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Introduction. Market evolution requires a constant improvement of monetary relations. Commercial credit expands the ability of enterprises to maneuver their working capital. It also mobilizes and redistributes free commodity resources in the production sector. The paper presents a holistic research in the field of credit risk assessment in a particular sector of commercial lending. Study objects and methods. The theoretic section of this publication identifies the design features of a commercial loan and the specific credit risks. The theoretical studies were performed in the context of the classical, legislative, scientific, and synthesized copyright formats. To conduct an assessment, it is necessary to focus on a separate segment of the commercial loan market, with a given regional and industry affiliation. By sorting the market participants according to the balance of outstanding pending debts, the authors chose the metallurgical enterprises of the Kemerovo region as research object. Results and discussion. The applied section reflects the authentic three-stage methodological approach, which includes the following stages of experimental and analytical work. The first stage involves structuring the risk situation and the structural elements of credit risk. The macroeconomic level involves three zones of indirect impact: state, region, and industry. At the microeconomic level, the authors identified several types of risk, in the order of their manifestation. The first one is the risk of delay in repayment of debt arising from the risk of capital structure and business risk. The second type involves subsequent risk of default on the loan, associated mainly with the potential risk of bankruptcy of a potential debtor. The second stage reflects the identification of private indicators for assessing credit risk in the context of its structural elements as based on 17 popular techniques, models, and recommendations of leading foreign and domestic scientists. The targeted selection was based on a given preference criterion, i.e. frequency of applying the coefficient in analytical practice. Thus, the authors obtained the following thematically differentiated combinations: financial independence ratio (capital structure risk indicator), indicators of the quality and correlation of receivables and payables (business risk indicators), coefficient current liquidity and the ratio of own working capital (bankruptcy risk indicators). The third stage involves an analysis of private indicators of the main components of credit risk. The analysis is based on the formed valuation design and the synthesis of valuation characteristics at a given regional and industry level, as compared with all-Russian trends. Conclusion. The analysis of most indicators revealed an unstable situation in the credit policy of metallurgical enterprises in the region, i.e. huge arrays and a high share of overdue debts, an irrational capital structure, a low level of liquidity of the balance sheet, and a significant proportion of unprofitable enterprises. Thus, a high level of risk of delay in repayment of debt and an increasing risk of bankruptcy can increase the level of risk of loan default.

Financial policy of any entity comes down to managing economic parameters and relies on exploration of the strength of relations and dependencies between them. By means of analysis of the given indicators and identification of the degree of their correlation with the basic indicators, financial engineers get vast opportunities concerning economic processes modeling and optimization. Thus, in the sector of commercial credit, which is characterized by the absence of complete Russian procedures that would help assess the risk of the creditor, the study of credit analysis exhibitors system provides the key to the development of modern models and methodological assessment technologies. The present scientific work includes theoretical, methodological, analytical and financial engineering components. The theoretical part has to provide the theoretical basis for the research, reflect the terms and definitions overview and show the development of the basic complex concept – algorithmic modeling of commercial debtor segmentation. The methodological component is devoted to the study of the fundamental principles which help construct the system of analytical indicators and establish their connection with the algorithmic model. The analytical and financial-engineering component of the scientific work which is of fundamental importance (as it reflects the implementation of the research focus), consists of five stages: 1) identification and thematic grouping of the creditor's risk indicators; 2) indicators unification in the form of the commercial debtor segmentation algorithm; 3) algorithmic model testing and performance evaluation; 4) explanation of cause-effect relationships strength between the interpenetrating exponents of the algorithmic model; 5) identification of the most valuable parameters (identifying factors) of credit analysis in the commercial lending sector. Studies were carried out using selected materials taken from Kemerovo Region agricultural companies. Thus, the result of the research is the author's debtor segmentation. The model makes it possible to form risk groups in the commercial lending sector. The analytical structure is based on the combination of key credit risk parameters taking regional and industry specific features of businesses operation into account and justified by strong correlation of the algorithm elements. That helps financial analysts save time and have equivalent effect of credit risk assessment procedure.

Multifaceted, multifactor and multicomponent nature of credit risk makes it possible to consider it as an integral hypothetical unit which consists of the autonomous diverse segments specifying risky situations. As the given article is focused on the mechanism of loan fund circulation within foreign currency loan the author considers the combination of credit, interest rate, foreign exchange and inflation risks within the aggregate (total, combined) credit risk. Foreign exchange and inflation risks generate special interest in relation to evaluation procedures as there can be statutory regulation of interest rate risk and well-functioning mechanism of debt capacity analysis as the main factor of credit risk. As commercial loans and bank credits taken by Russian companies are wide spread the authors of the article suggest an innovative procedure of aggregate credit risk assessment considering agricultural companies, as well as companies belonging to chemical and machine-building industries as «pure borrowers» (debtors). The research has a set sequence of procedures. During the first stage the authors structured a risky situation in the lending process, determined specific constituents and performed their further strategic agreement. The second stage implies the analysis of the possibilities and specific characteristics of the preliminary segment assessment of the risk level. The third stage involves the development of experimental synthetic approach to the segment assessment of the aggregate credit risk in case of foreign exchange rate and interest rate volatility when there are inflation expectations. The procedure considers the following scenarios: 1) isolated assessment of inflation risk; 2) isolated assessment of exchange rate risk; 3) complex assessment of inflation and exchange rate risks.

