Search

Despite experiencing a significant trauma, only a subset of World Trade Center (WTC) rescue and recovery workers developed posttraumatic stress disorder (PTSD). Identification of biomarkers is critical to the development of targeted interventions for treating disaster responders and potentially preventing the development of PTSD in this population. Analysis of gene expression from these individuals can help in identifying biomarkers of PTSD. We established a well-phenotyped sample of 371 WTC responders, recruited from a longitudinal WTC responder cohort using stratified random sampling, by obtaining blood, self-reported and clinical interview data. Using bulk RNA-sequencing from whole blood, we examined the association between gene expression and WTC-related PTSD symptom severity on (i) highest lifetime Clinician-Administered PTSD Scale (CAPS) score, (ii) past-month CAPS score, and (iii) PTSD symptom dimensions using a 5-factor model of re-experiencing, avoidance, emotional numbing, dysphoric arousal and anxious arousal symptoms. We corrected for sex, age, genotype-derived principal components and surrogate variables. Finally, we performed a meta-analysis with existing PTSD studies (total N = 1016), using case/control status as the predictor and correcting for these variables. We identified 66 genes significantly associated with total highest lifetime CAPS score (FDR-corrected p 0.05), and 31 genes associated with total past-month CAPS score. Our more granular analyses of PTSD symptom dimensions identified additional genes that did not reach statistical significance in our analyses with total CAPS scores. In particular, we identified 82 genes significantly associated with lifetime anxious arousal symptoms. Several genes significantly associated with multiple PTSD symptom dimensions and total lifetime CAPS score (SERPINA1, RPS6KA1, and STAT3) have been previously associated with PTSD. Geneset enrichment of these findings has identified pathways significant in metabolism, immune signaling, other psychiatric disorders, neurological signaling, and cellular structure. Our meta-analysis revealed 10 genes that reached genome-wide significance, all of which were downregulated in cases compared to controls (CIRBP, TMSB10, FCGRT, CLIC1, RPS6KB2, HNRNPUL1, ALDOA, NACA, ZNF429 and COPE). Additionally, cellular deconvolution highlighted an enrichment in CD4 T cells and eosinophils in responders with PTSD compared to controls. The distinction in significant genes between total lifetime CAPS score and the anxious arousal symptom dimension of PTSD highlights a potential biological difference in the mechanism underlying the heterogeneity of the PTSD phenotype. Future studies should be clear about methods used to analyze PTSD status, as phenotypes based on PTSD symptom dimensions may yield different gene sets than combined CAPS score analysis. Potential biomarkers implicated from our meta-analysis may help improve therapeutic target development for PTSD.

Background Nearly 20 years after the terrorist attacks of September 11, 2001, multiple studies have documented the adverse mental consequences among World Trade Center (WTC) rescue, recovery, and clean-up workers. However, scarce research has examined mental health stigma and barriers to care in WTC-exposed individuals, and no known study has examined whether rates of endorsement may differ between police and "nontraditional" responders, the latter comprising a heterogeneous group of workers and volunteers. Objective To identify the prevalence and correlates of mental health stigma and barriers to care in WTC responders. Methods Mental health stigma and barriers to care and their correlates were examined in 6,777 police and 6,272 nontraditional WTC responders. Results Nontraditional responders endorsed more stigma or barriers to care concerns than police responders. Within a subsample who screened positive for a psychiatric disorder, police were more likely than nontraditional responders to endorse "concerns that negative job consequences might result" (17.9% vs. 9.1%), while nontraditional responders were more likely to endorse "I don't know where to go to find counseling services" (18.4% vs.6.6%). Within this subsample, mental health service need and more severe WTC-related posttraumatic stress disorder symptoms were associated with increased likelihood of endorsing stigma or barriers; pre-9/11 psychiatric history and non-Hispanic Black race/ethnicity were associated with lower likelihood of endorsing stigma or barriers. Conclusions Results of this study underscore the burden of mental health stigma and barriers to care in WTC responders, and highlight the need for targeted interventions to address these concerns and promote mental healthcare utilization in this population.

