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Lyme disease, caused by spirochetes in the Borrelia burgdorferi sensu lato clade within the Borrelia genus, is transmitted by Ixodes ticks and is currently the most prevalent and rapidly expanding tick-borne disease in Europe and North America. We report complete genome sequences of 47 isolates that encompass all established species in this clade while highlighting the diversity of the widespread human pathogenic species B. burgdorferi. A similar set of plasmids has been maintained throughout Borrelia divergence, indicating that they are a key adaptive feature of this genus. Phylogenetic reconstruction of all sequenced Borrelia genomes revealed the original divergence of Eurasian and North American lineages and subsequent dispersals that introduced B. garinii, B. bavariensis, B. lusitaniae, B. valaisiana, and B. afzelii from East Asia to Europe and B. burgdorferi and B. finlandensis from North America to Europe. Molecular phylogenies of the universally present core replicons (chromosome and cp26 and lp54 plasmids) are highly consistent, revealing a strong clonal structure. Nonetheless, numerous inconsistencies between the genome and gene phylogenies indicate species dispersal, genetic exchanges, and rapid sequence evolution at plasmid-borne loci, including key host-interacting lipoprotein genes. While localized recombination occurs uniformly on the main chromosome at a rate comparable to mutation, lipoprotein-encoding loci are recombination hotspots on the plasmids, suggesting adaptive maintenance of recombinant alleles at loci directly interacting with the host. We conclude that within- and between-species recombination facilitates adaptive sequence evolution of host-interacting lipoprotein loci and contributes to human virulence despite a genome-wide clonal structure of its natural populations. IMPORTANCE: Lyme disease (also called Lyme borreliosis in Europe), a condition caused by spirochete bacteria of the genus Borrelia, transmitted by hard-bodied Ixodes ticks, is currently the most prevalent and rapidly expanding tick-borne disease in the United States and Europe. Borrelia interspecies and intraspecies genome comparisons of Lyme disease-related bacteria are essential to reconstruct their evolutionary origins, track epidemiological spread, identify molecular mechanisms of human pathogenicity, and design molecular and ecological approaches to disease prevention, diagnosis, and treatment. These Lyme disease-associated bacteria harbor complex genomes that encode many genes that do not have homologs in other organisms and are distributed across multiple linear and circular plasmids. The functional significance of most of the plasmid-borne genes and the multipartite genome organization itself remains unknown. Here we sequenced, assembled, and analyzed whole genomes of 47 Borrelia isolates from around the world, including multiple isolates of the human pathogenic species. Our analysis elucidates the evolutionary origins, historical migration, and sources of genomic variability of these clinically important pathogens. We have developed web-based software tools (BorreliaBase.org) to facilitate dissemination and continued comparative analysis of Borrelia genomes to identify determinants of human pathogenicity.
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STUDY OBJECTIVES: Insufficient sleep costs the U.S. economy over $411 billion per year. However, most studies investigating economic costs of sleep rely on one-time measures of sleep, which may be prone to recall bias and cannot capture variability in sleep. To address these gaps, we examined how sleep metrics captured from daily sleep diaries predicted medical expenditures. METHODS: Participants were 391 World Trade Center responders enrolled in the World Trade Center Health Program (mean age = 54.97 years, 89% men). At baseline, participants completed 14 days of self-reported sleep and stress measures. Mean sleep, variability in sleep, and a novel measure of sleep reactivity (i.e., how much people's sleep changes in response to daily stress) were used to predict the subsequent year's medical expenditures, covarying for age, race/ethnicity, sex, medical diagnoses, and body mass index. RESULTS: Mean sleep efficiency did not predict mental healthcare utilization. However, greater sleep efficiency reactivity to stress (b=$191.75, p=.027), sleep duration reactivity to stress (b=$206.33, p=.040), variability in sleep efficiency (b=$339.33, p=.002), variability in sleep duration (b=$260.87, p=.004), and quadratic mean sleep duration (b=$182.37, p=.001) all predicted greater mental healthcare expenditures. Together, these sleep variables explained 12% of the unique variance in mental healthcare expenditures. No sleep variables were significantly associated with physical healthcare expenditures. CONCLUSIONS: People with more irregular sleep, more sleep reactivity, and either short or long sleep engage in more mental healthcare utilization. It may be important to address these individuals' sleep problems to improve mental health and reduce healthcare costs.