Introduction. Bankruptcy is the most important element of legal regulation of modern market relations. National economy has to be able to predict a potential default in the general system of anti-crisis management. Therefore, it needs advanced techniques and tools of anti-crisis diagnostics for the timely management solutions. Study objects and methods. The analytical information presented in this work is multi-tiered and reflects the all-Russian, industrywide, regional, regional-industry, and corporate levels. The research featured agricultural enterprises of the Kemerovo region. The information underwent three types of formatting: legislative, statistical, and diagnostic. Results and discussion. During the first stage, the authors assessed external factors and trends in individual components of anti-crisis diagnostics in a given economy sector against the background of all-Russian and industry-wide trends. Enterprises appeared sensitive to bankruptcy risk; the trend decreased in 2014–2018. The second stage involved developing of a selective-indicative model for diagnosing insolvency of Russian organizations. The model took into account regional and industrial traits and focuses on large and medium-sized agricultural enterprises in the region. The model selected general indicators from a set of studied parameters, formed from fifty financial ratios presented in twenty-two of the most well-known methods of anti-crisis analysis. Bankruptcy was diagnosed on the basis of preference matrix, according to the criterion of the active use of coefficients in analytical practice. A comparative analysis of bankruptcy criteria and indicators made it possible to define the degree of adequacy of the set of indicators. Four analytical vectors were defined after thematic grouping of the identified indicators: balance sheet liquidity (current liquidity ratio), property and capital structure (financial dependence and asset mobility ratios), security (working capital ratio with own circulating assets), efficiency (economic profitability, or loss ratio, and the ratio of business activity in the market). The equation of rating assessment of the insolvency probability demonstrated the total impact of these indicators, taking into account their individual «equity participation» in the aggregate of key parameters. Conclusion. The final set of general exponents of the diagnostic model can be qualified as a neuro-analogue of «classical» models that ignores the values of the regression coefficients, which are usually not adapted to Russian realities. The model built on the basis of bankruptcy indicators, taking into account their individual «equity participation» in the rating number, can be used as a flexible methodological tool for diagnosing bankruptcy in the national economy of Russia.

Evaluating the performance of university faculty is a hard task because of the diversity of the work performed. The authors assume that the founder of the university evaluates the effectiveness of the university according to performing the teaching staff. The aim of the study is to improve the monitoring of key performance indicators of the university teaching staff based on data management. The authors present an information system to support decision-making related to the teaching staff at Kemerovo State University. The authors of the paper describe creating such a system using Business Intelligence technologies step by step. The authors identified data sources, designed the structure of the data mart and built ETL-processes for its filling, implemented various analytical dashboards. Implementing the information system in the daily activities of the university allows responding promptly to changes in the key indicators, forecasting their further change, deciding on activation of efforts in the chosen direction or types of work.

One of the main goals of the companies is to form and sustain their competitive advantage for a long time. However, this can be possible if the company raises quality level, implements innovative technologies to reduce costs and enters new markets. To tackle these issues it is necessary to sustain high level and quality of fixed assets which should be up-to-date. The analysis of agricultural companies fixed assets condition revealed that they have high degree of wear and tear. The proportion of fully worn funds is increasing. The possibilities of using company’s own sources for investment in the fixed assets are limited due to the presence of unprofitable enterprises and ineffective depreciation funds formation. Depreciation has not become the source of financing replacement of fully depreciated equipment. This takes place as many companies spend accumulated depreciation charges to increase current assets. Besides, there is no depreciation fund as depreciation is added to accumulation fund and then joint resources are spent to satisfy the current needs of the company. Feasibility evaluation of the measures and ways to renew agricultural companies fixed assets and analysis of enhancing the role company’s own investment sources are the main current objectives. If one reaches them it will become possible for companies to strengthen their position in the market and be competitive in the long run.Depreciation policy aimed at increasing the role of depreciation charges as an important source of fixed assets reproduction is one of the most important measures to solve the problem of fixed assets reproduction in companies operating in agro-industrial complex.

Modern economic notions make the market participants introduce new competitive technologies of business management as well as consider and analyze more and more factors influencing success of business management. Fast moving consumer goods market is one of the the most dynamically developing segments of the market. It demonstrates high competition level and opposition and generates research interest. JSC «Tander» was chosen as a subject of the research. Russian and foreign economists’ works considering trading company competitive ability formed the theoretical basis of the research. The authors used analysis, synthesis, grouping and generalization of scientific data as the basic methods. The research has shown that network retail occupies the first place in the structure of retail trade format. Besides, there is an upward trend in the share of goods sold by means of promotional activities. There is a change in sales structure towards the decrease in the premium segment share and increase in an economy segment share. The share of sales in discounters is growing. Also there is a decrease in fresh products share in Russian people’s consumer goods basket. As Russian people prefer to cook at home more and more often there is a significant growth in sales of various ingredients for dishes and pastries cooking. As food is the last thing the consumers save money on this makes FMCG market (goods of daily consumption) the steadiest one even during economic downturn.

Due to the fact that commercial crediting is a relatively new form of credit relations in modern Russia, there are no complete methodical technologies aimed at credit risk estimate in production sphere in home literature. This explains the interest of the authors to recommendations of foreign scientists in the field of estimating procedures including those based on the quality vector of debit and credit debts as key characteristics of a commercial credit. Analytical and financial-engineering studies have been carried out in 2 stages: the identification and grouping of credit risk indicators in the field of commercial credit; unification of credit risk indicators in the form of the discursive algorithm. The identified credit risk indicators are of interest not so much from the standpoint of their private studies but in terms of the possibility of analytical tools engineering based on them. Construction of a new analytical scheme has been preceded by a thematic grouping of indicators necessary to highlight the key vectors in the estimating procedure. Five trends in credit risk estimate are clearly traced within the commercial credit analysis: the quality of debit indebtedness, the quality of creditor indebtedness, the degree of their contingency, liquidity, and stock dynamics. Based on the results of the thematic grouping of indicators, the authors have developed a discursive algorithm of debtors’ differentiation for credit risk groups taking into account their region-and-branch sectors.

Features of autism spectrum disorder, attention-deficit/hyperactivity disorder, learning disorders, intellectual disabilities, and communication and motor disorders usually emerge early in life and are associated with atypical neurodevelopment. These "neurodevelopmental conditions" are grouped together in the DSM-5 and ICD-11 to reflect their shared characteristics. Yet, reliance on categorical diagnoses poses significant challenges in both research and clinical settings (e.g., high co-occurrence, arbitrary diagnostic boundaries, high within-disorder heterogeneity). Taking a transdiagnostic dimensional approach provides a useful alternative for addressing these limitations, accounting for shared underpinnings across neurodevelopmental conditions, and characterizing their common co-occurrence and developmental continuity with other psychiatric conditions. Neurodevelopmental features have not been adequately considered in transdiagnostic psychiatric frameworks, although this would have fundamental implications for research and clinical practices. Growing evidence from studies on the structure of neurodevelopmental and other psychiatric conditions indicates that features of neurodevelopmental conditions cluster together, delineating a "neurodevelopmental spectrum" ranging from normative to impairing profiles. Studies on shared genetic underpinnings, overlapping cognitive and neural profiles, and similar developmental course and efficacy of support/treatment strategies indicate the validity of this neurodevelopmental spectrum. Further, characterizing this spectrum alongside other psychiatric dimensions has clinical utility, as it provides a fuller view of an individual's needs and strengths, and greater prognostic utility than diagnostic categories. Based on this compelling body of evidence, we argue that incorporating a new neurodevelopmental spectrum into transdiagnostic frameworks has considerable potential for transforming our understanding, classification, assessment, and clinical practices around neurodevelopmental and other psychiatric conditions., (© 2024 World Psychiatric Association.)

