Transdiagnostic biomarkers of mental illness across the lifespan: A systematic review examining the genetic and neural correlates of latent transdiagnostic dimensions of psychopathology in the general population.

This systematic review synthesizes evidence from research investigating the biological correlates of latent transdiagnostic dimensions of psychopathology (e.g., the p-factor, internalizing, externalizing) across the lifespan. Eligibility criteria captured genomic and neuroimaging studies investigating general and/or specific dimensions in general population samples across all age groups. MEDLINE, Embase, and PsycINFO were searched for relevant studies published up to March 2023 and 46 studies were selected for inclusion. The results revealed several biological correlates consistently associated with transdiagnostic dimensions of psychopathology, including polygenic scores for ADHD and neuroticism, global surface area and global gray matter volume. Shared and unique associations between symptom dimensions are highlighted, as are potential age-specific differences in biological associations. Findings are interpreted with reference to key methodological differences across studies. The included studies provide compelling evidence that the general dimension of psychopathology reflects common underlying genetic and neurobiological vulnerabilities that are shared across diverse manifestations of mental illness. Substantive interpretations of general psychopathology in the context of genetic and neurobiological evidence are discussed.

Examining the relationship between genetic risk for depression and youth episodic stress exposure.

BACKGROUND: Offspring of depressed mothers have elevated risk of developing depression because they are exposed to greater stress. While generally assumed that youth's increased exposure to stress is due to the environmental effects of living with a depressed parent, youth's genes may influence stress exposure through gene-environment correlations (rGEs). To understand the relationship between risk for depression and stress, we examined the effects of polygenic risk for depression on youth stress exposure. METHODS: We examined the relations of a polygenic risk score (PRS) for depression (DEP-PRS), as well as PRSs for 5 other disorders, with youth stress exposure. Data were from a longitudinal study of a community sample of youth and their parents (n = 377) focusing on data collected at youth's aged 12 and 15 assessments. RESULTS: Elevated youth DEP-PRS was robustly associated with increased dependent stress, particularly interpersonal events. Exploratory analyses indicated that findings were driven by major stress and were not moderated by maternal nor paternal history of depression, and of the 5 additional PRSs tested, only elevated genetic liability for bipolar I was associated with increased dependent stress-particularly non-interpersonal events. LIMITATIONS: Like other PRS studies, we focused on those of European ancestry thus, generalizability of findings is limited. CONCLUSION: Polygenic risk contributes to youth experiencing stressful life events which are dependent on their behavior. This rGE appears to be specific to genetic risk for mood disorders.

Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies.

Genome-wide association studies (GWAS) provide biological insights into disease onset and progression and have potential to produce clinically useful biomarkers. A growing body of GWAS focuses on quantitative and transdiagnostic phenotypic targets, such as symptom severity or biological markers, to enhance gene discovery and the translational utility of genetic findings. The current review discusses such phenotypic approaches in GWAS across major psychiatric disorders. We identify themes and recommendations that emerge from the literature to date, including issues of sample size, reliability, convergent validity, sources of phenotypic information, phenotypes based on biological and behavioral markers such as neuroimaging and chronotype, and longitudinal phenotypes. We also discuss insights from multi-trait methods such as genomic structural equation modelling. These provide insight into how hierarchical 'splitting' and 'lumping' approaches can be applied to both diagnostic and dimensional phenotypes to model clinical heterogeneity and comorbidity. Overall, dimensional and transdiagnostic phenotypes have enhanced gene discovery in many psychiatric conditions and promises to yield fruitful GWAS targets in the years to come.

General v. specific vulnerabilities: polygenic risk scores and higher-order psychopathology dimensions in the Adolescent Brain Cognitive Development (ABCD) Study.

BACKGROUND: Polygenic risk scores (PRSs) capture genetic vulnerability to psychiatric conditions. However, PRSs are often associated with multiple mental health problems in children, complicating their use in research and clinical practice. The current study is the first to systematically test which PRSs associate broadly with all forms of childhood psychopathology, and which PRSs are more specific to one or a handful of forms of psychopathology. METHODS: The sample consisted of 4717 unrelated children (mean age = 9.92, s.d. = 0.62; 47.1% female; all European ancestry). Psychopathology was conceptualized hierarchically as empirically derived general factor (p-factor) and five specific factors: externalizing, internalizing, neurodevelopmental, somatoform, and detachment. Partial correlations explored associations between psychopathology factors and 22 psychopathology-related PRSs. Regressions tested which level of the psychopathology hierarchy was most strongly associated with each PRS. RESULTS: Thirteen PRSs were significantly associated with the general factor, most prominently Chronic Multisite Pain-PRS (r = 0.098), ADHD-PRS (r = 0.079), and Depression-PRS (r = 0.078). After adjusting for the general factor, Depression-PRS, Neuroticism-PRS, PTSD-PRS, Insomnia-PRS, Chronic Back Pain-PRS, and Autism-PRS were not associated with lower order factors. Conversely, several externalizing PRSs, including Adventurousness-PRS and Disinhibition-PRS, remained associated with the externalizing factor (|r| = 0.040-0.058). The ADHD-PRS remained uniquely associated with the neurodevelopmental factor (r = 062). CONCLUSIONS: PRSs developed to predict vulnerability to emotional difficulties and chronic pain generally captured genetic risk for all forms of childhood psychopathology. PRSs developed to predict vulnerability to externalizing difficulties, e.g. disinhibition, tended to be more specific in predicting behavioral problems. The results may inform translation of existing PRSs to pediatric research and future clinical practice.

