Posttraumatic Stress Disorder Status Research Articles

An Empirical Crosswalk for the PTSD Checklist: Translating DSM-IV to DSM-5 Using a Veteran Sample.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced numerous revisions to the fourth edition's (DSM-IV) criteria for posttraumatic stress disorder (PTSD), posing a challenge to clinicians and researchers who wish to assess PTSD symptoms continuously over time. The aim of this study was to develop a crosswalk between the DSM-IV and DSM-5 versions of the PTSD Checklist (PCL), a widely used self-rated measure of PTSD symptom severity. Participants were 1,003 U.S. veterans (58.7% with PTSD) who completed the PCL for DSM-IV (the PCL-C) and DSM-5 (the PCL-5) during their participation in an ongoing longitudinal registry study. In a randomly selected training sample (n = 800), we used equipercentile equating with loglinear smoothing to compute a "crosswalk" between PCL-C and PCL-5 scores. We evaluated the correspondence between the crosswalk-determined predicted scores and observed PCL-5 scores in the remaining validation sample (n = 203). The results showed strong correspondence between crosswalk-predicted PCL-5 scores and observed PCL-5 scores in the validation sample, ICC = .96. Predicted PCL-5 scores performed comparably to observed PCL-5 scores when examining their agreement with PTSD diagnosis ascertained by clinical interview: predicted PCL-5, κ = 0.57; observed PCL-5, κ = 0.59. Subsample comparisons indicated that the crosswalk's accuracy did not differ across characteristics including gender, age, racial minority status, and PTSD status. The results support the validity of this newly developed PCL-C to PCL-5 crosswalk in a veteran sample, providing a tool with which to interpret and translate scores across the two measures.

S52DNA METHYLATION IN LINE-1 CPGS SITES ARE ASSOCIATED WITH POSTTRAUMATIC STRESS DISORDER, IN FEMALE RAPE VICTIMS

FK506-binding protein 5 (FKBP5) binds to glucocorticoid receptors and modulates glucocorticoid sensitivity. The FKBP5 gene has been implicated in the dysregulation of human stress responses, contributing to the risk and treatment response of stress-related disorders. The present study examined whether epigenetic changes in FKBP5 are associated with chronic post-traumatic stress disorder (PTSD) status in the context of FKBP5 genetic variation (rs1360780 polymorphism) among male veterans exposed to combat trauma.Korean male veterans who served on active duty during the Vietnam War were categorized into 2 groups: with PTSD (n = 123) and without PTSD (n = 116). The genotype of FKBP5 rs1360780 and DNA methylation levels of two CpG sites at the FKBP5 intron 7 region were assessed in peripheral blood. Analysis of covariance was performed to examine main and interaction effects of PTSD status and FKBP5 genotype on FKBP5 DNA methylation level, with age, trauma levels, and alcohol use as covariates.A significant main effect of FKBP5 rs1360780 and PTSD and an interaction effect between genotype and PTSD status were found on mean FKBP5 DNA methylation level. The T allele of rs1360780 was associated with lower FKBP5 methylation level. In addition, the PTSD group showed significantly higher methylation than did the non-PTSD group among veterans carrying the risk T allele (n = 96), while no group difference was observed on methylation levels among veterans with the CC genotype (n = 143). Among veterans carrying the T allele, FKBP5 methylation levels were positively correlated with the severity of PTSD symptoms.The present study demonstrated different FKBP5 methylation levels in PTSD depending on FKBP5 genetic variation among veterans exposed to combat trauma. The present finding suggests that the genetic and epigenetic modulation of FKBP5 is involved in the pathophysiology of PTSD. Further longitudinal research involving people exposed to trauma is required to understand causal relationships of FKBP5 in the development and recovery of PTSD.

Comparative Efficacy and Acceptability of Pharmaceutical Management for Adults with Post-Traumatic Stress Disorder: A Systematic Review and Meta-Analysis

