Jessica Gill

PTSD is Associated With an Excess of Inflammatory Immune Activities

PURPOSE. Post-traumatic stress disorder (PTSD) is associated with inflammatory-related medical conditions. This review examines studies of immune function in individuals with PTSD to determine if excessive inflammation is associated with PTSD. CONCLUSIONS. Current studies suggest an excess of inflammatory actions of the immune system in individuals with chronic PTSD. High levels of inflammatory cytokines have also been linked to PTSD vulnerability in traumatized individuals. There is also evidence that excessive inflammation is in part due to insufficient regulation by cortisol. PRACTICE IMPLICATIONS. An excess of inflammatory immune activity may contribute to health declines in individuals with PTSD, and treating PTSD symptoms may reduce these risks.

Low cortisol, high DHEA, and high levels of stimulated TNF‐α, and IL‐6 in women with PTSD

Posttraumatic stress disorder (PTSD) has been associated with hypothalamic-pituitary-adrenal (HPA) axis and immune function alterations; however, few studies have simultaneously investigated these systems in participants with PTSD. In this study, HPA axis and immune function in 26 women with PTSD with and without major depressive disorder was compared to 24 traumatized controls and to 21 nontraumatized controls. Posttraumatic stress disorder was associated with low cortisol and higher levels of DHEA and greater production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) compared to traumatized and healthy controls. Women with PTSD and depression exhibited greater production of IL-6 and higher levels of dehydroepiandrosterone (DHEA) than those with PTSD, but without depression. These findings suggest dysregulated HPA axis and immune function in women with PTSD, and that comorbid depression may contribute to these abnormalities.

Peripheral Total Tau in Military Personnel Who Sustain Traumatic Brain Injuries During Deployment.

IMPORTANCE Approximately one-third of military personnel who deploy for combat operations sustain 1 or more traumatic brain injuries (TBIs), which increases the risk for chronic symptoms of postconcussive disorder, posttraumatic stress disorder, and depression and for the development of chronic traumatic encephalopathy. Elevated concentrations of tau are observed in blood shortly following a TBI, but, to our knowledge, the role of tau elevations in blood in the onset and maintenance of chronic symptoms after TBI has not been investigated. OBJECTIVES To assess peripheral tau levels in military personnel exposed to TBI and to examine the relationship between chronic neurological symptoms and tau elevations. DESIGN, SETTING, AND PARTICIPANTS Observational assessment from September 2012 to August 2014 of US military personnel at the Madigan Army Medical Center who had been deployed within the previous 18 months. Plasma total tau concentrations were measured using a novel ultrasensitive single-molecule enzyme-linked immunosorbent assay. Classification of participants with and without self-reported TBI was made using the Warrior Administered Retrospective Casualty Assessment Tool. Self-reported symptoms of postconcussive disorder, posttraumatic stress disorder, and depression were determined by the Neurobehavioral Symptom Inventory, the Posttraumatic Stress Disorder Checklist Military Version, and the Quick Inventory of Depressive Symptomatology, respectively. Group differences in tau concentrations were determined through analysis of variance models, and area under the receiver operating characteristic curve determined the sensitivity and specificity of tau concentrations in predicting TBI and chronic symptoms. Seventy participants with self-reported TBI on the Warrior Administered Retrospective Casualty Assessment Tool and 28 control participants with no TBI exposure were included. MAIN OUTCOMES AND MEASURES Concentration of total tau in peripheral blood. RESULTS Concentrations of plasma tau were significantly elevated in the 70 participants with self-reported TBI compared with the 28 controls (mean [SD], 1.13 [0.78] vs 0.63 [0.48] pg/mL, respectively; F1,97 = 4.97; P = .03). Within the self-reported TBI cases, plasma total tau concentrations were significantly associated with having a medical record of TBI compared with self-reported TBI only (mean [SD], 1.57 [0.92] vs 0.85 [0.52] pg/mL, respectively; F1,69 = 6.15; P = .02) as well as reporting the occurrence of 3 of more TBIs during deployment compared with fewer than 3 TBIs (mean [SD], 1.52 [0.82] vs 0.82 [0.60] pg/mL, respectively; F1,69 = 8.57; P = .008). The severity of total postconcussive symptoms correlated with total tau concentrations in the self-reported TBI group (r = 0.37; P = .003). CONCLUSIONS AND RELEVANCE Military personnel who report multiple TBIs have long-term elevations in total tau concentration. The total tau concentration relates to symptoms of postconcussive disorder.

