Clinical High-risk Populations Research Articles

Psychosis and the self: How spontaneous discussions of subjective experiences compare in the clinical high-risk and first-episode psychosis populations.

Prior qualitative studies show that individuals with psychoticlike experiences express difficulties concerning their identity. However, previous work has studied individuals at clinical high risk for psychosis (CHR) and individuals with first-episode psychosis (FEP) separately. Here, we compare the experiences of individuals at CHR, individuals with FEP, and healthy individuals. Participants included 70 individuals at CHR (57% female, Mage = 19.2 ± 3.0), 50 individuals with FEP (56% female, Mage = 20.4 ± 2.9), and 70 healthy individuals (67% female, Mage = 21.1 ± 2.8). Participants completed 30-45-min open-ended interviews. Trained research staff reviewed interview transcripts and conducted an iterative thematic analysis to identify major themes. Themes related to distress, social difficulties, trauma, gratitude, and communication were spontaneously described by both individuals at CHR and individuals with FEP, with individuals at CHR describing suspiciousness more than individuals with FEP (42% vs. 22%), χ²(1, 120) = 4.95, p = .03, and individuals with FEP discussing adaptive integration of mental health struggles into their identity more than individuals at CHR (56% vs. 36%), χ²(1, 120) = 4.87, p = .03. Healthy individuals endorsed future orientation more than individuals at CHR (69% vs. 49%), χ²(1, 140) = 5.77, p = .02, and individuals with FEP (69% vs. 48%) χ²(1, 120) = 5.14, p = .02. All groups endorsed essentialist beliefs: CHR (31%), FEP (43%), and healthy controls (44%). Individuals at CHR and with FEP spontaneously discuss issues related to their identities in ways that are informed and shaped by the social milieu. The bidirectional nature of these struggles reinforces a need for integrated care through psychiatric rehabilitation, with a specific focus on identity development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for Psychosis and the Self: How Spontaneous Discussions of Subjective Experiences Compare in the Clinical High-Risk and First-Episode Psychosis Populations

Supplemental Material for Psychosis and the Self: How Spontaneous Discussions of Subjective Experiences Compare in the Clinical High-Risk and First-Episode Psychosis Populations

Evidence of altered monoamine oxidase B, an astroglia marker, in early psychosis and high-risk state.

A novel radiotracer, [11C]SL25.1188, targets monoamine oxidase-B (MAO-B) enzyme, found primarily in astrocytes, which metabolizes monoamines (including dopamine), particularly in subcortical regions. Altered astrocyte function in schizophrenia is supported by convergent evidence from post-mortem, genetic, transcriptomic, peripheral and preclinical findings. We aimed to test whether levels of MAO-B, an index of astrocyte function are low in the living brains of early psychosis and their high-risk states. Thirty-eight participants including antipsychotic-free/minimally exposed clinical participants with first-episode psychosis (FEP), clinical high-risk (CHR) individuals and healthy volunteers (HVs) underwent a 90-min positron emission tomography (PET) scan with [11C]SL25.1188, to measure MAO-B VT, an index of MAO-B concentration. Participants were excluded if tested positive on urine drug screen (except for cannabis). This study of 14 FEP (mean[SD] age, 25.7[5.7] years; 6 F), 7 CHR (mean[SD] age, 20.9[3.7] years; 4 F) and 17 HV (mean[SD] age, 31.2[13.9] years; 9 F) demonstrated significant group differences in regional MAO-B VT (F(2,37.42) = 4.56, p = 0.02, Cohen's f = 0.49), controlling for tobacco (F (1,37.42) = 5.37, p = 0.03) and cannabis use (F(1,37.42) = 5.11, p = 0.03) with significantly lower MAO-B VT in CHR compared to HV (Cohen's d = 0.99). We report a significant cannabis effect on MAO-B VT (F(1,39.19) = 12.57, p = 0.001, Cohen's f = 0.57), with a significant group-by-cannabis interaction (F(2,37.30) = 3.82, p = 0.03, Cohen's f = 0.45), indicating lower MAO-B VT in cannabis-using clinical groups. Lower MAO-B VT levels were more robust in striatal than cortical regions, in both clinical groups (F(12,46.84) = 2.08, p = 0.04, Cohen's f = 0.73) and in cannabis users (F(6,46.84) = 6.42, p < 0.001, Cohen's f = 0.91). Lower MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP clinical populations. Lower MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia.