Polygenic risk scores for asthma and allergic disease associate with COVID-19 severity in 9/11 responders.

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 (ß = .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.

Genetic Liability, Exposure Severity, and Post-Traumatic Stress Disorder Predict Cognitive Impairment in World Trade Center Responders.

BACKGROUND: There is a high incidence of cognitive impairment among World Trade Center (WTC) responders, comorbid with post-traumatic stress disorder (PTSD). Yet, it remains unknown whether genetic liability for Alzheimer's disease, PTSD, educational attainment, or for a combination of these phenotypes, is associated with cognitive impairment in this high-risk population. Similarly, whether the effects of genetic liability are comparable to PTSD and indicators of exposure severity remains unknown. OBJECTIVE: In a study of 3,997 WTC responders, polygenic scores for Alzheimer's disease, PTSD, and educational attainment were used to test whether genome-wide risk for one or more of these phenotypes is associated with cognitive impairment, controlling for population stratification, while simultaneously estimating the effects of demographic factors and indicators of 9/11 exposure severity, including symptoms of PTSD. RESULTS: Polygenic scores for Alzheimer's disease and educational attainment were significantly associated with an increase and decrease, respectively, in the hazard rate of mild cognitive impairment. The polygenic score for Alzheimer's disease was marginally associated with an increase in the hazard rate of severe cognitive impairment, but only age, exposure severity, and symptoms of PTSD were statistically significant predictors. CONCLUSION: These results add to the emerging evidence that many WTC responders are suffering from mild cognitive impairments that resemble symptoms of Alzheimer's disease, as genetic liability for Alzheimer's disease predicted incidence of mild cognitive impairment. However, compared to polygenic scores, effect sizes were larger for PTSD and the type of work that responders completed during rescue and recovery efforts.

Discovery and replication of blood-based proteomic signature of PTSD in 9/11 responders.

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 (ß = 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.

Longitudinal associations between PTSD and sleep disturbances among World Trade Center responders.

OBJECTIVE/BACKGROUND: Post-traumatic stress disorder (PTSD) is characterized by substantial disruptions in sleep quality, continuity, and depth. Sleep problems also may exacerbate PTSD symptom severity. Understanding how PTSD and sleep may reinforce one another is critical for informing effective treatments. PATIENTS/METHODS: In a sample of 452 World Trade Center 9/11 responders (mean age = 55.22, 89.4% male, 66.1% current or former police), we examined concurrent and cross-lagged associations between PTSD symptom severity, insomnia symptoms, nightmares, and sleep quality at 3 time points ∼1 year apart. Data were analyzed using random intercept cross-lagged panel models. RESULTS: PTSD symptom severity and sleep variables were relatively stable across time (intraclass correlation coefficients: 0.63 to 0.84). Individuals with more insomnia symptoms, more nightmares, and poorer sleep quality had greater PTSD symptom severity, on average. Within-person results revealed that greater insomnia symptoms and nightmares at Time 1 were concurrently associated with greater PTSD symptoms at Time 1. Insomnia symptoms were also concurrently associated with PTSD symptoms at Times 2 and 3, respectively. Cross-lagged and autoregressive results revealed that PTSD symptoms and nightmares predicted nightmares at the next timepoint. CONCLUSIONS: Overall, results suggest PTSD and sleep problems may be linked at the same point in time but may not always influence each other longitudinally. Further, individuals who experience more sleep disturbances on average may suffer from more debilitating PTSD. Evidence-based treatments for PTSD may consider incorporating treatment of underlying sleep disturbances and nightmares.

Investigating the molecular genetic, genomic, brain structural, and brain functional correlates of latent transdiagnostic dimensions of psychopathology across the lifespan: Protocol for a systematic review and meta-analysis of cross-sectional and longitudinal studies in the general population.

