Posttraumatic Stress Disorder and Obstructive Sleep Apnea in Twins.

Importance: Obstructive sleep apnea (OSA) is a common condition in older adult (aged >65 years) populations, but more mechanistic research is needed to individualize treatments. Previous evidence has suggested an association between OSA and posttraumatic stress disorder (PTSD) but is limited by possible selection bias. High-quality research on this association with a careful evaluation of possible confounders may yield important mechanistic insight into both conditions and improve treatment efforts. Objective: To investigate the association of current PTSD symptoms and PTSD diagnosis with OSA. Design, Setting, and Participants: This cross-sectional study of twin pairs discordant for PTSD, which allows for adjustment for familial factors, was conducted using in-laboratory polysomnography from March 20, 2017, to June 3, 2019. The study sample comprised male veteran twins recruited from the Vietnam Era Twin Registry. The data analysis was performed between June 11, 2022, and January 30, 2023. Exposure: Symptoms of PTSD in twins who served in the Vietnam War. Diagnosis of PTSD was a secondary exposure. Main Outcomes and Measures: Obstructive sleep apnea was assessed using the apnea-hypopnea index (AHI) (≥4% oxygen saturation criterion as measured by events per hour) with overnight polysomnography. Symptoms of PTSD were assessed using the PTSD Checklist (PCL) and structured clinical interview for PTSD diagnosis. Results: A total of 181 male twins (mean [SD] age, 68.4 [2.0] years) including 66 pairs discordant for PTSD symptoms and 15 pairs discordant for a current PTSD diagnosis were evaluated. In models examining the PCL and OSA within pairs and adjusted for body mass index (BMI) and other sociodemographic, cardiovascular, and psychiatric risk factors (including depression), each 15-point increase in PCL was associated with a 4.6 (95% CI, 0.1-9.1) events-per-hour higher AHI. Current PTSD diagnosis was associated with an adjusted 10.5 (95% CI, 5.7-15.3) events-per-hour higher AHI per sleep-hour. Comparable standardized estimates of the association of PTSD symptoms and BMI with AHI per SD increase (1.9 events per hour; 95% CI, 0.5-3.3 events per hour) were found. Conclusions and Relevance: This cross-sectional study found an association between PTSD and sleep-disordered breathing. The findings have important public health implications and may also enhance understanding of the many factors that potentially affect OSA pathophysiology.

Melioidosis and Activation from Latency: The "Time Bomb" Has Not Occurred.

Burkholderia pseudomallei, the causative agent of melioidosis has long been considered able to exist in a latent form. Seropositivity among U.S. soldiers returning from the Vietnam conflict led to melioidosis being dubbed "the Vietnamese time bomb." Cases assigned to "(re)activation from latency" over 30 years of the Darwin Prospective Melioidosis Study (DPMS) were reviewed and reassessed and additional cases from DPMS years 31-34 were added. Historical reports of melioidosis attributed to activation from latency were reviewed. Some earlier DPMS cases and most historical cases described as activation from latency more accurately reflect undiagnosed chronic melioidosis, often with relapsing-remitting courses, rather than truly latent, asymptomatic infection. Such protracted disease should now be diagnosable much earlier, provided melioidosis is considered and laboratory facilities are available. The longest plausible duration of asymptomatic latency remains 29 years. In conclusion, activation from latency is a rare event in melioidosis, accounting in our analysis for under 3% of DPMS cases, consistent with why the Vietnamese time bomb never eventuated.

Agent orange exposure and prostate cancer risk in the million veteran program.

BACKGROUND: The US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk. PATIENTS AND METHODS: Participants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470). Agent Orange exposure was determined using the US government definition. Genetic risk was assessed via a validated polygenic hazard score. Associations with age at diagnosis of any PCa, metastatic PCa, and death from PCa were assessed via Cox proportional hazards models. RESULTS AND INTERPRETATION: On univariable analysis, exposure to Agent Orange was not associated with increased PCa (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.00-1.04, p = 0.06), metastatic PCa (HR: 0.98, 95% CI: 0.91-1.05, p = 0.55), or fatal PCa (HR: 0.94, 95% CI: 0.79-1.09, p = 0.41). When accounting for race/ethnicity and family history, Agent Orange exposure was independently associated with slightly increased risk of PCa (HR: 1.06, 95% CI: 1.04-1.09, <10-6) but not with metastatic PCa (HR: 1.07, 95% CI: 0.98-1.15, p = 0.10) or PCa death (HR: 1.02, 95% CI: 0.83-1.23, p = 0.09). Similar results were found when accounting for genetic risk. Agent Orange exposure history may not improve modern PCa risk stratification.

