employing a narrative review approach and highlighting work from the United States, sociocultural and contextual factors potentially affecting the screening, assessment, and service utilization of youth at CHR were reviewed from the current literature.ResultsExisting literature suggests that contextual factors impact the predictive performance of widely used psychosis-risk screening tools and may introduce systemic bias and challenges to differential diagnosis in clinical assessment. Factors reviewed include racialized identity, discrimination, neighborhood context, trauma, immigration status, gender identity, sexual orientation, and age. Furthermore, racialized identity and traumatic experiences appear related to symptom severity and service utilization among this population.ConclusionsCollectively, a growing body of research from the United States and beyond suggests that considering context in psychosis-risk assessment can provide a more accurate appraisal of the nature of risk for psychosis, render more accurate results improving the field's prediction of conversion to psychosis, and enhance our understanding of psychosis-risk trajectories. More work is needed in the U.S. and across the globe to uncover how structural racism and systemic biases impact screening, assessment, treatment, and clinical and functional outcomes for those at CHR.

There is a clinical high-risk period (CHR) before the onset of schizophrenia. Early detection and early treatment are crucial for the prognosis of the disease. Event-related potential (ERP) is a special brain evoked potential. Different ERP components can reflect the neuroelectrophysiological changes of the brain in different cog- nitive processes. Exploring the ERP components of CHR abnormalities may have an important role in the early rec- ognition of diseases and transformation risk. This review found that P300 and MMN have predictive effects on the risk of mental illness conversion, while other ERP components such as P50, P1. and N400 require more research to verify their reliability as risk markers for mental illness conversion in high-risk populations. [ABSTRACT FROM AUTHOR]

The complement system is an important part of the innate immune system and plays a key role in inflammatory processes. Concentrations of complement activation fragments in plasma are markers of systemic activation and have been found to be altered in a wide range of diseases. Some plasma activation marker levels can be influenced by sample processing and storage time. We quantified seven complement activation markers (C4a, C4d, C3a, iC3b, Bb, C5a, and sC5b-9 (TCC)) in EDTA-plasma as part of a multi-centre clinical study analysing complement activation in individuals with clinical high-risk (CHR) for psychosis compared with healthy controls. Samples had been collected, processed, and subsequently stored at -80°C over a period of 9.5–13.6 years, according to a standard operating protocol (SOP). Complement activation markers were quantified using commercially available and standardised enzyme-linked immunosorbent assays (ELISA). In a post hoc analysis of variables affecting the analyses we investigated the impact of EDTA-to-freezer processing time (

Aim: Rates of attenuated psychotic symptoms (APS) have increased during the COVID‐19 pandemic; however, it is unclear whether this is most evident among individuals from marginalized racial groups. Methods: The current study evaluated APS screening data across a six‐year period in the state of Georgia in the United States, spanning several years prior to and during the COVID‐19 pandemic to evaluate interactions between time and race. Participants included 435 clinical help‐seeking individuals. Results: The rate of individuals scoring above the APS screening cut‐off was higher during the pandemic compared to pre‐pandemic (41% vs 23%). This pandemic‐related increase in APS was significant for Black, but not White or Asian participants. Conclusions: Findings indicate APS are increasing during the COVID‐19 pandemic among clinical help‐seeking populations. Black individuals may be at greater risk for developing a psychotic disorder during the pandemic, suggesting increased need for screening, mental health monitoring, and treatment. [ABSTRACT FROM AUTHOR]

Background: Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models. Methods: Participants from both the NAPLS2 and NAPLS3 samples were classified as either 'long' or 'short' symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis. Results: The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78). Conclusions: These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes. [ABSTRACT FROM AUTHOR]

Recent evidence has highlighted the benefits of early detection and treatment for better clinical outcomes in patients with psychosis. Biological markers of the disease have become a focal point of research. This study aimed to identify protein markers detectable in the early stages of psychosis and indicators of progression by comparing them with those of healthy controls (HC) and first episode psychosis (FEP). The participants comprised 28 patients in the clinical high-risk (CHR) group, 49 patients with FEP, and 61 HCs aged 15–35 years. Blood samples were collected and analyzed using multiple reaction monitoring-mass spectrometry to measure the expression of 158 peptide targets. Data were adjusted for age, sex, and use of psychotropic drugs. A total of 18 peptides (17 proteins) differed significantly among the groups. The protein PRDX2 was higher in the FEP group than in the CHR and HC groups and showed increased expression according to disease progression. The levels of six proteins were significantly higher in the FEP group than in the CHR group. Nine proteins differed significantly in the CHR group compared to the other groups. Sixteen proteins were significantly correlated with symptom severity. These proteins are primarily related to the coagulation cascade, inflammatory response, brain structure, and synaptic plasticity. Our findings suggested that peripheral protein markers reflect disease progression in patients with psychosis. Further longitudinal research is needed to confirm these findings and to identify the specific roles of these markers in the pathogenesis of schizophrenia. [ABSTRACT FROM AUTHOR]

Negative symptoms are prominent in individuals with schizophrenia (SZ) and youth at clinical high-risk for psychosis (CHR). In SZ, negative symptoms are linked to reinforcement learning (RL) dysfunction; however, previous research suggests implicit RL remains intact. It is unknown whether implicit RL is preserved in the CHR phase where negative symptom mechanisms are unclear, knowledge of which may assist in developing early identification and prevention methods. Participants from two studies completed an implicit RL task: Study 1 included 53 SZ individuals and 54 healthy controls (HC); Study 2 included 26 CHR youth and 23 HCs. Bias trajectories reflecting implicit RL were compared between groups and correlations with negative symptoms were examined. Cluster analysis investigated RL profiles across the combined samples. Implicit RL was comparable between HC and their corresponding SZ and CHR groups. However, cluster analysis was able to parse performance heterogeneity across diagnostic boundaries into two distinct RL profiles: a Positive/Early Learning cluster (65% of participants) with positive bias scores increasing from the first to second task block, and a Negative/Late Learning cluster (35% of participants) with negative bias scores increasing from the second to third block. Clusters did not differ in the proportion of CHR vs. SZ cases; however, the Negative/Late Learning cluster had more severe negative symptoms. Although implicit RL is intact in CHR similar to SZ, distinct implicit RL phenotypic profiles with elevated negative symptoms were identified trans-phasically, suggesting distinct reward-processing mechanisms can contribute to negative symptoms independent of phases of illness. [ABSTRACT FROM AUTHOR]

