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Genetic and non-genetic predictors of risk for opioid dependence
- Peter J. Na, Joseph D. Deak, Henry R. Kranzler, Robert H. Pietrzak, Joel Gelernter
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 06 February 2024, pp. 1-8
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Background
Elucidation of the interaction of biological and psychosocial/environmental factors on opioid dependence (OD) risk can inform our understanding of the etiology of OD. We examined the role of psychosocial/environmental factors in moderating polygenic risk for opioid use disorder (OUD).
MethodsData from 1958 European ancestry adults who participated in the Yale-Penn 3 study were analyzed. Polygenic risk scores (PRS) were based on a large-scale multi-trait analysis of genome-wide association studies (MTAG) of OUD.
ResultsA total of 420 (21.1%) individuals had a lifetime diagnosis of OD. OUD PRS were positively associated with OD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.21–1.66). Household income and education were the strongest correlates of OD. Among individuals with higher OUD PRS, those with higher education level had lower odds of OD (OR 0.92, 95% CI 0.85–0.98); and those with posttraumatic stress disorder (PTSD) were more likely to have OD relative to those without PTSD (OR 1.56, 95% CI 1.04–2.35).
ConclusionsResults suggest an interplay between genetics and psychosocial environment in contributing to OD risk. While PRS alone do not yet have useful clinical predictive utility, psychosocial factors may help enhance prediction. These findings could inform more targeted clinical and policy interventions to help address this public health crisis.
The Functional Significance of a Novel Conceptualization of Intrusion Symptoms of PTSD
- T. R. Spiller, G. Gross, O. Duek, R. H. Pietrzak, I. Harpaz-Rotem
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S476-S477
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Introduction
Intrusion symptoms are a core defining feature of posttraumatic stress disorder (PTSD). It was recently proposed that intrusions may be comprised of two distinct underlying processes: internally-cued intrusions (e.g., memories), and externally-cued intrusions (e.g., reactions to one’s environment). Preliminary empirical evidence demonstrated superior fit of an 8-factor model of PTSD, separating intrusion symptoms into an in internally-cued and externally-cued symptom cluster over other factor models of PTSD. However, whether these two clusters are related differently with functional outcomes was not investigated previously.
ObjectivesThis is the first study to examine the functional correlates of the internally-cued and externally-cued intrusion symptom clusters in PTSD to assess whether separating intrusion symptoms into these two clusters is of clinical and scientific relevance.
MethodsParticipants included 7460 veterans discharged from 40 VA PTSD residential treatment programs (RRTPs) across the United States in fiscal years 2018 through 2020. Demographic data was collected using a self-report form during the admission process. Symptoms of PTSD, anxiety, depression, and emotional and physical functioning were assessed with the PTSD Checklist for DSM-5, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder Questionnaire-7, and the corresponding subscales of the Short Form 12-item Health Survey, respectively. Latent network modeling was used to test the fit of the 8-factor model of PTSD. Structural equation modelling was used to investigate the associations between the factors of PTSD and the functional outcomes. All associations were adjusted for demographic characteristics, and standardized.
ResultsThe 8-factor model, with separate intrusion factors, showed good model fit (CFI 0.965, RMSEA 0.045, χ2 2453.022, and P <.001). Internally-cued intrusions were negatively associated with physical functioning and positively with emotional functioning. No relationship with depression or anxiety was found. In contrast, externally-cued intrusions were negatively associated with emotional functioning and positively associated with anxiety, but not related to physical functioning and depression.
ConclusionsThis study provides initial support for the functional utility of distinguishing between internally- and externally-cued intrusions in veterans with PTSD. Consequently, researchers focusing on the biological underpinnings of intrusion symptoms (e.g., in imaging or genetic studies) should account for differences in the origin of the cue triggering intrusions. Our findings are of potential clinical relevance as they might help patients adapt their coping strategies for intrusions depending on whether they originate internally (e.g., thoughts) or externally (e.g., loud noises).
