Dale W. Russell

Telomere length - a cellular aging marker for depression and Post-traumatic Stress Disorder.

Telomeres play a central role in cell fate and aging by adjusting the cellular response to both biological and psychological stress. Human telomeres are regions of tandem TTAGGG repeats at chromosomal ends that protect chromosomes from degradation, fusion, and recombination. They are made up of approximately 1000-2500 copies of the repeated DNA sequence. Over time, at each cell division, the telomere ends become shorter. Thus, telomere length (TL) has been considered a cellular marker for age-related diseases. In addition to biochemical stressors such as oxidation and inflammation, psychosocial traumatic stress has also been linked to shorter telomeres. TL is significantly inversely correlated with long-term depression, even after controlling for age. Average TL in depressed subjects, who were above the median of lifetime depression, was 281 base pairs shorter than that in controls, corresponding to approximately 7years of accelerated cell aging. Several recent studies have also demonstrated an inverse relationship between leukocyte telomere length (LTL) and the risk of PTSD. TL was inversely correlated with the duration of caregiving and PTSD. Here, we focus on the discussion of findings in studies of the relationships between stress-related disorders (e.g., depression and PTSD) and telomeres. We also present direct evidence that TL is associated with traumatic stress, depression, and PTSD, and hypothesize that traumatic stress affects not only mental disorders but also cellular aging. The nature of this relationship between stress and TL warrants further evaluation in psychiatry.

Killing versus witnessing trauma: Implications for the development of PTSD in combat medics.

Killing in combat uniquely predicts elevated PTSD symptomatology among military veterans. This study investigated the effects of combat killing in a sample of 345 U.S. Army combat medics who had recently returned from operational deployments to Iraq or Afghanistan. Combat medics provide frontline medical care before, during, and after battles but also fight alongside other soldiers when under attack. Attempting to kill in combat was a significant predictor of PTSD symptomatology even after accounting for passively witnessing trauma in fellow soldiers. Medics may be well prepared to cope with the passive experiencing and witnessing of war-zone trauma, but may benefit from training to cope with the negative consequences of taking actions to kill.

Mitochondria-focused gene expression profile reveals common pathways and CPT1B dysregulation in both rodent stress model and human subjects with PTSD

Posttraumatic stress disorder (PTSD), a trauma-related mental disorder, is associated with mitochondrial dysfunction in the brain. However, the biologic approach to identifying the mitochondria-focused genes underlying the pathogenesis of PTSD is still in its infancy. Previous research, using a human mitochondria-focused cDNA microarray (hMitChip3) found dysregulated mitochondria-focused genes present in postmortem brains of PTSD patients, indicating that those genes might be PTSD-related biomarkers. To further test this idea, this research examines profiles of mitochondria-focused gene expression in the stressed-rodent model (inescapable tail shock in rats), which shows characteristics of PTSD-like behaviors and also in the blood of subjects with PTSD. This study found that 34 mitochondria-focused genes being upregulated in stressed-rat amygdala. Ten common pathways, including fatty acid metabolism and peroxisome proliferator-activated receptors (PPAR) pathways were dysregulated in the amygdala of the stressed rats. Carnitine palmitoyltransferase 1B (CPT1B), an enzyme in the fatty acid metabolism and PPAR pathways, was significantly over-expressed in the amygdala (P<0.007) and in the blood (P<0.01) of stressed rats compared with non-stressed controls. In human subjects with (n=28) or without PTSD (n=31), significant over-expression of CPT1B in PTSD was also observed in the two common dysregulated pathways: fatty acid metabolism (P=0.0027, false discovery rate (FDR)=0.043) and PPAR (P=0.006, FDR=0.08). Quantitative real-time polymerase chain reaction validated the microarray findings and the CPT1B result. These findings indicate that blood can be used as a specimen in the search for PTSD biomarkers in fatty acid metabolism and PPAR pathways, and, in addition, that CPT1B may contribute to the pathology of PTSD.