Evidence of elevated peripheral Neurofilament light-chain (NfL) as a biomarker of neuronal injury can be utilized to reveal nonspecific axonal damage, which could reflect altered neuroimmune function. To date, only a few studies have investigated NfL as a fluid biomarker in schizophrenia primarily, though none in its putative prodrome (Clinical High-Risk, CHR) or in untreated first-episode psychosis (FEP). Further, it is unknown whether peripheral NfL is associated with 18 kDa translocator protein (TSPO), a validated neuroimmune marker. In this secondary study, we investigated for the first time (1) serum NfL in early stages of psychosis including CHR and FEP as compared to healthy controls, and (2) examined its association with brain TSPO, using [18F]FEPPA positron emission tomography (PET). Further, in the exploratory analyses, we aimed to assess associations between serum NfL and symptom severity in patient group and cognitive impairment in the combined cohort. A large cohort of 84 participants including 27 FEP (24 antipsychotic-naive), 41 CHR (34 antipsychotic-naive) and 16 healthy controls underwent structural brain MRI and [18F]FEPPA PET scan and their blood samples were obtained and assessed for serum NfL concentrations. We found no significant differences in serum NfL levels across clinical groups, controlling for age. We also found no significant association between NfL levels and brain TSPO in the entire cohort. We observed a negative association between serum NfL and negative symptom severity in CHR. Our findings suggest that neither active neuroaxonal deterioration as measured with NfL nor associated neuroimmune activation (TSPO) is clearly identifiable in an early mostly untreated psychosis sample including its putative high-risk.

Background: Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics and to antidepressants in individuals at clinical high-risk for psychosis (CHR-P) have opposite prognostic effects as regards imminent transition to psychosis, with antipsychotics associated with higher risk and antidepressants associated with a lower risk in comparison to not-exposed individuals. Despite their common use, baseline exposure to benzodiazepines (BDZ) in CHR-P has surprisingly received poor attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap. Methods: Systematic scrutiny of Medline and Cochrane library, performed up to 31 December 2022, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on BDZ baseline exposure in relation to such outcome. Results: Of 1893 identified records, five studies were included in the systematic review and meta-analysis. The proportion of participants with exposure to BDZ at baseline ranged from 5.5% (one study) to 46.2%, with an average of 16.8%. At the end of the period of observation, i.e., the follow-up as reported in the study, 28.4% [95% confidence interval (CI) 19.7–39.1%] participants developed psychosis among the BDZ-exposed against 9.3% (7.3 to 11.9%) among the controls. CHR-P participants who were already under BDZ treatment at baseline had more than double chance of transition to psychosis than CHR-P participants who were BDZ-naïve. The risk ratio (RR) was 2.42 (95% CI 1.38–4.23) in the common effects model (z = 3.09; p = 0.002), and 2.40 (1.53 to 3.77) in the random-effects model (z = 5.40; p = 0.006; tau-squared = 0.0). There was no relevant heterogeneity: Cochran's Q = 1.49; df = 4; p = 0.828; I 2 = 0.0% (95% CI 0.0–79%). Quality was good in four studies. Conclusions: Ongoing BDZ exposure at inception in CHR-P is associated with a higher risk of transition to psychosis at follow up. This meta-analytic association, which echoes a similar effect of baseline antipsychotic exposure, plausibly indicates that the clinicians' prescription of pharmacological intervention captures some form of prognostically-relevant information (e.g. an anxiety permeated mental state requiring BDZ prescription) that are not adequately encompassed by current CHR-P categorical criteria. [ABSTRACT FROM AUTHOR]

Aim: Suicide risk is elevated among individuals at clinical high risk for psychosis (CHR‐P). The current study examined variability in suicidal ideation during treatment for individuals at CHR‐P. Methods: A retrospective chart review was used to examine the course of suicidal ideation during 16 sessions of individual psychotherapy for 25 individuals at CHR‐P. Results: Suicidal ideation was reported by 24% of participants at session 1 and 16% at session 16, with minimal within‐subject change in the presence of suicidal ideation across the two time points. However, a more fine‐grained investigation at each session indicated that 60% of individuals at CHR‐P experienced suicidal ideation at least once during treatment. Additionally, there was great variability in suicidal ideation both within and between participants over the course of the 16 sessions. Conclusions: These findings highlight the importance of repeated assessment when examining suicidal ideation as a treatment outcome for individuals at CHR‐P. [ABSTRACT FROM AUTHOR]

Background: Negative symptoms such as blunted facial expressivity are characteristic of schizophrenia. However, it is not well-understood if and what abnormalities are present in individuals at clinical high-risk (CHR) for psychosis. Methods: This experimental study employed facial electromyography (left zygomaticus major and left corrugator supercilia) in a sample of CHR individuals (N = 34) and healthy controls (N = 32) to detect alterations in facial expressions in response to emotionally evocative film clips and to determine links with symptoms. Results: Findings revealed that the CHR group showed facial blunting manifested in reduced zygomatic activity in response to an excitement (but not amusement, fear, or sadness) film clip compared to controls. Reductions in zygomatic activity in the CHR group emerged in response to the emotionally evocative peak period of the excitement film clip. Lower zygomaticus activity during the excitement clip was related to anxiety while lower rates of change in zygomatic activity during the excitement video clip were related to higher psychosis risk conversion scores. Conclusions: Together, these findings inform vulnerability/disease driving mechanisms and biomarker and treatment development. [ABSTRACT FROM AUTHOR]

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

Familial emotional word usage has long been implicated in symptom progression in schizophrenia. However, few studies have examined caregiver emotional word usage prior to the onset of psychosis, among those with a clinical high-risk (CHR) syndrome. The current study examined emotional word usage in a sample of caregivers of CHR individuals (N = 37) and caregivers of healthy controls (N = 40) and links with clinical symptoms in CHR individuals. Caregivers completed a speech sample task in which they were asked to speak about the participant; speech samples were then transcribed and analyzed for general positive (e.g. good) and negative (e.g., worthless) emotional words as well as words expressing three specific negative emotions (i.e., anxiety, anger, and sadness) using Linguistic Inquiry and Word Count (LIWC). Findings indicated that (1) CHR caregivers used more negative and anxiety words compared to control caregivers; and (2) less positive word usage among CHR caregivers were related to more positive symptomatology among CHR individuals. These findings point toward the utility of automated language analysis in assessing the intersections between caregiver emotional language use and psychopathology. [ABSTRACT FROM AUTHOR]