Disclosure of InterestNone Declared
Childhood adversities and risk of posttraumatic stress disorder and major depression following a motor vehicle collision in adulthood
- H. N. Ziobrowski, B. Holt-Gosselin, M. V. Petukhova, A. J. King, S. Lee, S. L. House, F. L. Beaudoin, X. An, J. S. Stevens, D. Zeng, T. C. Neylan, G. D. Clifford, S. D. Linnstaedt, L. T. Germine, K. A. Bollen, S. L. Rauch, J. P. Haran, A. B. Storrow, C. Lewandowski, P. I. Musey, P. L. Hendry, S. Sheikh, C. W. Jones, B. E. Punches, M. C. Kurz, R. A. Swor, L. A. Hudak, J. L. Pascual, M. J. Seamon, E. Harris, C. Pearson, R. C. Merchant, R. M. Domeier, N. K. Rathlev, B. J. O'Neil, P. Sergot, L. D. Sanchez, S. E. Bruce, M. W. Miller, R. H. Pietrzak, J. Joormann, D. M. Barch, D. A. Pizzagalli, S. E. Harte, J. M. Elliott, K. J. Ressler, S. A. McLean, K. C. Koenen, R. C. Kessler
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 32 / 2023
- Published online by Cambridge University Press:
- 10 January 2023, e1
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Aims
Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions.
MethodsData came from n = 999 patients ages 18–75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models.
ResultsMost participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31–1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65–2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43–2.87) and bullying (RR = 1.44; 95% CI = 0.99–2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE.
ConclusionsAlthough individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.
Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma
- N. G. Harnett, N. M. Dumornay, M. Delity, L. D. Sanchez, K. Mohiuddin, P. I. Musey, Jr., M. J. Seamon, S. A. McLean, R. C. Kessler, K. C. Koenen, F. L. Beaudoin, L. A. M. Lebois, S. J. H. van Rooij, N. A. Sampson, V. Michopoulos, J. L. Maples-Keller, J. P. Haran, A. B. Storrow, C. Lewandowski, P. L. Hendry, S. Sheikh, C. W. Jones, B. E. Punches, M. C. Kurz, R. A. Swor, M. E. McGrath, L. A. Hudak, J. L. Pascual, S. L. House, X. An, J. S. Stevens, T. C. Neylan, T. Jovanovic, S. D. Linnstaedt, L. T. Germine, E. M. Datner, A. M. Chang, C. Pearson, D. A. Peak, R. C. Merchant, R. M. Domeier, N. K. Rathlev, B. J. O'Neil, P. Sergot, S. E. Bruce, M. W. Miller, R. H. Pietrzak, J. Joormann, D. M. Barch, D. A. Pizzagalli, J. F. Sheridan, J. W. Smoller, B. Luna, S. E. Harte, J. M. Elliott, K. J. Ressler
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- Journal:
- Psychological Medicine / Volume 53 / Issue 6 / April 2023
- Published online by Cambridge University Press:
- 31 January 2022, pp. 2553-2562
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Background
Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time.
MethodsAs part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors.
ResultsRacial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants.
ConclusionsThe present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.
Post-traumatic growth among veterans in the USA: results from the National Health and Resilience in Veterans Study
- J. Tsai, R. El-Gabalawy, W. H. Sledge, S. M. Southwick, R. H. Pietrzak
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- Journal:
- Psychological Medicine / Volume 45 / Issue 1 / January 2015
- Published online by Cambridge University Press:
- 02 June 2014, pp. 165-179
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Background
There is increasing recognition that, in addition to negative psychological consequences of trauma such as post-traumatic stress disorder (PTSD), some individuals may develop post-traumatic growth (PTG) following such experiences. To date, however, data regarding the prevalence, correlates and functional significance of PTG in population-based samples are lacking.
MethodData were analysed from the National Health and Resilience in Veterans Study, a contemporary, nationally representative survey of 3157 US veterans. Veterans completed a survey containing measures of sociodemographic, military, health and psychosocial characteristics, and the Posttraumatic Growth Inventory-Short Form.
ResultsWe found that 50.1% of all veterans and 72.0% of veterans who screened positive for PTSD reported at least ‘moderate’ PTG in relation to their worst traumatic event. An inverted U-shaped relationship was found to best explain the relationship between PTSD symptoms and PTG. Among veterans with PTSD, those with PTSD reported better mental functioning and general health than those without PTG. Experiencing a life-threatening illness or injury and re-experiencing symptoms were most strongly associated with PTG. In multivariable analysis, greater social connectedness, intrinsic religiosity and purpose in life were independently associated with greater PTG.
ConclusionsPTG is prevalent among US veterans, particularly among those who screen positive for PTSD. These results suggest that there may be a ‘positive legacy’ of trauma that has functional significance for veterans. They further suggest that interventions geared toward helping trauma-exposed US veterans process their re-experiencing symptoms, and to develop greater social connections, sense of purpose and intrinsic religiosity may help promote PTG in this population.