Background: The current clinical guidelines on post-traumatic stress disorder (PTSD) recommend selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) of drugs. However, there is uncertainty about the efficacy of other drugs and selecting which treatments work best for which patients. Therefore, we aimed to estimate efficacy and acceptability of pharmaceutical management for adults with PTSD. Methods: We searched the Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and ISIWeb of Science for randomized controlled trials (RCTs) until June 21, 2019. We included placebo-controlled and active-comparators trials of pharmaceutical management for adults with PTSD diagnosed according to standard operationalized criteria. The outcomes were defined as efficacy (improvement in symptoms of PTSD, based on evaluation results of clinician rating scales or interview instruments; core symptoms, including re-experiencing, avoidance, and hyperarousal; other symptoms, including depression and anxiety) and acceptability (all-cause discontinuation, and discontinuation due to adverse effects). Findings: 66 studies with 78 trials comprising of 8,083 patients diagnosed with PTSD were identified. There were two kind of comparisons in included studies, one of them was the comparison between 31 active drugs and placebo, another comparison was active-comparator between 12 active drugs aiming at exploring the differences among different drugs. In terms of efficacy, all active drugs demonstrated superior effect than placebo (SMD = -0.33, 95%CI: -0.43 to -0.23). The medications were superior to placebo in reducing the symptom of re-experiencing, avoidance, hyperarousal, depression, and anxiety. For acceptability, medicine interventions for PTSD showed no increase in all-cause discontinuation compared with placebo (RR = 0.95, 95%CI: 0.88 to 1.03). Nevertheless, in terms of safety, medicine interventions indicated a higher risk of adverse effect compared with placebo (RR = 1.47, 95%CI: 1.24 to 1.75). Compared with placebo, the SSRIs and atypical antipsychotics drugs had significant efficacy whether in patients with severe or extremely severe PTSD status. However, only atypical antipsychotics (SMD = -0.29, 95%CI: -0.48 to -0.10) showed superior efficacy than placebo in veterans. Interpretation: Medication management could be effective in intervention of PTSD, which demonstrated a sufficient improvement in the core symptoms. This meta-analysis supports the status of SSRIs and SNRIs as recommended pharmacotherapy for PTSD. However, patients with different clinical characteristics of PTSD should consider individualized drug management. Furthermore, more high-quality researches are required to confirm these findings. Funding Statement: The authors stated that no funding was received for this research. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The authors used the guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement.

Pilot Data on Effects of Community Dance for Veterans with PTSD and their Family Members

Prior research has shown that there are several symptoms of Post-Traumatic Stress Disorder (PTSD) that are persistently hard to treat and critically important for full recovery. Community reintegration can be an especially challenging aspect of returning home from combat duty. The purpose of this study was to test the effects of a community dance program on some of these psychological symptoms. Community dance has been shown to strengthen cognitive plasticity which is often a problem for veterans with PTSD. This program also includes predictable gentle touch and family involvement, two elements that can predict stress reduction and successful community reintegration in those with PTSD. Before and after each ten-week community dance program, seventeen veterans and accompanying family members were measured on connectedness using the Interpersonal Needs Questionnaire, Revised (INQ-R) (Van Orden, Witte, Gordon, Bender, & Joiner, 2008), experience avoidance using the Acceptance and Action Questionnaire, Version 2 (AAQ-II) (Bond, et al., 2011), and hope and optimism using a modified Life Orientation Test, Revised questionnaire (LOT-r ) Scheier, Carver, & Bridges, 1994), combined into a wellness score. Each ten-week program consisted of weekly, 90-minute community dances with live music and a nationally recognized dance caller. We found improvements in wellness scores for all participants, regardless of PTSD status, partial h2 =0.52. We think this program, and programs like it, show great promise in treating some of the most persistent symptoms of PTSD in veterans and in their families.

Association between posttraumatic stress disorder severity and amygdala habituation to fearful stimuli

Amygdala hyperreactivity to threat has been proposed to be a causal contributor to posttraumatic stress disorder (PTSD). However, emerging literature in healthy samples shows higher test-retest reliability for amygdala habituation (the change over time in response to repeated stimuli) than for its reactivity to threat. Amygdala habituation has received relatively little attention in relationship to PTSD, despite the key role of this region in the etiology of the disorder. Thus, we investigated habituation to repeated fearful face stimuli and PTSD, in a large sample of trauma exposed African American women. African American women (N = 100) were recruited from a nonprofit hospital serving a largely low-income population with a high risk of trauma exposure. Participants underwent functional magnetic resonance imaging, passively viewing fearful and neutral face stimuli, and reported their history of trauma exposure and current PTSD symptoms. We examined associations between PTSD symptom severity and amygdala reactivity (fearful > neutral) and habituation (early > late) to fearful faces. Secondary analyses tested whether amygdala habituation to fearful faces mediated the association between childhood trauma and PTSD. PTSD symptom severity and PTSD status (based on self-report measure) were both positively associated with amygdala habituation to repeated fearful face stimuli. Whole-brain analysis showed that this association extended to the bilateral hippocampus and left fusiform gyrus. The association held when controlling for trauma history and depressive symptoms. Amygdala habituation to fearful faces partially mediated the association between childhood trauma severity and PTSD symptom severity. Individuals with greater PTSD symptom severity showed greater amygdala habituation to social threat cues (fearful faces), and greater habituation may partly explain the association between childhood trauma exposure and current PTSD symptoms. Further examination of the dynamics of the amygdala response to threat cues may lead to new insights in the understanding and treatment of stress-related disorders.