Despite experiencing a significant trauma, only a subset of World Trade Center (WTC) rescue and recovery workers developed posttraumatic stress disorder (PTSD). Identification of biomarkers is critical to the development of targeted interventions for treating disaster responders and potentially preventing the development of PTSD in this population. Analysis of gene expression from these individuals can help in identifying biomarkers of PTSD.We established a well-phenotyped sample of 371 WTC responders, recruited from a longitudinal WTC responder cohort, by obtaining blood, self-reported and clinical interview data. Using bulk RNA-sequencing from whole blood, we examined the association between gene expression and WTC-related PTSD symptom severity on (i) highest lifetime Clinician-Administered PTSD Scale (CAPS) score, (ii) past-month CAPS score, and (iii) PTSD symptom dimensions using a 5-factor model of re-experiencing, avoidance, emotional numbing, dysphoric arousal and anxious arousal symptoms. We corrected for sex, age, genotype-derived principal components and surrogate variables. Finally, we performed a meta-analysis with existing PTSD studies (total N=1,016), using case/control status as the predictor and correcting for these variables.We identified 66 genes significantly associated with highest lifetime CAPS score (FDR-corrected pSERPINA1, RPS6KA1,andSTAT3) have been previously associated with PTSD. Geneset enrichment of these findings has identified pathways significant in metabolism, immune signaling, other psychiatric disorders, neurological signaling, and cellular structure. Our meta-analysis revealed 10 genes that reached genome-wide significance, all of which were down-regulated in cases compared to controls (CIRBP, TMSB10, FCGRT, CLIC1, RPS6KB2, HNRNPUL1, ALDOA, NACA, ZNF429 and COPE). Additionally, cellular deconvolution highlighted an enrichment in CD4 T cells and eosinophils in responders with PTSD compared to controls.The distinction in significant genes between lifetime CAPS score and the anxious arousal symptom dimension of PTSD highlights a potential biological difference in the mechanism underlying the heterogeneity of the PTSD phenotype. Future studies should be clear about methods used to analyze PTSD status, as phenotypes based on PTSD symptom dimensions may yield different gene sets than combined CAPS score analysis. Potential biomarkers implicated from our meta-analysis may help improve therapeutic target development for PTSD.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition triggered by exposure to trauma. The study of PTSD is complicated by highly heterogeneous presentations and experiences of trauma between individuals. Capitalizing on the existence of the World Trade Center General Responder Cohort (WTC-GRC) of rescue, recovery and clean-up workers who responded during and in the aftermath of the World Trade Center (WTC) 9/11/2001 attacks, we studied genetic correlates of PTSD in a sample of 371 WTC responders, selected from the WTC-GRC utilizing stratified random sampling. This deeply phenotyped sample of WTC responders – ranging from no/low PTSD symptom levels to severe PTSD– provide a unique opportunity to study genetic risk factors for PTSD severity and chronicity following a single, shared, well-documented trauma, also incorporating measures of childhood and other lifetime traumas.We examined associations of polygenic risk scores (PRS) –derived from a range of genome-wide association studies (GWAS) of behavioral traits, psychiatric disorders, and brain volumetric phenotypes– with PTSD severity and chronicity among these 371 individuals. Our results demonstrate significant genetic regulation of lifetime PTSD severity, assessed with the lifetime version Clinician-Administered PTSD Scale (CAPS), and chronicity, assessed with the past-month CAPS. PRS derived from GWAS of attention deficit-hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and brain imaging phenotypes (amygdala and putamen volumes) were associated with several PTSD symptom dimensions. Interestingly, we found greater genetic contribution to PTSD among cases compared to our full sample. In addition, we tested for associations between exposures to traumatic stressors, including WTC-related exposures, childhood trauma, and other lifetime traumatic life events in our full sample. Together, polygenic risk and exposures to traumatic stress explained ~45% of variance in lifetime CAPS (R2=0.454), and ~48% of variance in past-month CAPS (R2=0.480) in the full sample.These participants represent a highly vulnerable population, with exposures to severe trauma during 9/11 and the following days and months. These novel identified associations between PTSD and PRS of behavioral traits and brain volume phenotypes, as well as replicated associations with PRS of other psychiatric disorders, may contribute to understanding the biological factors associated with risk for and chronicity of PTSD. In particular, the identification of neuroimaging phenotypes indicates that coupling of neuroimaging with genetic risk score calculations may predict PTSD outcomes.

