Ultra-high Risk Group Research Articles

Vocational functioning in young people accessing services for first-episode psychosis and ultra-high risk of psychosis: A longitudinal naturalistic cohort study.

Young people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment. This is a naturalistic sample of young people aged 12-25 with FEP (n = 1574) and UHR (n = 1515), accessing treatment in the headspace Early Psychosis (hEP) programme. Engagement in education and employment was assessed at baseline and every 90 days in treatment. Mixed effects logistic regression were used to analyse changes over time. On entering the hEP programme, approximately 49% of the young people with FEP and 28% of the young people at UHR status identified as Not in Education, Employment or Training (NEET). The odds of being NEET were reduced by 27% (95% confidence interval = [14, 39]) for every 6 months treatment for the FEP group, but no change in NEET status was observed in the UHR group. In both groups, absence from daily activities was significantly reduced during time in treatment. While there are methodological challenges analysing real-world non-control group cohort data, the findings indicate positive effects of the hEP programme on vocational and daily activity engagement for young people with FEP and at UHR status. A large proportion of the young people still identified as NEET after receiving treatment services, suggesting further refinement to ensure targeted and consistent vocational support throughout care.

Abstract PO3-02-04: Comparison of OncotypeDX Recurrence Scores (RS) and MammaPrint (MP) scores, and chemotherapy indications in early-stage Estrogen Receptor positive/HER2 negative (ER-/HER2-) breast cancer

Abstract Background: Both RS and MP are endorsed by ASCO and NCCN practice guidelines to estimate prognosis of early-stage ER+/HER2- breast cancers and results guide adjuvant chemotherapy treatment recommendations. Earlier studies reported around 30% discordance in risk assignments by different genomic assays, but these comparisons were complicated by the 3-way (low, intermediate, high) versus 2-way (low, high) risk assignment by RS and MP respectively. More recently, RS thresholds were re-evaluated in the context of the TAILORx and RxPONDER randomized clinical trials and RS >25 is now considered indication for adjuvant chemotherapy. MP results are now also reported as continuous scores similar to RS, and MP high risk patients can be subdivided into MP1 (high) and MP2 (ultra-high) risk groups. The goal of this analysis was to assess correlation between RS and MP scores as continuous variables and examine concordance in chemotherapy eligibility and risk category assignments. Methods: 168 patients treated at the West Cancer Center and Research Institute had patients with both MP and RS results available for the same patient generated by Agendia as a research activity and Exact Sciences in the context of routine care. Molecular class was assigned by the MammaPrint Blueprint assay. Results and clinical information were retrieved from the medical records. Median age was 64 years (range 25-92), 77% were postmenopausal, 59% White, 37% Black and 4% other. 78% had histologic grade 1 or 2 cancers, 53%, 38%, and 8% were stage I, II, and III, respectively. 84% were invasive ductal carcinoma, 13% invasive lobular carcinoma, the rest mixed or other rare histologies. Patients were considered high-risk and chemotherapy eligible if the RS was >25 or the MP score was < 0 (i.e. any negative value), MP high-risk patients were further categorized into MP1 (MP score between 0 to -0.5699) and MP2 (MPs score -0.57 or less). Correlation between scores were assessed using Pearson correlation. Results: There was statistically significant correlation between RS and MP scores with a Pearson correlation coefficient of -0.61, (p< 0.0001). 51 (30%) cancers were MP low-risk (Luminal A), and 122 (73%) were RS low risk (RS≤25). Among the MP low-risk cancers, 47 (92%) had concordant low risk assignment by RS. Based on RS, 46 (27%) patients were high-risk chemotherapy eligible and 42 of these (91%) were concordantly classified as MP high-risk. MP high-risk cancers included 115 Luminal B and 1 Basal-like cancers, and 64% of these (n=74) had low-risk status by RS. When the MP high category was subdivided into MP 1 (n=105) and MP2 (n=11) subgroups, (35/105) 33% and (7/11) 64% of cases were RS >25, respectively. Black patients had a statistically higher mean index MP score of -0.191 compared to -0.082 for White patients (p=0.02). No statistical difference was noted by race for RS. Conclusions: There was strong concordance (92%) between low-risk MP and low-risk RS. Similar concordance was not identified when comparing chemotherapy eligible high-risk MP (MP1 and MP2) to high-risk ( >25) recurrence scores. Only 36% of chemotherapy eligible MP patients (MP1 and MP2) would be chemotherapy eligible by RS. Higher concordance (58%) for chemotherapy eligibility was seen when limited to the ultra-high (MP2) scores. By contrast most (92%) of chemotherapy eligible patients by RS (>25) were considered high risk by MP (MP1 or MP2). Table1. RS and MP risk categories Citation Format: Rishika Singh, William Barlow, Nupur Singh, James Elliott, Richard Fine, Michael Berry, Erin Cobain, Lajos Pusztai, Gregory Vidal. Comparison of OncotypeDX Recurrence Scores (RS) and MammaPrint (MP) scores, and chemotherapy indications in early-stage Estrogen Receptor positive/HER2 negative (ER-/HER2-) breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-04.