Cognitive function following early life war-time stress exposure in a cohort of Vietnamese older adults.

Although Alzheimer's Disease is a leading cause of death in Vietnam and other post-conflict, low- and middle-income countries, aside from studies of veterans in western populations, research on war-related violence and deprivation as risk factors for cognitive disorders remains sparse. Using data from the Vietnam Health and Aging Study, which relied upon a multistage probability sample of 2447 older adults residing in districts of northern Vietnam differentially exposed to wartime bombing and numerous war-related stressors, this paper investigates associations between early-life war-related stressors and later-life cognitive function in a cohort whose transition to adulthood took place during the American-Vietnam War. Relationships among experiences of severe childhood hunger, war-related violence and environmental hardships, military service, and cognitive function in an analytical sample of 2162 Vietnamese older adults are estimated using quantile regression. Cognitive function is assessed by a modified Mini-Mental State Examination (MMSE) score. Analyses also address posttraumatic stress disorder (PTSD), cardiovascular health, and health behaviors as potential mediators between early life war-related stressors and current cognitive function. Results indicate that experiences of severe hunger in childhood and environmental hardships are associated with poorer cognitive function in older adulthood. PTSD, cardiovascular risk (i.e., hypertension) and disease (i.e., stroke), each of which is heightened by exposure to wartime stressors, are associated with lower cognitive scores. Results suggest that certain war exposures, like involvement in combat duties, are associated with higher cognitive function scores, suggesting that military service either positively selects for cognitive function, or certain forms of service may impart cognitive resilience. Following recent calls to incorporate population-specific stressors to advance explanatory models of cognitive function, these findings suggest that it is critical to assess the enduring scars and resilience of armed conflict in global efforts to understand, prevent, and treat cognitive impairment, Alzheimer's Disease, and related dementias.

The long-term association between exposure to wartime bombing earlier in life and post-traumatic stress later in life among today's older Vietnamese population.

This analysis examines the relationship between exposure to American wartime bombardments earlier in life and later-life PTSD among current surviving Vietnamese aged 59+. It also assesses whether the relationship varies by military status during the war - formal military, informal military, or civilian - and whether associations are explained by exposure to violence and malevolent conditions. Data link survey responses from the 2018 Vietnam Health and Aging Study to provincial-wide level bombing intensity using U.S. Department of Defense records from the Theater History of Operations Vietnam database. PTSD measured using nine items from the PTSD Checklist. Analyses employ multivariate logistic quantile regression. Findings examined for a sample of 2290 Vietnamese survivors and a subsample of 736 Vietnamese that moved at least once during wartime. Results show a robust and significant positive association between province-wide bombing intensity and later-life PTSD scores. Interaction effects indicate civilians have overall lower levels of PTSD than those that were in the formal or informal military, but the association between bombing and PTSD is stronger among civilians. Much of the association is a function of exposure to violence and less is a function of exposure to malevolent conditions. Findings confirm earlier studies that have shown severe deleterious impacts of war trauma, and arial bombardments particularly, on long-term psychological health, while extending extant literature to civilian populations living in Vietnam during intense aerial bombing episodes.

Comparing neuropsychological, typical, and ADNI criteria for the diagnosis of mild cognitive impairment in Vietnam-era veterans.

OBJECTIVE: Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer's disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD. METHOD: 267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] p-tau181, t-tau, and Aß42) by diagnostic criteria. Logistic regressions adjusting for age and education assessed the effects of TBI severity and PTSD symptom severity simultaneously on MCI classification by each criteria. RESULTS: Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF p-tau181 and t-tau. Typical and ADNI criteria were not associated with CSF biomarkers. PTSD symptom severity predicted MCI diagnosis by neuropsychological and ADNI criteria. History of moderate/severe TBI predicted MCI by typical and ADNI criteria. CONCLUSIONS: MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.