Sleep Disorders in US Military Personnel: A High Rate of Comorbid Insomnia and Obstructive Sleep Apnea

BACKGROUND Sleep disturbances are among the most common symptoms of military personnel who return from deployment. The objective of our study was to determine the presence of sleep disorders in US military personnel referred for evaluation of sleep disturbances after deployment and examine associations between sleep disorders and service-related diagnoses of depression, mild traumatic brain injury, pain, and posttraumatic stress disorder (PTSD). METHODS This was a cross-sectional study of military personnel with sleep disturbances who returned from combat within 18 months of deployment. Sleep disorders were assessed by clinical evaluation and polysomnogram with validated instruments to diagnose service-related illnesses. RESULTS Of 110 military personnel included in our analysis, 97.3% were men (mean age, 33.6 ± 8.0 years; mean BMI, 30.0 ± 4.3 kg/m2), and 70.9% returned from combat within 12 months. Nearly one-half (47.3%) met diagnostic criteria for two or more service-related diagnoses. Sleep disorders were diagnosed in 88.2% of subjects; 11.8% had a normal sleep evaluation and served as control subjects. Overall, 62.7% met diagnostic criteria for obstructive sleep apnea (OSA) and 63.6% for insomnia. The exclusive diagnoses of insomnia and OSA were present in 25.5% and 24.5% of subjects, respectively; 38.2% had comorbid insomnia and OSA. Military personnel with comorbid insomnia and OSA were significantly more likely to meet criteria for depression (P < .01) and PTSD (P < .01) compared with control subjects and those with OSA only. CONCLUSIONS Comorbid insomnia and OSA is a frequent diagnosis in military personnel referred for evaluation of sleep disturbances after deployment. This diagnosis, which is difficult to treat, may explain the refractory nature of many service-related diagnoses.

Traumatic Brain Injury in Intimate Partner Violence: A Critical Review of Outcomes and Mechanisms

The prevalence of intimate partner violence (IPV) is striking, as are its consequences to the lives of women. The IPV often includes physical assault, which can include injuries to the head and attempted strangulation injuries. Both types of injuries can result in traumatic brain injury (TBI). The TBI sustained during IPV often occurs over time, which can increase the risk for health declines and postconcussive syndrome (PCS). Current studies have identified sequelae of cognitive dysfunction, posttraumatic stress disorder, and depression in women experiencing IPV, yet, most fail to determine the role of TBI in the onset and propagation of these disorders. Although imaging studies indicate functional differences in neuronal activation in IPV, they also have not considered the possibility of TBI contributing to these outcomes. This review highlights the significant gaps in current findings related to neuropsychological complications and medical and psychosocial symptoms that likely result in greater morbidity, as well as the societal costs of failing to acknowledge the association of IPV and TBI in women.

Sustained Elevation of Serum Interleukin-6 and Relative Insensitivity to Hydrocortisone Differentiates Posttraumatic Stress Disorder with and Without Depression

BACKGROUND Elevated levels of proinflammatory cytokines, especially interleukin-6 (IL-6), can mediate the greater risk for cardiovascular disease in individuals with posttraumatic stress disorder (PTSD), particularly in those with comorbid major depressive disorder (MDD). However, IL-6 levels are not consistently elevated in either PTSD or MDD. Although PTSD is associated with supersensitivity to glucocorticoids; prior studies have not evaluated the effect of comorbid MDD. METHODS Serum IL-6 levels were measured hourly between 7:00 pm and 7:00 am in individuals with PTSD with comorbid MDD (PTSD + MDD) (n = 9) and compared with those with PTSD without MDD (PTSD - MDD) (n = 9) and nontraumatized healthy control subjects (n = 14). Group differences in serum IL-6, plasma adrenocorticotropic hormone (ACTH), and plasma cortisol response to 30 mg of intravenous hydrocortisone were evaluated using linear mixed models. RESULTS Only subjects with PTSD + MDD exhibited higher, overnight serum IL-6 levels compared with individuals with PTSD - MDD (p < .01) and healthy control subjects (p < .001). Peak overnight IL-6 levels positively correlated with severity of PTSD (r = .56, p < .01) and depressive symptoms (r = .54, p < .01). Hydrocortisone administration significantly reduced IL-6 levels in both PTSD groups; however, IL-6 levels in PTSD + MDD were higher than both PTSD - MDD (p < .05) and healthy control subjects (p < .01). Following hydrocortisone administration, there was a greater reduction in levels of ACTH in PTSD - MDD compared with control subjects (p < .01). CONCLUSIONS Sustained elevations of overnight IL-6 levels and relatively decreased sensitivity to hydrocortisone distinguish PTSD + MDD from PTSD - MDD. Novel strategies that decrease IL-6 levels offer a new direction in the prevention and treatment of PTSD and associated comorbid medical illnesses.

Corticotropin-releasing factor, interleukin-6, brain-derived neurotrophic factor, insulin-like growth factor-1, and substance P in the cerebrospinal fluid of civilians with posttraumatic stress disorder before and after treatment with paroxetine.