Psychopathology, including depression, anxiety, and post-traumatic stress, is a significant yet inadequately addressed feature of moderate-severe traumatic brain injury (TBI). Progress in understanding and treating post-TBI psychopathology may be hindered by limitations associated with conventional diagnostic approaches, specifically the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD) . The Hierarchical Taxonomy of Psychopathology (HiTOP) offers a promising, transdiagnostic alternative to psychiatric classification that may more effectively capture the experiences of individuals with TBI. However, HiTOP lacks validation in the TBI population. To address this gap, we administered a comprehensive questionnaire battery, including 56 scales assessing homogeneous symptom components and maladaptive traits within HiTOP, to 410 individuals with moderate-severe TBI. We evaluated the reliability and unidimensionality of each scale and revised those with psychometric problems. Using a top-down, exploratory latent variable approach (bass-ackwards modeling), we subsequently constructed a hierarchical model of psychopathological dimensions tailored to TBI. The results showed that, relative to norms, participants with moderate-severe TBI experienced greater problems in the established HiTOP internalizing and detachment spectra, but fewer problems with thought disorder and antagonism. Fourteen of the 56 scales demonstrated psychometric problems, which often appeared reflective of the TBI experience and associated disability. The Hierarchical Taxonomy of Psychopathology Following Traumatic Brain Injury (HiTOP-TBI) model encompassed broad internalizing and externalizing spectra, splitting into seven narrower dimensions: Detachment , Dysregulated Negative Emotionality , Somatic Symptoms , Compensatory and Phobic Reactions , Self-Harm and Psychoticism , Rigid Constraint , and Harmful Substance Use . This study presents the most comprehensive empirical classification of psychopathology after TBI to date. It introduces a novel, TBI-specific transdiagnostic questionnaire battery and model, which addresses the limitations of conventional DSM and ICD diagnoses. The empirical structure of psychopathology after TBI largely aligned with the established HiTOP model (e.g., a detachment spectrum). However, these constructs need to be interpreted in relation to the unique experiences associated with TBI (e.g., considering the injury's impact on the person's social functioning). By overcoming the limitations of conventional diagnostic approaches, the HiTOP-TBI model has the potential to accelerate our understanding of the causes, correlates, consequences, and treatment of psychopathology after TBI.

Importance: Reports suggest that the individuals who served in rescue operations following the terrorist attacks on the World Trade Center (WTC) have poorer brain health than expected., Objective: To assess the incidence of dementia before age 65 years in a prospective study of WTC responders and to compare incidence among responders with severe exposures to debris vs responders not exposed to building debris or who wore personalized protective equipment (PPE)., Design, Setting, and Participants: This prospective cohort study was conducted from November 1, 2014, to January 1, 2023, in an academic medical monitoring program available to verified WTC responders residing on Long Island, New York. Responders 60 years of age or younger without dementia at the time of their first cognitive assessment were followed up every 18 months, on average, for up to 5 years., Exposures: Exposure severity was based on responses to a detailed questionnaire of WTC exposures and exposure-related activities that included exposures to fine particulate dust and potentially neurotoxic debris, duration of work, and the use of PPE. Exposure level was divided into 5 categories ranging from low to severe., Main Outcomes and Measures: Incidence of all-cause dementia before age 65 years was the primary outcome. Dementia was diagnosed following standard guidelines relying on repeated measures of cognition., Results: Of 9891 responders, 5010 were eligible for inclusion in this study of cognitive function (median [IQR] age, 53 [48-57] years; 4573 [91.3%] male). There were 228 cases of dementia identified during 15 913.1 person-years of follow-up. Increasing WTC exposure severity was associated with incremental increases in the incidence rate of dementia per 1000 person-years (low, 2.95 [95% CI, 1.07-11.18]; mild, 12.16 [95% CI, 10.09-14.79]; moderate, 16.53 [95% CI, 13.30-20.81]; high, 30.09 [95% CI, 21.35-43.79]; and severe, 42.37 [95% CI, 24.86-78.24]). Adjusting for social, demographic, and relevant medical factors, each unit increase in exposure severity was associated with increased incidence of dementia (adjusted hazard ratio, 1.42 [95% CI, 1.18-1.71]; P < .001; mean risk difference, 9.74 [95% CI, 2.94-32.32] per 1000 person-years; P < .001)., Conclusions and Relevance: In this cohort study of WTC responders who survived these unique exposures and participated in a longitudinal follow-up study of cognition from 2014 through 2022, when compared with responders with the lowest exposure levels or responders who used PPE, more severe exposure to dust or debris was significantly associated with a higher risk of dementia before 65 years of age. This study suggests that the reliable use of PPE might help prevent the onset of dementia before age 65 years among individuals exposed to an uncontrolled building collapse. Future research is warranted to determine cerebral biomarkers for individuals with exposure-associated dementia.

Facial emotion expressions play a central role in interpersonal interactions; these displays are used to predict and influence the behavior of others. Despite their importance, quantifying and analyzing the dynamics of brief facial emotion expressions remains an understudied methodological challenge. Here, we present a method that leverages machine learning and network modeling to assess the dynamics of facial expressions. Using video recordings of clinical interviews, we demonstrate the utility of this approach in a sample of 96 people diagnosed with psychotic disorders and 116 never-psychotic adults. Participants diagnosed with schizophrenia tended to move from neutral expressions to uncommon expressions (e.g., fear, surprise), whereas participants diagnosed with other psychoses (e.g., mood disorders with psychosis) moved toward expressions of sadness. This method has broad applications to the study of normal and altered expressions of emotion and can be integrated with telemedicine to improve psychiatric assessment and treatment., Competing Interests: Competing interests statement:The authors declare no competing interest.