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Background: The emergency personnel who responded to the World Trade Center (WTC) attacks endured severe occupational exposures, yet the prevalence of cognitive impairment remains unknown among WTC-exposed-FDNY-responders. The present study screened for mild and severe cognitive impairment in WTC-exposed FDNY responders using objective tests, compared prevalence rates to a cohort of non-FDNY WTC-exposed responders, and descriptively to meta-analytic estimates of MCI from global, community, and clinical populations. Methods: A sample of WTC-exposed-FDNY responders (n = 343) was recruited to complete an extensive battery of cognitive, psychological, and physical tests. The prevalences of domain-specific impairments were estimated based on the results of norm-referenced tests, and the Montreal Cognitive Assessment (MoCA), Jak/Bondi criteria, Petersen criteria, and the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria were used to diagnose MCI. NIA-AA criteria were also used to diagnose severe cognitive impairment. Generalized linear models were used to compare prevalence estimates of cognitive impairment to a large sample of WTC-exposed-non-FDNY responders from the General Responder Cohort (GRC; n = 7102) who completed the MoCA during a similar time frame. Result: Among FDNY responders under 65 years, the unadjusted prevalence of MCI varied from 52.57% to 71.37% depending on the operational definition of MCI, apart from using a conservative cut-off applied to MoCA total scores (18 < MoCA < 23), which yielded a markedly lower crude prevalence (24.31%) compared to alternative criteria. The prevalence of MCI was higher among WTC-exposed-FDNY-responders, compared to WTC-exposed-non-FDNY-GRC-responders (adjusted RR = 1.53, 95% C.I. = [1.24, 1.88], p < .001) and meta-analytic estimates from different global, community, and clinical populations. Following NIA-AA diagnostic guidelines, 4.96% of WTC-exposed-FDNY-responders met the criteria for severe impairments (95% CI = [2.91% to 7.82%]), a prevalence that remained largely unchanged after excluding responders over the age of 65 years. Discussion: There is a high prevalence of mild and severe cognitive impairment among WTC-responders highlighting the putative role of occupational/environmental and disaster-related exposures in the etiology of accelerated cognitive decline.
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Background: The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues. Here, we aim to identify blood DNAm differences associated with PTSD and characterize the underlying biological mechanisms by examining the extent to which they mirror associations across multiple brain regions. Methods: As the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, we conducted the largest cross-sectional meta-analysis of epigenome-wide association studies (EWASs) of PTSD to date, involving 5077 participants (2156 PTSD cases and 2921 trauma-exposed controls) from 23 civilian and military studies. PTSD diagnosis assessments were harmonized following the standardized guidelines established by the PGC-PTSD Workgroup. DNAm was assayed from blood using either Illumina HumanMethylation450 or MethylationEPIC (850K) BeadChips. A common QC pipeline was applied. Within each cohort, DNA methylation was regressed on PTSD, sex (if applicable), age, blood cell proportions, and ancestry. An inverse variance-weighted meta-analysis was performed. We conducted replication analyses in tissue from multiple brain regions, neuronal nuclei, and a cellular model of prolonged stress. Results: We identified 11 CpG sites associated with PTSD in the overall meta-analysis (1.44e-09 < p < 5.30e-08), as well as 14 associated in analyses of specific strata (military vs civilian cohort, sex, and ancestry), including CpGs in AHRR and CDC42BPB. Many of these loci exhibit blood-brain correlation in methylation levels and cross-tissue associations with PTSD in multiple brain regions. Methylation at most CpGs correlated with their annotated gene expression levels. Conclusions: This study identifies 11 PTSD-associated CpGs, also leverages data from postmortem brain samples, GWAS, and genome-wide expression data to interpret the biology underlying these associations and prioritize genes whose regulation differs in those with PTSD.
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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 15â¯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.