Methylomic profiles reveal sex-specific differences in leukocyte composition associated with post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a debilitating mental disorder precipitated by trauma exposure. However, only some persons exposed to trauma develop PTSD. There are sex differences in risk; twice as many women as men develop a lifetime diagnosis of PTSD. Methylomic profiles derived from peripheral blood are well-suited for investigating PTSD because DNA methylation (DNAm) encodes individual response to trauma and may play a key role in the immune dysregulation characteristic of PTSD pathophysiology. In the current study, we leveraged recent methodological advances to investigate sex-specific differences in DNAm-based leukocyte composition that are associated with lifetime PTSD. We estimated leukocyte composition on a combined methylation array dataset (483 participants, ∼450 k CpG sites) consisting of two civilian cohorts, the Detroit Neighborhood Health Study and Grady Trauma Project. Sex-stratified Mann-Whitney U test and two-way ANCOVA revealed that lifetime PTSD was associated with significantly higher monocyte proportions in males, but not in females (Holm-adjusted p-val < 0.05). No difference in monocyte proportions was observed between current and remitted PTSD cases in males, suggesting that this sex-specific difference may reflect a long-standing trait of lifetime history of PTSD, rather than current state of PTSD. Associations with lifetime PTSD or PTSD status were not observed in any other leukocyte subtype and our finding in monocytes was confirmed using cell estimates based on a different deconvolution algorithm, suggesting that our sex-specific findings are robust across cell estimation approaches. Overall, our main finding of elevated monocyte proportions in males, but not in females with lifetime history of PTSD provides evidence for a sex-specific difference in peripheral blood leukocyte composition that is detectable in methylomic profiles and that may reflect long-standing changes associated with PTSD diagnosis.

Treating Alcohol Use Disorder in U.S. Veterans: The Role of Traumatic Brain Injury.

The authors examined the efficacy of valproate to reduce relapse to heavy drinking among veterans with alcohol use disorder (AUD) and neuropsychiatric comorbidities and whether antecedent traumatic brain injury (TBI) or posttraumatic stress disorder (PTSD) affected treatment response. Participants were male veterans 18-60 years old with an AUD and no other substance use besides nicotine or cannabis. Sixty-two patients were randomly assigned to receive either valproate or naltrexone. Participants were evaluated at baseline and followed weekly for 24 weeks. All participants received standardized psychosocial interventions as well as treatment for coexistent psychiatric conditions. During the follow-up period, nine study subjects in the naltrexone group and 14 in the valproate group relapsed to heavy drinking, but the difference did not reach statistical significance. Participants with a history of moderate to severe TBI were more likely to relapse to heavy drinking compared with those with no TBI (hazard ratio=4.834, 95% CI=1.103-21.194, p=0.033). PTSD status did not significantly affect outcome. Intensive outpatient programs are efficacious alternatives to treat AUD in veterans, although the role of pharmacological treatment is not completely elucidated. Glutamatergic agents appear to be less effective than opiate antagonists to prevent relapse to heavy drinking and to increase cumulative abstinence. Future studies should examine novel pharmacological and nonpharmacological options.

Posttraumatic stress disorder among patients with oral and maxillofacial trauma in a South Indian population.

To determine the incidence and severity of Post-Traumatic Stress Disorder (PTSD) in maxillofacial trauma patients and to assess the predisposing factors. Post-Traumatic Stress Disorder (PTSD) was assessed as per the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. The PTSD checklist for DSM-5 (PCL-5), was used initially to screen patients for PTSD for a provisional diagnosis. These provisionally diagnosed patients were then subjected to a structured interview by a Clinician Administered PTSD Scale for DSM-5 (CAPS-5). The PTSD status outcome of PCL-5 and CAPS-5 were correlated. PTSD was compared among patients with different types of facial fractures/injuries and also compared based on their anatomic location. The reliability of PCL-5 scale in relation to the structured CAPS-5 was assessed and the specificity was found to be 71.4%. Patients with both aesthetic and functional deformity exhibited greater severity of injury and showed higher incidence of PTSD with higher conversion rate from the 1st month to 3rd month. The frequency of PTSD in deformities with higher severity like zygomaticomaxillary complex injuries was found to be statistically significant. A high incidence of PTSD is associated with maxillofacial trauma and early detection is essential.