Plasma neurofilament light chain is not elevated in people with first-episode psychosis or those at ultra-high risk for psychosis

IntroductionNeurofilament light chain (NfL), a blood biomarker of neuronal injury, shows promise in distinguishing neurodegenerative disorders from psychiatric conditions. This is especially relevant in psychosis, given neurological conditions such as autoimmune encephalitis and Niemann Pick Type C disease (NPC) may initially present with psychotic symptoms. Whilst NfL levels have been studied in established schizophrenia cases, their levels in first-episode psychosis (FEP) and ultra-high risk (UHR) for psychosis individuals remain largely unexplored. This study aimed to compare plasma NfL in people with FEP or UHR with healthy controls, as well as explore its associations with clinical data. MethodWe retrospectively analysed plasma NfL in 63 participants, consisting of 29 individuals with FEP, 10 individuals with UHR, and 24 healthy controls. We used general linear models (GLM), which were bootstrapped, to compute bias-corrected and accelerated (BCa) 95 % confidence intervals (CIs). ResultsMean NfL levels were 5.2 pg/mL in FEP, 4.9 pg/mL in UHR, and 5.9 pg/mL in healthy controls. Compared to healthy controls, there were no significant differences in NfL levels in the FEP group (β = −0.22, 95 % CI [−0.86, 0.39], p = 0.516) nor UHR group (β = −0.37, 95 % CI [−0.90, 0.19], p = 0.182). There were no significant associations between NfL levels and clinical variables in the FEP group. DiscussionOur study is the first to demonstrate that plasma NfL levels are not significantly elevated in individuals at UHR for psychosis compared to healthy controls, a finding also observed in the FEP cohort. These findings bolster the potential diagnostic utility of NfL in differentiating between psychiatric and neurodegenerative disorders.

Clinical features and demographic characteristics of gestational trophoblastic neoplasia: Single center experience and the SEER database.

The aim of this study was to analyze the clinical features and demographic characteristics of gestational trophoblastic neoplasia (GTN) patients, specifically choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), and epithelioid trophoblastic tumor (ETT). We utilized data from a local hospital and the SEER database, as well as survival outcomes of CC in SEER database. Additionally, we used multiple risk factors to create a prognostic nomogram model for CC patients. The study included GTN patients from the SEER database between 1975 and 2016 as well as those from the First Affiliated Hospital of Xi 'an Jiaotong University between January 2005 and May 2022. Related factors of patients were compared using the chi-square (χ2) or Fisher's exact test. For assessing overall survival we employed the Kaplan-Meier method and log-rank test. To construct the nomogram, we used Cox regression. Statistically significant differences were found between CC and PSTT/ETT patients in terms of surgery in local hospital, as well as age and year of diagnosis in the SEER database. Moreover, significant differences were observed between low and high (HR) /ultra-high risk (UHR) groups regarding FIGO stage, surgery and chief complaint at the local hospital, and FIGO stage, surgery and unemployment in the SEER database. The Cox regression analysis confirmed that age, race, surgery, marital status, FIGO stage, and unemployment were correlated with CC prognosis. Furthermore, the analysis showed that patients aged 40 years or older and those with FIGO Ⅲ/Ⅳ were independent prognostic factors of CC. The study indicates that atypical symptoms or signs may be the main reasons for HR /UHR patients to seek medical treatment. Therefore, providing multidisciplinary care is recommended for CC patients experiencing psychological distress due to unfavorable marital status or unemployment.

Gamma-band harmonic responses for beta-band auditory steady-state response are intact in patients with early stage schizophrenia.