Background: Research using latent variable modelling has identified a superordinate general dimension of psychopathology, as well as several specific/lower-order transdiagnostic dimensions (e.g., internalising and externalising) within the meta-structure of psychiatric symptoms. These models can facilitate discovery in genetic and neuroscientific research by providing empirically derived psychiatric phenotypes, offering greater validity and reliability than traditional diagnostic categories. The prospective review outlined in this protocol aims to integrate and assess evidence from research investigating the biological correlates of general psychopathology and specific/lower-order transdiagnostic symptom dimensions. Cross-sectional and longitudinal studies investigating general population samples of any age group or developmental period will be included to capture evidence from across the lifespan. Methods and analysis: MEDLINE, Embase, and PsycINFO databases will be systematically searched for relevant literature. The review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligibility criteria were designed to capture psychiatric genetic (i.e., molecular genetic and genomic) and neuroimaging (i.e., brain structural and brain functional) studies investigating latent transdiagnostic dimension(s) or structural model(s) of psychopathology across any age group. Studies which include or exclude participants based on clinical symptoms, disorders, or relevant risk factors (e.g., history of abuse, neglect, and trauma) will be excluded. Biometric genetic research (e.g., twin and family studies), candidate gene studies, neurophysiology studies, and other non-imaging based neuroscientific studies (e.g., post-mortem studies) will be excluded. Study quality and risk of bias will be assessed using the Joanna Briggs Checklist for Analytical Cross-Sectional Studies, the Joanna Briggs Checklist for Cohort Studies, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. Meta-analysis will be conducted if sufficient data is available. Discussion: This protocol outlines the first systematic review to examine evidence from studies investigating the latent structure and underlying biology of psychopathology and to characterise these relationships developmentally across the lifespan. The prospective review will cover a broad range of statistical techniques and models used to investigate latent transdiagnostic dimensions of psychopathology, as well as a numerous genetic and neuroscientific methods. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier[CRD42021262717].

The Role of Personality in the Mental and Physical Health of World Trade Center Responders: Self- versus Informant-Reports.

Personality is linked to important health outcomes, but most prior studies have relied on self-reports, making it possible that shared-method variance explains the associations. The present study examined self- versus informant-reports of personality and multi-method outcomes. World Trade Center (WTC) responders and informants, 283 pairs, completed five-factor model personality measures and multi-method assessments of stressful events, functioning, mental disorders, 9/11-related treatment costs, BMI, and daily activity across three years. Self-reports were uniquely related to stressful events and functioning. Both self-reports and informant-reports showed incremental validity over one another for mental disorder diagnoses and treatment costs. For objective outcomes daily activity and BMI, informant-reports showed incremental validity over self-reports, accounting for all self-report variance and more. The findings suggest that informant-reports of personality provide better validity for objective health outcomes, which has implications for understanding personality and its role in mental and physical health.

Polygenic association of glomerular filtration rate decline in world trade center responders.

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 m2/year) or "empirical" (lower most quartile of eGFR slopes). RESULTS: The mean baseline eGFR was ~ 86 ml/min/1.73 m2. 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.

The prognostic utility of personality traits versus past psychiatric diagnoses: Predicting future mental health and functioning.

Past psychiatric diagnoses are central to patient case formulation and prognosis. Recently, alternative classification models such as the Hierarchical Taxonomy of Psychopathology (HiTOP) proposed to assess traits to predict clinically-relevant outcomes. The current study directly compared personality traits and past diagnoses as predictors of future mental health and functioning in three independent, prospective samples. Regression analyses found that personality traits significantly predicted future first onsets of psychiatric disorders (ΔR2=06-.15), symptom chronicity (ΔR2=.03-.06), and functioning (ΔR2=.02-.07), beyond past and current psychiatric diagnoses. Conversely, past psychiatric diagnoses did not provide an incremental prediction of outcomes when personality traits and other concurrent predictors were already included in the model. Overall, personality traits predicted a variety of outcomes in diverse settings, beyond diagnoses. Past diagnoses were generally not informative about future outcomes when personality was considered. Together, these findings support the added value of personality traits assessment in case formulation, consistent with HiTOP model.

The Hierarchical Taxonomy of Psychopathology (HiTOP) in psychiatric practice and research.

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

The Impact of World Trade Center Related Medical Conditions on the Severity of COVID-19 Disease and Its Long-Term Sequelae.