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

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

The great recession, neurotic personality, and subjective sleep quality among patients with mood disorders

Previous studies exploring the effects of the business cycle on sleep have mostly focused on the general population, and their results have been inconclusive. This study aimed to explore the effects of the 2008 economic crisis and personality traits on the subjective sleep quality of outpatients with mood disorders. In this cross-sectional study, patients with mood disorders were recruited from two medical centers and a psychiatric hospital. Socio-demographics, the Eysenck Personality Questionnaire-Revised, and the Pittsburgh Sleep Quality Index (PSQI) were collected through in-person interviews. Candidate predictors significantly associated with PSQI scores in univariate analysis were included in a multiple linear regression model. There were 334 participants; 29% had unipolar depression, and 71% had bipolar affective disorder. The average PSQI score was 11.0 (±4.0). A higher degree of neuroticism [β(se) = 0.49 (0.07), p < 0.001] and recession period (vs. recovery period) [β(se) = 1.72 (0.47), p < 0.001] were associated with a higher PSQI score after adjusting for education, occupational class, and diagnosis. In conclusion, neuroticism and macroeconomy were independent predictors of subjective sleep quality in patients with mood disorders. This study suggests that large-scale economic crises have negative impacts on the sleep health of high-risk clinical populations.

S53 - Investigation of Life Events Associated With Development of OUD in Young Adults: A Longitudinal Study of a High-Risk Clinical Population

S53 - Investigation of Life Events Associated With Development of OUD in Young Adults: A Longitudinal Study of a High-Risk Clinical Population

Establishment of a risk prediction model for olfactory disorders in patients with transnasal pituitary tumors by machine learning

To construct a prediction model of olfactory dysfunction after transnasal sellar pituitary tumor resection based on machine learning algorithms. A cross-sectional study was conducted. From January to December 2022, 158 patients underwent transnasal sellar pituitary tumor resection in three tertiary hospitals in Sichuan Province were selected as the research objects. The olfactory status was evaluated one week after surgery. They were randomly divided into a training set and a test set according to the ratio of 8:2. The training set was used to construct the prediction model, and the test set was used to evaluate the effect of the model. Based on different machine learning algorithms, BP neural network, logistic regression, decision tree, support vector machine, random forest, LightGBM, XGBoost, and AdaBoost were established to construct olfactory dysfunction risk prediction models. The accuracy, precision, recall, F1 score, and area under the ROC curve (AUC) were used to evaluate the model's prediction performance, the optimal prediction model algorithm was selected, and the model was verified in the test set of patients. Of the 158 patients, 116 (73.42%) had postoperative olfactory dysfunction. After missing value processing and feature screening, an essential order of influencing factors of olfactory dysfunction was obtained. Among them, the duration of operation, gender, type of pituitary tumor, pituitary tumor apoplexy, nasal adhesion, age, cerebrospinal fluid leakage, blood scar formation, and smoking history became the risk factors of olfactory dysfunction, which were the key indicators of the construction of the model. Among them, the random forest model had the highest AUC of 0.846, and the accuracy, precision, recall, and F1 score were 0.750, 0.870, 0.947, and 0.833, respectively. Compared with the BP neural network, logistic regression, decision tree, support vector machine, LightGBM, XGBoost, and AdaBoost, the random forest model has more advantages in predicting olfactory dysfunction in patients after transnasal sellar pituitary tumor resection, which is helpful for early identification and intervention of high-risk clinical population, and has good clinical application prospects.