A Cognitive Reserve and Social Support-Focused Latent Class Analysis to Predict Self-Reported Confusion or Memory Loss among Middle-Aged World Trade Center Health Registry Enrollees.

The World Trade Center Health Registry includes 9/11 survivors who have been surveyed about their health conditions over time. The prevalence of posttraumatic stress disorder (PTSD) remains high among the cohort and is a risk factor for cognitive impairment or dementia. We thus sought to examine the degree to which confusion or memory loss (CML)—potential symptoms of cognitive decline—are occurring among enrollees aged 35–64 years. Cognitive reserve theory suggests that higher levels of education and engaging in cognitively challenging activities can create stronger neural connections, offering protection against cognitive decline. We hypothesized that enrollees with less cognitive reserve would be more likely to report CML. In this study, we: (1) estimated the incidence of CML in our study sample; (2) identified indicators of cognitive reserve (e.g., indicators of educational attainment, social support); and (3) determined whether CML is associated with cognitive reserve level, stratified by PSTD status. First, we described demographics of the study sample (n = 14,574) and probable PTSD status, also stratifying by CML. Next, we conducted a latent class analysis on two groups: those with probable PTSD and those without probable PTSD, creating classes with varying cognitive reserve levels. Finally, using adjusted log binomial models, we predicted risk of CML based on cognitive reserve level. The probable PTSD group (n = 1213) and not probable PTSD group (n = 13,252) each had four latent classes: low, medium-low, medium-high, and high cognitive reserve. In the probable PTSD model, compared to the high cognitive reserve class, those with medium-low cognitive reserve were 35% more likely to report CML (relative risk (RR) = 1.4, 95% confidence interval (CI): 1.1, 1.7). Among the not probable PTSD group, those with low and medium levels of cognitive reserve were significantly more likely to report CML (RR = 1.8 and 1.4, respectively). Overall, those with less cognitive reserve were more likely to report CML regardless of PTSD status.

Posttraumatic Stress Disorder Symptoms and Criminal Behavior in U.S. Army Populations: The Mediating Role of Psychopathy and Suicidal Ideation

Abstract Whereas past research has demonstrated the relationship between posttraumatic stress disorder (PTSD) and criminal behavior, the present study examines the underlying mechanisms driving this association. The primary objective was to determine the role of psychopathy and suicidal ideation as mediating factors in the relationship between military PTSD symptoms and criminal behavior (defined as incarceration status). A correlational study using archival data from the U.S. Disciplinary Barracks (USDB) and a control population of U.S. Army soldiers was conducted. The USDB provided data from 310 incarcerated male U.S. Army soldiers. Data were also collected from 310 nonincarcerated, male U.S. Army soldiers in the greater Fort Rucker, Alabama area. Data validity checks eliminated some cases, thus yielding a final dataset of 246 USDB and 252 control participants. The results suggested partial mediation, in that PTSD symptoms had a direct effect on incarceration status, and significant indirect effects through suicidal ideation and psychopathy while controlling for intelligence and warmth. In furnishing evidence of how psychopathy and suicidal ideation mediate the relationship between PTSD and incarceration status in military personnel, this research highlights specific internalization and externalization mechanisms that may increase the tendencies of people with greater PTSD symptoms to engage in criminal behaviors. By adding to the small amount of prior research on why PTSD sometimes leads people to engage in criminal behaviors, our research provides specific, observable symptoms that clinicians may use to identify, treat, and possibly ameliorate facets of PTSD that can lead affected people to engage in criminal behaviors.

Associations Among Hair Cortisol Concentrations, Posttraumatic Stress Disorder Status, and Amygdala Reactivity to Negative Affective Stimuli in Female Police Officers.

