Altered gene expression and PTSD symptom dimensions in World Trade Center responders.

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.

Mental Healthcare Needs in World Trade Center Responders: Results from a Large, Population-Based Health Monitoring Cohort.

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. Data were analyzed from 16,170 WTC responders, including 8881 police responders and 7289 non-traditional responders, who completed their first annual health monitoring visit with the WTC Health Program an average of 6.5 years after September 11, 2001. Predisposing, enabling, and need-based factors associated with perceived need for mental health care were examined using multivariable logistic regression analyses. 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. 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.