Mortality of Women Vietnam War-Era Veterans.

PURPOSE: Our objectives were to 1) understand the scope of the current mortality literature on U.S. women Vietnam War-era veterans and 2) identify major themes and knowledge gaps that might guide future research. METHODS: A systematic scoping review was conducted. Electronic bibliographic databases were searched for studies published on women Vietnam War-era veterans' mortality between 1973 and 2020. Inclusion and exclusion criteria were applied, study information was charted using pre-established design parameters, and studies deemed eligible were retained for a more in-depth review. FINDINGS: One hundred nineteen studies were initially identified. Of these, six were ultimately retained for critical review. External cause, all-cause, cancer, and cardiovascular mortality were prominent outcomes across studies. Although both methodology and outcomes varied by study, unifying themes emerged. Prominent themes included a) historic barriers to accurately identifying and classifying this veteran cohort, b) historic barriers to comprehensive assessment of their health and mortality risk, and c) the healthy soldier effect and its limitations. Research gaps identified in this review reflect a need to pay more attention to sex differences in mortality risk and military occupational and sex-specific health risk confounders in mortality models. CONCLUSIONS: The research literature examining mortality among women Vietnam War-era veterans is circumscribed in size and scope. Questions about the roles of salient military occupational exposures and health risk factors on mortality risks and trends in this cohort remain unaddressed. These questions should be areas of focus in next steps research.

Risk factors for suicide in the Vietnam-era twin registry.

BACKGROUND: The risk of suicide among Veterans is of major concern, particularly among those who experienced a combat deployment and/or have a history of PTSD. DESIGN AND METHODS: This was a retrospective cohort study of post-discharge suicide among Vietnam-era Veterans who are members of the Vietnam Era Twin (VET) Registry. The VET Registry is a national sample of male twins from all branches of the military, both of whom served on active duty between 1964 and 1975. Military service and demographic factors were available from the military records. Service in-theater was based on military records; combat exposure and PTSD symptoms were assessed in 1987 by questionnaire. Mortality follow-up, from discharge to 2016, is identified from Department of Veterans Affairs, Social Security Administration, and National Death Index records; suicide as a cause of death is based on the International Classification of Death diagnostic codes from the death certificate. Statistical analysis used Cox proportional hazards regression to estimate the association of Vietnam-theater service, combat exposure, and PTSD symptoms with suicide while adjusting for military service and demographic confounding factors. RESULTS: From the 14,401 twins in the VET Registry, there were 147 suicide deaths during follow-up. In adjusted analyses, twins who served in the Vietnam theater were at similar risk of post-discharge suicide compared with non-theater Veterans; there was no association between combat and suicide. An increase in severity of PTSD symptoms was significantly associated with an increased risk of suicide in adjusted analyses (hazard ratio = 1.13 per five-point increase in symptom score; 95% CI: 1.02-1.27). CONCLUSIONS: Service in the Vietnam theater is not associated with greater risk of suicide; however, PTSD symptom severity poses a degree of risk of suicide in Vietnam-era Veterans. Adequate screening for PTSD in Veterans may be promising to identify Veterans who are at increased risk of suicide.

Cohort Profile: The Korean Vietnam War Veterans' Health Study Cohort (KOVECO).

During the Vietnam War, many troops and citizen were exposed to large amounts of Agent Orange (AO), and the hazardous effects of AO are continuously being researched and reported. The Korean Vietnam War Veterans' Health Study Cohort (KOVECO) is a retrospective cohort to demonstrate the health status of the Korean Vietnam War veterans and their second-generation offsprings. The KOVECO is a collaboration of data from the Ministry of Patriots and Veterans Affairs and the National Health Insurance Sharing Service from 2002 to 2018. The study participants were all Korean Vietnam War veterans and their second-generation offsprings, and the references were the general population in which gender and region were matched with the participants. As of 2002, 191,272 Vietnam War veterans (1,000,320 comparisons) and 1,963,402 s-generations (1,173,061 references) were included in the cohort. The KOVECO consists of personal information, medical facility visit information, and general health examination information. The KOVECO could act as a health surveillance system, which would be able to detect long-term health effects caused by exposure to AO and provide a direction for policy making through academic research.