Posttraumatic stress disorder (PTSD) is associated with altered hypothalamic‐pituitary‐adrenal (HPA) axis function. Measurement of hair cortisol concentrations (HCC) allows retrospective assessment of HPA axis regulation over prolonged periods of time. Currently, research investigating HCC in PTSD remains sparse. Previous cross‐sectional studies have included only civilian populations, although it is known that trauma type moderates associations between PTSD status and HPA axis function. We investigated differences in HCC between trauma‐exposed female police officers with current PTSD (n = 13) and without current and lifetime PTSD (n = 15). To investigate whether HCC was associated with neural correlates of PTSD, we additionally performed exploratory correlational analyses between HCC and amygdala reactivity to negative affective stimuli. We observed significantly lower HCC in participants with PTSD than in participants without PTSD, d = 0.89. Additionally, within participants with PTSD, we observed positive correlations between HCC and right amygdala reactivity to negative affective (vs. happy/neutral) faces, r = .806 (n = 11) and left amygdala reactivity to negative affective (vs. neutral) pictures, r = .663 (n = 10). Additionally, left amygdala reactivity to negative faces was positively correlated with HCC in trauma‐exposed controls, r = .582 (n = 13). This indicates that lower HCC is associated with diminished amygdala differentiation between negative affective and neutral stimuli. Thus, we observed lower HCC in trauma‐exposed noncivilian women with PTSD compared to those without PTSD, which likely reflects prolonged HPA axis dysregulation. Additionally, HCC was associated with hallmark neurobiological correlates of PTSD, providing additional insights into pathophysiological processes in PTSD.

Posttraumatic stress disorder and total amyloid burden and amyloid-β 42/40 ratios in plasma: Results from a pilot study of World Trade Center responders

IntroductionChronic posttraumatic stress disorder (PTSD) is associated with poor memory and increased burden of various degenerative cerebral neuropathologies. The goal of this pilot study was to determine whether PTSD was associated with changes in plasma-based neuropathological biomarkers of neurodegeneration among World Trade Center (WTC) responders. MethodsThirty-four WTC responders had blood drawn and flash-frozen within 15 minutes of retrieval. PTSD symptoms were assessed at that time. Age, sex, and WTC exposure duration were obtained from medical records. Plasma was assayed in duplicate using an ultra-sensitive single-molecule enzyme-linked immunosorbent assay to examine the distribution of amyloid-β (Aβ) 42/40 ratios, total Aβ, total tau, and neurofilament light (NfL). The comparison group was drawn from a bank of healthy controls collected and assayed at the same facility. ResultsThe average age of WTC responders at blood draw was 53 years. Half were PTSD positive (PTSD+) as indicated by symptom severity. WTC responders had lower Aβ42/Aβ40 ratios but higher total tau and NfL levels in the plasma than healthy controls. PTSD+ status was associated with lower plasma Aβ load and higher Aβ42/Aβ40 ratios. DiscussionFindings suggest that PTSD may be associated with alterations in plasma markers related to Aβ, tau, and NfL, highlighting the potential association between PTSD status and neurodegenerative neuropathology in WTC responders.

Behavioral and neural correlates of memory suppression in PTSD

Previous work has shown that healthy individuals can actively suppress emotional memories through recruitment of the lateral prefrontal cortex. By contrast, individuals with posttraumatic stress disorder (PTSD) frequently experience unwanted memories of their traumatic experiences, even when making explicit efforts to avoid them. However, little is known regarding the behavioral and neural effects of memory suppression among individuals with PTSD. We examined memory suppression associated with PTSD using the Think-No-Think paradigm in an event-related functional magnetic resonance imaging (fMRI) study. We studied three groups: PTSD (n = 16), trauma exposure without PTSD (n = 19), and controls (i.e., no trauma exposure or PTSD; n = 13). There was a main effect of memory suppression such that participants remembered fewer face-picture pairs during the suppress condition than the remember condition. However, trauma-exposed participants (regardless of PTSD status) were less likely to successfully suppress memory than non-trauma-exposed controls. Neuroimaging data revealed that trauma-exposed individuals showed reduced activation in the right middle frontal gyrus during memory suppression. These results suggest that trauma exposure is associated with neural and behavioral disruptions in memory suppression and point to the possibility that difficulty in active suppression of memories may be just one of several likely factors contributing to the development of PTSD.

Abstract P1-10-06: High participation of African-American women veterans in high risk breast cancer screening pilot program