PURPOSE. Nearly two decades after the 9/11 attacks on the World Trade Center (WTC), the prevalence of mental disorders remains elevated among traditional (e.g., police) and non-traditional (e.g., construction workers) responders who were involved in the WTC rescue, recovery, and clean-up efforts. To date, however, scarce research has examined factors associated with perceived need for mental health care, which is critical to promoting engagement in mental health treatment in this population. METHODS. Data were analyzed from 16,170 WTC responders, including 8,881 police responders and 7,289 non-traditional responders, who completed their first annual health monitoring visit with the WTC Health Program an average of 6.5 years after 9/11/2001. Predisposing, enabling, and need-based factors associated with perceived need for mental health care were examined using multivariable logistic regression analyses. RESULTS. Nearly half (48.7%) of non-traditional responders and a fifth (20.6%) of police responders reported a need for mental health care. The most common perceived needs were for psychotropic medication, individual psychotherapy, and stress management counseling. Predisposing (e.g., female gender) and need-based factors (e.g., WTC-related posttraumatic stress disorder) predicted perceived need for mental health care in both groups. Among non-traditional responders, Hispanic ethnicity and current suicidal ideation were additionally associated with this outcome. CONCLUSIONS. Non-traditional WTC responders are substantially more likely than police WTC responders to perceive a need for mental health treatment. Characterization of factors associated with perceived need for treatment can help inform population-based outreach and monitoring efforts designed to promote engagement in mental health treatment in WTC responders.

BackgroundPost-traumatic stress disorder (PTSD) in response to the World Trade Center (WTC) disaster of 11 September 2001 (9/11) is one of the most prevalent and persistent health conditions among both professional (e.g. police) and non-traditional (e.g. construction worker) WTC responders, even several years after 9/11. However, little is known about the dimensionality and natural course of WTC-related PTSD symptomatology in these populations.MethodData were analysed from 10 835 WTC responders, including 4035 police and 6800 non-traditional responders who were evaluated as part of the WTC Health Program, a clinic network in the New York area established by the National Institute for Occupational Safety and Health. Confirmatory factor analyses (CFAs) were used to evaluate structural models of PTSD symptom dimensionality; and autoregressive cross-lagged (ARCL) panel regressions were used to examine the prospective interrelationships among PTSD symptom clusters at 3, 6 and 8 years after 9/11.ResultsCFAs suggested that five stable symptom clusters best represent PTSD symptom dimensionality in both police and non-traditional WTC responders. This five-factor model was also invariant over time with respect to factor loadings and structural parameters, thereby demonstrating its longitudinal stability. ARCL panel regression analyses revealed that hyperarousal symptoms had a prominent role in predicting other symptom clusters of PTSD, with anxious arousal symptoms primarily driving re-experiencing symptoms, and dysphoric arousal symptoms primarily driving emotional numbing symptoms over time.ConclusionsResults of this study suggest that disaster-related PTSD symptomatology in WTC responders is best represented by five symptom dimensions. Anxious arousal symptoms, which are characterized by hypervigilance and exaggerated startle, may primarily drive re-experiencing symptoms, while dysphoric arousal symptoms, which are characterized by sleep disturbance, irritability/anger and concentration difficulties, may primarily drive emotional numbing symptoms over time. These results underscore the importance of assessment, monitoring and early intervention of hyperarousal symptoms in WTC and other disaster responders.

Trajectories of disaster-related posttraumatic stress disorder (PTSD) symptoms are often heterogeneous, and associated with common and unique risk factors, yet little is known about potentially modifiable psychosocial characteristics associated with low-symptom and recovering trajectories in disaster responders. A total of 4487 rescue and recovery workers (1874 police and 2613 non-traditional responders) involved during and in the aftermath of the unprecedented World Trade Center (WTC) attacks, were assessed an average of 3, 6, 8, and 12 years post-9/11/2001. Among police responders, WTC-related PTSD symptoms were characterized by four trajectories, including no/low-symptom (76.1%), worsening (12.1%), improving (7.5%), and chronic (4.4%) trajectories. In non-traditional responders, a five-trajectory solution was optimal, with fewer responders in a no/low-symptom trajectory (55.5%), and the remainder in subtly worsening (19.3%), chronic (10.8%), improving (8.5%), and steeply worsening (5.9%) trajectories. Consistent factors associated with symptomatic PTSD trajectories across responder groups included Hispanic ethnicity, pre-9/11 psychiatric history, greater WTC exposure, greater medical illness burden, life stressors and post-9/11 traumas, and maladaptive coping (e.g., substance use, avoidance coping). Higher perceived preparedness, greater sense of purpose in life, and positive emotion-focused coping (e.g., positive reframing, acceptance) were negatively associated with symptomatic trajectories. Findings in this unique cohort indicate considerable heterogeneity in WTC-related PTSD symptom trajectories over 12 years post-9/11/2001, with lower rates of elevated PTSD symptoms in police than in non-traditional responders. They further provide a comprehensive risk prediction model of PTSD symptom trajectories, which can inform prevention, monitoring, and treatment efforts in WTC and other disaster responders.