Mental health and comorbidities in U.S. Military members

OBJECTIVES Using data from a prospective cohort study of U.S. service members who joined after September 11, 2001 to determine incidence rates and comorbidities of mental and behavioral disorders. METHODS Calculated age and sex adjusted incidence rates of mental and behavioral conditions determined by validated instruments and electronic medical records. RESULTS Of 10,671 service members, 3,379 (32%) deployed between baseline and follow-up, of whom 49% reported combat experience. Combat deployers had highest incidence rates of post-traumatic stress disorder (PTSD) (25 cases/1,000 person-years [PY]), panic/anxiety (21/1,000 PY), and any mental disorder (34/1,000 PY). Nondeployers had substantial rates of mental conditions (11, 13, and 18 cases/1,000 PY). Among combat deployers, 12% screened positive for mental disorder, 59% binge drinking, 16% alcohol problem, 19% cigarette smoking, and 20% smokeless tobacco at follow-up. Of those with recent PTSD, 73% concurrently developed >1 incident mental or behavioral conditions. Of those screening positive for PTSD, 11% had electronic medical record diagnosis. CONCLUSIONS U.S. service members joining during recent conflicts experienced high rates of mental and behavioral disorders. Highest rates were among combat deployers. Most cases were not represented in medical codes, suggesting targeted interventions are needed to address the burden of mental disorders among service members and Veterans.

Embedded behavioral health providers: an assessment with the Army National Guard.

Although the Army has recently begun the practice of embedding behavioral health care providers (EBHP) in units in an effort to improve soldier well-being, the efficacy of this practice has not been evaluated. This study assesses 1 of the first programs implemented by the military. Using cross-sectional data obtained from a confidential survey of 12 company-level units in the California Army National Guard (n = 1,132), this study examines differences between units with and without EBHPs across a number of measures. Multilevel analysis of behavioral health symptoms, unit climate, perceptions of stigma, and practical barriers to care failed to detect main effects between units with EBHPs relative to those without. However, cross-level interactions were detected between unit EBHP status and soldiers reporting close relationship (e.g., spouse, girlfriend/boyfriend) impairment. Exploratory findings suggest that, among soldiers reporting close relationship impairment, those belonging to units with EBHPs reported significantly lower behavioral health symptoms and significantly more positive unit climates. Based on these limited exploratory finings, this study suggests that EBHPs in reserve units may have a positive effect on a subset of soldiers (i.e., those reporting close relationship impairment). More assessments of embed programs should be conducted, particularly using prospective longitudinal data among randomized units.

Changes in alcohol use after traumatic experiences: The impact of combat on Army National Guardsmen

OBJECTIVE This research documents the impact of combat experiences on alcohol use and misuse among National Guard soldiers. Whereas much research regarding combat personnel is based on post-experience data, this studys design uses both pre- and post-deployment data to identify the association between different types of combat experiences and changes in substance use and misuse. METHOD A National Guard Infantry Brigade Combat Team was surveyed before and after its deployment to Iraq in 2005-2006. Members of the unit completed anonymous surveys regarding behavioral health and alcohol use and, in the post-survey, the combat experiences they had during deployment. The unit was surveyed 3 months prior to its deployment and 3 months after its deployment. RESULTS Prevalence rates of alcohol use increased from 70.8% pre-deployment to 80.5% post-deployment. Prevalence rates of alcohol misuse more than doubled, increasing from 8.51% before deployment to 19.15% after deployment. However, among the combat experiences examined in this study, changes in alcohol misuse post-deployment appear to be solely affected by the combat experience of killing. Alcohol misuse decreased amongst those who experienced killing during combat. CONCLUSIONS This study highlights the role of combat experiences on substance use.