Abstract SPECIFIC AIMS: To assess breast cancer risk in Women Veterans. BACKGROUND/RATIONALE: Women are the fastest growing segment of patients numbering over 2 million and breast cancer incidence has more than tripled from 1995 to 2012 within the Veterans Health Administration (VHA). Preliminary data suggest that Women Veterans may be at an increased breast cancer risk based on unique service-related exposures (e.g., burn pits, depleted uranium) and Post Traumatic Stress Disorder (PTSD). Historically, breast cancer rates among African Americans (AA) are lower than those seen in the general population (8.2-13.3%). METHODS: A pilot study was conducted at Bronx, NY and Washington, DC Veterans Affairs Medical Centers. Participants were enrolled at their regular visit to Women's Health Clinics or at breast cancer education and awareness events. 5-year and lifetime risks of developing invasive breast cancer were calculated using the Gail Breast Cancer Risk Assessment Tool (BCRAT). Demographics, PTSD status, eligibility for chemoprevention and genetic counseling using the Breast Cancer Genetics Referral Screening Tool (B-RST), were also determined. ELIGIBILITY CRITERIA: Women Veterans age ≥ 35 years with no personal history of breast cancer. RESULTS: A total of 99 Women Veterans with an average age of 54 years participated between 2015 and 2018; 60% African American (AA); 13% Hispanic; 14% non-Hispanic White and 13% as other. In total, 35% (35/99) were considered high risk with a 5-year BCRAT of &amp;gt;1.66% and of these, 51% were AA; 14% Hispanic and 17 % were other. Prior breast biopsies were performed in only 22% (22/99) of our entire Veteran population; 57% (56/99) having a family history positive for breast cancer. Comparatively, in our high risk AA alone, 33% (6/18) had prior breast biopsies with 94% (17/18) having a positive family history. High risk patients were referred for chemoprevention; 5 (19%) accepted; and 13/35 (37%) patients were referred for genetic counseling. PTSD was present in 29% overall and in 31% of the high risk subgroup. IMPLICATIONS: The VHA, which leads the nation in mammogram compliance, is an untapped potential resource for the study of breast cancer. To our knowledge, this is the only study with 60% AA Women Veterans. High participation rates among AA in this pilot study have uncovered the potential for further inquiry into this population, which is otherwise dramatically under-represented in research. Over half (51%) of AA in this pilot study had a high risk score, likely linked to a high rate of prior breast biopsies and family history. Limitations of this study include the small sample size, exclusively urban population, geography and self-selection for screening due to a higher level of concern for breast cancer. If Women Veterans are at higher risk of breast cancer, it has been assumed that this would be related to service-related exposures, PTSD and other factors. However this pilot study, which was not designed or powered to do more than raise questions, suggests the additional possibility of an innate or genetic risk, especially in AAs. Future directions include the evaluation of genetic and molecular mutations in high risk AA Women Veterans, possibly even a role for PTSD epigenetic changes and tumorigenesis. Citation Format: Park Y-HA, Keller AT, Bidassie B, Venne VL, Heron BB, Hoffman-Hōgg L, Hawley DK, Hsu T-CM, Colonna SV, Aggarwal A. High participation of African-American women veterans in high risk breast cancer screening pilot program [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-10-06.

Exposure to multiple disasters: The long-term effect of Hurricane Sandy (October 29, 2012) on NYC survivors of the September 11, 2001 World Trade Center attack

This study evaluated the impact of pre-Hurricane Sandy (Sandy) post-traumatic stress disorder (PTSD) trajectories on the relationship between Sandy exposures and post-Sandy 9/11-related PTSD among World Trade Center Health Registry (Registry) enrollees. The study population included 3,199 adult Registry enrollees who completed three surveys prior to Sandy in 2003–4, 2006–7, and 2011–12; a post-Hurricane Sandy survey (2013); and a follow-up survey in 2015–16. PTSD was assessed using the PTSD Checklist (PCL). Latent class growth analysis was used to identify groups of enrollees who shared a similar trajectory of change in PCL score in the time period prior to Sandy. We compared enrollees in each trajectory group to assess the impact of Sandy-related PTSD, Sandy exposures, and optimism on 9/11-related PTSD status post-Sandy (2015–16) using bivariate analyses and multivariable log-binomial regression. Sandy-related PTSD was the strongest predictor of subsequent 9/11-related PTSD. Lower optimism and higher Sandy exposure significantly predicted 9/11-related PTSD only in some trajectory groups. Hurricane Sandy may have exacerbated previously resolved symptoms of 9/11-related PTSD. This indicates a need after a disaster to assess and address mental health sequelae from previous traumatic exposures.

Acceptance and Commitment Therapy for Chronic Pain: Does Post-traumatic Stress Disorder Influence Treatment Outcomes?

