UNASSIGNED: The Accelerating Medicines Partnership Schizophrenia (AMP SCZ) funds a longitudinal study of 43 research sites across 5 continents to develop tools to stratify developmental trajectories of youth at clinical high risk for psychosis (CHR) and identify homogenous targets for future clinical trials. However, there are no sites in Africa, leaving a critical gap in our knowledge of clinical and biological outcomes among CHR individuals.
UNASSIGNED: We describe the development of the Kenya Psychosis-Risk Outcomes Study (KePROS), a 5-year NIH-funded project in Kenya designed to harmonize with AMP SCZ. The study will recruit over 100 CHR and 50 healthy participants and conduct multiple clinical and biomarker assessments over 2 years. Capacity building is a key component of the study, including the construction of an electroencephalography (EEG) laboratory and the upgrading of a local 3 T magnetic resonance imaging (MRI) machine. We detail community recruitment, study methodologies and protocols, and unique challenges with this pioneering research in Africa.
UNASSIGNED: This paper is descriptive only. Planned future analyses will investigate possible predictors of clinical outcomes and will be compared to results from other global populations.
UNASSIGNED: KePROS will provide the research community with a rich longitudinal clinical and biomarker dataset from an African country in the developing Global South, which can be used alongside AMP SCZ data to delineate CHR outcome groups for future treatment development. Training in mental health assessment and investment in cutting-edge biomarker assessment and other technologies is needed to facilitate the inclusion of African countries in large-scale research consortia.

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

Individuals at clinical high risk for psychosis (CHR) present subsyndromal psychotic symptoms that can escalate and lead to the transition to a diagnosable psychotic disorder. Identifying biological parameters that are sensitive to these symptoms can therefore help objectively assess their severity and guide early interventions in CHR. Reduced slow wave oscillations (∼1 Hz) during non-rapid eye movement sleep were recently observed in first-episode psychosis patients and were linked to the intensity of their positive symptoms. Here, we collected overnight high-density EEG recordings from 37 CHR and 32 healthy control (HC) subjects and compared slow wave (SW) activity and other SW parameters (i.e., density and negative peak amplitude) between groups. We also assessed the relationships between clinical symptoms and SW parameters in CHR. While comparisons between HC and the entire CHR group showed no SW differences, CHR individuals with higher positive symptom severity (N = 18) demonstrated a reduction in SW density in an EEG cluster involving bilateral prefrontal, parietal, and right occipital regions compared to matched HC individuals. Furthermore, we observed a negative correlation between SW density and positive symptoms across CHR individuals, suggesting a potential target for early treatment interventions.

Wilson disease (WD) is a rare hereditary copper metabolism disorder, wherein cognitive impairment is a common clinical symptom. Chrysophanol (CHR) is an active compound with neuroprotective effects. The study aims to investigate the neuroprotective effect of CHR in WD and attempted to understand the potential mechanisms. Network pharmacology analysis was applied to predict the core target genes of CHR against cognitive impairment in WD. The rats fed with copper-laden diet for 12 weeks, and the effect of CHR on the copper content in liver and 24-h urine, the learning and memory ability, the morphological changes and the apoptosis level of neurons in hippocampal CA1 region, the expression level of Bax, Bcl-2, Cleaved Caspase-3, p-PI3K, PI3K, p-AKT, and AKT proteins were detected. Network pharmacology analysis showed that cell apoptosis and PI3K-AKT signaling pathway might be the main participants in CHR against cognitive impairment in WD. The experiments showed that CHR could reduce the copper content in liver, increase the copper content in 24-h urine, improve the ability of the learning and memory, alleviate the damage and apoptosis level of hippocampal neurons, down-regulate the expression of Bax, Cleaved Caspase-3, and up-regulate the expressions of Bcl-2, p-PI3K/PI3K, p-AKT/AKT. These results suggested that CHR could alleviate cognitive impairment in WD by inhibiting cell apoptosis and triggering the PI3K-AKT signaling pathway.