Suicidal ideation (SI) is prevalent among individuals at clinical high-risk for psychosis (CHR). Natural language processing (NLP) provides an efficient method to identify linguistic markers of suicidality. Prior work has demonstrated that an increased use of "I", as well as words with semantic similarity to "anger", "sadness", "stress" and "lonely", are correlated with SI in other cohorts. The current project analyzes data collected in an SI supplement to an NIH R01 study of thought disorder and social cognition in CHR. This study is the first to use NLP analyses of spoken language to identify linguistic correlates of recent suicidal ideation among CHR individuals. The sample included 43 CHR individuals, 10 with recent suicidal ideation and 33 without, as measured by the Columbia-Suicide Severity Rating Scale, as well as 14 healthy volunteers without SI. NLP methods include part-of-speech (POS) tagging, a GoEmotions-trained BERT Model, and Zero-Shot Learning. As hypothesized, individuals at CHR for psychosis who endorsed recent SI utilized more words with semantic similarity to "anger" compared to those who did not. Words with semantic similarity to "stress", "loneliness", and "sadness" were not significantly different between the two CHR groups. Contrary to our hypotheses, CHR individuals with recent SI did not use the word "I" more than those without recent SI. As anger is not characteristic of CHR, findings have implications for the consideration of subthreshold anger-related sentiment in suicidal risk assessment. As NLP is scalable, findings suggest that language markers may improve suicide screening and prediction in this population. [ABSTRACT FROM AUTHOR]

BackgroundRisk calculators are useful tools that can help clinicians and researchers better understand an individual's risk of conversion to psychosis. The North American Prodrome Longitudinal Study (NAPLS2) Individualized Risk Calculator has good predictive accuracy but could be potentially improved by the inclusion of a biomarker. Baseline cortisol, a measure of hypothalamic-pituitary-adrenal (HPA) axis functioning that is impacted by biological vulnerability to stress and exposure to environmental stressors, has been shown to be higher among individuals at clinical high-risk for psychosis (CHRP) who eventually convert to psychosis than those who do not. We sought to determine whether the addition of baseline cortisol to the NAPLS2 risk calculator improved the performance of the risk calculator.MethodsParticipants were drawn from the NAPLS2 study. A subset of NAPLS2 participants provided salivary cortisol samples. A multivariate Cox proportional hazards regression evaluated the likelihood of an individual's eventual conversion to psychosis based on demographic and clinical variables in addition to baseline cortisol levels.ResultsA total of 417 NAPLS2 participants provided salivary cortisol and were included in the analysis. Higher levels of cortisol were predictive of conversion to psychosis in a univariate model (C-index = 0.59, HR = 21.5, p-value = 0.004). The inclusion of cortisol in the risk calculator model resulted in a statistically significant improvement in performance from the original risk calculator model (C-index = 0.78, SE = 0.028).ConclusionsSalivary cortisol is an inexpensive and non-invasive biomarker that could improve individual predictions about conversion to psychosis and treatment decisions for CHR-P individuals.

Comorbid diagnoses are common in youth who are at clinical high-risk (CHR) for developing psychosis, with depression being the most common. The aim of this paper is to examine depression over two years in a large sample of CHR youth who do not make the transition to psychosis, considering both categorical and dimensional ratings of depression severity. The sample consisted of 267 CHR youth who were followed for two years. Based on DSM-IV diagnoses over this time period, 100 CHR individuals never received a diagnosis of depression, 64 individuals continuously met criteria for depression, 92 individuals received a diagnosis of depression at one or more timepoints, and 11 participants had a diagnosis of depression only at 24-months. These groupings were supported by six-monthly ratings on the Calgary Depression Scale. The majority of this sample experienced a major depressive episode on more than one occasion, suggesting that depression and depressive symptoms identify a domain of substantial unmet clinical need. Recommendations are that depression in CHR youth and young adults should be monitored more frequently and that there is a need for clinical trials to address depression systematically in this vulnerable population.

Negative symptoms (i.e., anhedonia, avolition, asociality, blunted affect, alogia) are frequently observed in the schizophrenia-spectrum (SZ) and associated with functional disability. While semi-structured interviews of negative symptoms represent a gold-standard approach, they require specialized training and may be vulnerable to rater biases. Thus, brief self-report questionnaires measuring negative symptoms may be useful. Existing negative symptom questionnaires demonstrate that this approach may be promising in schizophrenia, but no measure has been devised for use across stages of psychotic illness. The present study reports initial psychometric validation of the Negative Symptom Inventory-Self-Report (NSI-SR), the self-report counterpart of the Negative Symptom Inventory-Psychosis Risk clinical interview. The NSI-SR is a novel transphasic negative symptoms measure assessing the domains of anhedonia, avolition, and asociality. The NSI-SR and related measures were administered to two samples: 1) undergraduates (n = 335), 2) community participants, including: SZ (n = 32), clinical-high risk for psychosis (CHR, n = 25), and healthy controls matched to SZ (n = 31) and CHR (n = 30). The psychometrically trimmed 11-item NSI-SR showed good internal consistency and a three-factor solution reflecting avolition, asociality, and anhedonia. The NSI-SR demonstrated convergent validity via moderate to large correlations with clinician-rated negative symptoms and related constructs in both samples. Discriminant validity was supported by lower correlations with positive symptoms in both samples; however, correlations with positive symptoms were still significant. These initial psychometric findings suggest that the NSI-SR is a reliable and valid brief questionnaire capable of measuring negative symptoms across phases of psychotic illness. [ABSTRACT FROM AUTHOR]

Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n = 41) and ESZ (n = 70) relative to healthy controls (HC; n = 74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (p s <.024) relative to HC and CHR-P, with this reduction specific to the rich-club even after accounting for other connections in ESZ relative to HC (p s <.048). There was also cortical thinning of rich-club regions in ESZ (p s <.013). In contrast, there was no strong evidence of global network organization differences among the three groups. Although connectome abnormalities were not present in CHR-P overall, CHR-P converters to psychosis (n = 9) had fewer connections among rich-club regions (p s <.037) and greater modularity (p s <.037) compared to CHR-P non-converters (n = 19). Lastly, symptom severity and antipsychotic dosage were not significantly associated with connectome metrics (p s <.012). Findings suggest that rich-club and connectome organization abnormalities are present early in schizophrenia and in CHR-P individuals who subsequently transition to psychosis. [ABSTRACT FROM AUTHOR]

Background: Beliefs about the usefulness and controllability of emotions are associated with emotion regulation and psychological distress in the general population. Although individuals with schizophrenia-spectrum disorders evidence emotion regulation abnormalities, it is unclear whether emotional beliefs contribute to these difficulties and their associated poor clinical outcomes. Methods: Participants included 72 individuals with schizophrenia-spectrum diagnoses (outpatients with schizophrenia n = 38; youth at clinical high-risk for psychosis, n = 34) and healthy controls (CN: n = 61) who completed the Emotional Beliefs Questionnaire, Emotion Regulation Questionnaire, and measures of clinical symptom severity. Results: Those with schizophrenia-spectrum diagnoses reported believing that emotions were less controllable than CN; however, groups did not differ regarding beliefs about the usefulness of emotion. Greater beliefs of the uncontrollability of emotion were associated with greater use of suppression, less use of reappraisal, and increased negative symptoms. Emotion regulation partially mediated the association between emotional beliefs and negative symptoms. Conclusions: Individuals in the schizophrenia-spectrum display superordinate beliefs that emotions are uncontrollable. These beliefs may influence emotion regulation strategy selection and success, which contributes to negative symptoms. Findings suggest that beliefs of emotional uncontrollability reflect a novel process related to both emotion regulation and negative symptoms that could be targeted in psychosocial treatments. [ABSTRACT FROM AUTHOR]