Posttraumatic stress disorder symptom severity is associated with reduced Montreal Cognitive Assessment scores in a sample of Vietnam War Veterans.

The goal of the present study was to examine associations between posttraumatic stress disorder (PTSD) symptom severity, the number of stressors experienced, and cognitive outcomes in a sample of U.S. Vietnam War Veterans (N = 274). Adults between 60 and 85 years of age completed a Vietnam Veterans Alzheimer's Disease Neuroimaging Initiative Project visit. A modified version of the Life Stressor Checklist-Revised (LSC-R) was used to assess the number of stressful experiences participants experienced, current PTSD severity scores were measured via the Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV), and cognition was assessed using the Montreal Cognitive Assessment (MoCA). Linear regressions were conducted to examine the effect of CAPS-IV and LSC-R scores on cognitive performance. Higher CAPS-IV scores were associated with worse cognitive outcomes on the MoCA, ΔF(1, 264) = 12.686, p < .001, R2 = .142. In contrast, the number of reported stressful experiences was not associated with cognitive outcomes. After accounting for multiple comparisons, findings indicated that CAPS-IV severity scores were significantly associated with the MoCA memory index. In a sample of older Veterans, PTSD symptom severity, but not the number of reported stressors, was associated with poorer performance on a well-established cognitive function screening tool. Analyses of specific MoCA domains indicated that memory may be driving this association. These findings suggest that highly arousing stressors characteristic of PTSD, rather than stressful experiences more broadly, contribute to this association. Future work can use these findings to explore whether treating PTSD symptoms may help maintain cognitive function during the aging process.

The mental health of Vietnam theater veterans-the lasting effects of the war: 2016-2017 Vietnam Era Health Retrospective Observational Study.

Mental health data from the 2016-2017 Vietnam Era Health Retrospective Observational Study (VE-HEROeS) were analyzed by cohort, represented by United States Vietnam theater veterans (VTs) who served in Vietnam, Cambodia, and Laos; nontheater veterans (NTs) without theater service; and age- and sex-matched nonveterans (NVs) without military service. The exposure of interest was Vietnam theater service. Surveys mailed to random samples of veterans (n = 42,393) and nonveterans (n = 6,885) resulted in response rates of 45.0% for veterans (n = 6,735 VTs, Mage = 70.09, SE = 0.04; n = 12,131 NTs) and 67.0% for NVs (n = 4,530). We examined self-report data on four mental health outcomes: probable posttraumatic stress disorder (PTSD), depression, psychological distress, and overall mental health functioning. Weighted adjusted odds ratios (aORs) between each outcome and cohort were estimated, controlling for covariates in four models: cohort plus sociodemographic variables (Model 1), Model 1 plus physical health variables (Model 2), Model 2 plus potentially traumatic events (PTEs; Model 3), and Model 3 plus other military service variables (Model 4). Mental health outcome prevalence was highest for VTs versus other cohorts, with the largest aOR, 2.88, for PTSD, 95% CI [2.46, 3.37], p < .001 (Model 4, VT:NT). Physical health and PTEs contributed most to observed effects; other service variables contributed least to aORs overall. Mental health dysfunction persists among VTs years after the war's end. The present results reaffirm previous findings and highlight the need for continued mental health surveillance in VTs.

Delayed-Onset Neuropathological Complications From a Foramen Magnum and Occipital Crest-Focused Traumatic Brain Injury of the Vietnam War and Other Conflicts: Part II, Research Analysis.

INTRODUCTION: Much of the research impacting diagnosis, outcome, and treatment of traumatic brain injuries (TBIs) has favored time of consciousness criteria indicative of hemispheric blast focus alone. However, recent animal-based research has widely expanded the diagnostic knowledge base and potential treatment options. METHODS: Recent animal-based research findings of foramen magnum and occipital crest-focused blast injuries in laboratory rats were reviewed and compared to the Part I human case report. RESULTS: Comparing the human case report (Part I) to that of animal research studies found very similar neuropathological outcomes, many deep and delayed, and supports why non-cerebral-focused TBIs have gone unrecognized. The overpressure wave is funneled through skull openings of the foramen magnum, with the possibility of a rebound secondary contrecoup injury impacting the orbits, oral-nasal cavity, and ears resulting in additional occult axonal and white matter injury. CONCLUSIONS: Research analysis prompted by a human case report (Part I) has helped identify mechanisms that assist in recognizing and defining non-cerebral hemispheric-focused TBI injuries. Position of the head in relationship to the blast wave, the setting in which the blast occurs, and close diagnostic follow-up are critical to the recognition, diagnosis, and treatment of injuries that have otherwise gone unrecognized and unstudied in humans since the Vietnam War.