UNASSIGNED: Mentalization is an umbrella concept defined as the ability to interpret one\'s and others\' mental states. Previous studies have hypothesized that mentalization may be a crucial resilience factor that significantly moderates the likelihood of developing psychotic disorders in individuals with both state and trait risk factors for the illness.
UNASSIGNED: The study reviews the role of mentalizing abilities (e.g., reflective functioning, Theory of Mind (ToM), and metacognition) in young adults with At-Risk Mental States (ARMS) and schizotypal traits. Specifically, the objective is to include articles that (a) evaluate the links between low mentalizing and both state (ARMS/CHR) and trait (schizotypy) risk for psychosis (b) compare the differences in mentalizing abilities between individuals with ARMS, schizotypy, full-blown psychosis, and healthy controls.
UNASSIGNED: Electronic databases (PsycINFO, PubMed, Scopus, and Google Scholar) were used to search for articles, while Rayyan was employed to facilitate the screening and selection of studies. Eligible studies are original English-language; peer-reviewed research articles on populations that met validated risk diagnostic criteria for psychosis, ARMS, and healthy controls; empirical studies evaluating the association or differences between psychotic risk and mentalizing abilities. Non-English language studies, the ones not considering state or trait risk for psychosis, and qualitative studies were excluded. After the application of the PRISMA checklist and the inclusion and exclusion criteria previously mentioned, 10 articles were extracted. The systematic review has been registered on Prospero (CRD42023397594).
UNASSIGNED: Low levels of reflective functioning and metacognition may predict a transition to psychosis. In addition, reflective functioning and metacognitive impairments are associated with attenuated psychotic symptoms in both state risk groups and in non-clinical individuals with schizotypal traits. Concerning ToM tasks, mixed results emerged.
UNASSIGNED: The results obtained from the review suggest that the application of strategies to attenuate maladaptive metacognitive beliefs and low mentalization may be equally effective in improving psychotic symptoms. The assessment of mentalization and metacognition could potentially provide additional prognostic value over factors predisposing to psychosis. Good mentalization and metacognition functioning should be considered as protective factors able to minimize the transition to psychosis.

BACKGROUND: Detection of iron deficiency (ID) remains challenging. We aimed to evaluate the performance of reticulocyte hemoglobin equivalent (Ret-He) as a potential diagnostic marker to assess ID and iron deficiency anemia (IDA) in a large pediatric cohort.
METHODS: A total of 3158 patients (aged 15 days to 19 years with a median age of 8.5 years; 60.2% female) were retrospectively studied. Statistical analysis was performed (a) to evaluate relationship of Ret-He with other relevant complete blood count and iron panel parameters; (b) to compare the levels of Ret-He in ID and IDA groups to a control group; and (c) to assess sensitivity and specificity of Ret-He in ID, IDA, and anemia without ID groups.
RESULTS: Ret-He values were significantly positively correlated to ferritin and transferrin saturation (TSAT). The median Ret-He was significantly lower in ID. A Ret-He cutoff of ≤30.0 pg distinguished cases of ID from the control group with a sensitivity of 90.2%, specificity of 59.5%, and area under curve (AUC) of 0.88. Ret-He showed better diagnostic performance in the IDA group and acceptable performance for ID without anemia. The sensitivity, specificity, and AUC were 90.1%, 80.9%, and 0.93 for IDA at cutoff value of ≤27.4 pg, and 80.8%, 51.1%, and 0.70 for ID without anemia at cutoff value of ≤30.8 pg, respectively.
CONCLUSIONS: Our large pediatric tertiary care hospital study demonstrates that Ret-He is a reliable marker to help confirm IDA in pediatric population. However, further studies are needed for its use to capture the early stages of ID.

UNASSIGNED: Schizotypal traits and disturbances in mentalizing (the capacity to understand the mental states driving one\'s own and others\' behaviors) have been implicated in increased vulnerability for psychosis. Therefore, we explored the associations linking schizotypal traits, mentalizing difficulties and their interactions to clinical high-risk for psychosis (CHR-P), as captured by the Basic Symptoms (BS) approach, during adolescence and young adulthood.
UNASSIGNED: Eighty-seven adolescents and young adults from the general population (46% male, 44% female; age: 14-23 years) were assessed with the Schizophrenia Proneness Interview (SPI-CY/A) for 11 perceptive and cognitive BS, with the Schizotypal Personality Questionnaire (SPQ) for schizotypal traits, and with the Reflective Functioning Questionnaire (RFQ) for self-reported mentalizing abilities. The RFQ evaluates the level of certainty (RFQc scale) and uncertainty (RFQu scale) with which individuals use mental state information to explain their own and others\' behaviors.
UNASSIGNED: Logistic regression models showed significant positive effects of the SPQ disorganization scale on perceptive BS and of the SPQ interpersonal scale on cognitive BS. Post-hoc analyses revealed that schizotypal features pertaining to odd speech and social anxiety, respectively, were associated with perceptive and cognitive BS. Furthermore, higher scores on the RFQu scale and lower scores on the RFQc scale independently explained the presence of cognitive BS. Finally, significant interaction effects between RFQc and SPQ odd speech on perceptive BS, and between RFQc and SPQ social anxiety on cognitive BS were found.
UNASSIGNED: Our findings suggest that schizotypal traits and mentalizing significantly relate both independently and through their interactions to the presence of cognitive and perceptive BS included in CHR-P criteria. Furthermore, mentalizing dysfunction may contribute in the relation between schizotypal traits and early state signs of CHR-P. Mentalizing may support both detection and early treatment of CHR-P among adolescents and young adults who present with trait risk for psychosis.