Advancements and Future Directions in Prevention Based on Evaluation for Individuals With Clinical High Risk of Psychosis: Insights From the SHARP Study.

This review examines the evolution and future prospects of prevention based on evaluation (PBE) for individuals at clinical high risk (CHR) of psychosis, drawing insights from the SHARP (Shanghai At Risk for Psychosis) study. It aims to assess the effectiveness of non-pharmacological interventions in preventing psychosis onset among CHR individuals. The review provides an overview of the developmental history of the SHARP study and its contributions to understanding the needs of CHR individuals. It explores the limitations of traditional antipsychotic approaches and introduces PBE as a promising framework for intervention. Three key interventions implemented by the SHARP team are discussed: nutritional supplementation based on niacin skin response blunting, precision transcranial magnetic stimulation targeting cognitive and brain functional abnormalities, and cognitive behavioral therapy for psychotic symptoms addressing symptomatology and impaired insight characteristics. Each intervention is evaluated within the context of PBE, emphasizing the potential for tailored approaches to CHR individuals. The review highlights the strengths and clinical applications of the discussed interventions, underscoring their potential to revolutionize preventive care for CHR individuals. It also provides insights into future directions for PBE in CHR populations, including efforts to expand evaluation techniques and enhance precision in interventions.

Abstract PO1-02-05: An exploratory comparison of MINDACT and TAILORx genomic risk proportions and outcomes in patients with HR+/HER2-, node-negative early-stage breast cancer, stratified by clinical risk

Abstract Introduction: Genomic tests provide physicians with critical information to evaluate the risk of distant metastasis and inform treatment plans by identifying those patients who may safely avoid chemotherapy (CT). The 70-gene signature (MammaPrint, MP) through the MINDACT trial and the 21-gene signature (Oncotype DX, ODx) through the TAILORx trial are the only tests validated with level 1A evidence that can be used for CT de-escalation decisions. Differences in trial design have made direct comparison of results difficult. We provide a comparison of MammaPrint and ODx genomic risk distributions and associated survival in patients with HR+/HER2-, node-negative (N0) early-stage breast cancer (EBC), stratified by clinical risk. Methods: Data from the MINDACT 2021 publication in The Lancet Oncology and landmark TAILORx 2019 publication in The New England Journal of Medicine were reviewed, in addition to publicly available data submitted to the Dutch Health Technology Assessment (HTA) authorities regarding survival data in patients with clinical High Risk in TAILORx. In MINDACT, patients were randomized based on both clinical (as per MINDACT definition) and genomic risk (clinical high/MP low, randomized to treatment according to clinical risk [i.e. CT] vs treatment according to MammaPrint risk [i.e. no CT]), while in TAILORx randomization was based on genomic risk alone. In TAILORx, enrollment for the population in the RS 11–25 group was enriched by 73% to account for the larger than expected non-adherence to randomized treatment plan based on the ODx results, as described in the original publication. This enrichment was only done for the RS 11–25 group. In this analysis, this enrollment enrichment was removed by applying the same proportional 73% corrective factor to the RS 11–25 group. Outcome data are reported for Overall Survival (OS), the only comparable endpoint used in both trials. Results: This explorative comparison focuses on patients with HR+/HER2- and N0 EBC in MINDACT (n=4,225) and TAILORx (n=6,686, without population enrichment). Similar proportions of patients identified as candidates for CT de-escalation (MP Low Risk or ODx RS≤25) were observed in this population of MINDACT (75%) and TAILORx (80%) when removing the RS 11–25 population enrichment in TAILORx (Table). In clinical high risk patients, the proportion with genomic low risk of distant metastasis were also comparable between MINDACT (55%) and TAILORx (63%) (Table). In the original clinical high risk but MammaPrint Low Risk population treated without CT in MINDACT the reported 8-year OS was 93.9%. In TAILORx, the comparable population of patients (ie. clinical high risk, low genomic risk, not treated with CT) had a 9-year OS of 89.2% in the RS 0–10 group and 91.6% in the RS 11–25 group (Table). Conclusions: Accounting for differences in trial design and population, comparable proportions of patients with genomic low risk results were observed between MP and ODx, justifying similar rates of CT de-escalation. Patients with clinical high risk tumors who are MammaPrint Low Risk had an excellent survival at 8 years. Genomic risk distributions and associated OS in HR+HER2- N0 patients in MINDACT and TAILORx MP, MammaPrint; OS, Overall Survival; RS, Recurrence Score. Number of patients in the TAILORx RS 11 – 25 group are adjusted to remove the proportional enrichment in the trial. OS data presented per original MINDACT and TAILORx populations. Citation Format: Patrick Neven, Josephine Lopes-Cardozo, Fatima Cardoso, Laura Van ’t Veer. An exploratory comparison of MINDACT and TAILORx genomic risk proportions and outcomes in patients with HR+/HER2-, node-negative early-stage breast cancer, stratified by clinical risk [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 PO1-02-05.