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Demência , Socorristas , Ataques Terroristas de 11 de Setembro , Humanos , Demência/epidemiologia , Masculino , Feminino , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Socorristas/estatística & dados numéricos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Cidade de Nova Iorque/epidemiologia , Adulto , Trabalho de Resgate/estatística & dados numéricos , Equipamento de Proteção Individual/estatística & dados numéricosRESUMO
BACKGROUND: Posttraumatic stress disorder (PTSD) symptomatology and poorer pulmonary function are highly prevalent psychiatric and medical conditions. In the present study, we tested for the individual, additive, and modifying associations of PTSD symptomatology and pulmonary function with cognitive performance. METHODS: In this cross-sectional study, a total of 1,401 World Trade Center (WTC) responders (mean age = 53, SD = 8 years, 92% males) participated in the study. Cogstate assessment measured cognitive performance. PTSD symptomatology was measured using the trauma-specific version of the posttraumatic stress disorder checklist (PCL-17) adapted for the WTC attacks. The 1-second forced expiratory volume and forced vital capacity (FEV1/FVC) ratio was used to measure pulmonary function. Linear regressions with cognitive performance as the outcome were conducted to assess individual, additive, and moderating associations of PTSD symptomatology and pulmonary function. RESULTS: Higher PTSD symptomatology and poorer pulmonary function were negatively associated with cognitive performance. A 10% increase on the FEV1/FVC ratio moderated the association between PTSD symptomatology and cognition, whereby its association with cognition was stronger when PTSD symptomatology was higher (est. = 0.01, 95%CI = 0.004, 0.01, p < 0.001). When stratified by responder type, these associations persisted in trained (est. = 0.01, 95%CI = 0.01, 0.02, p < 0.001), but not in non-trained (est. = 0.004, 95% C.I. = -0.01, 0.02, p = 0.39) responders. CONCLUSIONS: In the presence of higher PTSD, better pulmonary functioning is associated with better cognitive performance. Early intervention efforts to mitigate preventable cognitive decline in high-risk populations should be studied, especially since intervention in one modality may have an impact on others.
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Cognição , Ataques Terroristas de 11 de Setembro , Transtornos de Estresse Pós-Traumáticos , Humanos , Masculino , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Ataques Terroristas de 11 de Setembro/psicologia , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Adulto , Socorristas/psicologia , Socorristas/estatística & dados numéricos , Capacidade Vital , Volume Expiratório Forçado , Pulmão/fisiopatologia , Cidade de Nova Iorque/epidemiologiaRESUMO
Symptoms of coronavirus disease 2019 (COVID-19) can persist for months or years after infection, a condition called Post-Acute Sequelae of COVID-19 (PASC). Whole-brain white matter and cortical gray matter health were assessed using multi-shell diffusion tensor imaging. Correlational tractography was utilized to dissect the nature and extent of white matter changes. In this study of 42 male essential workers, the most common symptoms of Neurological PASC (n = 24) included fatigue (n = 19) and headache (n = 17). Participants with neurological PASC demonstrated alterations to whole-brain white matter health when compared to controls made up of uninfected, asymptomatic, or mildly infected controls (n = 18). Large differences were evident between PASC and controls in measures of fractional anisotropy (Cohen's D=-0.54, P = 0.001) and cortical isotropic diffusion (Cohen's D = 0.50, P = 0.002). Symptoms were associated with white matter fractional anisotropy (fatigue: rho = -0.62, P< 0.001; headache: rho = -0.66, P < 0.001), as well as nine other measures of white and gray matter health. Brain fog was associated with improved cerebral functioning including improved white matter isotropic diffusion and quantitative anisotropy. This study identified changes across measures of white and gray matter connectivity, neuroinflammation, and cerebral atrophy that were interrelated and associated with differences in symptoms of PASC. These results provide insights into the long-term cerebral implications of COVID-19.