A Longitudinal Comparison of Posttraumatic Stress Disorder and Depression Among Military Service Components

The purpose of this study was to longitudinally investigate PTSD and depression between Reserve, National Guard, and active duty continuously and dichotomously. The study consisted of Millennium Cohort Study participants and used self-reported symptoms. Repeated measures modeling assessed PTSD and depression continuously and dichotomously over time. A subanalysis among only recently deployed personnel was conducted. Of the 52,653 participants for the PTSD analysis, the adjusted PCL-C means were 34.6 for Reservists, 34.4 for National Guardsmen, and 34.7 for active duty members, respectively. Of the 53,073 participants for depression analysis, the adjusted PHQ-9 means were 6.8, 6.7, and 7.2, respectively. In dichotomous models, Reservists and National Guardsmen did not have a higher risk of PTSD or depression compared with active duty members. Among deployers, Reservists and National Guardsmen had higher odds (odds ratio = 1.16, 95% confidence limit [CL] [1.01, 1.34] and OR = 1.19, 95% CL [1.04, 1.36], respectively) of screening positive for PTSD, but not depression. Although Reserve and National Guard deployers had modestly increased odds of PTSD compared with active duty members, overall there were minimal differences in the risk and symptom scores of PTSD and depression between service components.

Social Support and Mental Health Outcomes Among U.S. Army Special Operations Personnel

Mental health disorders continue to plague service members and veterans; thus, new approaches are required to help address such outcomes. The identification of risk and resilience factors for these disorders in specific populations can better inform both treatment and prevention strategies. This study focuses on a unique population of U.S. Army Special Operations personnel to assess how specific avenues of social support and personal morale are related to mental health outcomes. The results indicate that, whereas personal morale and friend support reduce the relationship between combat experiences and posttraumatic stress disorder (PTSD), strong unit support exacerbates the negative effects of combat experiences in relation to PTSD. The study thus shows that although informal social support can lessen postdeployment mental health concerns, military populations with strong internal bonds may be at greater risk of PTSD because the support that they receive from fellow service members may heighten the traumatic impact of combat experiences.

Combat Experiences Predict Postdeployment Symptoms in U.S. Army Combat Medics

U.S. Army combat medics who were three months postdeployment reported higher prevalence of post-traumatic stress disorder (PTSD) and aggressive behaviors than did medics who had never been deployed to a combat zone. Combat experiences were then separated into six categories: killing, fighting, threat to oneself, death and injury of others, providing aid to the wounded, and saving a life. After controlling for socially desirable response bias, providing aid and threat to oneself predicted post-traumatic stress; providing aid predicted depression; and reports of killing predicted aggressive behaviors in postdeployed medics. Despite their noncombatant status and primary role as health care providers, medics report behavioral health symptoms in association with combat experiences.

PTSD symptom severity and sensitivity to blood, injury, and mutilation in U.S. army special operations soldiers

Sensitivity to blood, injury, and mutilation (SBIM) may increase risk for posttraumatic stress disorder (PTSD), given that traumatic events often involve actual or perceived threat of bodily harm to oneself and/or others, including exposure to blood and other mutilation-related stimuli. A self-report questionnaire was administered to male, active duty, U.S. Army Special Operations Command soldiers who had deployed to Iraq and Afghanistan (n =694 males). We first used exploratory factor analysis to examine whether the 30-item Mutilation Questionnaire (Klorman et al., 1974) comprised a unitary measure of SBIM, finding that 10 of the items form a cohesive SBIM factor. Summed, those 10 SBIM items had a significant bivariate correlation with PTSD symptom severity. In a multiple regression analysis that included demographic characteristics and lifetime trauma exposure, SBIM was positively associated with PTSD symptom severity. Other significant multivariate predictors were high lifetime trauma exposure and junior enlisted rank. When trait neuroticism was added to the model to test the robustness of these findings, the association of SBIM with PTSD symptom severity remained significant. The results suggest that SBIM may be a risk factor for PTSD in male soldiers. Further research is warranted to improve measurement and understanding of SBIM.