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Molecular linkage between post-traumatic stress disorder and cognitive impairment: a targeted proteomics study of World Trade Center responders.

ABSTRACT: Existing work on proteomics has found common biomarkers that are altered in individuals with post-traumatic stress disorder (PTSD) and mild cognitive impairment (MCI). The current study expands our understanding of these biomarkers by profiling 276 plasma proteins with known involvement in neurobiological processes using the Olink Proseek Multiplex Platform in individuals with both PTSD and MCI compared to either disorder alone and with unaffected controls. Participants were World Trade Center (WTC) responders recruited through the Stony Brook WTC Health Program. PTSD and MCI were measured with the PTSD Checklist (PCL) and the Montreal Cognitive Assessment, respectively. Compared with unaffected controls, we identified 16 proteins associated with comorbid PTSD-MCI at P?

SUBMITTER: Kuan PF

PROVIDER: S-EPMC7403297 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Molecular linkage between post-traumatic stress disorder and cognitive impairment: a targeted proteomics study of World Trade Center responders.

Kuan Pei-Fen PF Clouston Sean S Yang Xiaohua X Kotov Roman R Bromet Evelyn E Luft Benjamin J BJ

Translational psychiatry 20200804 1

Existing work on proteomics has found common biomarkers that are altered in individuals with post-traumatic stress disorder (PTSD) and mild cognitive impairment (MCI). The current study expands our understanding of these biomarkers by profiling 276 plasma proteins with known involvement in neurobiological processes using the Olink Proseek Multiplex Platform in individuals with both PTSD and MCI compared to either disorder alone and with unaffected controls. Participants were World Trade Center ( ...[more]

PMID: 32753605

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

Project description:BackgroundThere 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.ObjectiveIn 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.ResultsPolygenic 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.ConclusionThese 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.

| S-EPMC10648279 | biostudies-literature

Mapping the transcriptomics landscape of post-traumatic stress disorder symptom dimensions in World Trade Center responders

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

2021-06-03 | GSE164877 | GEO

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Reduced cerebellar cortical thickness in World Trade Center responders with cognitive impairment.

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| S-EPMC7896635 | biostudies-literature

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Project description:The gene expression approach has provided promising insights into the pathophysiology of PTSD. However, few studies used hypothesis-free transcriptome-wide expression approach. Transcriptome-wide expression study using RNA sequencing (RNA-Seq) of whole blood was conducted in 324 World Trade Center responders (201 with never, 81 current and 42 past PTSD). The current and never PTSD samples were randomly split to form both discovery (N=195) and replication (N=87) cohorts. Differentially expressed genes identified in RNA-Seq were used in pathway analysis and to create a polygenic expression score. There were 448 differentially expressed genes in the discovery cohort, of which 99 remained significant in the replication cohort, and 5 (FKBP5, NDUFA1, CCDC85B, SNORD54, SNORD46) showed >1.2-fold difference in expression consistently between the discovery and replication cohorts. Several enriched biological pathways were found, including glucocorticoid receptor signaling and immunity-related pathways, but were not significant following FDR correction. The gene expression score achieved sensitivity of 0.917 and specificity of 0.508 for identifying PTSD cases in the replication cohort. It was similar in current and past PTSD, with both groups scoring higher than trauma-exposed controls. We confirmed the role of FKBP5 in PTSD and identified four additional differentially expressed genes that may constitute biomarkers for this condition. Together with the pathway analysis results, these findings point to HPA-axis and immune dysregulation as key biological processes underpinning PTSD. A novel polygenic expression aggregate that differentiates PTSD patients from trauma-exposed controls might be a useful screening tool for research and clinical practice, if replicated in other populations.

2018-02-13 | GSE97356 | GEO

DSM-IV post-traumatic stress disorder among World Trade Center responders 11-13 years after the disaster of 11 September 2001 (9/11).

Project description:Post-traumatic symptomatology is one of the signature effects of the pernicious exposures endured by responders to the World Trade Center (WTC) disaster of 11 September 2001 (9/11), but the long-term extent of diagnosed Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) post-traumatic stress disorder (PTSD) and its impact on quality of life are unknown. This study examines the extent of DSM-IV PTSD 11-13 years after the disaster in WTC responders, its symptom profiles and trajectories, and associations of active, remitted and partial PTSD with exposures, physical health and psychosocial well-being.Master's-level psychologists administered sections of the Structured Clinical Interview for DSM-IV and the Range of Impaired Functioning Tool to 3231 responders monitored at the Stony Brook University World Trade Center Health Program. The PTSD Checklist (PCL) and current medical symptoms were obtained at each visit.In all, 9.7% had current, 7.9% remitted, and 5.9% partial WTC-PTSD. Among those with active PTSD, avoidance and hyperarousal symptoms were most commonly, and flashbacks least commonly, reported. Trajectories of symptom severity across monitoring visits showed a modestly increasing slope for active and decelerating slope for remitted PTSD. WTC exposures, especially death and human remains, were strongly associated with PTSD. After adjusting for exposure and critical risk factors, including hazardous drinking and co-morbid depression, PTSD was strongly associated with health and well-being, especially dissatisfaction with life.This is the first study to demonstrate the extent and correlates of long-term DSM-IV PTSD among responders. Although most proved resilient, there remains a sizable subgroup in need of continued treatment in the second decade after 9/11.

| S-EPMC4754831 | biostudies-literature

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