Introduction: Illness course plays a crucial role in delineating psychiatric disorders. However, existing nosologies consider only its most basic features (e.g., symptom sequence, duration). We developed a Dynamic Causal Model (DCM) that characterizes course patterns more fully using dense timeseries data. This foundational study introduces the new modeling approach and evaluates its validity using empirical and simulated data., Methods: A three-level DCM was constructed to model how latent dynamics produce symptoms of depression, mania, and psychosis. This model was fit to symptom scores of nine patients collected prospectively over four years, following first hospitalization. Simulated subjects based on these empirical data were used to evaluate model parameters at the subject-level. At the group-level, we tested the accuracy with which the DCM can estimate the latent course patterns using Parametric Empirical Bayes (PEB) and leave-one-out cross-validation., Results: Analyses of empirical data showed that DCM accurately captured symptom trajectories for all nine subjects. Simulation results showed that parameters could be estimated accurately (correlations between generative and estimated parameters >= 0.76). Moreover, the model could distinguish different latent course patterns, with PEB correctly assigning simulated patients for eight of nine course patterns. When testing any pair of two specific course patterns using leave-one-out cross-validation, 30 out of 36 pairs showed a moderate or high out-of-samples correlation between the true group-membership and the estimated group-membership values., Conclusion: DCM has been widely used in neuroscience to infer latent neuronal processes from neuroimaging data. Our findings highlight the potential of adopting this methodology for modeling symptom trajectories to explicate nosologic entities, temporal patterns that define them, and facilitate personalized treatment., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

The field of psychiatry is hampered by a lack of robust, reliable and valid biomarkers that can aid in objectively diagnosing patients and providing individualized treatment recommendations. Here we review and critically evaluate the evidence for the most promising biomarkers in the psychiatric neuroscience literature for autism spectrum disorder, schizophrenia, anxiety disorders and post-traumatic stress disorder, major depression and bipolar disorder, and substance use disorders. Candidate biomarkers reviewed include various neuroimaging, genetic, molecular and peripheral assays, for the purposes of determining susceptibility or presence of illness, and predicting treatment response or safety. This review highlights a critical gap in the biomarker validation process. An enormous societal investment over the past 50 years has identified numerous candidate biomarkers. However, to date, the overwhelming majority of these measures have not been proven sufficiently reliable, valid and useful to be adopted clinically. It is time to consider whether strategic investments might break this impasse, focusing on a limited number of promising candidates to advance through a process of definitive testing for a specific indication. Some promising candidates for definitive testing include the N170 signal, an event-related brain potential measured using electroencephalography, for subgroup identification within autism spectrum disorder; striatal resting-state functional magnetic resonance imaging (fMRI) measures, such as the striatal connectivity index (SCI) and the functional striatal abnormalities (FSA) index, for prediction of treatment response in schizophrenia; error-related negativity (ERN), an electrophysiological index, for prediction of first onset of generalized anxiety disorder, and resting-state and structural brain connectomic measures for prediction of treatment response in social anxiety disorder. Alternate forms of classification may be useful for conceptualizing and testing potential biomarkers. Collaborative efforts allowing the inclusion of biosystems beyond genetics and neuroimaging are needed, and online remote acquisition of selected measures in a naturalistic setting using mobile health tools may significantly advance the field. Setting specific benchmarks for well-defined target application, along with development of appropriate funding and partnership mechanisms, would also be crucial. Finally, it should never be forgotten that, for a biomarker to be actionable, it will need to be clinically predictive at the individual level and viable in clinical settings., (© 2023 World Psychiatric Association.)

Background: Chronically re-experiencing the memory of a traumatic event might cause a glial response. This study examined whether glial activation would be associated with PTSD in a study of responders present after the 9/11 World Trade Center attacks without comorbid cerebrovascular disease., Methods: Plasma was retrieved from 1,520 WTC responders and stored for a cross-sectional sample of responders of varying levels of exposure and PTSD. Plasma levels (pg/ml) of glial fibrillary acidic protein (GFAP) were assayed. Because stroke and other cerebrovascular diseases cause distributional shifts in GFAP levels, multivariable-adjusted finite mixture models analyzed GFAP distributions in responders with and without possible cerebrovascular disease., Results: Responders were aged 56.3 years and primarily male; 11.07% (n = 154) had chronic PTSD. Older age was associated with increased GFAP, whereas higher body mass was associated with decreased GFAP. Multivariable-adjusted finite mixture models revealed that severe re-experiencing trauma from 9/11 was associated with lower GFAP (B = -0.558, p = 0.003)., Conclusion: This study presents evidence of reduced plasma GFAP levels among WTC responders with PTSD. Results suggest re-experiencing traumatic events might cause glial suppression., Competing Interests: This is an epidemiological study examining biomarkers associated with posttraumatic stress disorder. The authors have no conflicts of interest to disclose., (© 2023 The Authors.)