Gamma oscillations, thought to arise from the activity of ɣ-aminobutyric acid (GABA)ergic interneurons, have potential as a biomarker for schizophrenia. Gamma-band auditory steady-state responses (ASSRs) are notably reduced in both chronic and early-stage schizophrenia patients. Furthermore, alterations in gamma-band ASSRs have been demonstrated in animal models through translational research. However, the 40-Hz harmonic responses of the 20-Hz ASSR are not as well-characterized, despite the possibility that these harmonic oscillatory responses may reflect resonant activity in neural circuits. In this study, we investigated the 40-Hz harmonic response to the 20-Hz ASSR in the early stages of schizophrenia. The study recruited 49 participants, including 15 individuals at ultra-high-risk (UHR) for psychosis, 13 patients with first-episode schizophrenia (FES), and 21 healthy controls (HCs). The 40-Hz harmonic responses of the 20-Hz ASSR were evident in all groups. Interestingly, while previous report observed reduced 40-Hz ASSRs, the 40-Hz harmonic responses of the 20-Hz ASSR were not reduced in the UHR or FES groups. These findings suggest that the gamma-band ASSR and its harmonic responses may represent distinct aspects of pathophysiology in the early stages of schizophrenia.

Gene Polymorphisms and Expression of NRG1, DAOA, and DISC1 Genes in a Chinese Han Population with an Ultra-High Risk for Psychosis.

Although there is previous evidence supporting that ultra-high risk (UHR) for psychosis transformation is associated with NRG1, DAOA, and DISC1 genes, there have been no relevant studies in the Chinese population. The objective of the current study was to explore the gene polymorphism and expression of NRG1, DAOA, and DISC1 genes in a Han population with UHR for psychosis in China. Eighteen UHR individuals, 61 first-degree relatives of patients with schizophrenia (FDR), 55 first-episode psychosis individuals (FEP), and 61 healthy controls (HC) were enrolled in the study. The genotypes at four loci of the NRG1 gene, four loci of the DAOA gene, and two loci of the DISC1 gene were tested for all subjects, and mRNAs of NRG1 and DISC1 were examined and analyzed in a pairwise comparison among the four groups. Statistical analysis of genetics was performed using snpStats software. For the case-control association analysis, a single site association study, epistatic effect analysis, and haplotype analysis were used to explore the association of the above genes. This study found that rs3918341 in the DAOA gene was associated with susceptibility to UHR by single site association analysis. Epistatic effect analysis results showed that the NRG1 gene interacted with the DAOA gene and DISC1 gene in the susceptibility to UHR. Haplotype association analysis showed that all haplotypes were not significantly associated with UHR. NRG1 mRNA was significantly downregulated in the UHR group compared with the HC group as well as the FEP group. Our preliminary results show that NRG1, DAOA, and DISC1 genes may play a role in psychosis onset, opening the way to the identification of prognostic biomarkers.

Personality functioning and self-disorders in individuals at ultra-high risk for psychosis, with first-episode psychosis and with borderline personality disorder.

Assessment of personality functioning in different stages of psychotic disorders could provide valuable information on psychopathology, course of illness and treatment planning, but empirical data are sparse. To investigate personality functioning and sense of self in individuals at ultra-high risk (UHR) for psychosis and with first-episode psychosis (FEP) in comparison with a clinical control group of individuals with borderline personality disorder (BPD) and healthy controls. In a cross-sectional design, we investigated personality functioning (Structured Interview of Personality Organization, STIPO; Level of Personality Functioning Scale, LPFS) and disturbances of the basic self (Examination of Anomalous Self-Experience, EASE) in 107 participants, comprising 24 individuals at UHR, 29 individuals with FEP, 27 individuals with BPD and 27 healthy controls. The UHR, FEP and BPD groups had moderate to severe deficits in personality organisation (STIPO) compared with the healthy control group. Self-functioning with its subdomain (facet) 'self-direction' (LPFS) was significantly worse in participants with manifest psychosis (FEP) compared with those at-risk for psychosis (UHR). The FEP group showed significantly worse overall personality functioning than the UHR group and significantly higher levels of self-disturbance (EASE) than the BPD group, with the UHR group lying between these diagnostic groups. Hierarchical cluster analysis based on the seven STIPO domains yielded three clusters differing in level of personality functioning and self-disturbances. Our data demonstrate that psychotic disorders are associated with impaired personality functioning and self-disturbances. Assessment of personality functioning can inform treatment planning for patients at different stages of psychotic disorder.