Aim: This study examines associations between premorbid adjustment and comorbid disorders in individuals at ultra‐high risk (UHR) for psychosis. Methods: Premorbid social and academic adjustment data were collected from 146 UHR individuals using the Premorbid Adjustment Scale. Comorbid disorders were determined by the Structural Clinical Interview for DSM‐IV. Results: Logistic regressions showed lower premorbid social adjustment associated with personality disorders. Lower premorbid academic adjustment associated with affective disorders. More specifically, poor premorbid social adjustment in early and late adolescence associated with personality disorders. Lower premorbid social adjustment in late adolescence and lower premorbid academic adjustment in early adolescence associated with affective disorders. Conclusion: Partly corroborating evidence from schizophrenia samples, our findings suggest that poor premorbid adjustment relate to distinct comorbid disorders in UHR individuals. If replicated, it indicates that premorbid adjustment deficits may be a key area for targeted interventions improving the clinical prognosis of UHR individuals. [ABSTRACT FROM AUTHOR]

Individuals at ultra high-risk (UHR) of psychosis exhibit significantly higher stress levels than healthy controls (HC). This study investigates how physiological stress measures differ between HC and UHR individuals and how physiological stress is associated with attenuated psychotic symptoms and changes over time in UHR individuals. Additionally, it examines how the use of medication affects physiological levels of stress. The study included 72 UHR individuals and 36 HC. UHR were included according to the comprehensive assessment of at-risk mental state (CAARMS); a total-CAARMS score measured the attenuated psychotic symptoms and was calculated from the four psychosis subscales. HC and UHR were examined at baseline, and 47 UHR individuals were followed up after six months. Physiological stress measures were salivary cortisol, alpha-amylase (SAA) and heart-rate variability (HRV). Saliva was collected at four-time points during the day. There was no significant difference regarding cortisol (awakening response) or SAA measures between HC and UHR individuals. The use of antipsychotics and antidepressants was associated with low HRV in UHR individuals. In an exploratory analysis of 19 UHR individuals, we found an association between the change in total-CAARMS (six months total-CAARMS minus baseline total CAARMS) and the change in HRV during sleep (six months HRV minus baseline HRV). Our findings indicate that the use of antipsychotics and antidepressants could be associated with lower HRV in UHR individuals. There might be potential to investigate how HRV develops during the course of illness in UHR individuals. [ABSTRACT FROM AUTHOR]

While individuals at clinical high-risk (CHR) for psychosis experience higher levels of discrimination than healthy controls, it is unclear how these experiences contribute to the etiology of attenuated positive symptoms. The present study examined the association of perceived discrimination with positive symptoms in a cohort from the North American Prodrome Longitudinal Study (NAPLS2). It predicted that CHR individuals will report higher levels of lifetime and past year perceived discrimination related to their race and ethnicity (ethnoracial discrimination) and that this form of discrimination will be significantly associated with baseline positive symptoms. Participants included 686 CHR and 252 healthy controls. The present study examined data from the perceived discrimination (PD) scale, the Brief Core Schema Scale, and the Scale for the Psychosis-Risk Symptoms. Structural equation modeling was employed to examine whether negative schema of self and others mediated the relation of past year ethnoracial PD to baseline suspiciousness symptoms. CHR individuals report higher levels of past year and lifetime PD compared to healthy controls. Lifetime ethnoracial PD was associated with suspiciousness and total positive symptoms. Negative schema of self and others scores partially mediated the relation of past year ethnoracial PD to suspiciousness, one of five positive symptom criteria for CHR. For CHR individuals, past year ethnoracial discrimination was associated with negative beliefs about themselves and others, which was associated with suspiciousness. These findings contribute to an emerging literature characterizing the mechanisms by which discrimination contributes to the positive symptoms characterizing the CHR syndrome. [ABSTRACT FROM AUTHOR]

No systematic review has estimated the consistency and the magnitude of the risk of developing bipolar disorder I-II (BD-I/II) in individuals at clinical high risk for bipolar disorder (CHR-BD). PubMed and Web of Science databases were searched until April 2022 in this pre-registered (PROSPERO CRD42022346515) PRISMA-compliant systematic review to identify longitudinal studies in individuals meeting pre-defined CHR-BD criteria. The risk of bias was assessed using the Newcastle-Ottawa Scale, and results were systematically synthesized around CHR-BD criteria across follow-up periods and different subgroups. Altogether, 13 studies were included reporting on nine prospective independent cohorts (n = 678 individuals at CHR-BD). The mean age of participants was 15.7 years (range 10.1–22.6 years), and 54.2 % were females. The most common CHR-BD subgroup was subthreshold mania (55.5 %), followed by BD-Not Otherwise Specified (BD-NOS: 33.3 %). Development of BD I/II ranged from 7.1 % to 23.4 % after 2 years. Development of BD-I ranged from 3.4 % at 4 years to 23 % at 8 years. Development of BD-II ranged from 10 % at 2 years to 63.8 % at 4 years. The risk of developing BD-I appeared highest in those meeting BD-NOS criteria (23 % at eight years). Predictors of development of BD were identified but remained mostly unreplicated. The quality of the included studies was moderate (NOS = 5.2 ± 1.1). Emerging data from research studies point towards the promising utility of CHR-BD criteria. These studies may pave the way to the next generation of research, implementing detection, prognostication, and preventive interventions in individuals at CHR-BD identified and followed in clinical practice. • This review evaluated the magnitude of the risk of developing bipolar disorder I-II in individuals at clinical high-risk. • Most common clinical high-risk for bipolar disorder (CHR-BD) subgroups were subthreshold mania and BD-Not Otherwise Specified (BD-NOS). • Development of BD I/II ranged from 3 % after 0.7 years to 23.4 % after 2 years. Development of BD-I ranged from 3.4 % at 4 years to 23 % at 8 years. • The risk of developing BD-I appeared highest in those meeting BD-NOS criteria (23 % at eight years). • Predictors of development of BD included an earlier age of onset of mood symptoms and family history of mania/hypomania. [ABSTRACT FROM AUTHOR]