Notes on contributors
- Edited by R. Barton Palmer, Clemson University, South Carolina, William Robert Bray, Middle Tennessee State University
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- Modern British Drama on Screen
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- 05 December 2013
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- 05 December 2013, pp xi-xiv
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Dimensional structure and course of post-traumatic stress symptomatology in World Trade Center responders
- R. H. Pietrzak, A. Feder, C. B. Schechter, R. Singh, L. Cancelmo, E. J. Bromet, C. L. Katz, D. B. Reissman, F. Ozbay, V. Sharma, M. Crane, D. Harrison, R. Herbert, S. M. Levin, B. J. Luft, J. M. Moline, J. M. Stellman, I. G. Udasin, R. El-Gabalawy, P. J. Landrigan, S. M. Southwick
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- Journal:
- Psychological Medicine / Volume 44 / Issue 10 / July 2014
- Published online by Cambridge University Press:
- 02 December 2013, pp. 2085-2098
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Background
Post-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 PTSD risk and resilience in World Trade Center responders: an 8-year prospective cohort study
- R. H. Pietrzak, A. Feder, R. Singh, C. B. Schechter, E. J. Bromet, C. L. Katz, D. B. Reissman, F. Ozbay, V. Sharma, M. Crane, D. Harrison, R. Herbert, S. M. Levin, B. J. Luft, J. M. Moline, J. M. Stellman, I. G. Udasin, P. J. Landrigan, S. M. Southwick
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- Psychological Medicine / Volume 44 / Issue 1 / January 2014
- Published online by Cambridge University Press:
- 03 April 2013, pp. 205-219
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Background
Longitudinal symptoms of post-traumatic stress disorder (PTSD) are often characterized by heterogeneous trajectories, which may have unique pre-, peri- and post-trauma risk and protective factors. To date, however, no study has evaluated the nature and determinants of predominant trajectories of PTSD symptoms in World Trade Center (WTC) responders.
MethodA total of 10835 WTC responders, including 4035 professional police responders and 6800 non-traditional responders (e.g. construction workers) who participated in the WTC Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the WTC attacks.
ResultsAmong police responders, longitudinal PTSD symptoms were best characterized by four classes, with the majority (77.8%) in a resistant/resilient trajectory and the remainder exhibiting chronic (5.3%), recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non-traditional responders, a six-class solution was optimal, with fewer responders in a resistant/resilient trajectory (58.0%) and the remainder exhibiting recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%), delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical conditions were most strongly associated with symptomatic trajectories of PTSD symptoms in both groups of responders, whereas greater education and family and work support while working at the WTC site were protective against several of these trajectories.
ConclusionsTrajectories of PTSD symptoms in WTC responders are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk and protective factors. Police responders were more likely than non-traditional responders to exhibit a resistant/resilient trajectory. These results underscore the importance of prevention, screening and treatment efforts that target high-risk disaster responders, particularly those with prior psychiatric history, high levels of trauma exposure and work-related medical morbidities.
Subsyndromal depression in the United States: prevalence, course, and risk for incident psychiatric outcomes
- R. H. Pietrzak, J. Kinley, T. O. Afifi, M. W. Enns, J. Fawcett, J. Sareen
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- Journal:
- Psychological Medicine / Volume 43 / Issue 7 / July 2013
- Published online by Cambridge University Press:
- 31 October 2012, pp. 1401-1414
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Background
Subsyndromal depression (SD) may increase risk for incident major depressive and other disorders, as well as suicidality. However, little is known about the prevalence, course, and correlates of SD in the US general adult population.
MethodStructured diagnostic interviews were conducted to assess DSM-IV Axis I and II disorders in a nationally representative sample of 34 653 US adults who were interviewed at two time-points 3 years apart.
ResultsA total of 11.6% of US adults met study criteria for lifetime SD at Wave 1. The majority (9.3%) had <5 total symptoms required for a diagnosis of major depression; the remainder (2.3%) reported ⩾5 symptoms required for a diagnosis of major depression, but denied clinically significant distress or functional impairment. SD at Wave 1 was associated with increased likelihood of developing incident major depression [odds ratios (ORs) 1.72–2.05], as well as dysthymia, social phobia, and generalized anxiety disorder (GAD) at Wave 2 (ORs 1.41–2.92). Among respondents with SD at Wave 1, Cluster A and B personality disorders, and worse mental health status were associated with increased likelihood of developing incident major depression at Wave 2.