Delayed-Onset Neuropathological Complications From a Foramen Magnum and Occipital Crest Focused TBI of the Vietnam War and Other Conflicts: Part III, Critique of Existing TBI Criteria and Their Operational Controversies.

INTRODUCTION: In this report, we discuss the controversy of the diverse traumatic brain injury (TBI) categorization and taxonomy and the need to develop a new multidimensional and multidisciplinary categorization system that can be an aid in improved diagnostic and prognostic outcomes. Of interest, the heterogeneity of TBI marks the major obstacle to develop effective therapeutic interventions. Currently, the Glasgow Coma Scale has been utilized to guide in the prognosis and clinical management of TBI; it does not encompass the pathophysiological mechanisms leading to neurological deficits that can impede therapeutic interventions and consequently the failure of clinical trials. An unfortunate gap exists between advances in TBI research and existing U.S. Department of Defense (DoD) definitions, categorization, and management. Part I illustrates a unique posterior-focused TBI case report that does not fit any existing TBI definitions. Part II summarizes new animal-based TBI research that supports the case report as a legitimate TBI category. Part III critiques existing TBI criteria and their controversies. METHODS: Current DoD definitions and decision-making protocols based on concussion time alone are reviewed and compared to the myriad of additional TBI definitions that further illustrate the marked differences in definitions, especially in mild TBIs. RESULTS: The DoD definitions are not consistent with what academic research and science bring to the debate. With increasing world conflicts and wars, evaluators are not prepared to accept, evaluate, and properly manage those TBIs that are not associated with immediate levels of unconsciousness alone as the prime determinant of diagnosis and long-term severity. Despite comprehensive research, current understanding among decision-makers of progressive pathology of non-hemispheric TBIs remains limited, inconsistent, and confusing. CONCLUSIONS: This dilemma requires a multidisciplinary, science/medicine-led panel to actively reassess TBI criteria that take into consideration the latest research including non-cerebral hemispheric injuries. We recommend that DoD/Veterans Affairs establish a commission to regularly review the academic-related scientific evidence and incorporate these findings in a timely fashion into their operational definitions. This would guarantee that recognition, diagnosis, and follow-up of all TBIs are properly understood, managed, and documented.

Early-Life War Exposure and Later-Life Frailty Among Older Adults in Vietnam: Does War Hasten Aging?

OBJECTIVES: This study aimed to assess the nature and degree of association between exposure to potentially traumatic wartime experiences in early life, such as living in a heavily bombed region or witnessing death firsthand, and later-life frailty. METHOD: The Vietnam Health and Aging Study included war survivors in Vietnam, 60+, who completed a survey and health exam between May and August 2018. Latent class analysis (LCA) is used to construct classes exposed to similar numbers and types of wartime experiences. Frailty is measured using a deficit accumulation approach that proxies biological aging. Fractional logit regression associates latent classes with frailty scores. Coefficients are used to calculate predicted frailty scores and expected age at which specific levels of frailty are reached across wartime exposure classes. RESULTS: LCA yields 9 unique wartime exposure classes, ranging from extreme exposure to nonexposed. Higher frailty is found among those with more heavy/severe exposures with a combination of certain types of experiences, including intense bombing, witnessing death firsthand, having experienced sleep disruptions during wartime, and having feared for one's life during war. The difference in frailty-associated aging between the most and least affected individuals is more than 18 years. DISCUSSION: War trauma hastens aging and warrants greater attention toward long-term implications of war on health among vast postconflict populations across the globe.

Vulnerability and resilience among older South Korean Vietnam war veterans: A latent profile analysis.