Background: Since its inception, research in the clinical high-risk (CHR) phase of psychosis has included identifying and exploring the impact of relevant socio-demographic factors. Employing a narrative review approach and highlighting work from the United States, sociocultural and contextual factors potentially affecting the screening, assessment, and service utilization of youth at CHR were reviewed from the current literature. Results: Existing literature suggests that contextual factors impact the predictive performance of widely used psychosis-risk screening tools and may introduce systemic bias and challenges to differential diagnosis in clinical assessment. Factors reviewed include racialized identity, discrimination, neighborhood context, trauma, immigration status, gender identity, sexual orientation, and age. Furthermore, racialized identity and traumatic experiences appear related to symptom severity and service utilization among this population. Conclusions: Collectively, a growing body of research from the United States and beyond suggests that considering context in psychosis-risk assessment can provide a more accurate appraisal of the nature of risk for psychosis, render more accurate results improving the field's prediction of conversion to psychosis, and enhance our understanding of psychosis-risk trajectories. More work is needed in the U.S. and across the globe to uncover howstructural racismand systemic biases impact screening, assessment, treatment, and clinical and functional outcomes for those at CHR. [ABSTRACT FROM AUTHOR]

Aim: Language disturbances are a candidate biomarker for the early detection of psychosis. Temporal and prosodic abnormalities have been observed in schizophrenia patients, while there is conflicting evidence whether such deficits are present in participants meeting clinical high‐risk for psychosis (CHR‐P) criteria. Methods: Clinical interviews from CHR‐P participants (n = 50) were examined for temporal and prosodic metrics and compared against a group of healthy controls (n = 17) and participants with affective disorders and substance abuse (n = 23). Results: There were no deficits in acoustic variables in the CHR‐P group, while participants with affective disorders/substance abuse were characterized by slower speech rate, longer pauses and higher unvoiced frames percentage. Conclusion: Our finding suggests that temporal and prosodic aspects of speech are not impaired in early‐stage psychosis. Further studies are required to clarify whether such abnormalities are present in sub‐groups of CHR‐P participants with elevated psychosis‐risk. [ABSTRACT FROM AUTHOR]

Extensive research has demonstrated racial disparities, particularly among Black individuals, in both presentation and course of psychosis spectrum disorders. Few studies, however, have examined racial differences in the clinical high-risk (CHR) phase of illness. It is unclear if functional deficits seen in association with CHR symptoms generalize to marginalized racial groups, or whether race may play a role in the link between symptoms and functioning. In a sample of youth at CHR (N = 46), the present study examined the effect of race (Black and White represented in this sample) on the relation between CHR symptoms and social/role functioning. Race had a moderating effect on the relation between CHR symptoms and social functioning for total positive symptom score (p <.04, f 2 = 0.10). Although positive symptoms were associated with worse social functioning for White participants, no association was found for Black participants. Follow up analyses indicated suspiciousness was a statistically significant predictor of social functioning for White participants but was unrelated to functioning for Black participants. Results may be indicative of phenomenon experienced by individuals within racial minority groups (e.g., "healthy suspiciousness") or potential measurement validity concerns. Findings further the understanding of racial differences in the CHR phase of illness among White and Black youth and highlight limitations of the existing CHR literature and assessment tools for diverse youth. [ABSTRACT FROM AUTHOR]

Intervention strategies for those diagnosed with psychotic disorders such as schizophrenia can be effective in reducing symptoms and improving quality of life. While strides have been made in developing prevention and intervention strategies earlier on in the disease progression, among those at clinical high-risk (CHR) for psychosis, challenges with heterogeneity can limit symptom and diagnosis specific treatment. Here, we discuss a newly developed therapy skills group called the Skills Program for Awareness, Connectedness, and Empowerment (SPACE) that integrates different types of behavioral skills – standard and radically open dialectical behavioral therapy as well as cognitive behavioral therapy – for CHR youth between the ages of 13–18 years. With the diathesis-stress framework serving as a foundation, the intervention is divided into three stages. These stages target specific signs and symptoms contributing to the progression of CHR symptoms. Stage 1 targets stress (with the goal of developing awareness and reducing distress), stage 2 targets self-disturbances (with a goal of increasing self-connectedness), and stage 3 targets social connectedness (with a goal of improving social domains of functioning). The focus of this article is to introduce the theoretical framework underlying the pilot skills group and discuss ongoing progress. [ABSTRACT FROM AUTHOR]

Neuroinflammatory events prior to the diagnosis of schizophrenia may play a role in transition to illness. To date only one in-vivo study has investigated this association between peripheral proinflammatory cytokines and brain markers of inflammation (e.g., mitochondrial 18 kDa translocator protein, TSPO) in schizophrenia, but none in its putative prodrome.In this study, we primarily aimed to (Barron et al., 2017) test study group (clinical high-risk (CHR) and healthy controls) differences in peripheral inflammatory markers and test for any associations with symptom measures, (Hafizi et al., 2017a) investigate the interaction between brain TSPO levels (dorsolateral prefrontal cortex (DLPFC) and hippocampus) and peripheral inflammatory clusters (entire cohort and (CHR) group independently) within a relatively large group of individuals at CHR for psychosis (N = 38) and healthy controls (N = 20). Participants underwent structural brain magnetic resonance imaging (MRI) and TSPO [18F]FEPPA positron emission tomography (PET) scans. Serum samples were assessed for peripheral inflammatory markers (i.e., CRP and interleukins). For exploratory analysis, we aimed to examine cluster differences for symptom measures and identify independent peripheral predictors of brain TSPO expression.Here, we report increased IL-8 levels that are positively correlated with prodromal general symptom severity and showed trend-level association with apathy in CHR. We identified distinct inflammatory clusters characterized by inflammatory markers (IL-1 β, IL-2, IFN-γ) that were comparable between entire cohort and CHR. TSPO levels did not differ between inflammatory clusters (entire cohort or CHR). Finally, we show that CRP, IL-1 β, TNF-α, and IFN-γ levels were the independent peripheral predictors of brain TSPO expression.Thus, alterations in brain TSPO expression in response to inflammatory processes are not evident in CHR. Taken together, clustering by inflammatory status is a promising strategy to characterize the interaction between brain TSPO and peripheral markers of inflammation.

BackgroundSince its inception, research in the clinical high-risk (CHR) phase of psychosis has included identifying and exploring the impact of relevant socio-demographic factors. Employing a narrative review approach and highlighting work from the United States, sociocultural and contextual factors potentially affecting the screening, assessment, and service utilization of youth at CHR were reviewed from the current literature.ResultsExisting literature suggests that contextual factors impact the predictive performance of widely used psychosis-risk screening tools and may introduce systemic bias and challenges to differential diagnosis in clinical assessment. Factors reviewed include racialized identity, discrimination, neighborhood context, trauma, immigration status, gender identity, sexual orientation, and age. Furthermore, racialized identity and traumatic experiences appear related to symptom severity and service utilization among this population.ConclusionsCollectively, a growing body of research from the United States and beyond suggests that considering context in psychosis-risk assessment can provide a more accurate appraisal of the nature of risk for psychosis, render more accurate results improving the field's prediction of conversion to psychosis, and enhance our understanding of psychosis-risk trajectories. More work is needed in the U.S. and across the globe to uncover how structural racism and systemic biases impact screening, assessment, treatment, and clinical and functional outcomes for those at CHR.