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Objective: Responders of the World Trade Center (WTC) disaster suffer from co-morbidities. A Mediterranean Diet (MedDiet) nutrition intervention with physical activity was implemented among WTC responders with overweight/obesity and post-traumatic stress disorder (PTSD). Methods: WTC Health Program members (N = 62), 45-65 years, males 87%, body mass index (BMI) 27-45 kg/m2 randomized to MedDiet (n = 31) or usual nutrition counseling (n = 31). The 10-week intervention included online nutrition education, text messages, and group experiential cooking; both groups had three in-person individual nutrition counseling. Anthropometrics, serum biomarkers, psychosocial factors, MedDiet score, and PTSD symptoms were assessed at baseline, post-intervention, and 3-months (follow-up). The primary outcome was intervention feasibility and secondary outcomes were within- and between-group changes of all measures at post-intervention and follow-up. Nonparametric Wilcoxon rank sum tests for between-group comparisons and Wilcoxon signed rank tests for pre-post within-group comparisons. Results: A total of 58(94%) and 46(74%) participants completed the post-intervention and follow-up measurements, respectively. Both groups experienced significant improvements in anthropometrics, MedDiet score, oxidized low-density lipoprotein, and PTSD symptoms. Baseline median (range) were weight 100.42 (73.66-135.17) kg, BMI 33.20 (27.50-41.75) kg/m2, and Waist circumference (WC) 109.22 (90.17-150.62) cm. Median % weight loss at post-intervention was MedDiet: -3% (-11%-7%), p = 0.0002; Control: -1% (-13%-4%), p = 0.008 and at follow-up MedDiet: -2% (-14%-12%), p = 0.07; Control: -2% (-20%-3%), p = 0.006. The overall BMI was reduced by -0.68 kg/m2 (-4.61-2.09) kg/m2 p < 0.0001 at post-intervention and by -0.60 kg/m2 (-6.91-3.39) kg/m2, p < 0.0009 at follow-up. Overall, median WC was reduced (p < 0.0001); post-intervention -3.81 cm (-33.00-3.30)cm and follow-up -4.45(-38.10-4.57)cm. There were group differences in HbA1c (p = 0.019) and serum ω6/ω3 (p = 0.029) at post-intervention. Conclusion: Online intervention with personal counseling was feasible in this population. Improvements in anthropometrics, MedDiet score, selected serum biomarkers and PTSD symptoms were found in both groups; group differences in HbA1c and serum ω6/ω3. A larger study with a delayed control is needed to better assess intervention effects.
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Objective: World Trade Center (WTC) responders are susceptible to both cognitive and neuropsychiatric impairments, particularly chronic posttraumatic stress disorder. The present study examined self-reported behavioral impairments in a sample of 732 WTC responders, 199 of whom were determined to have high risk of WTC-related cortical atrophy by an artificial neural network. Results: We found that responders at increased risk of cortical atrophy showed behavioral impairment across five domains: motivation, mood, disinhibition, empathy, and psychosis (14.6% vs 3.9% in the low-risk group; P = 3.90 × 10-7). Factor analysis models revealed that responders at high risk of cortical atrophy tended to have deficits generalized across all aspects of behavioral impairment with focal dysfunction in sensory psychosis. We additionally describe how relationships are modulated by exposure severity and pharmacological treatments. Discussion: Our findings suggest a potential link between sensory deficits and the development of cortical atrophy in WTC responders and may indicate symptoms consistent with a clinical portrait of parietal dominant Alzheimer's disease or a related dementia (ADRD). Results underscore the importance of investigating neuropsychiatric symptomatology in clinical evaluations of possible ADRD.