Background: Genetic factors contribute to individual differences in the severity of coronavirus disease 2019 (COVID-19). A portion of genetic predisposition can be captured using polygenic risk scores (PRS). Relatively little is known about the associations between PRS and COVID-19 severity or post-acute COVID-19 in community-dwelling individuals., Methods: Participants in this study were 983 World Trade Center responders infected for the first time with SARS-CoV-2 (mean age at infection = 56.06; 93.4% male; 82.7% European ancestry). Seventy-five (7.6%) responders were in the severe COVID-19 category; 306 (31.1%) reported at least one post-acute COVID-19 symptom at 4-week follow-up. Analyses were adjusted for population stratification and demographic covariates., Findings: The asthma PRS was associated with severe COVID-19 category (odds ratio [OR] = 1.61, 95% confidence interval: 1.17-2.21) and more severe COVID-19 symptomatology (β = .09, p = .01), independently of respiratory disease diagnosis. Severe COVID-19 category was also associated with the allergic disease PRS (OR = 1.97, [1.26-3.07]) and the PRS for COVID-19 hospitalization (OR = 1.35, [1.01-1.82]). PRS for coronary artery disease and type II diabetes were not associated with COVID-19 severity., Conclusion: Recently developed polygenic biomarkers for asthma, allergic disease, and COVID-19 hospitalization capture some of the individual differences in severity and clinical course of COVID-19 illness in a community population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Waszczuk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: World Trade Center (WTC) responders are experiencing a high risk of mild cognitive impairment (MCI) and dementia, though the etiology remains inadequately characterized. This study investigated whether WTC exposures and chronic post-traumatic stress disorder (PTSD) were correlated with plasma biomarkers characteristic of Alzheimer's disease (AD) neuropathology., Methods: Eligible participants included WTC-exposed individuals with a baseline cognitive assessment and available plasma sample. We examined levels of the amyloid beta (Aβ)40/42 ratio, phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) and associations with a WTC exposures (duration on site ≥15 weeks, dust cloud), the PTSD Symptom Checklist for Diagnostic and Statistical Manual of Mental Disorders, 4th edition PTSD, and classification of amyloid/tau/neurodegeneration (AT[N]) profiles. Multinomial logistic regressions assessed whether biomarkers predicted increased risk of MCI or dementia., Results: Of 1179 eligible responders, 93.0% were male, mean (standard deviation) age 56.6 years (7.8). Aβ40/42, p-tau181, and NfL intercorrelated and increased with age. In subgroup analyses of responders with available neuroimaging data ( n = 75), Aβ40/42 and p-tau181 were further associated with decreased hippocampal volume (Spearman's  ρ = -0.3). Overall, 58.08% of responders with dementia had ≥1 elevated biomarker, and 3.45% had elevations across all biomarkers. In total, 248 (21.05%) had MCI and 70 (5.94%) had dementia. Increased risk of dementia was associated with plasma AT(N) profile T+ or A+N+. Exposure on site ≥15 weeks was independently associated with T+ (adjusted risk ratio [aRR] = 1.03 [1.01-1.05], P = 0.009), and T+N+ profile (aRR = 2.34 [1.12-4.87]). The presence of PTSD was independently associated with risk of A+ (aRR = 1.77 [1.11-2.82])., Discussion: WTC exposures and chronic PTSD are associated with plasma biomarkers consistent with neurodegenerative disease., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Proteomics provides an opportunity to develop biomarkers for the early detection and monitoring of post-traumatic stress disorder (PTSD). However, research to date has been limited by small sample sizes and a lack of replication. This study performed Olink Proseek Multiplex Platform profiling of 81 proteins involved in neurological processes in 936 responders to the 9/11 disaster (mean age at blood draw = 55.41 years (SD = 7.93), 94.1% white, all men). Bivariate correlations and elastic net regressions were used in a discovery subsample to identify concurrent associations between PTSD symptom severity and the profiled proteins, and to create a multiprotein composite score. In hold-out subsamples, nine bivariate associations between PTSD symptoms and differentially expressed proteins were replicated: SKR3, NCAN, BCAN, MSR1, PVR, TNFRSF21, DRAXIN, CLM6, and SCARB2 (|r| = 0.08-0.17, p < 0.05). There were three replicated bivariate associations between lifetime PTSD diagnosis and differentially expressed proteins: SKR3, SIGLEC, and CPM (OR = 1.38-1.50, p < 0.05). The multiprotein composite score retained 38 proteins, including 10/11 proteins that replicated in bivariate tests. The composite score was significantly associated with PTSD symptom severity (β = 0.27, p < 0.001) and PTSD diagnosis (OR = 1.60, 95% CI: 1.17-2.19, p = 0.003) in the hold-out subsample. Overall, these findings suggest that PTSD is characterized by altered expression of several proteins implicated in neurological processes. Replicated associations with TNFRSF21, CLM6, and PVR support the neuroinflammatory signature of PTSD. The multiprotein composite score substantially increased associations with PTSD symptom severity over individual proteins. If generalizable to other populations, the current findings may inform the development of PTSD biomarkers., (© 2023. The Author(s).)

Background and Objectives: Posttraumatic stress disorder (PTSD) has been linked to increased risk of cognitive dysfunction and physical functional impairment (PFI). The objective of this prospective cohort study was to examine whether PFI was associated with increased risk of incident mild cognitive impairment (MCI) among World Trade Center (WTC) responders with PTSD. We hypothesized that responders with PTSD would have an elevated risk of incident MCI and that PFI would mediate this increase., Methods: We examined responder participants in the WTC Aging Study whose baseline physical assessments were completed by May 2016-April 2017 and were followed up at least once before December 2019. Those without complete demographic, medical, or behavioral data were excluded. PFI was assessed using measures of upper body strength (maximal handgrip strength [HGS]) and lower extremity physical functioning (Short Physical Performance Battery). PTSD was rated using a diagnostic interview and symptom checklist; MCI and dementia were assessed using the Montreal Cognitive Assessment and diagnosed using the National Institute on Aging-Alzheimer's Association criteria. Group differences and longitudinal comparisons were examined. Cox proportional hazards models were evaluated from time to incident MCI and conversion to dementia. A mediation analysis examined whether PFI mediated associations between PTSD and MCI., Results: Within the sample of 2,687 WTC responders, 324 (12.06%, 95% CI = [10.83-13.29]) had lower extremity PFI. Responders with lower extremity PFI were older, had lower education and higher body mass, and were at a higher risk of pulmonary embolisms and PTSD. Responders with lower extremity PFI demonstrated lower baseline cognition and had increased hazards of MCI (multivariable-adjusted hazards ratio [aHR] = 1.55 [95% CI 1.21-1.98]); those with MCI converted to dementia more rapidly than those without PFI (2.73 [1.38-5.39] p = 0.004). In addition, each standard deviation decrease in HGS was associated with increased hazards of developing MCI (aHR = 1.35 [95% CI 1.10-1.66]). A mediation model suggested PFI played an intermediary role in the relationship between PTSD and MCI., Discussion: WTC responders with PFI demonstrated worse cognitive and behavioral outcomes, and PFI played an intermediary role in the relationship between PTSD and incident MCI, suggesting that PFI may be an early indicator of MCI in responders with PTSD. Regular monitoring of PFI should be considered among PTSD populations., (© 2022 American Academy of Neurology.)