Intervention strategies for those diagnosed with psychotic disorders such as schizophrenia can be effective in reducing symptoms and improving quality of life. While strides have been made in developing prevention and intervention strategies earlier on in the disease progression, among those at clinical high-risk (CHR) for psychosis, challenges with heterogeneity can limit symptom and diagnosis specific treatment. Here, we discuss a newly developed therapy skills group called the Skills Program for Awareness, Connectedness, and Empowerment (SPACE) that integrates different types of behavioral skills – standard and radically open dialectical behavioral therapy as well as cognitive behavioral therapy – for CHR youth between the ages of 13–18 years. With the diathesis-stress framework serving as a foundation, the intervention is divided into three stages. These stages target specific signs and symptoms contributing to the progression of CHR symptoms. Stage 1 targets stress (with the goal of developing awareness and reducing distress), stage 2 targets self-disturbances (with a goal of increasing self-connectedness), and stage 3 targets social connectedness (with a goal of improving social domains of functioning). The focus of this article is to introduce the theoretical framework underlying the pilot skills group and discuss ongoing progress.Clinical Trial RegistrationNCT05398120; https://clinicaltrials.gov/ct2/show/NCT05398120.

Epidemiological evidence has linked an array of sociodemographic and psychosocial factors with an increased risk of developing psychosis. However, research in samples from low- and middle-income countries is still scarce. This study used a Mexican sample to explore (i) sociodemographic and psychosocial differences between individuals with and without a positive screen for Clinical High-Risk for psychosis (CHR), and (ii) sociodemographic and psychosocial factors associated with screening positive for CHR. The sample consisted of 822 individuals from the general population who completed an online survey. Of the participants, 17.3% (n = 142) met the CHR screening criteria. Comparisons between those who screened positive (CHR-positive group) and those who did not (Non-CHR group) showed that participants in the CHR-positive group were younger, had a lower educational level, and reported more mental health problems than the Non-CHR group. Furthermore, relative to the Non-CHR group, the CHR-positive group had a greater prevalence of medium/high risk associated with cannabis use, a higher prevalence of adverse experiences (bullying, intimate partner violence, and experiencing a violent or unexpected death of a relative or friend), as well as higher levels of childhood maltreatment, poorer family functioning, and more distress associated with the COVID-19 pandemic. Groups did not differ in sex, marital/relationship status, occupation, and socio-economic status. Finally, when examined in multivariate analyses, the variables associated with screening positive for CHR were: having an unhealthy family functioning (OR= 2.75, 95%CI 1.69-4.46), a higher risk associated with cannabis use (OR= 2.75, 95%CI 1.63-4.64), a lower level of education (OR= 1.55, 95%CI 1.003-2.54), having experienced a major natural disaster (OR= 1.94, 95%CI 1.18-3.16), having experienced a violent or unexpected death of a relative or friend (OR= 1.85, 95%CI 1.22-2.81), higher levels of childhood emotional abuse (OR= 1.88, 95%CI 1.09-3.25), physical neglect (OR= 1.68, 95%CI 1.08-2.61), and physical abuse (OR= 1.66, 95%CI 1.05-2.61), and higher COVID-related distress (OR= 1.10, 95%CI 1.01-1.20). An older age was a protective factor for screening positive for CHR (OR= 0.96, 95%CI 0.92-0.99). Overall, the findings highlight the importance of examining potential psychosocial contributors to psychosis vulnerability across different sociocultural contexts to delineate risk and protective processes relevant to specific populations and better target preventive intervention efforts. [ABSTRACT FROM AUTHOR]

Epidemiological evidence has linked an array of sociodemographic and psychosocial factors with an increased risk of developing psychosis. However, research in samples from low- and middle-income countries is still scarce. This study used a Mexican sample to explore (i) sociodemographic and psychosocial differences between individuals with and without a positive screen for Clinical High-Risk for psychosis (CHR), and (ii) sociodemographic and psychosocial factors associated with screening positive for CHR. The sample consisted of 822 individuals from the general population who completed an online survey. Of the participants, 17.3% (n = 142) met the CHR screening criteria. Comparisons between those who screened positive (CHR-positive group) and those who did not (Non-CHR group) showed that participants in the CHR-positive group were younger, had a lower educational level, and reported more mental health problems than the Non-CHR group. Furthermore, relative to the Non-CHR group, the CHR-positive group had a greater prevalence of medium/high risk associated with cannabis use, a higher prevalence of adverse experiences (bullying, intimate partner violence, and experiencing a violent or unexpected death of a relative or friend), as well as higher levels of childhood maltreatment, poorer family functioning, and more distress associated with the COVID-19 pandemic. Groups did not differ in sex, marital/relationship status, occupation, and socio-economic status. Finally, when examined in multivariate analyses, the variables associated with screening positive for CHR were: having an unhealthy family functioning (OR = 2.75, 95%CI 1.69–4.46), a higher risk associated with cannabis use (OR = 2.75, 95%CI 1.63–4.64), a lower level of education (OR = 1.55, 95%CI 1.003–2.54), having experienced a major natural disaster (OR = 1.94, 95%CI 1.18–3.16), having experienced a violent or unexpected death of a relative or friend (OR = 1.85, 95%CI 1.22–2.81), higher levels of childhood emotional abuse (OR = 1.88, 95%CI 1.09–3.25), physical neglect (OR = 1.68, 95%CI 1.08–2.61), and physical abuse (OR = 1.66, 95%CI 1.05–2.61), and higher COVID-related distress (OR = 1.10, 95%CI 1.01–1.20). An older age was a protective factor for screening positive for CHR (OR = 0.96, 95%CI 0.92–0.99). Overall, the findings highlight the importance of examining potential psychosocial contributors to psychosis vulnerability across different sociocultural contexts to delineate risk and protective processes relevant to specific populations and better target preventive intervention efforts.

Individuals at clinical high-risk (CHR) for psychosis are characterized by attenuated psychotic symptoms. Only a minority of CHR individuals convert to full-blown psychosis. Therefore, there is a strong interest in identifying neurobiological abnormalities underlying the psychosis risk syndrome. Dynamic functional connectivity (DFC) captures time-varying connectivity over short time scales, and has the potential to reveal complex brain functional organization. Based on resting-state functional magnetic resonance imaging (fMRI) data from 70 healthy controls (HCs), 53 CHR individuals, and 58 early illness schizophrenia (ESZ) patients, we applied a novel group information guided ICA (GIG-ICA) to estimate inherent connectivity states from DFC, and then investigated group differences. We found that ESZ patients showed more aberrant connectivities and greater alterations than CHR individuals. Results also suggested that disease-related connectivity states occurred in CHR and ESZ groups. Regarding the dominant state with the highest contribution to dynamic connectivity, ESZ patients exhibited greater impairments than CHR individuals primarily in the cerebellum, frontal cortex, thalamus and temporal cortex, while CHR and ESZ populations shared common aberrances mainly in the supplementary motor area, parahippocampal gyrus and postcentral cortex. CHR-specific changes were also found in the connections between the superior frontal gyrus and calcarine cortex in the dominant state. Our findings suggest that CHR individuals generally show an intermediate functional connectivity pattern between HCs and SZ patients but also have unique connectivity alterations.