A Recovery-Oriented Approach: Application of Metacognitive Reflection and Insight Therapy (MERIT) for Youth with Clinical High Risk (CHR) for Psychosis.

Clinical High Risk for psychosis (CHR) refers to a phase of heightened risk for developing overt psychosis. CHR often emerges during adolescence or early adulthood. CHR has been identified as a group to target for intervention, with the hope that early intervention can both stave off prolonged suffering and intervene before mental health challenges become part of an individual's identity. However, there are few treatment modalities that can address some of the specific needs of CHR. Metacognitive Reflection and Insight Therapy (MERIT) is an integrative psychotherapy that can be applied to the CHR population. MERIT offers unique advantages to working with the CHR population as it aims to improve self-direction and recovery through stimulation of metacognitive capacity, a phenomenon that has been associated with recovery. This paper explores unique aspects of the CHR population and how MERIT can address barriers to recovery for individuals experiencing psychosis-like symptoms. Several case examples and a clinical vignette using MERIT to support patients with CHR are offered to exemplify this approach. MERIT offers a way to assist persons with CHR to address barriers to their personal recovery and to develop nuanced understandings of ways to master challenges.

Diminished differentiation of rewards in individuals at clinical high-risk for psychosis.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as "adaptive coding." Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally.

Identification of distinct clinical profiles and trajectories in individuals at high risk of developing psychosis: A latent profile analysis of the north American prodrome longitudinal study consortium-3 dataset.

People at clinical high risk (CHR) for psychosis are a heterogeneous population in regard to clinical presentation and outcome. It is unclear, however, if their baseline clinical characteristics can be used to construct orthogonal subgroups that differ in their clinical trajectory to provide early identification of individuals in need of tailored interventions. We used latent profile analysis (LPA) to determine the number of distinct clinical profiles within the CHR population using the NAPLS-3 dataset, focusing on the clinical features incorporated in the NAPLS psychosis risk calculator (including age, unusual thought content and suspiciousness, processing speed, verbal learning and memory function, social functioning decline, life events, childhood trauma, and family history of psychosis). We then conducted a between-profile comparisons of clinical trajectories based on psychotic and depressive symptoms as well as substance use disorder (SUD) related features over time. Two distinct profiles emerged. One profile, comprising approximately 25% of the sample, was significantly older, displayed better cognitive performance, experienced more types of traumatic and undesirable life events, exhibited a greater decline in functioning in the past year, and was more likely to have relatives with psychosis. This group showed worse positive symptoms and SUD-related features over time, although groups did not differ in the proportion of individuals who developed psychosis. LPA results suggest CHRs can be segregated into two profiles with different clinical trajectories. Characterizing individuals within these clinical profiles may help understand the divergent outcomes of this population and ultimately facilitate the development of specialized interventions.