Chronic pain is a significant public health problem and is exacerbated by stress. The World Trade Center (WTC) Disaster represents a unique stressor, and responders to the WTC disaster are at increased risk for pain and other health complaints. Therefore, there is a significant need to identify vulnerability factors for exacerbated pain experience among this high-risk population. Anxiety sensitivity (AS), defined as fear of anxiety-related sensations, is one such vulnerability factor associated with pain intensity and disability. Yet, no work has tested the predictive effects of AS on pain, limiting conclusions regarding the predictive utility and direction of associations. Therefore, the current study examined the prospective associations of AS, pain intensity, and pain interference among 452 (M age = 55.22, SD = 8.73, 89.4% male) responders to the WTC disaster completing a 2-week daily diary study. Using multi-level modeling, AS total score was positively associated with both pain intensity and pain interference, and that AS cognitive concerns, but not social or physical concerns, were associated with increased pain. These results highlight the importance of AS as a predictor of pain complaints among WTC responders and provide initial empirical evidence to support AS as a clinical target for treating pain complaints among WTC responders., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The factors associated with estimated glomerular filtrate rate (eGFR) decline in low risk adults remain relatively unknown. We hypothesized that a polygenic risk score (PRS) will be associated with eGFR decline., Methods: We analyzed genetic data from 1,601 adult participants with European ancestry in the World Trade Center Health Program (baseline age 49.68 ± 8.79 years, 93% male, 23% hypertensive, 7% diabetic and 1% with cardiovascular disease) with ≥ three serial measures of serum creatinine. PRSs were calculated from an aggregation of single nucleotide polymorphisms (SNPs) from a recent, large-scale genome-wide association study (GWAS) of rapid eGFR decline. Generalized linear models were used to evaluate the association of PRS with renal outcomes: baseline eGFR and CKD stage, rate of change in eGFR, stable versus declining eGFR over a 3-5-year observation period. eGFR decline was defined in separate analyses as "clinical" (> -1.0 ml/min/1.73 m 2 /year) or "empirical" (lower most quartile of eGFR slopes)., Results: The mean baseline eGFR was ~ 86 ml/min/1.73 m 2 . Subjects with decline in eGFR were more likely to be diabetic. PRS was significantly associated with lower baseline eGFR (B = -0.96, p = 0.002), higher CKD stage (OR = 1.17, p = 0.010), decline in eGFR (OR = 1.14, p = 0.036) relative to stable eGFR, and the lower quartile of eGFR slopes (OR = 1.21, p = 0.008), after adjusting for established risk factors for CKD., Conclusion: Common genetic variants are associated with eGFR decline in middle-aged adults with relatively low comorbidity burdens., (© 2022. The Author(s).)

Metabolomics has yielded promising insights into the pathophysiology of post-traumatic stress disorder (PTSD). The current study expands understanding of the systems-level effects of metabolites by using global metabolomics and complex lipid profiling in plasma samples from 124 World Trade Center responders (56 PTSD, 68 control) on 1628 metabolites. Differential metabolomics analysis identified hexosylceramide HCER(26:1) associated with PTSD at FDR < 0.1. The multi-metabolite composite score achieved an AUC of 0.839 for PTSD versus unaffected control classification. Independent component analysis identified three metabolomic modules significantly associated with PTSD. These modules were significantly enriched in bile acid metabolism, fatty acid metabolism and pregnenolone steroids, which are involved in innate immunity, inflammatory process and neuronal excitability, respectively. Integrative analysis of metabolomics and our prior proteomics datasets on subsample of 96 responders identified seven proteomic modules significantly correlated with metabolic modules. Overall, our findings shed light on the molecular alterations and identify metabolomic-proteomic signatures associated with PTSD by using machine learning and network approaches to enhance understanding of the pathways implicated in PTSD. If present results are confirmed in follow-up studies, they may inform development of novel treatments., (© 2022. The Author(s).)

Elevations in body mass index (BMI) among World Trade Center (WTC) responders may be associated with poor mental health outcomes. The current study examined the association of BMI with anxious arousal, depressive, and insomnia symptoms among this group. Participants were 412 WTC responders (89.4% male, M age = 55.3 years, SD = 8.66) who completed health monitoring assessments (self-report and objective) as part of the Long Island site of the WTC Health Program (LI-WTC-HP). Results suggested BMI was statistically significant only in relation to anxious arousal ( sr 2 = .02, p = .008), after accounting for age and sex. The current study suggests that weight management programs may aid in promoting additional benefits for WTC responders by reducing anxious arousal symptoms as a function of reduced BMI.

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a quantitative nosological system that addresses shortcomings of traditional mental disorder diagnoses, including arbitrary boundaries between psychopathology and normality, frequent disorder co-occurrence, substantial heterogeneity within disorders, and diagnostic unreliability over time and across clinicians. This paper reviews evidence on the validity and utility of the internalizing and somatoform spectra of HiTOP, which together provide support for an emotional dysfunction superspectrum. These spectra are composed of homogeneous symptom and maladaptive trait dimensions currently subsumed within multiple diagnostic classes, including depressive, anxiety, trauma-related, eating, bipolar, and somatic symptom disorders, as well as sexual dysfunction and aspects of personality disorders. Dimensions falling within the emotional dysfunction superspectrum are broadly linked to individual differences in negative affect/neuroticism. Extensive evidence establishes that dimensions falling within the superspectrum share genetic diatheses, environmental risk factors, cognitive and affective difficulties, neural substrates and biomarkers, childhood temperamental antecedents, and treatment response. The structure of these validators mirrors the quantitative structure of the superspectrum, with some correlates more specific to internalizing or somatoform conditions, and others common to both, thereby underlining the hierarchical structure of the domain. Compared to traditional diagnoses, the internalizing and somatoform spectra demonstrated substantially improved utility: greater reliability, larger explanatory and predictive power, and greater clinical applicability. Validated measures are currently available to implement the HiTOP system in practice, which can make diagnostic classification more useful, both in research and in the clinic., (© 2022 World Psychiatric Association.)

Background: One of the challenges in human neuroscience is to uncover associations between brain organization and psychopathology in order to better understand the biological underpinnings of mental disorders. Here, we aimed to characterize the neural correlates of psychopathology dimensions obtained using two conceptually different data-driven approaches., Methods: Dimensions of psychopathology that were either maximally dissociable or correlated were respectively extracted by independent component analysis (ICA) and exploratory factor analysis (EFA) applied to the Childhood Behavior Checklist items from 9- to 10-year-olds (n = 9983; 47.8% female, 50.8% white) participating in the Adolescent Brain Cognitive Development study. The patterns of brain morphometry, white matter integrity and resting-state connectivity associated with each dimension were identified using kernel-based regularized least squares and compared between dimensions using Spearman's correlation coefficient., Results: ICA identified three psychopathology dimensions, representing opposition-disinhibition, cognitive dyscontrol, and negative affect, with distinct brain correlates. Opposition-disinhibition was negatively associated with cortical surface area, cognitive dyscontrol was negatively associated with anatomical and functional dysconnectivity while negative affect did not show discernable associations with any neuroimaging measure. EFA identified three dimensions representing broad externalizing, neurodevelopmental, and broad Internalizing problems with partially overlapping brain correlates. All EFA-derived dimensions were negatively associated with cortical surface area, whereas measures of functional and structural connectivity were associated only with the neurodevelopmental dimension., Conclusions: This study highlights the importance of cortical surface area and global connectivity for psychopathology in preadolescents and provides evidence for dissociable psychopathology dimensions with distinct brain correlates.