Suicide risk among individuals at Ultra-High Risk (UHR) of psychosis in a developing North African country: A 12-month naturalistic prospective cohort study from the TRIP project

BackgroundThe limited studies that focused on suicidality in individuals at Ultra-High Risk (UHR) of psychosis were predominantly cross-sectional, emerging from Western countries. We aimed to examine suicide risk among Tunisian UHR and First Episode Psychosis (FEP) patients at baseline, and to evaluate the evolution and correlates of suicidal ideation over a 12-month period in the UHR group exclusively. Methods35 UHR (aged 22.8 ± 4.0 years, 45.7% male) and 33 FEP (aged 27.3 ± 4.8 years, 63.6% male) participants were included. The Comprehensive Assessment of at Risk Mental States, the Positive and Negative Syndrome Scale (PANSS), The Rosenberg Self-Esteem Scale, and The Multidimensional Scale of Perceived Social Support were used. ResultsNo significant differences were found between the UHR and the FEP groups with regard to levels of suicidal ideation at baseline. Suicidal ideation scores showed a significant decrease over time in UHR participants (p=.014; η2=0.242). An increase in total PANSS scores at 1 year (Beta=0.03; p=.048; 95%CI 0.001, 0.060; η2=0.182) significantly increased suicidal ideation scores at 1 year in the UHR group. ConclusionOur findings contribute to the limited body of evidence on this topic by providing new prospective data from a population, country and region that has never been researched previously.

Alterations of auditory-evoked gamma oscillations are more pronounced than alterations of spontaneous power of gamma oscillation in early stages of schizophrenia

Several animal models of schizophrenia and patients with chronic schizophrenia have shown increased spontaneous power of gamma oscillations. However, the most robust alterations of gamma oscillations in patients with schizophrenia are reduced auditory–oscillatory responses. We hypothesized that patients with early-stage schizophrenia would have increased spontaneous power of gamma oscillations and reduced auditory–oscillatory responses. This study included 77 participants, including 27 ultra-high-risk (UHR) individuals, 19 patients with recent-onset schizophrenia (ROS), and 31 healthy controls (HCs). The auditory steady-state response (ASSR) and spontaneous power of gamma oscillations measured as induced power during the ASSR period were calculated using electroencephalography during 40-Hz auditory click-trains. The ASSRs were lower in the UHR and ROS groups than in the HC group, whereas the spontaneous power of gamma oscillations in the UHR and ROS groups did not significantly differ from power in the HC group. Both early-latency (0–100 ms) and late-latency (300–400 ms) ASSRs were significantly reduced and negatively correlated with the spontaneous power of gamma oscillations in the ROS group. In contrast, UHR individuals exhibited reduced late-latency ASSR and a correlation between the unchanged early-latency ASSR and the spontaneous power of gamma oscillations. ASSR was positively correlated with the hallucinatory behavior score in the ROS group. Correlation patterns between the ASSR and spontaneous power of gamma oscillations differed between the UHR and ROS groups, suggesting that the neural dynamics involved in non-stimulus-locked/task modulation change with disease progression and may be disrupted after psychosis onset.

A PREDICTIVE MODEL FOR ULTRA‐HIGH RISK IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: A SINGLE‐CENTER STUDY IN CHINA