The aim of this study was to determine whether post-traumatic stress disorder (PTSD) moderates treatment outcomes in Acceptance and Commitment Therapy for chronic pain. Longitudinal. Veterans Affairs San Diego Healthcare System. A total of 126 veterans with chronic pain participating in an Acceptance and Commitment Therapy intervention for chronic pain. A structured clinical interview was used at baseline to designate PTSD-positive (N = 43) and -negative groups (N = 83). Linear mixed-effects models to determine whether PTSD moderated change in pain interference, pain severity, pain acceptance, depressive symptoms, or pain-related anxiety at post-treatment and six-month follow-up. Participants with co-occurring PTSD reported greater pain interference, pain severity, depressive symptoms, and pain-related anxiety at baseline. PTSD status did not moderate treatment effects post-treatment. Rather, there were significant improvements on all study measures across groups (P < 0.001). PTSD status moderated change in depressive symptoms at six-month follow-up (P < 0.05). Specifically, participants with chronic pain alone demonstrated improvement in depressive symptoms compared with pretreatment levels, whereas participants with PTSD regressed to pretreatment levels. PTSD status did not significantly affect treatment outcomes, with the exception of depressive symptoms at six-month follow-up. Overall, Acceptance and Commitment Therapy for chronic pain appears helpful for improving outcomes among veterans with co-occurring PTSD; however, veterans with co-occurring PTSD may experience fewer long-term gains compared with those with chronic pain alone.

SA57 - GENETIC AND EPIGENETIC INVOLVEMENT OF THE FKPB5 GENE IN POSTTRAUMATIC STRESS DISORDER AFTER COMBAT TRAUMA

Background FK506 binding protein 5 (FKBP5) is a major regulatory protein of the HPA axis, which binds to the glucocorticoid receptors and modulate glucocorticoid sensitivity. The FKBP5 genes have been implicated in dysregulation of human stress responses, contributing to vulnerable phenotypes such as depression and anxiety. The present study aimed to investigate whether genetic and epigenetic factors of the FKBP5 are a predictive biomarker of Posttraumatic Stress Disorder (PTSD) among veterans exposed to combat. In addition, the influence of potentially associated factors, including combat exposure levels and alcohol problem, was examined in the pathophysiology of PTSD. Methods All subjects were Korean male veterans who served on active duty during the Vietnam War and the Combat Exposure Scale (CES) was used for assessing the level of wartime stressors experienced by combatants. Using the Clinician-Administered PTSD Scale (CAPS), combat veterans were grouped into those with (n=124) and without (n=120) PTSD. Three SNPs of the FKBP5 locus (rs9296158, rs1360780, and rs9470080) were genotyped with single base primer extension assay using the ABI PRISM SNaPShot Multiplex kit. DNA methylation levels at two CpG sites in the FKBP5 intron 7 region were quantified in the peripheral blood using the bisulfite pyrosequencing method. The effects of FKBP5 variants, the DNA methylation levels and clinical factors on the diagnosis of PTSD were tested using binary logistic regression analysis. Results Since a significant interaction effect between alcohol problem and FKBP5 variants was found for PTSD symptom, logistic regression analyses stratified by presence of alcohol problem were performed. Among combat-exposed individuals without alcohol problem, the risk allele of FKBP5 rs1360780, higher methylation levels at the FKBP5 CpG1 site, high combat exposure significantly predicted PTSD diagnosis in combat-exposed individuals (Model Summary: -2 Log likelihood=144.07, Nagelkerke R2=0.279; Overall percentage of correct classification resulting from the model=72.9%). In the logistic model among subjects with alcohol problem, the combat exposure level was an only significant predictor of PTSD status. Discussion The present study demonstrated the involvement of FKBP5 genetic variants and higher DNA methylation of the FKBP5 in PTSD status without alcohol problem. The present findings suggest that the external traumatic events may influence PTSD pathophysiology via genetic and epigenetic modulation of the FKBP5 and alcohol problem may be a moderating factor of PTSD. Further prospective research examining genetic variants and epigenetic changes of FKBP5 locus in people exposed to trauma might shed light on the role and the biological basis of FKBP5 in susceptibility to PTSD.

Sexual trauma history is associated with reduced orbitofrontal network strength in substance-dependent women.