ConclusionsSD is prevalent in the US population, and associated with elevated rates of Axis I and II psychopathology, increased psychosocial disability, and risk for incident major depression, dysthymia, social phobia, and GAD. These results underscore the importance of a dimensional conceptualization of depressive symptoms, as SD may serve as an early prognostic indicator of incident major depression and related disorders, and could help identify individuals who may benefit from preventive interventions.
Diagnostic utility and factor structure of the PTSD Checklist in older adults
- Robert H. Pietrzak, Peter H. Van Ness, Terri R. Fried, Sandro Galea, Fran Norris
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- International Psychogeriatrics / Volume 24 / Issue 10 / October 2012
- Published online by Cambridge University Press:
- 30 May 2012, pp. 1684-1696
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Background: Little research has examined the diagnostic utility and factor structure of commonly used posttraumatic stress disorder (PTSD) assessment instruments in older persons.
Methods: A total of 206 adults aged 60 or older (mean age = 69 years; range = 60–92), who resided in the Galveston Bay area when Hurricane Ike struck in September 2008, completed a computer-assisted telephone interview two–five months after this disaster. Using the PTSD Checklist (PCL), PTSD symptoms were assessed related both to this disaster and to participants’ worst lifetime traumatic event. Total PCL scores were compared to PCL-based, Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-derived probable diagnoses of PTSD to determine optimal cut scores. Confirmatory factor analyses (CFAs) were conducted to evaluate PTSD symptom structure.
Results: Receiver operating characteristic analyses indicated that a PCL score of 39 achieved optimal sensitivity and specificity in assessing a PCL-based, algorithm-derived DSM-IV diagnosis of worst event-related PTSD; and that a score of 37 optimally assessed probable Ike-related PTSD. CFAs revealed that a recently proposed five-factor model – comprised of re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal factors – provided a better fitting representation of both worst event- and disaster-related PTSD symptoms than alternative models. Current Ike-related anxious arousal symptoms demonstrated a significantly stronger association with current generalized anxiety than depressive symptoms, thereby supporting the construct validity of this five-factor model of PTSD symptomatology.
Conclusions: A PCL score of 37 to 39 may help identify probable PTSD in older persons. The expression of PTSD symptoms in older adults may be best characterized by a recently proposed five-factor model with distinct dysphoric arousal and anxious arousal clusters.
Exposure, probable PTSD and lower respiratory illness among World Trade Center rescue, recovery and clean-up workers
- B. J. Luft, C. Schechter, R. Kotov, J. Broihier, D. Reissman, K. Guerrera, I. Udasin, J. Moline, D. Harrison, G. Friedman-Jimenez, R. H. Pietrzak, S. M. Southwick, E. J. Bromet
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- Journal:
- Psychological Medicine / Volume 42 / Issue 5 / May 2012
- Published online by Cambridge University Press:
- 18 November 2011, pp. 1069-1079
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Background
Thousands of rescue and recovery workers descended on the World Trade Center (WTC) in the wake of the terrorist attack of September 11, 2001 (9/11). Recent studies show that respiratory illness and post-traumatic stress disorder (PTSD) are the hallmark health problems, but relationships between them are poorly understood. The current study examined this link and evaluated contributions of WTC exposures.
MethodParticipants were 8508 police and 12 333 non-traditional responders examined at the WTC Medical Monitoring and Treatment Program (WTC-MMTP), a clinic network in the New York area established by the National Institute for Occupational Safety and Health (NIOSH). We used structural equation modeling (SEM) to explore patterns of association among exposures, other risk factors, probable WTC-related PTSD [based on the PTSD Checklist (PCL)], physician-assessed respiratory symptoms arising after 9/11 and present at examination, and abnormal pulmonary functioning defined by low forced vital capacity (FVC).
ResultsFewer police than non-traditional responders had probable PTSD (5.9% v. 23.0%) and respiratory symptoms (22.5% v. 28.4%), whereas pulmonary function was similar. PTSD and respiratory symptoms were moderately correlated (r=0.28 for police and 0.27 for non-traditional responders). Exposure was more strongly associated with respiratory symptoms than with PTSD or lung function. The SEM model that best fit the data in both groups suggested that PTSD statistically mediated the association of exposure with respiratory symptoms.
ConclusionsAlthough longitudinal data are needed to confirm the mediation hypothesis, the link between PTSD and respiratory symptoms is noteworthy and calls for further investigation. The findings also support the value of integrated medical and psychiatric treatment for disaster responders.