Introduction: Although novel therapies have significantly improved the prognosis of multiple myeloma (MM) patients, there are still a subgroup of MM patients experienced early relapse or disease progression. To early identify the patients with compromised prognosis in our center, the study aimed to establish a predictive model for ultra-high risk (UHR) in MM. Methods: A study from a tertiary hospital in western China analyzed the patients with newly diagnosed MM (NDMM) receiving bortezomib and/or lenalidomide-included regimens from January 2015 to June 2021. The last follow-up date was December 31, 2022. The patients were randomly divided (2:1) into training and validation cohorts, and the patients with progression-free survival (PFS) less than 12 months were defined as UHR. Univariate and multivariate Cox regression analyses were performed for clinical feature selection. Independent baseline factors were incorporated and scored to develop the predictive model. The UHR group was then defined beyond the optimal cut-off value of total scores. Results: A total of 314 MM patients were enrolled and 102 (32.5%) patients underwent autologous hemopoietic stem cell transplantation (ASCT). The median time of follow-up was 36.6 months. Disease progression and death occurred in 178 (56.7%) and 69 (22.0%) patients. The median PFS (mPFS) was 36.5 months, and the median overall survival (mOS) was not reached. The mPFS of patients stratified into R-ISS III, R2-ISS III, R2-ISS IV, IMWG high-risk and mSMART double/triple hit was 23.8, 25.6, 10.0, 17.2 and 10.5 months, respectively. Among 54 patients at UHR, less than half of them could be identified by the aboved stratification systems. In the training cohort, elevated LDH, hypercalcemia, 1q21 gain/amplification (1q+) and the presence of extramedullary disease (EMD) showed significant association with UHR in NDMM. Referring to the results, the UHR predictive model was developed as 5 points for elevated LDH, 6 points for hypercalcemia, 7 points for 1q+ and 10 points for EMD. Patients with total scores of more than 12 points can be predicated as UHR. This model identified UHR and non-UHR groups with significantly different mPFS (9.8 v.s. 37.5 months, HR = 3.24, 95% CI:2.09-5.03, P < 0.001) and 5-year OS (63.3% vs. 83.8%, HR = 2.92, 95% CI: 1.47-5.81, P = 0.002). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.77, and in the validation cohort, the UHR model kept good discrimination (AUC: 0.79) at the latest follow-up. Conclusions: In this study, elevated LDH, hypercalcemia, 1q+ and EMD were selected and scored to develop the UHR model for NDMM patients. At present, the extension of follow-up time and expansion of sample size in the validation cohort are still ongoing. External validity is also designed to verify the generalizability of the model. The research was funded by: Natural Science Foundation of Sichuan Province, China, Grant/Award Number: 2022NSFSC1299 Keywords: Risk Models, Multiple Myeloma No conflicts of interests pertinent to the abstract.

Study protocol: Epigenetic variations associated to the conversion of schizophrenia in ultra-high risk adolescents, a 4-year follow-up study

IntroductionSchizophrenia is a severe mental disorder characterized by negative (e.g., social withdrawal, apathy, anhedonia) and positive (e.g., hallucinations, delusions, disorganized behaviour) symptoms. Schizophrenia prodromal symptoms typically emerge during the adolescence. These symptoms consist of attenuated and/or intermittent psychotic symptoms and define the ultra-high risk (UHR) states of schizophrenia. Approximately, 30% of UHR individuals develop schizophrenia. It is important to find biomarkers associated with the conversion of schizophrenia in UHR individuals in order to develop preventive and therapeutic strategies, as well as to gain knowledge in the ethiopathology of the disorder. In this regard, epigenetic variations have been identified as potential biomarkers associated with the conversion to schizophrenia, but the lack of research prevent to draw final conclusions.ObjectivesThe objective of this communication is to report the study protocol of the research project named “Epigenetic variations associated with the conversion of schizophrenia in ultra-high risk adolescents”. Its aim is to analyze the epigenetic marks that predict the development of schizophrenia in UHR youths.MethodsA 4-year observational follow-up study will be conducted, assessing three groups of adolescents who have sought clinical hep: 1) UHR group composed of individuals who have developed schizophrenia at the end of the follow-up; 2) UHR group composed of individuals who did not develop schizophrenia at the end of the follow-up; 3) a group composed of non-UHR individuals. Epigenetic marks will be analyzed in the peripheral blood of all the participants each 6 months. Clinical (i.e., positive and negative symptoms, depressive symptoms, anxiety symptoms, global functioning, traumatic events, alcohol and other toxics consumption) and sociodemographic data (i.e., age, sex, migration status, ethnicity, socio-cultural status, academic achievements) will be also assessed through standardized questionnaires.ResultsWe hypothesize that specific epigenetic marks will predict the conversion of schizophrenia in the UHR group. Moreover, interactions between epigenetic variations and sociodemographic data will differentiate the three groups after the follow-up.ConclusionsThe findings of this project will help to develop preventive and therapeutic strategies, as well as to gain knowledge in the etiopathological pathways of schizophrenia.Disclosure of InterestNone Declared

Identifying populations at ultra-high risk of suicide using a novel machine learning method