Background: To clarify if blood proteins can predict disease progression among individuals at clinical high-risk of severe mental illness (CHR-SMI), we developed a statistical model incorporating clinical and blood protein markers to distinguish the transition group (who developed severe mental illness) (CHR-SMI-T) and from non-transition group (CHR-SMI-NT) at baseline., Methods: Ninety individuals (74 at CHR-SMI: 16 patients) were monitored for ≤4 years and were the focus of predictive models. Three predictive models (1 [100 clinical variables], 2 [158 peptides], and 3 [100 clinical variables +158 peptides]) were evaluated using area under the receiver operating characteristic (AUROC) values. Clinical and protein feature patterns were evaluated by linear mixed-effect analysis within the model at 12 and 24 months among patients who did (CHR-SMI-T) and did not transition (CHR-SMI-NT) and the entire group., Result: Eighteen CHR-SMI individuals with major psychiatric disorders (first episode psychosis: 2; bipolar II disorder: 13; major depressive disorder; 3) developed disorders over an average of 17.7 months. The combined model showed the highest discriminatory performance (AUROC = 0.73). Cytosolic malate dehydrogenase and transgelin-2 levels were lower in the CHR-SMI-T than the CHR-SMI-NT group. Complement component C9, inter-alpha-trypsin inhibitor heavy chain H4, von Willebrand factor, and C-reactive protein were lower in the patient than the CHR-SMI-NT group. These differences were non-significant after FDR adjustment., Limitations: Small sample, no control for medication use., Conclusion: This exploratory study identified clinical and proteomic markers that might predict severe mental illness early onset, which could aid in early detection and intervention. Future studies with larger samples and controlled variables are needed to validate these findings., Competing Interests: Declaration of competing interest YMA receives research support from or serves as a speaker for Janssesn Korea Ltd., Lundbeck Korea Co. Ltd., and Korea Otsuka Pharmaceutical. The remaining authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Help-seeking barriers differ according to the sociocultural context and country-specific mental healthcare system. More research is needed in low-middle-income countries, where early psychosis programs are still scarce, and the mental health care gap is wide. This study aims to explore predisposing, enabling, and need factors associated with mental health service utilization in 481 Mexicans self-reporting psychosis risk symptoms, as well as differences between those who were currently mental health service users (MHSU) and those who were not (non-MHSU). Participants responded to self-reported measures through an online survey. The factors associated with an increased probability of using mental health services were having an occupation, having a medium/high socioeconomic status, an intention to seek help from a mental health professional, fewer help-seeking barriers, moderate/severe anxious symptoms, higher distress associated with psychosis risk symptoms and social functioning impairment. Findings provide relevant information for designing more effective strategies to improve help-seeking, early identification, and timely treatment delivery in Mexico. The need to generate strategies focused on reducing stigma, enhancing psychosis literacy in the community, and increasing the identification of emerging signs of psychosis in primary healthcare professionals is highlighted, mainly when co-occurring with other psychiatric symptoms., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: Psychosis is characterized by both alterations in emotional functioning and environmental stressors including bullying victimization. Recent evidence suggests that some alterations in emotional functioning (e.g., blunted positive facial expressions) are already present in the psychosis risk period. Yet, some clinically relevant facial emotions have not been investigated such as genuine smiles (thought to reflect genuine positive emotions) and non‐genuine smiles (thought to fake positive or mask negative emotions) in individuals meeting criteria for a clinical high‐risk (CHR) syndrome. Further, despite a compelling conceptual basis to suggest a link between affective expression and exposure to environmental stress, to date, no investigations have sought to examine this association. Here, we aim to assess differences between a sample of CHR (N = 65) and control (N = 67) individuals in genuine and non‐genuine smiles and associations with bullying victimization. Methods: Smiles (i.e., genuine; non‐genuine) were objectively coded on a second‐by‐second basis using the Facial Action Coding System during a digitally recorded clinical interview segment. Bullying victimization was measured via parent report. Results: Findings revealed that the CHR group (1) showed blunted genuine (but not non‐genuine) smiles compared to controls. Moreover, (2) bullying victimization was related to blunted genuine smiles, but not non‐genuine smiles. Conclusion: These findings expand our understanding of emotional alterations in this group with implications for diagnosis (highlighting blunted genuine smiles as a specific marker) and etiology (underscoring the role of bullying victimization in the etiology of emotional dysfunction). [ABSTRACT FROM AUTHOR]

Background: Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders.Methods: This magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups.Results: Pineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups.Conclusion: These results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis. [ABSTRACT FROM AUTHOR]

Introduction In addition to the psychosis onset, patients at clinical high-risk (CHR) show a decrease of functioning. This may not be related to the degree and persistence of the attenuated positive symptom (APS). Other clinical factors also predict the level of remission. Objectives Revealing the predictors of the functioning in the 5-year follow-up in patients at CHR. Methods 124 young depressive patients at CHR were examined. Depression symptoms were assessed on the HDRS scale, and the CHR symptoms were assessed on the SOPS scale. The follow-up examination was conducted after 5 years with the determination of functioning on the PSP scale. A correlative analysis of the predictors of the level of remission was conducted. Results The functioning level was inversely related to the length of a depressive episode with the CHR symptoms (r=-0,432, p˂0.05), to the negative sub-scale SOPS score (r=0.312, p˂0.05) and to the symptoms of disorganization sub-scale SOPS score (r=0.246, p˂0.05) in the primary assessment. Insufficient reduction of the positive, negative symptoms and symptoms of disorganization on the SOPS during in-patient treatment was also a predictor of the worst outcome at the 5-year follow-up (r=-0,206, p˂0,05; r=-0,309, p˂0,05; r=-0,355, p˂0,05, and r=-0,349, p˂0,05, respectively). Conclusions There are some factors, except the severity of APS, that may be considered as the predictors of functioning level in patients at CHR. Disclosure No significant relationships.