This study assessed changes in measures of personality traits across a 12-month combat deployment in a sample of conventional US Army soldiers. Results revealed Impulsive Sensation-Seeking (ImpSS) and Sociability (Sy) decreased significantly, whereas Neuroticism-Anxiety (N-Anx) increased. Changes in ImpSS scores were mainly attributed to age, but were inversely related to increases in traumatic stress symptoms. Combat exposure, concussion, age, education, and changes in traumatic stress scores all independently contributed to changes in N-Anx scores. Changes in Sy were not associated with any of the data available from pre-deployment or deployment measures. Changes in Aggression-hostility (Agg-Hos) and Activity (Act) across the deployment were not significant. The findings suggest significant variability in the stability of personality traits when exposed to combat stress and injury while deployed, which may be influenced by factors such as age and education., Competing Interests: No potential conflict of interest was reported by the author(s)., (This work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law.)

Approximately 23% of World Trade Center (WTC) responders are experiencing chronic posttraumatic stress disorder (PTSD) associated with their exposures at the WTC following the terrorist attacks of 9/11/2001, which has been demonstrated to be a risk factor for cognitive impairment raising concerns regarding their brain health. Cortical complexity, as measured by analyzing Fractal Dimension (FD) from T 1 MRI brain images, has been reported to be reduced in a variety of psychiatric and neurological conditions. In this report, we hypothesized that FD would be also reduced in a case-control sample of 99 WTC responders as a result of WTC-related PTSD. The results of our surface-based morphometry cluster analysis found alterations in vertex clusters of complexity in WTC responders with PTSD, with marked reductions in regions within the frontal, parietal, and temporal cortices, in addition to whole-brain absolute bilateral and unilateral complexity. Furthermore, region of interest analysis identified that the magnitude of changes in regional FD severity was associated with increased PTSD symptoms (reexperiencing, avoidance, hyperarousal, negative affect) severity. This study confirms prior findings on FD and psychiatric disorders and extends our understanding of FD associations with posttraumatic symptom severity. The complex and traumatic experiences that led to WTC-related PTSD were associated with reductions in cortical complexity. Future work is needed to determine whether reduced cortical complexity arose prior to, or concurrently with, onset of PTSD., (© 2021. The Author(s).)

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical, dimensional model of psychological symptoms and functioning. Its goals are to augment the use and address the limitations of traditional diagnoses, such as arbitrary thresholds of severity, within-disorder heterogeneity, and low reliability. HiTOP has made inroads to addressing these problems, but its prognostic validity is uncertain. The present study sought to test the prediction of long-term outcomes in psychotic disorders was improved when the HiTOP dimensional approach was considered along with traditional (ie, DSM) diagnoses. We analyzed data from the Suffolk County Mental Health Project (N = 316), an epidemiologic study of a first-admission psychosis cohort followed for 20 years. We compared 5 diagnostic groups (schizophrenia/schizoaffective, bipolar disorder with psychosis, major depressive disorder with psychosis, substance-induced psychosis, and other psychoses) and 5 dimensions derived from the HiTOP thought disorder spectrum (reality distortion, disorganization, inexpressivity, avolition, and functional impairment). Both nosologies predicted a significant amount of variance in most outcomes. However, except for cognitive functioning, HiTOP showed consistently greater predictive power across outcomes-it explained 1.7-fold more variance than diagnoses in psychiatric and physical health outcomes, 2.1-fold more variance in community functioning, and 3.4-fold more variance in neural responses. Even when controlling for diagnosis, HiTOP dimensions incrementally predicted almost all outcomes. These findings support a shift away from the exclusive use of categorical diagnoses and toward the incorporation of HiTOP dimensions for better prognostication and linkage with neurobiology., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Neuroinflammation has long been theorized to arise from exposures to fine particulate matter and to be modulated when individuals experience chronic stress, both of which are also though to cause cognitive decline in part as a result of neuroinflammation., Objectives: Hypothesizing that neuroinflammation might be linked to experiences at the World Trade Center (WTC) events, this study explored associations between glial activation and neuropsychological measures including post-traumatic stress disorder (PTSD) symptom severity and WTC exposure duration., Methods: Translocator protein 18-kDa (TSPO) is overexpressed by activated glial cells, predominantly microglia and astrocytes, making TSPO distribution a putative biomarker for neuroinflammation. Twenty WTC responders completed neuropsychological assessments and in vivo PET brain scan with [ 18 F]-FEPPA. Generalized linear modeling was used to test associations between PTSD, and WTC exposure duratiioni as the predictor and both global and regional [ 18 F]-FEPPA total distribution volumes as the outcomes., Result: Responders were 56.0 ​± ​4.7 years-old, and 75% were police officers on 9/11/2001, and all had at least a high school education. Higher PTSD symptom severity was associated with global and regional elevations in [ 18 F]-FEPPA binding predominantly in the hippocampus ( d  ​= ​0.72, P  ​= ​0.001) and frontal cortex ( d  ​= ​0.64, P  ​= ​0.004). Longer exposure duration to WTC sites was associated with higher [ 18 F]-FEPPA binding in the parietal cortex., Conclusion: Findings from this study of WTC responders at midlife suggest that glial activation is associated with PTSD symptoms, and WTC exposure duration. Future investigation is needed to understand the important role of neuroinflammation in highly exposed WTC responders., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Previous studies have documented the utility of a transdiagnostic internalizing factor in predicting important future outcomes (e.g., subsequent mental disorder diagnoses). To date, however, no study has investigated whether an internalizing factor predicts mortality risk. Also, while pre-vious studies of mortality risk have emphasized its associations with particular internalizing disorders, no study has assessed how the transdiagnostic internalizing factor vs. disorder-specific variance differently predict that risk. The primary aims of this study were to explore: a) whether the internalizing factor predicts mortality risk, b) whether particular internalizing psychopathologies uniquely predict mortality risk over and beyond the transdiagnostic internalizing factor, and c) whether there is a significant interaction of internalizing with self-reported health in the prediction of mortality risk. We utilized a large national sample of American adults from the Midlife in the United States (MIDUS), a longitudinal study that examined midlife development of individuals across multiple waves between 1995 and 2015. Data were analyzed for the 6,329 participants who completed the phone interview and self-administered questionnaire in MIDUS 1 (1995-1996) and were then followed up until October 31, 2015 or until death. To investigate the association between internalizing and mortality risk, we used the semi-parametric proportional hazards Cox model, where survival time was regressed on a latent internalizing factor. Overall findings indicate that a transdiagnostic internalizing factor significantly predicts mortality risk over a 20-year period (hazard ratio, HR=1.12, 95% CI: 1.05-1.16, p<0.01) and that internalizing outperforms disorder-specific variance (e.g., depression-specific variance) in the prediction of that risk. Further, there was a significant interaction between transdiagnostic internalizing and self-reported health, whereby internalizing psychopathology had a specific association with early death for individuals with excellent self-reported health condition (HR=1.50, 95% CI: 1.17-1.84, p<0.05). This highlights the clinical utility of using the transdiagnostic internalizing factor for prediction of an important future outcome, and supports the argument that internalizing psychopathology can be a meaningful liability to explore in public health practice., (© 2021 World Psychiatric Association.)