BackgroundTargeted interventions for suicide prevention rely on adequate identification of groups at elevated risk. Several risk factors for suicide are known, but little is known about the interactions between risk factors. Interactions between risk factors may aid in detecting more specific sub-populations at higher risk. MethodsHere, we use a novel machine learning heuristic to detect sub-populations at ultra high-risk for suicide based on interacting risk factors. The data-driven and hypothesis-free model is applied to investigate data covering the entire population of the Netherlands. FindingsWe found three sub-populations with extremely high suicide rates (i.e. >50 suicides per 100,000 person years, compared to 12/100,000 in the general population), namely: (1) people on unfit for work benefits that were never married, (2) males on unfit for work benefits, and (3) those aged 55–69 who live alone, were never married and have a relatively low household income. Additionally, we found two sub-populations where the rate was higher than expected based on individual risk factors alone: widowed males, and people aged 25–39 with a low level of education. InterpretationOur model is effective at finding ultra-high risk groups which can be targeted using sub-population level interventions. Additionally, it is effective at identifying high-risk groups that would not be considered risk groups based on conventional risk factor analysis.

Neuronal dysfunction in individuals at early stage of schizophrenia, A resting-state fMRI study

Schizophrenia has been associated with abnormal intrinsic brain activity, involving various cognitive impairments. Qualitatively similar abnormalities are seen in individuals at ultra-high risk (UHR) for psychosis. In this study, resting-state fMRI (rs-fMRI) data were collected from 44 drug-naïve first-episode schizophrenia (Dn-FES) patients, 48 UHR individuals, and 40 healthy controls (HCs). The fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and functional connectivity (FC), were performed to evaluate resting brain function. A support vector machine (SVM) was applied for classification analysis. Compared to HCs, both clinical groups showed increased fALFF in the central executive network (CEN), decreased ReHo in the ventral visual pathway (VVP) and decreased FC in temporal-sensorimotor regions. Excellent performance was achieved by using fALFF value in distinguishing both FES (sensitivity=83.21%, specificity=80.58%, accuracy=81.37%, p=0.009) and UHR (sensitivity=75.88%, specificity=85.72%, accuracy=80.72%, p<0.001) from HC group. Moreover, the study highlighted the importance of frontal and temporal alteration in the pathogenesis of schizophrenia. However, no fMRI features were observed that could well distinguish Dn-FES from UHR group. To conclude, fALFF in the CEN may provide potential power for identifying individuals at the early stage of schizophrenia and the alteration in the frontal and temporal lobe may be important to these individuals.

Visual illusions in young people reporting psychotic-like experiences

Background and objectivesA disruption in the co-ordination of bottom-up and top-down processing is thought to underlie anomalous perceptual experiences in psychosis. Visual illusions represent a valuable methodology in exploring this disruption. Here, we examined visual illusions in a group of young people having psychotic-like experiences. We also examined the relationship between illusion susceptibility and appraisal of psychotic-like experiences as well as depression, anxiety and stress levels. Method25 young people reporting psychotic-like experiences and 53 healthy participants performed an adjustment task that measured susceptibility to a battery of 13 visual illusions. Levels of depression, anxiety and stress were quantified in both groups. The clinical group also completed measures examining frequency, appraisals and emotional responses to psychotic-like experiences. ResultsA general increase of illusion susceptibility was found in the clinical group compared to the control group. However, when depression, anxiety and stress levels were controlled for, this difference disappeared. Stress turned out to be the best predictor of illusion susceptibility in the clinical group, whereas anomalous experiences, depression and anxiety were unrelated to overall illusion strength. LimitationsThis study is limited to young participants reporting significant mental health difficulties and psychotic-like experiences. Findings should be replicated in an Ultra High Risk (prodromal) group. ConclusionsIncreased levels of stress explained the enhanced vulnerability to illusions in the clinical group. This increased susceptibility suggests a perceptual style that relies too heavily on prior expectations at the expense of the true sensory evidence, potentially leading to an altered perceptual experience of the world.

Effectiveness of a two-stage strategy using the 16-item Prodromal Questionnaire (PQ16/fPQ16) and the Comprehensive Assessment of At Risk Mental States (CAARMS) in the early detection of Ultra High Risk (UHR) patients in Lebanon: a cross-sectional pilot study