Relatively little is known about South Korean Vietnam War veterans, despite their being the second largest contingent of troops during the Vietnam War. Earlier research found elevated levels (39%) of post-traumatic stress disorder (PTSD) in this older population, due to high exposure to combat and malevolent environments (Lee et al., 2020). The present study investigated classes of vulnerability and resilience among older South Korean Vietnam War veterans, using a latent profile analysis (LPA) on PTSD symptoms, late onset stress symptomology (LOSS), and mental well-being (MWB). The sample consisted of 367 older male veterans from South Korea (Mage = 72, SD = 2.66) who completed surveys. The LPA yielded five classes. The largest (38%) was Average (average PTSD, LOSS, and MWB levels), and the second largest (31%) was characterized by Moderate Distress (moderately high PTSD and LOSS, average MWB). A small group (13%) reported Low Affect (low PTSD, LOSS, and MWB levels), and 7% expressed Severe Distress (high LOSS and PTSD levels, average MWB). Only a small percentage (12%) were characterized by Resilience (low PTSD, average LOSS, high MWB). Optimism, positive appraisals of military service, and social support from family, significant others, friends, and military peers were highest among veterans in the Resilience class. To our knowledge, this is the first study of resilience among East Asian military veterans, and more research is needed on how resilience can be improved. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

An Exploration of Implicit Racial Bias as a Source of Diagnostic Error.

Recent events led this author to realize that an error made during the Vietnam War by him and others had been due to focusing too narrowly on predisposing factors for PTSD while failing to consciously acknowledge acute systemic stressors. In not accepting that along with the stress of combat, Black troops daily experienced acute pervasive systemic racism, he failed to understand correctly their disproportionately higher levels of PTSD when compared to white troops. Motivating factors to examine this error included a recent movie by Spike Lee. Oral histories of Black veterans were then used to research the experience of Blacks in the military in two world wars and the Vietnam War. Little change in the treatment of Black service members was evident across the time frame which included WWI, WWII and the Vietnam War. An understanding of Shay's concept of moral injury was found very valuable in understanding the consequences of PTSD.

The Impact of Early Life War Exposure on Mental Health among Older Adults in Northern and Central Vietnam.

Most Vietnamese young adults who experienced the American War were exposed to war-related violence, which can exert a lifelong impact. We analyze survey data collected among northern and central Vietnamese older adults in the 2018 Vietnam Health and Aging Study (N = 2,447) to examine the association between various war traumas, psychological distress, and suicidal ideation. Informed by life course and stress process perspectives, we use structural equation models with multiple mediators to analyze the relationship between mental health outcomes and five types of wartime stress exposure: loss of family and friends, witnessing death, malevolent living conditions, life threat, and moral injury. Our findings reveal enduring mental health impacts of war among survivors. Wartime stress exposure's influence on mental health is mediated by recent comorbidities and stressful life events. Loss of family members, witnessing death, and malevolent living conditions during war are particularly salient risks for psychological distress.

Investigation of C-reactive protein and AIM2 methylation as a marker for PTSD in Australian Vietnam veterans.

Chronic inflammation is a key factor in symptomology and comorbidities of post-traumatic stress disorder (PTSD). Levels of a proinflammatory marker, C-reactive protein (CRP) are increased in individuals with PTSD but it is not clear if this is due to trauma exposure or PTSD. Our study aimed to assess the relationship between serum CRP levels, CRP SNPs, methylation, mRNA expression and PTSD in a homogenous trauma exposed Australian Vietnam veteran cohort. We hypothesized that decreased DNA methylation would be associated with increased gene expression and increased peripheral CRP levels in PTSD patients and that this would be independent of trauma. Participants were 299 Vietnam veterans who had all been exposed to trauma and approximately half were diagnosed with PTSD. We observed higher levels of serum CRP in the PTSD group compared to the non-PTSD group but after controlling for BMI and triglycerides the association did not remain significant. No association was found between CRP SNPs and PTSD or CRP levels. Absent in Melanoma 2 (AIM2) which is a mediator of inflammatory response and a determinant of CRP levels was analysed for DNA methylation and mRNA expression. We observed a trend level association between PTSD and AIM2 methylation after controlling for age, smoking, triglycerides, BMI and cell types. There was no significant interaction between PTSD and CRP levels on AIM2 methylation after controlling for covariates. We observed that as AIM2 methylation levels decreased, AIM2 mRNA expression increased. Elevated CRP levels were associated with AIM2 mRNA in the trauma exposed cohort but there was no significant interaction effect with PTSD. Our results could not confirm that CRP is a marker of PTSD independent of trauma in this group of older veterans. CRP may be a broad marker of disease risk, or a marker of PTSD in younger cohorts than those in this study.