A Qualitative Analysis of Perspectives on Self-directed Violence in a Prospective Longitudinal Study of Young Women With and Without Childhood ADHD

Objective: Non-suicidal self-directed violence (NSSDV) is a significant and growing youth public health crisis. Girls with ADHD are at increased risk of engaging in NSSDV, yet qualitative studies with this population—to better understand manifestations, motivations, and developmental course—are lacking. Method: We conducted semi-structured, qualitative interviews with a sub-sample of 57 young women (32 with childhood ADHD, 25 neurotypical comparisons; mean age of 27 years, part of a larger prospective longitudinal study) regarding histories and manifestations of NSSDV. Results: Inductive and deductive analysis revealed several key themes, including self-perceived reasons for engaging in NSSDV (affect regulation, attention seeking, self-punishment, asserting control), impulsivity, secretiveness, and in some cases motivations for desistance. Conclusion: Findings underscore the importance of early education and screening, especially among high-risk clinical populations. Increased resources and supports for professionals, parents, and peers are indicated, along with countering the persistent stigma associated with ADHD and NSSDV.

A mixed-methods study to evaluate the feasibility and preliminary efficacy of delivering the optimal health program (OHP) for youth at clinical high risk (CHR) for psychosis: A study protocol.

Individuals with clinical high risk (CHR) for psychosis experience significant distress, impaired general functioning and a high lifetime risk of self-harm and attempted suicide. The CHR period is an important phase in an individual's mental health where appropriate interventions may reduce the risk of progression to several negative outcomes, including the development of schizophrenia. Given that up to 80% of individuals with CHR have another diagnosable mental illness and almost half experience poor psychosocial functioning, developing interventions that address psychosocial functioning in young people with CHR is of great importance. This mixed-methods study aims to employ qualitative and quantitative methods to adapt an evidence-based comprehensive psychosocial and mental health self-efficacy program, the Optimal Health Program (OHP), and evaluate the feasibility, acceptability and preliminary clinical efficacy in young people with CHR. We aim to recruit 30 CHR participants (age 16-29 years) in a single-arm 12-week exploratory clinical trial. Feasibility metrics will include recruitment, retention, and data completion rates. Acceptability will be informed by the Client Satisfaction Questionnaire. Clinical assessments (psychosis spectrum symptoms, depression, and anxiety), functional measures, and cognitive outcomes will be completed at study entry and repeated post-intervention at 12-weeks. We will run pre-post test data analysis to examine changes following engagement in the OHP intervention. Qualitative interviews will be conducted post-intervention to further evaluate the acceptability of the intervention and the trial design, and will be analyzed using thematic analysis. OHP may enhance the long-term mental health, well-being and functioning of CHR youth. However, the intervention must first be adapted to a CHR population; then, the feasibility and preliminary efficacy of delivering an intervention tailored around the varied needs of the CHR group must be established before a larger-scale appropriately powered study is pursued. Trial registration: The trial is registered with ClinicalTrials.gov NCT05757128.

Functional connectivity in people at clinical and familial high risk for schizophrenia

Patients diagnosed with schizophrenia (SZ) exhibit compromised functional connectivity within extensive brain networks. However, the precise development of this impairment during disease progression in the clinical high-risk (CHR) population and their relatives remains unclear. Our study leveraged data from 128 resting electroencephalography (EEG) channels acquired from 30 SZ patients, 21 CHR individuals, 17 unaffected healthy relatives (RSs; those at heightened SZ risk due to family history), and 31 healthy controls (HCs). These data were harnessed to establish functional connectivity patterns. By calculating the geometric distance between EEG sequences, we unveiled local and global nonlinear relationships within the entire brain. The process of dimensionality reduction led to low-dimensional representations, providing insights into high-dimensional EEG data. Our findings indicated that CHR participants exhibited aberrant functional connectivity across hemispheres, whereas RS individuals showcased anomalies primarily concentrated within hemispheres. In the realm of low-dimensional analysis, RS participants' third-dimensional occipital lobe values lay between those of the CHR individuals and HCs, significantly correlating with scale scores. This low-dimensional approach facilitated the visualization of brain states, potentially offering enhanced comprehension of brain structure, function, and early-stage functional impairment, such as occipital visual deficits, in RS individuals before cognitive decline onset.