ObjectivesThis study aims to identify the prevalence of Ultra High Risk (UHR) adults in a sample of patients in Lebanon and to compare screening and diagnostic tools. MethodsThis is a cross-sectional pilot study which targeted patients aged 17–30 years willingly seeking psychiatric care in a university hospital in Beirut, Lebanon. Participants were invited to fill either the English or the French version of the Prodromal Questionnaire (respectively, PQ16 or fPQ16). The abbreviated version of the “Comprehensive Assessment of At-Risk Mental States” (CAARMS) was then administered to all participants. The latter were subsequently sorted into one of the three UHR groups – vulnerability group, attenuated psychosis (APS), intermittent psychosis (BLIPS) – or were diagnosed as suffering from a psychotic disorder. ResultsThirty-one patients participated in this study. The prevalence of positive screening on the PQ16/fPQ16 and positive diagnosis of UHR on the CAARMS were respectively of 61.29% and 45%. The APS group was the most prevalent (71.42%). A positive psychosis screening on PQ16/fPQ16 was statistically related to a UHR diagnosis on CAARMS (p-value: 0.011 on Chi2 test), OR=8.5 (95% CI: 1.4–50.9; p-value: 0.018). No relation was found between PQ16/fPQ16 results and risk stratification or between the number of “True” responses on PQ16/fPQ16 and the intensity of symptoms on CAARMS. PQ16/fPQ16 statements 5, 9, 11 and 16 predicted a UHR diagnosis on CAARMS (p-value of 0.045, 0.006, 0.045 and 0.045, respectively). ConclusionThis two-stage strategy for identifying UHR patients can be adopted in a tertiary health care center.

Personality traits and transition to psychosis one year after the first assessment.

Several studies have identified ultra-high-risk criteria that may characterize an at-risk mental state and predict the transition of psychotic evolution. Personality traits may play a crucial role in this process. The current study aims to: (a) explore the evolution of an initial diagnosis over 12 months; (b) assess differences in social and occupational functioning; (c) identify common (trans-diagnostic) personality traits of psychotic risk. The sample includes 97 (44 males and 53 females) young adults. They completed an assessment that consists of socio-demographic data, the Social and Occupational Functioning Scale, the Early Recognition Inventory-retrospective assessment onset of schizophrenia, and the Personality Inventory for DSM-5 (PID-5). According to the tests' assessment, the sample was divided into three different groups: Ultra-High Risk (UHR), At-Risk, and Not at risk. One year after the first evaluation, psychiatrists administered the QuickSCID-5 to verify the diagnostic trajectories of the sample. Overall, the most prevalent category diagnoses were anxiety/depression, personality disorders, and psychosis. Specifically, the most common diagnosis in the UHR group was psychosis. Moreover, in the UHR group, the social and occupational functioning score was the lowest. In terms of differences in PID-5 personality traits, the At-risk and UHR groups scored highest in detachment and disinhibition. No statistically significant differences were found between the groups for negative affectivity, antagonism, and psychoticism traits. Results obtained by the current study should be considered an attempt to better understand the diagnostic trajectories and trans-diagnostic personality traits in a group of young help-seekers, specifically in UHR. Findings highlight both the importance of diagnosis and personality traits evaluation to customize a specific intervention based on the level of psychotic risk. Clinical suggestions are reported.

IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals.

Dysregulation of immunity, such as levels of inflammatory factors, has been regarded as a sign of schizophrenia. Changes in cytokine levels are not only described in the early onset of disease, but also observed in ultra-high risk (UHR) individuals. This study aimed to investigate the potential of cytokines as biomarkers for psychotic disorders and in individuals at UHR of developing a psychotic disorder in the future. The Luminex liquid chip technology was used to detect the concentrations of Interferon-gamma (INF-γ), Interleukin (IL)-2, Interleukin (IL)-4, Interleukin (IL)-6, Interleukin (IL)-17, Interleukin-1beta (IL-1β), and Tumor Necrosis Factor-beta (TNF-β) in the plasma of all subjects. Meanwhile, the plasma level of Tumor Necrosis Factor-Alpha (TNF-α) was measured with the enzyme-linked immunosorbent assay (ELISA) kits. Then, the levels of these cytokines were compared among patients with Drug-naïve first-episode schizophrenia (FES; n = 40), UHR population (UHR; n = 49), and healthy controls (HCs; n = 30). Baseline cytokine levels were compared among UHR individuals who later transitioned (UHR-T; n = 14), those who did not transition (UHR-NT; n = 35), and HCs (n = 30). Our analysis results showed that IL-1β levels were significantly higher in UHR group than HC group (p = 0.015). Meanwhile, TNF-α concentration was significantly increased in FES group compared with HC group (p = 0.027). IL-17 (p = 0.04) and TNF-β (p = 0.008) levels were significantly higher in UHR-T group compared with UHR-NT group. In conclusion, our findings suggest that the immuno-inflammatory activation level is increased in the early stage of psychosis before psychotic conversion and the Drug-naïve FES. IL-1β and TNF-α are the representatives of the specific biomarkers for UHR and FES, respectively. IL-17 and TNF-β may be the potential selective predictive biomarkers for future transition in UHR individuals.