The individuals who served our country in the aftermath of the attacks on the World Trade Center (WTC) following the attacks of 11 September 2001 have, since then, been diagnosed with a number of conditions as a result of their exposures. In the present study, we sought to determine whether these conditions were risk factors for increased COVID-19 disease severity within a cohort of N = 1280 WTC responders with complete information on health outcomes prior to and following COVID-19 infection. We collected data on responders diagnosed with COVID-19, or had evidence of receiving positive SARS-CoV-2 polymerase chain reaction or antigen testing, or were asymptomatic but had IgG positive antibody testing. The presence of post-acute COVID-19 sequelae was measured using self-reported symptom severity scales. Analyses revealed that COVID-19 severity was associated with age, Black race, obstructive airway disease (OAD), as well as with worse self-reported depressive symptoms. Similarly, post-acute COVID-19 sequelae was associated with initial analysis for COVID-19 severity, upper respiratory disease (URD), gastroesophageal reflux disease (GERD), OAD, heart disease, and higher depressive symptoms. We conclude that increased COVID-19 illness severity and the presence of post-acute COVID-19 sequelae may be more common in WTC responders with chronic diseases than in those responders without chronic disease processes resulting from exposures at the WTC disaster.

Anxiety sensitivity and Pain Experience: a prospective investigation among World Trade Center Responders.

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 (Mage = 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.

Answering questions about the Hierarchical Taxonomy of Psychopathology (HiTOP): Analogies to whales and sharks miss the boat.

This commentary discusses questions and misconceptions about HiTOP raised by Haeffel et al. (2021). We explain what the system classifies and why it is descriptive and atheoretical, highlighting benefits and limitations of this approach. We clarify why the system is organized according to patterns of covariation or comorbidity among signs and symptoms of psychopathology, and we discuss how it is designed to be falsifiable and revised in a manner that is responsive to data. We refer to the body of evidence for HiTOP's external validity and for its scientific and clinical utility. We further describe how the system is currently used in clinics. In sum, many of Haeffel et al.'s concerns about HiTOP are unwarranted, and for those concerns that reflect real current limitations of HiTOP, our consortium is working to address them, with the aim of creating a nosology that is comprehensive and useful to both scientists and clinicians.

Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): III. Emotional dysfunction superspectrum.

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.

Association of attention and memory biases for negative stimuli with post-traumatic stress disorder symptoms.

Cognitive models have highlighted the role of attentional and memory biases towards negatively-valenced emotional stimuli in the maintenance of post-traumatic stress disorder (PTSD). However, previous research has focused mainly on attentional biases towards distracting (task-irrelevant) negative stimuli. Furthermore, attentional and memory biases have been examined in isolation and the links between them remain underexplored. We manipulated attention during encoding of trauma-unrelated negative and neutral words and examined the differential relationship of their encoding and recall with PTSD symptoms. Responders to the World Trade Center disaster (N = 392) performed tasks in which they read negative and neutral words and reported the color of another set of such words. Subsequently, participants used word stems to aid retrieval of words shown earlier. PTSD symptoms were associated with slower response times for negative versus neutral words in the word-reading task (r = 0.170) but not color-naming task. Furthermore, greater PTSD symptom severity was associated with more accurate recall of negative versus neutral words, irrespective of whether words were encoded during word-reading or color-naming tasks (F = 4.11, p = 0.044, ηp2 = 0.018). Our results show that PTSD symptoms in a trauma-exposed population are related to encoding of trauma-unrelated negative versus neutral stimuli only when attention was voluntarily directed towards the emotional aspects of the stimuli and to subsequent recall of negative stimuli, irrespective of attention during encoding.

Artificial intelligence language predictors of two-year trauma-related outcomes.

BACKGROUND: Recent research on artificial intelligence has demonstrated that natural language can be used to provide valid indicators of psychopathology. The present study examined artificial intelligence-based language predictors (ALPs) of seven trauma-related mental and physical health outcomes in responders to the World Trade Center disaster. METHODS: The responders (N = 174, Mage = 55.4 years) provided daily voicemail updates over 14 days. Algorithms developed using machine learning in large social media discovery samples were applied to the voicemail transcriptions to derive ALP scores for several risk factors (depressivity, anxiousness, anger proneness, stress, and personality). Responders also completed self-report assessments of these risk factors at baseline and trauma-related mental and physical health outcomes at two-year follow-up (including symptoms of depression, posttraumatic stress disorder, sleep disturbance, respiratory problems, and GERD). RESULTS: Voicemail ALPs were significantly associated with a majority of the trauma-related outcomes at two-year follow-up, over and above corresponding baseline self-reports. ALPs showed significant convergence with corresponding self-report scales, but also considerable uniqueness from each other and from self-report scales. LIMITATIONS: The study has a relatively short follow-up period relative to trauma occurrence and a limited sample size. CONCLUSIONS: This study shows evidence that ALPs may provide a novel, objective, and clinically useful approach to forecasting, and may in the future help to identify individuals at risk for negative health outcomes.