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical effort to address limitations of traditional mental disorder diagnoses. These include arbitrary boundaries between disorder and normality, disorder co-occurrence in the modal case, heterogeneity of presentation within dis-orders, and instability of diagnosis within patients. This paper reviews the evidence on the validity and utility of the disinhibited externalizing and antagonistic externalizing spectra of HiTOP, which together constitute a broad externalizing superspectrum. These spectra are composed of elements subsumed within a variety of mental disorders described in recent DSM nosologies, including most notably substance use disorders and "Cluster B" personality disorders. The externalizing superspectrum ranges from normative levels of impulse control and self-assertion, to maladaptive disinhibition and antagonism, to extensive polysubstance involvement and personality psychopathology. A rich literature supports the validity of the externalizing superspectrum, and the disinhibited and antagonistic spectra. This evidence encompasses common genetic influences, environmental risk factors, childhood antecedents, cognitive abnormalities, neural alterations, and treatment response. The structure of these validators mirrors the structure of the phenotypic externalizing superspectrum, with some correlates more specific to disinhibited or antagonistic spectra, and others relevant to the entire externalizing superspectrum, underlining the hierarchical structure of the domain. Compared with traditional diagnostic categories, the externalizing superspectrum conceptualization shows improved utility, reliability, explanatory capacity, and clinical applicability. The externalizing superspectrum is one aspect of the general approach to psychopathology offered by HiTOP and can make diagnostic classification more useful in both research and the clinic., (© 2021 World Psychiatric Association.)

Posttraumatic stress disorder (PTSD) is associated with shortened lifespan and healthspan, which suggests accelerated aging. Emerging evidence suggests that methylation age may be accelerated in PTSD. It is important to examine whether transcriptional age is also accelerated because transcriptome is highly dynamic, associated with age-related outcomes, and may offer greater insight into the premature aging in PTSD. This study is the first reported investigation of the relationship between transcriptional age and PTSD. Using RNA-Seq data from our previous study on 324 World Trade Center responders (201 never had PTSD, 81 with current PTSD, and 42 with past PTSD), as well as a transcriptional age calculator (RNAAgeCalc) recently developed by our group, we found that responders with current PTSD, compared with responders without a PTSD diagnosis, showed accelerated transcriptional aging (p = 0.0077) after adjustment for chronological age and race. We compared our results to the epigenetic aging results computed from several epigenetic clock calculators on matching DNA methylation data. GrimAge methylation age acceleration was also associated with PTSD diagnosis (p = 0.0097), and the results remained significant after adjustment for the proportions of immune cell types. PhenoAge, Hannum, and Horvath methylation age acceleration were not reliably related to PTSD. Both epigenetic and transcriptional aging may provide biological insights into the mechanisms underpinning aging in PTSD.

Gene expression has provided promising insights into the pathophysiology of post-traumatic stress disorder (PTSD); however, specific regulatory transcriptomic mechanisms remain unknown. The present study addressed this limitation by performing transcriptome-wide RNA-Seq of whole-blood samples from 226 World Trade Center responders. The investigation focused on differential expression (DE) at the gene, isoform, and for the first time, alternative splicing (AS) levels associated with the symptoms of PTSD: total burden, re-experiencing, avoidance, numbing, and hyperarousal subdimensions. These symptoms were associated with 76, 1, 48, 15, and 49 DE genes, respectively (FDR < 0.05). Moreover, they were associated with 103, 11, 0, 43, and 32 AS events. Avoidance differed the most from other dimensions with respect to DE genes and AS events. Gene set enrichment analysis (GSEA) identified pathways involved in inflammatory and metabolic processes, which may have implications in the treatment of PTSD. Overall, the findings shed a novel light on the wide range of transcriptomic alterations associated with PTSD at the gene and AS levels. The results of DE analysis associated with PTSD subdimensions highlights the importance of studying PTSD symptom heterogeneity.

Introduction: Recent research has found that World Trade Center (WTC) responders in their mid-50s have an elevated prevalence of mild cognitive impairment (MCI) that is associated with neural degeneration and subcortical thinning. This article extends our understanding of the molecular complexity of MCI through gene expression profiling of blood., Methods: The transcriptomics of 40 male WTC responders were profiled across two cohorts (discovery: nine MCI and nine controls; replication: 11 MCI and 11 controls) using CITE-Seq at single-cell resolution in blood., Results: Comparing the transcriptomic signatures across seven major cell subpopulations, the largest differences were observed in monocytes in which 226 genes were differentially expressed. Pathway analysis on the genes unique to monocytes identified processes associated with cerebral immune response., Discussion: Our findings suggested monocytes may constitute a key cell type to target in blood-based biomarker studies for early detection of risk of MCI and development of new interventions., Competing Interests: The authors reported no biomedical financial interests or other potential conflicts of interest., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)