BACKGROUND Posttraumatic stress disorder (PTSD) is associated with altered concentrations of stress-related neurohormones, neurotrophins, and neuropeptides in plasma and serum; however, few studies have examined central alterations of these measures in individuals with PTSD. Furthermore, no study to date has evaluated the effects of successful antidepressant treatment on cerebrospinal fluid (CSF) abnormalities in PTSD. METHOD Sixteen medication-free outpatients with chronic PTSD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) due to physical and/or sexual abuse or motor vehicle accidents (mean ± SD age = 36 ± 11.4 years, 12 women) and 11 nontraumatized healthy subjects (mean ± SD age = 35.3 ± 13.1 years, 7 women) underwent a lumbar puncture for collection of CSF. Seven PTSD patients had a repeat lumbar puncture 12 weeks later, after successful treatment of PTSD with paroxetine. CSF was analyzed for corticotropin-releasing factor (CRF), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and substance P concentrations. The study was conducted between January 2003 and August 2004. RESULTS Compared to nontraumatized healthy controls, patients with chronic PTSD had similar pretreatment concentrations of CSF CRF, IL-6, BDNF, IGF-1, and substance P. Posttreatment CSF measures did not change significantly in patients whose symptoms remitted with paroxetine. CONCLUSIONS Chronic, moderate PTSD due to civilian trauma, without psychotic symptoms and without significant rates of comorbid depression, alcohol dependence, or substance dependence, is not associated with abnormalities in CSF CRF, IL-6, BDNF, IGF-1, or substance P levels. Despite substantial reduction in PTSD symptoms, antidepressant treatment does not alter normal central concentrations of these neurochemicals, with the possible exception of substance P.

Medical conditions and symptoms associated with posttraumatic stress disorder in low-income urban women

BACKGROUND Epidemiological studies have consistently reported rates of posttraumatic stress disorder (PTSD) in women that are twice that of men. In men and women, PTSD has been associated with comorbid medical conditions, medical symptoms and lower self-rating of health. In low-income urban women, rates of PTSD are even more elevated than in suburban women and may be related to observed health disparities. METHODS In this study, 250 women seeking healthcare at an urban clinic were interviewed for a PTSD diagnosis, major depressive disorder (MDD), the experience of traumatic events, the experience of current and past common medical conditions and symptoms, and subjective rating of health. A chart review was used to assess healthcare use in the past year. RESULTS More current (5.2 vs. 3.8, p < 0.05) and past medical conditions (4.6 vs. 3.3, p < 0.05) were reported by women with a lifetime history of PTSD than by women without this history, after controlling for demographics and current depression. Women with lifetime PTSD also had more annual clinic appointments (5.9 vs. 3.8 p < 0.03) and were 2.4 times (p < 0.05) more likely to report lower appraisal of their physical health. CONCLUSIONS These findings suggest that urban health-seeking women with PTSD experience health impairments that may cause increased morbidity and that healthcare providers should consider the health ramifications of PTSD when providing medical care to women.

Experiences of Traumatic Events and Associations with PTSD and Depression Development in Urban Health Care-seeking Women

Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after a traumatic event and has been linked to psychiatric and physical health declines. Rates of PTSD are far higher in individuals with low incomes and who reside in urban areas compared to the general population. In this study, 250 urban health care-seeking women were interviewed for a diagnosis of PTSD, major depressive disorder, and also the experience of traumatic events. Multivariate logistic regressions were used to determine the associations between traumatic events and PTSD development. Survival analysis was used to determine if PTSD developed from assaultive and nonassaultive events differed in symptom duration. Eighty-six percent of women reported at least one traumatic event, 14.8% of women were diagnosed with current PTSD, and 19.6% with past PTSD. More than half of women with PTSD had comorbid depression. Assaultive traumatic events were most predictive of PTSD development. More than two thirds of the women who developed PTSD developed chronic PTSD. Women who developed PTSD from assaultive events experienced PTSD for at least twice the duration of women who developed PTSD from nonassaultive events. In conclusion, PTSD was very prevalent in urban health care-seeking women. Assaultive violence was most predictive of PTSD development and also nonremittance.

Women in recovery from PTSD have similar inflammation and quality of life as non-traumatized controls.

OBJECTIVE Post-traumatic stress disorder (PTSD) is associated with greater concentrations of inflammatory biomarkers as well as substantial medical burden; however, it is not clear if these morbidity risks change following recovery from PTSD. In this study we compare women who have recovered from PTSD, to those with current PTSD, and healthy controls on their perceived health and inflammatory and metabolic biomarkers. METHODS We studied 3 groups of women: those with current PTSD, those who reported recovery from PTSD, and healthy non-traumatized controls, which were determined using standard diagnostic instruments. We obtained a morning blood sample and examined concentrations of inflammatory biomarkers of: interleukin 6 (IL-6) and c-reactive protein (CRP), and lipid concentrations. Lastly, we evaluated health related quality of life (HRQOL). RESULTS Women who had recovered from PTSD had a similar HRQOL and inflammatory biomarkers as non-traumatized controls. Their concentrations of inflammatory biomarkers were lower than women with current PTSD, and similar to non-traumatized controls. CONCLUSION Health perception as well as biological indicators of health significantly differ in women in recovery from PTSD, compared to those who remain symptomatic. These findings suggest that the psychological recovery is associated with normal levels of inflammatory biomarkers and HRQOL.