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Socorristas , Ataques Terroristas de 11 de Setembro , Humanos , Socorristas/psicologia , Ataques Terroristas de 11 de Setembro/psicologia , Fatores de Risco , Autorrelato , AtrofiaRESUMO
OBJECTIVE: Posttraumatic stress disorder (PTSD) is common, debilitating, and associated with an increased risk of health problems, including cardiovascular disease. PTSD is related to poor autonomic function indicated by reduced heart rate variability (HRV). However, very little work has tested the timescale or direction of these effects, given that most evidence comes from cross-sectional studies. Documentation of when effects occur and in what direction can shed light on mechanisms of cardiovascular disease risk and inform treatment. The present study of 169 World Trade Center responders, oversampled for PTSD, tested how daily PTSD symptoms were associated with autonomic function as reflected through HRV. METHODS: Participants ( N = 169) completed surveys of PTSD symptoms three times a day at 5-hour intervals for 4 days while also wearing ambulatory monitors to record electrocardiograms to derive HRV (i.e., mean absolute value of successive differences between beat-to-beat intervals). RESULTS: HRV did not predict PTSD symptoms. However, PTSD symptoms during a 5-hour interval predicted reduced HRV at the next 5-hour interval ( ß = -0.09, 95% confidence interval = -0.16 to -0.02, p = .008). Results held adjusting for baseline age, current heart problems, and current PTSD diagnosis. CONCLUSIONS: Findings underscore growing awareness that PTSD symptoms are not static. Even their short-term fluctuations may affect cardiovascular functioning, which could have more severe impacts if disruption accumulates over time. Research is needed to determine if momentary interventions can halt increases in PTSD symptoms or mitigate their impact on cardiovascular health.
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Doenças Cardiovasculares , Transtornos de Estresse Pós-Traumáticos , Humanos , Frequência Cardíaca/fisiologia , Estudos Transversais , Sistema Nervoso AutônomoRESUMO
Background: Cognitive impairment is the most common and disabling manifestation of post-acute sequelae of SARS-CoV-2. There is an urgent need for the application of more stringent methods for evaluating cognitive outcomes in research studies. Objective: To determine whether cognitive decline emerges with the onset of COVID-19 and whether it is more pronounced in patients with Post-Acute Sequelae of SARS-CoV-2 or severe COVID-19. Methods: This longitudinal cohort study compared the cognitive performance of 276 patients with COVID-19 to that of 217 controls across four neuroinflammation or vascular disease-sensitive domains of cognition using data collected both before and after the pandemic starting in 2015. Results: The mean age of the COVID-19 group was 56.04±6.6 years, while that of the control group was 58.1±7.3 years. Longitudinal models indicated a significant decline in cognitive throughput ((ß=-0.168, P=.001) following COVID-19, after adjustment for pre-COVID-19 functioning, demographics, and medical factors. The effect sizes were large; the observed changes in throughput were equivalent to 10.6 years of normal aging and a 59.8% increase in the burden of mild cognitive impairment. Cognitive decline worsened with coronavirus disease 2019 severity and was concentrated in participants reporting post-acute sequelae of SARS-CoV-2. Conclusion: COVID-19 was most likely associated with the observed cognitive decline, which was worse among patients with PASC or severe COVID-19. Monitoring patients with post-acute sequelae of SARS-CoV-2 for declines in the domains of processing speed and visual working memory and determining the long-term prognosis of this decline are therefore warranted.
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World Trade Center (WTC) responders exposed to traumatic and environmental stressors during rescue and recovery efforts have a high prevalence of chronic WTC-related post-traumatic stress disorder (WTC-PTSD). We investigated neural mechanisms underlying WTC-PTSD by applying eigenvector centrality (EC) metrics and data-driven methods on resting state functional magnetic resonance (fMRI). We identified how EC differences relate to WTC-exposure and behavioral symptoms. We found that connectivity differentiated significantly between WTC-PTSD and non-PTSD responders in nine brain regions, as these differences allowed an effective discrimination of PTSD and non-PTSD responders based solely on analysis of resting state data. Further, we found that WTC exposure duration (months on site) moderates the association between PTSD and EC values in two of the nine brain regions; the right anterior parahippocampal gyrus and the left amygdala (p = 0.010; p = 0.005, respectively, adjusted for multiple comparisons). Within WTC-PTSD, a dimensional measure of symptom severity was positively associated with EC values in the right anterior parahippocampal gyrus and brainstem. Functional neuroimaging can provide effective tools to identify neural correlates of diagnostic and dimensional indicators of PTSD.
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Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Tonsila do Cerebelo/diagnóstico por imagem , Tronco Encefálico , Neuroimagem FuncionalRESUMO
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.