Introduction The clinical high-risk for psychosis (CHR) is mainly established by the presence of attenuated positive symptoms (APS), but there is evidence of the role of attenuated negative symptoms (ANS) in the development of psychotic spectrum disorders. It is important to establish a link between APS and ANS in patients at CHR in order to improve early detection of psychosis. Objectives Establish the relationship between APS and ANS in depressive patients at CHR. Methods 130 depressive young in-patients at CHR with APS (average age 19.5) and 71 ones with ANS (average age 19.5) were examined. The HDRS scale was used to assess depressive symptoms, the SOPS scale was used to assess APS and ANS, and the SANS scale was used to assess ANS. The results are presented in median values. Results No differences were found between two groups in the severity of depressive symptoms on the HDRS scale and CHR symptoms on the SOPS scale (22 vs 23.5 and 45 vs 43 respectively). Statistically valid differences have been established between the groups in the APS severity on the sub-scale of positive symptoms SOPS: 11 and 7 (p 0.001). No differences in the ANS severity on the sub-scale of negative symptoms were detected (17 and 18.5, p=0.207). There were also no differences in the ANS severity on the SANS scale (40 and 47, p=0.163). Conclusions It has been established that patients at CHR with APS also have ANS, which may have clinical significance for early detection of psychosis. Disclosure No significant relationships.

Introduction Early detection of psychosis is a promising area in preventive psychiatry. The use of early intervention can prevent the first episode psychosis and improve outcomes. Objectives Identification of premorbid features of depressive patients at clinical high risk for psychosis (CHR) comparing with depressive patients without CHR in order to improve early recognition of the psychotic process. Methods 219 young depressive in-patients with CHR criteria for SOPS with attenuated positive and attenuated negative symptoms and 52 young depressive in-patients without CHR were examined. Presence of obstetric complications, neurodevelopmental deviance, neurological and psychiatric signs at the premorbid stage, and the level of premorbid functioning on the PAS were examined. Results It has been established that depressive patients at CHR and without CHR had some obstetric complications (57.5% and 40.4%, respectively). Neurodevelopmental deviance in the first year of live was in 57.5% patients with CHR. At the age of 3-5 sleep disorders, ADHD and phobias were more common in patients at CHR than without it (58.8% and 32.7%, p=0.014). In pubertal, patients at CHR were more likely to show depression symptoms, obsessions, and aggression - 90.4% versus 76.9% (p=0.029). On the PAS scale, a decrease of the level of premorbid functioning has been observed in two groups of patients with and without CHR from the age of 12: from 12 to 15 years, 0.4 and 0.3 (p=0.004), from 16 to 18 years, 0.47 and 0.37 (p 0.001). Conclusions Premorbid functioning were worst in patients with CHR, which indicates the possibility of early clinical detection of psychosis. Disclosure No significant relationships.

Introduction At present, there is no universally approach to treating patients at clinical high-risk for psychosis (CHR) without comorbid mental disorders. However, if there are revealed depressive symptoms, proper treatment becomes necessary. Objectives Establish pharmacological classes and doses of drugs that have proved effective in treating depressive patients at CHR. Methods A comparative study of pharmacological classes and doses of drugs was carried out, showing the effectiveness in treatment of 219 depressive patients at CHR and 52 depressive patients without CHR. The treatment effectiveness was carried out on the reduction of depression symptoms on the HDRS scale, and the CHR symptoms on the SOPS scale. Results A significant reduction of depression symptoms was achieved in the group of depressive patients with and without CHR on the HDRS scale (67.9% and 76.6% respectively). The reductions of the CHR symptoms were 46.1% and 53.3% respectively. There were differences between the severity of depression symptoms and CHR symptoms before and after the treatment. Both groups used antidepressants followed by the prescription of antipsychotics to increase the effectiveness of the therapy. No difference was found in the doses of antidepressants for the fluoxetine equivalent (46.0 vs 42.6 mg per day, p 0.05) and some differences were found for the average effective doses of antipsychotics for the chlorpromazine equivalent (385.4 vs 230.8 mg per day, p 0.05). Conclusions The same pharmacological classes are used for the treatment of young depressive patients with and without CHR, but the former have significantly higher doses of antipsychotics. Disclosure No significant relationships.

Schizophrenia is characterised by cognitive impairments that are already present during early stages, including in the clinical high-risk for psychosis (CHR-P) state and first-episode psychosis (FEP). Moreover, data suggest the presence of distinct cognitive subtypes during early-stage psychosis, with evidence for spared vs. impaired cognitive profiles that may be differentially associated with symptomatic and functional outcomes. Using cluster analysis, we sought to determine whether cognitive subgroups were associated with clinical and functional outcomes in CHR-P individuals. Data were available for 146 CHR-P participants of whom 122 completed a 6- and/or 12-month follow-up; 15 FEP participants; 47 participants not fulfilling CHR-P criteria (CHR-Ns); and 53 healthy controls (HCs). We performed hierarchical cluster analysis on principal components derived from neurocognitive and social cognitive measures. Within the CHR-P group, clusters were compared on clinical and functional variables and examined for associations with global functioning, persistent attenuated psychotic symptoms and transition to psychosis. Two discrete cognitive subgroups emerged across all participants: 45.9% of CHR-P individuals were cognitively impaired compared to 93.3% of FEP, 29.8% of CHR-N and 30.2% of HC participants. Cognitively impaired CHR-P participants also had significantly poorer functioning at baseline and follow-up than their cognitively spared counterparts. Specifically, cluster membership predicted functional but not clinical outcome. Our findings support the existence of distinct cognitive subgroups in CHR-P individuals that are associated with functional outcomes, with implications for early intervention and the understanding of underlying developmental processes. [ABSTRACT FROM AUTHOR]

Psychosis involves changes in GABAergic and glutamatergic neurotransmission in auditory cortex that could be important for understanding sensory deficits and symptoms of psychosis. However, it is currently unclear whether such deficits are present in participants at clinical high-risk for psychosis (CHR-P) and whether they are associated with clinical outcomes. Magnetic Resonance Spectroscopy (MEGAPRESS, 1H-MRS at 3 Tesla) was used to estimate GABA, glutamate, and glutamate-plus-glutamine (Glx) levels in auditory cortex in a large sample of CHR-P (n = 99), CHR-N (clinical high-risk negative, n = 32), and 45 healthy controls. Examined were group differences in metabolite concentrations as well as relationships with clinical symptoms, general cognition, and 1-year follow-up clinical and general functioning in the CHR-P group. Results showed a marginal (p = 0.039) main group effect only for Glx, but not for GABA and glutamate concentrations, and only in left, not right, auditory cortex. This effect did not survive multiple comparison correction, however. Exploratory post-hoc tests revealed that there were significantly lower Glx levels (p = 0.029, uncorrected) in the CHR-P compared to the CHR-N group, but not relative to healthy controls (p = 0.058, uncorrected). Glx levels correlated with the severity of perceptual abnormalities and disorganized speech scores. However, in the CHR-P group, Glx levels did not predict clinical or functional outcomes. Accordingly, the findings from the present study suggest that MRS-measured GABA, glutamate and Glx levels in auditory cortex of CHR-P individuals are largely intact. [ABSTRACT FROM AUTHOR]