Short-chain fatty acids in patients with schizophrenia and ultra-high risk population.

Individuals who experience the prodromal phase of schizophrenia (SCZ), a common and complex psychiatric disorder, are referred to as ultra-high-risk (UHR) individuals. Short-chain fatty acid (SCFA) is imperative in the microbiota-gut-brain axis and brain function. Accumulating amount of evidence shows the connections between psychiatric disorders and SCFAs. This study aims to explore the underlying roles SCFAs play in SCZ by investigating the association of alterations in SCFAs concentrations with common cognitive functions in both the SCZ and UHR populations. The study recruited 59 SCZ patients (including 15 participants converted from the UHR group), 51 UHR participants, and 40 healthy controls (HC) within a complete follow-up of 2 years. Results of cognitive functions, which were assessed by utilizing HVLT-R and TMT, and serum concentrations of SCFAs were obtained for all participants and for UHR individuals at the time of their conversion to SCZ. Fifteen UHR participants converted to SCZ within a 2-year follow-up. Valeric acid concentration levels were lower in both the baseline of UHR individuals whom later converted to SCZ (p = 0.046) and SCZ patients (p = 0.036) than the HC group. Additionally, there were lower concentrations of caproic acid in the baseline of UHR individuals whom later transitioned to SCZ (p = 0.019) and the UHR group (p = 0.016) than the HC group. Furthermore, the caproic acid levels in the UHR group are significantly positively correlated with immediate memory (r = 0.355, p = 0.011) and negatively correlated with TMT-B (r = -0.366, p = 0.009). Significant differences in levels of acetic acid, butyric acid and isovaleric acid were absent among the three groups and in UHR individuals before and after transition to SCZ. Our study suggests that alterations in concentrations of SCFAs may be associated with the pathogenesis and the cognitive impairment of schizophrenia. Further researches are warranted to explore this association. The clinical implications of our findings were discussed.

Multi-omics integration reveals a six-malignant cell maker gene signature for predicting prognosis in high-risk neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor of childhood, arising from the sympathetic nervous system. High-risk neuroblastoma (HRNB) remains a major therapeutic challenge with low survival rates despite the intensification of therapy. This study aimed to develop a malignant-cell marker gene signature (MMGS) that might serve as a prognostic indicator in HRNB patients. Multi-omics datasets, including mRNA expression (single-cell and bulk), DNA methylation, and clinical information of HRNB patients, were used to identify prognostic malignant cell marker genes. MMGS was established by univariate Cox analysis, LASSO, and stepwise multivariable Cox regression analysis. Kaplan-Meier (KM) curve and time-dependent receiver operating characteristic curve (tROC) were used to evaluate the prognostic value and performance of MMGS, respectively. MMGS further verified its reliability and accuracy in the independent validation set. Finally, the characteristics of functional enrichment, tumor immune features, and inflammatory activity between different MMGS risk groups were also investigated. We constructed a prognostic model consisting of six malignant cell maker genes (MAPT, C1QTNF4, MEG3, NPW, RAMP1, and CDT1), which stratified patients into ultra-high-risk (UHR) and common-high-risk (CHR) group. Patients in the UHR group had significantly worse overall survival (OS) than those in the CHR group. MMGS was verified as an independent predictor for the OS of HRNB patients. The area under the curve (AUC) values of MMGS at 1-, 3-, and 5-year were 0.78, 0.693, and 0.618, respectively. Notably, functional enrichment, tumor immune features, and inflammatory activity analyses preliminarily indicated that the poor prognosis in the UHR group might result from the dysregulation of the metabolic process and immunosuppressive microenvironment. This study established a novel six-malignant cell maker gene prognostic model that can be used to predict the prognosis of HRNB patients, which may provide new insight for the treatment and personalized monitoring of HRNB patients.

611P Clinical characteristics and outcomes in ultra high-risk gestational trophoblastic neoplasia: Experience from an Indian cancer center

Gestational trophoblastic neoplasia (GTN) patients with WHO risk score ≥13, as well as those with brain, liver, or extensive metastasis fall in the ultra high-risk group. Available data on these patients is limited. This study aims to assess the clinical characteristics and prognosis of this group.