AimSubstance use disorders (SUDs) are highly comorbid with post-traumatic stress disorder (PTSD). PTSD-SUD comorbidity is associated with greater functional impairments and relapse risk. Women with SUDs experience markedly higher rates of trauma and PTSD compared to men with SUDs, particularly due to sexual and domestic abuse. Despite the strong association between trauma exposure and SUDs, the neurobiological correlates are understudied, particularly among females with SUDs. However, there is indication of abnormal somatic and interoceptive processing in women with PTSD. The present study examines interoception-linked differences in intrinsic brain networks in a group of women with SUDs and varying histories of trauma exposure, some of whom have a current PTSD diagnosis.MethodsPre-intervention data were analyzed from a subset (N = 43) of women in SUD residential treatment recruited for a mindfulness-based intervention efficacy clinical trial. Participants diagnosed with PTSD (n = 14) or not (n = 29) performed a task which involved attending to the somatic and visceral sensations of the breathing cycle (interoception) while undergoing a functional MRI (fMRI) scan. FMRI analysis employed independent components analysis and dual regression. First, we assessed differences in functional connectivity of interoception-modulated functional networks among those with and without PTSD. Second, we tested associations between network strength and lifetime sexual violence exposure across all participants on networks that showed significant group differences.ResultsPTSD diagnosis was associated with reduced functional connectivity of an orbitofrontal network with the precuneus, mid-posterior insula, lateral prefrontal cortex and angular gyrus. OFC network strength was inversely associated with sexual violence exposure over-and-above the contribution of PTSD status alone.ConclusionsOur findings provide a novel network-level account of brain activity associated with PTSD among women with SUDs, which may inform treatment response in this subpopulation.

Allele-specific DNA methylation level of FKBP5 is associated with post-traumatic stress disorder

BackgroundFK506-binding protein 5 (FKBP5) binds to glucocorticoid receptors and modulates glucocorticoid sensitivity. The FKBP5 gene has been implicated in the dysregulation of human stress responses, contributing to the risk and treatment response of stress-related disorders. The present study examined whether epigenetic changes in FKBP5 are associated with chronic post-traumatic stress disorder (PTSD) status in the context of FKBP5 genetic variation (rs1360780 polymorphism) among male veterans exposed to combat trauma. MethodsKorean male veterans who served on active duty during the Vietnam War were categorized into 2 groups: with PTSD (n = 123) and without PTSD (n = 116). The genotype of FKBP5 rs1360780 and DNA methylation levels of two CpG sites at the FKBP5 intron 7 region were assessed in peripheral blood. Analysis of covariance was performed to examine main and interaction effects of PTSD status and FKBP5 genotype on FKBP5 DNA methylation level, with age, trauma levels, and alcohol use as covariates. ResultsA significant main effect of FKBP5 rs1360780 and PTSD and an interaction effect between genotype and PTSD status were found on mean FKBP5 DNA methylation level. The T allele of rs1360780 was associated with lower FKBP5 methylation level. In addition, the PTSD group showed significantly higher methylation than did the non-PTSD group among veterans carrying the risk T allele (n = 96), while no group difference was observed on methylation levels among veterans with the CC genotype (n = 143). Among veterans carrying the T allele, FKBP5 methylation levels were positively correlated with the severity of PTSD symptoms. ConclusionsThe present study demonstrated different FKBP5 methylation levels in PTSD depending on FKBP5 genetic variation among veterans exposed to combat trauma. The present finding suggests that the genetic and epigenetic modulation of FKBP5 is involved in the pathophysiology of PTSD. Further longitudinal research involving people exposed to trauma is required to understand causal relationships of FKBP5 in the development and recovery of PTSD.

Effects of intranasal oxytocin on distraction as emotion regulation strategy in patients with post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is characterized by difficulty down-regulating emotional responses towards trauma-reminders. The neuropeptide oxytocin may enhance treatment response in PTSD, by dampening excessive fear and improving fear regulation. However, oxytocin effects on (neural correlates of) cognitive emotion regulation abilities have never been investigated in PTSD patients. Therefore, we investigated behavioral and neural effects of intranasal oxytocin administration (40IU) on distraction as emotion regulation strategy in male and female police officers with and without PTSD (n = 76), using a randomized placebo-controlled cross-over fMRI study. The distraction condition consisted of a working memory task while negative affective pictures were presented. Under placebo, male PTSD patients showed decreased right striatal activity during distraction compared to male trauma-exposed controls, which was unaffected by oxytocin. After oxytocin administration, left thalamus activity during distraction was enhanced in all participants, independent of PTSD status or sex. Although left thalamus activity during distraction did not differ between PTSD patients and controls under placebo, it was negatively correlated with error rates within PTSD patients. Furthermore, oxytocin administration increased functional connectivity between the left thalamus and amygdala in PTSD patients and male trauma-exposed controls. Upregulation of thalamus activity during distraction by oxytocin may enhance cognitive emotion regulation abilities during psychotherapy in PTSD, although this should still be investigated in a clinical setting. Our findings open an important research avenue into oxytocin effects on cognitive emotion regulation in PTSD and other psychiatric disorders characterized by deficient emotion regulation abilities. Registered in the Netherlands Trial Registry, registration number: NTR3516