Possible effects of agent orange and posttraumatic stress disorder on hyperglycemia in Korean veterans from the US-Vietnam war.

ABSTRACT: This study was conducted to examine whether Korean veterans from the US-Vietnam War who had a diagnosis of type II diabetes mellitus (T2DM) as well as past history of exposure to agent orange (AO) are vulnerable to hyperglycemia when receiving intra-articular corticosteroid injection (IACI) for pain relief.The current study included a total of 49 patients (n = 49) who received an injection of triamcinolone 20 or 40 mg to the shoulder under sonographic guidance or did that of dexamethasone 10 mg or triamcinolone 40 mg combined with dexamethasone 20 mg to the spine under fluoroscopic guidance. Their 7-day fasting blood glucose (FBG) levels were measured and then averaged, serving as baseline levels. This is followed by measurement of FBG levels for 14 days of IACI. Respective measurements were compared with baseline levels. The patients were also evaluated for whether there are increases in FBG levels depending on insulin therapy as well as HbA1c ≥ 7% or HbA1c < 7%.Overall, there were significant increases in FBG levels by 64.7 ±â€Š42.5 mg/dL at 1 day of IACI from baseline (P < .05). HbA1c ≥ 7% and HbA1c < 7% showed increases in FBG levels by 106.1 ±â€Š49.0 mg/dL and 46.5 ±â€Š3.8 mg/dL, respectively, at 1 day of IACI from baseline (P < .05). In the presence and absence of insulin therapy, there were significant increases in them by 122.6 ±â€Š48.7 mg/dL and 48.0 ±â€Š20.4 mg/dL, respectively, at 1 day of IACI from baseline (P < .05). But there were decreases in them to baseline levels at 2 days of IACI.Clinicians should consider the possibility of hyperglycemia when using corticosteroids for relief of musculoskeletal pain in Korean veterans from the US-Vietnam War who had a history of exposure to AO.

DNA methylation in the adipose tissue and whole blood of Agent Orange-exposed Operation Ranch Hand veterans: a pilot study.

BACKGROUND: Between 1962 and 1971, the US Air Force sprayed Agent Orange across Vietnam, exposing many soldiers to this dioxin-containing herbicide. Several negative health outcomes have been linked to Agent Orange exposure, but data is lacking on the effects this chemical has on the genome. Therefore, we sought to characterize the impact of Agent Orange exposure on DNA methylation in the whole blood and adipose tissue of veterans enrolled in the Air Force Health Study (AFHS). METHODS: We received adipose tissue (n = 37) and whole blood (n = 42) from veterans in the AFHS. Study participants were grouped as having low, moderate, or high TCDD body burden based on their previously measured serum levels of dioxin. DNA methylation was assessed using the Illumina 450 K platform. RESULTS: Epigenome-wide analysis indicated that there were no FDR-significantly methylated CpGs in either tissue with TCDD burden. However, 3 CpGs in the adipose tissue (contained within SLC9A3, LYNX1, and TNRC18) were marginally significantly (q < 0.1) hypomethylated, and 1 CpG in whole blood (contained within PTPRN2) was marginally significantly (q < 0.1) hypermethylated with high TCDD burden. Analysis for differentially methylated DNA regions yielded SLC9A3, among other regions in adipose tissue, to be significantly differentially methylated with higher TCDD burden. Comparing whole blood data to a study of dioxin exposed adults from Alabama identified a CpG within the gene SMO that was hypomethylated with dioxin exposure in both studies. CONCLUSION: We found limited evidence of dioxin associated DNA methylation in adipose tissue and whole blood in this pilot study of Vietnam War veterans. Nevertheless, loci in the genes of SLC9A3 in adipose tissue, and PTPRN2 and SMO in whole blood, should be included in future exposure analyses.