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Introduction: The clock drawing task (CDT) is frequently used to aid in detecting cognitive impairment, but current scoring techniques are time-consuming and miss relevant features, justifying the creation of an automated quantitative scoring approach. Methods: We used computer vision methods to analyze the stored scanned images (N = 7,109), and an intelligent system was created to examine these files in a study of aging World Trade Center responders. Outcomes were CDT, Montreal Cognitive Assessment (MoCA) score, and incidence of mild cognitive impairment (MCI). Results: The system accurately distinguished between previously scored CDTs in three CDT scoring categories: contour (accuracy = 92.2%), digits (accuracy = 89.1%), and clock hands (accuracy = 69.1%). The system reliably predicted MoCA score with CDT scores removed. Predictive analyses of the incidence of MCI at follow-up outperformed human-assigned CDT scores. Discussion: We created an automated scoring method using scanned and stored CDTs that provided additional information that might not be considered in human scoring.
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BACKGROUND: How sleep is impacted by stress ("sleep reactivity to stress") and how stress is impacted by sleep ("stress reactivity to sleep") are trait-like characteristics of individuals that predict depression, anxiety, and insomnia. However, pathways between reactivity and functional impairment (e.g., impairment in social relationships and interpersonal functioning) have not been explored, which may be a critical pathway in understanding the link between reactivity and the development of psychological disorders. PURPOSE: We examined associations between reactivity and changes in functional impairment among a cohort of 9/11 World Trade Center responders. METHODS: Data from 452 responders (Mage = 55.22 years; 89.4% male) were collected between 2014 and 2016. Four baseline sleep and stress reactivity indices (i.e., sleep duration and efficiency reactivity to stress; stress reactivity to sleep duration and efficiency) were calculated from 14 days of sleep and stress data using random slopes from multilevel models. Functional impairment was assessed approximately 1 year and 2 years after baseline via semi-structured interviews. Latent change score analyses examined associations between baseline reactivity indices and changes in functional impairment. RESULTS: Greater baseline sleep efficiency reactivity to stress was associated with decreases in functioning (ß = -0.05, pâ =â .039). In addition, greater stress reactivity to sleep duration (ß = -0.08, pâ =â .017) and sleep efficiency (ß = -0.22, pâ <â .001) was associated with lower functioning at timepoint one. CONCLUSION: People who are more reactive to daily fluctuations in stress and sleep have poorer interpersonal relationships and social functioning. Identifying individuals with high reactivity who could benefit from preventative treatment may foster better social integration.
How sleep is impacted by stress ("sleep reactivity to stress") and how stress is impacted by sleep ("stress reactivity to sleep") are trait-like characteristics of individuals that may contribute to an individual's risk of developing of psychological disorders, such as depression, anxiety, and insomnia. It is possible that individuals with high sleep-stress reactivity are more likely to experience long-term functional impairment (e.g., impairment in social relationships and interpersonal functioning)a predisposing factor for psychological disorders, yet this pathway has not been explored. Therefore, we examined associations between sleep-stress reactivity and changes in functional impairment across a 1-year period in a large sample of 9/11 World Trade Center responders. The study results suggest that 9/11 World Trade Center responders who are more reactive to daily fluctuations in stress and sleep have poorer interpersonal relationships and social functioning. Identifying individuals with high sleep-stress reactivity who could benefit from preventative treatment may foster better social integration.
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Depressão , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Feminino , Depressão/psicologia , Sono , Ansiedade/psicologia , Transtornos de AnsiedadeRESUMO
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.
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Asma , COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Feminino , COVID-19/genética , SARS-CoV-2/genética , Fatores de Risco , Asma/genética , Asma/diagnósticoRESUMO
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 (Aß)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). Aß40/42, p-tau181, and NfL intercorrelated and increased with age. In subgroup analyses of responders with available neuroimaging data (n = 75), Aß40/42 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.
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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.
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Doença de Alzheimer , Disfunção Cognitiva , Socorristas , Transtornos de Estresse Pós-Traumáticos , Humanos , Socorristas/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/psicologia , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/genética , ComorbidadeRESUMO
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.