The potential of digital behavioural tests as a diagnostic aid for psychosis.

Timely interventions have a proven benefit for people experiencing psychotic illness. One bottleneck to accessing timely interventions is the referral process to the specialist team for early psychosis (STEP). Many general practitioners lack awareness or confidence in recognising psychotic symptoms or state. Additionally, referrals for people without apparent psychotic symptoms, although beneficial at a population level, lead to excessive workload for STEPs. There is a clear unmet need for accurate stratification of STEPs users and healthy cohorts. Here we propose a new approach to addressing this need via the application of digital behavioural tests. To demonstrate that digital behavioural tests can be used to discriminate between the STEPs users (SU; n = 32) and controls (n = 32, age and sex matched), we compared performance of five different classifiers applied to objective, quantitative and interpretable features derived from the 'mirror game' (MG) and trail making task (TMT). The MG is a movement coordination task shown to be a potential socio-motor biomarker of schizophrenia, while TMT is a neuropsychiatric test of cognitive function. All classifiers had AUC in the range of 0.84-0.92. The best of the five classifiers (linear discriminant classifier) achieved an outstanding performance, AUC = 0.92 (95%CI 0.75-1), Sensitivity = 0.75 (95%CI 0.5-1), Specificity = 1 (95%CI 0.75-1), evaluated on 25% hold-out and 1000 folds. Performance of all analysed classifiers is underpinned by the large effect sizes of the differences between the cohorts in terms of the features used for classification what ensures generalisability of the results. We also found that MG and TMT are unsuitable in isolation to successfully differentiate between SU with and without at-risk-mental-state or first episode psychosis with sufficient level of performance. Our findings show that standardised batteries of digital behavioural tests could benefit both clinical and research practice. Including digital behavioural tests into healthcare practice could allow precise phenotyping and stratification of the highly heterogenous population of people referred to STEPs resulting in quicker and more personalised diagnosis. Moreover, the high specificity of digital behavioural tests could facilitate the identification of more homogeneous clinical high-risk populations, benefiting research on prognostic instruments for psychosis. In summary, our study demonstrates that cheap off-the-shelf equipment (laptop computer and a leap motion sensor) can be used to record clinically relevant behavioural data that could be utilised in digital mental health applications.

Examining the psychobiological response to acute social stress across clinical stages and symptom trajectories in the early psychosis continuum.

The stress-vulnerability model has been repeatedly highlighted in relation to the risk, onset and course of psychosis, and has been independently studied in clinical high-risk (CHR) and first-episode psychosis (FEP) populations. Notable in this literature, however, is that there are few studies directly comparing markers of stress response across progressive stages of illness. Here we examined the psychobiological response to the Trier Social Stress Test in 28 CHR (mean age 19.1) and 61 FEP (age 23.0) patients, in order to understand the stage(s) or trajectories in which differences in subjective stress or physiological response occur. The overall clinical sample had greater perceived stress and blunted cortisol (FEP + CHR, n = 89, age 21.7) compared with healthy controls (n = 45, age 22.9). Additional analyses demonstrated elevated heart rate and systolic blood pressure in FEP compared with CHR, but there were no further differences in physiological parameters (cortisol, heart rate, or blood pressure) between stage- or trajectory-based groups. Together, this suggests that individual stress response markers may differentially emerge at particular stages en route to psychosis - and demonstrates how stage-based analyses can shed light on the emergence and evolution of neurobiological changes in mental illness.