Chromofungin (CHR) is a biologically active peptide derived from chromogranin A that exhibits anti-inflammatory effects. However, it remains unclear whether and how CHR protects against sepsis-induced acute lung injury (ALI). A murine model of sepsis-induced ALI was established through cecal ligation and puncture, with intraperitoneal injection of CHR. Lung inflammation and macrophage polarization were examined by measuring the levels of cytokines and markers of M1 (CD86, inducible nitric oxide synthase [iNOS]) or M2 macrophages (arginase-1 [Arg1], resistin-like molecule α1 [Fizz1] and CD206). In vitro, mouse MH-S cells pretreated with CHR was employed to explore the interplay between the lipopolysaccharide-binding protein (LBP)/toll-like receptor 4 (TLR4) signaling pathway and M1/M2 polarity. The results revealed CHR\'s ability to enhance the 7-day survival rate and protect lung pathological injury in sepsis-induced ALI. CHR increased the expression of interleukin-4 and interleukin-10 but decreased the expression of tumour necrosis factor-α and interleukin-1β. In addition, CHR notably facilitated M2 macrophage polarization, while significantly suppressingM1 polarization of alveolar macrophages. Mechanistic investigations delineated CHR\'s role in macrophage polarization by downregulating nuclear factor-κB expression through modulation of the LBP/TLR4 signaling pathway. Therefore, CHR may represent a novel strategy for the prevention of sepsis-induced ALI.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) greatly affects postoperative lives of afflicted aged patients. This study aimed to determine whether preoperative high hs-CRP/HDL ratio (CHR) was associated with an increased risk of postoperative SIRS in the elderly population.
METHODS: This retrospective cohort study included data on patients aged ≥ 65 years who underwent general anesthesia surgery at two clinical centers between January 2015 and September 2020. The primary exposure was preoperative CHR which was divided into two groups (≤ 12.82 and > 12.82) based on its normal range in our hospital, and the primary outcome was the incidence of postoperative SIRS. Targeted maximum likelihood estimation analyses were used to model the exposure-outcome relationship.
RESULTS: The analysis included 5595 elderly patients, of whom 1410 (25.20%) developed SIRS within three postoperative days. Targeted maximum likelihood estimation analysis revealed that elderly patients with CHR > 12.82 vs. CHR ≤ 12.82 was associated with increased risk of postoperative SIRS (aOR = 1.40, 95% CI [1.33, 1.48], P < 0.001). Those results were consistent both in subgroup analyses and sensitivity analyses. Compared with patients with CHR ≤ 12.82, patients with CHR > 12.82 had a higher prevalence of postoperative SIRS (49.06% vs. 22.70%), postoperative in-hospital mortality (3.40% vs. 0.65%), a longer hospital stay after surgery [10 (IQR, 6-16) vs. 8 (IQR, 5-11) days] and higher direct medical cost [10070 (IQR, 6878-15577) vs. 7117 (IQR, 4079-10314) euros, all P < 0.001].
CONCLUSIONS: In elderly patients, preoperative CHR > 12.82 was significantly associated with a higher risk of postoperative SIRS.

The risk for developing schizophrenia is increased among first-degree relatives of those with psychotic disorders, but the risk is even higher in those meeting established criteria for clinical high risk (CHR), a clinical construct most often comprising of attenuated psychotic experiences. Conversion to psychosis among CHR youth has been reported to be about 15-35% over three years. Accurately identifying individuals whose psychotic symptoms will worsen would facilitate earlier intervention, but this has been difficult to do using behavior measures alone. Brain-based risk markers have the potential to improve the accuracy of predicting outcomes in CHR youth. This narrative review provides an overview of neuroimaging studies used to investigate psychosis risk, including studies involving structural, functional, and diffusion imaging, functional connectivity, positron emission tomography, arterial spin labeling, magnetic resonance spectroscopy, and multi-modality approaches. We present findings separately in those observed in the CHR state and those associated with psychosis progression or resilience. Finally, we discuss future research directions that could improve clinical care for those at high risk for developing psychotic disorders.