Changes in Inflammatory Markers in Clinical High Risk of Developing Psychosis

Introduction: Immune alterations are associated with the progression of psychosis. However, there are few studies designed to longitudinally measure inflammatory biomarkers during psychotic episodes. We aimed to assess changes in biomarkers from the prodromal phase to psychotic episodes in individuals with clinical high risk (CHR) of psychosis and compare converters and non-converters to psychosis as well as healthy controls (HCs). Methods: We enrolled 394 individuals with CHR and 100 HCs. A total of 263 individuals with CHR completed the 1-year follow-up, and 47 had converted to psychosis. Interleukin (IL)-1β, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor levels were measured at baseline and 1 year after completion of the clinical assessment. Results: The baseline serum levels of IL-10, IL-2, and IL-6 were significantly lower in the conversion group than in the non-conversion group (IL-10, p = 0.010; IL-2, p = 0.023; IL-6, p = 0.012) and HC (IL-6: p = 0.034). Self-controlled comparisons showed that IL-2 changed significantly (p = 0.028), and IL-6 levels tended toward significance (p = 0.088) in the conversion group. In the non-conversion group, serum levels of TNF-α (p = 0.017) and VEGF (p = 0.037) changed significantly. Repeated measures analysis of variance revealed a significant time effect related to TNF-α (F = 4.502, p = 0.037, effect size (η²) = 0.051), a group effect related to IL-1β (F = 4.590, p = 0.036, η² = 0.062), and IL-2 (F = 7.521, p = 0.011, η² = 0.212), but no time × group effect. Discussion: Alterations in the serum levels of inflammatory cytokines were found to precede the first episode of psychosis in the CHR population, particularly for those who later converted to psychosis. Longitudinal analysis supports the varied roles of cytokines in individuals with CHR with later psychotic conversion or non-conversion outcomes.

Novel Research Approaches to Improve Outcomes among People Aging with Serious Mental Illnesses

There is a growing need to improve health outcomes among people aging with schizophrenia due to the rapidly increasing population and unique health challenges. Middle-aged and older people with schizophrenia have unique needs compared to first-episode or clinical high-risk populations and often do not garner the same benefits from interventions developed and tested for younger and less chronic populations. The cumulative effects of neuroleptic medications, lifestyle factors such as smoking and sedentary behaviors, and longstanding cognitive deficits impact outcomes in this group.In this session, Ellen Lee, MD will present on her work in sleep disorders in middle-aged and older adults with schizophrenia - focusing on the impact of sleep-disordered breathing among this group. She will examine the relationships of sleep with psychopathology, functioning, physical health, and cognition.Tarek K. Rajji. MD will present on recent advances in psychosocial interventions for older adults with SMI, in particular on cognitive and social skills training for older adults with schizophrenia, aged 60 or above. He will also discuss potential predictors, moderators, and mediators for this training impact on these older adults functioning. Last, he will present on the possibility of combining this training with other interventions to optimize its impact.Karen L. Fortuna, PhD, LICSW. will present on the Collaborative Design for Recovery and Health (the “Collaborative”) as a hub for people with a SMI to partner with engineers, scientists, caregivers, policymakers and payer systems to develop and empirically test groundbreaking technologies designed to extend the lifespan of people with SMI, including (1) PeerTECH (i.e., a smartphone/tablet application that is designed to support certified peer support specialists in delivering peer support enhanced by peer-led evidence-based practices that support whole health), (2) MayaMind (i.e., a smartphone/tablet application that includes artificial intelligence designed to identify schizophrenia up to ten years before the onset of symptoms, thus, allowing for early intervention to offset progression); and (3) Supporting Older Adults Remotely (SOAR; i.e., a Medicaid reimbursable endorsement to certify peer support specialists as “Certified Older Adults Peer Support Specialists” to use the SOAR app to support successful aging among other older adults).Carl Cohen, MD will moderate and lead a discussion of how to translate these research findings to clinical applications and potential future directions of their work.

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): developing tools to enable early intervention in the psychosis highrisk state.

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): developing tools to enable early intervention in the psychosis highrisk state.