Chronic posttraumatic stress and its predictors in patients living with an implantable cardioverter defibrillator

Patients with an implantable cardioverter defibrillator (ICD) show clinically relevant depression and anxiety, but little is known about their levels of posttraumatic stress. We assessed chronic posttraumatic stress attributable to a traumatic cardiac event and its predictors in patients at two time points after ICD placement.

Diagnosis and treatment of an obsessive-compulsive disorder following traumatic brain injury: A single case and review of the literature

A 27-year-old patient with traumatic brain injury and neuropsychiatric symptoms fitting the obsessive-compulsive disorder was investigated. Brain CT-scan revealed left temporal and bilateral fronto-basal parenchymal contusions. Main Outcome Measure was the Yale-Brown Obsessive Compulsive Scale at pre- and post-treatment and at 6 months follow-up. The combination of pharmacotherapy and psychotherapy resulted in lower intensity and frequency of symptoms. Our case illustrates the importance of a detailed diagnostic procedure in order to provide appropriate therapeutic interventions. Further studies are needed to guide the clinician in determining which patients are likely to benefit from a psychotherapeutic intervention in combination with pharmacotherapy.

Unconscious Fearful Priming Followed by a Psychosocial Stress Test Results in Higher Cortisol Levels

Human perception of stress includes an automatic pathway that processes subliminal presented stimuli below the threshold of conscious awareness. Subliminal stimuli can therefore activate the physiologic stress system. Unconscious emotional signals were shown to significantly moderate reactions and responses to subsequent stimuli, an effect called 'priming'. We hypothesized that subliminal presentation of a fearful signal during the Stroop task compared with an emotionally neutral one will prime stress reactivity in a subsequently applied psychosocial stress task, thereby yielding a significant increase in salivary cortisol. Half of 36 participants were repeatedly presented either a fearful face or a neutral one. After this, all underwent a psychosocial stress task. The fearful group showed a significant increase in cortisol levels (p = 0.022). This change was not affected by sex, age and body mass index, and it also did not change when taking resting cortisol levels into account. Post-hoc analyses showed that the increase in cortisol in the fearful group started immediately after the psychosocial stress test. Hence, subliminal exposure to a fearful signal in combination with the Stroop and followed by a psychosocial stress test leads to an increase in stress reactivity. Copyright © 2012 John Wiley & Sons, Ltd.

Responsiveness and habituation of soluble icam-1 to acute psychosocial stress in men: determinants and efect of stress-hemoconcentration

We studied the psychophysiology of soluble intercellular adhesion molecule-1 (sICAM-1) in 25 apparently healthy middle-aged men who underwent an acute psychosocial stressor three times with one week apart. Measures of the biological stress response were obtained at week one and three. The magnitude of the sICAM-1 stress response showed no habituation between visits. At week one, cognitive stress appraisal independently predicted integrated sICAM-1 area under the curve (AUC) between rest, immediately post-stress, and 45 min and 105 min post-stress (beta=.67, p=.012, deltaR(2)=.41). Diastolic blood pressure AUC (beta=-.45, p=.048, deltaR(2)=.21) and heart rate (AUC) (beta=.44, p=.055, deltaR(2)=.21) were independent predictors of sICAM-1 (AUC) at week three. Adjustment for hemoconcentration yielded a decrease in sICAM-1 levels from rest to post-stress (p<.001). Stress responsiveness of plasma sICAM-1 was predicted by stress perception and hemodynamic reactivity and affected by stress-hemoconcentration but unrelated to cortisol reactivity and not readily adapting to stress repeats.

Effect of Alzheimer caregiving stress and age on frailty markers interleukin-6, C-reactive protein, and D-dimer

BACKGROUND: Elevated plasma levels of interleukin (IL)-6, C-reactive protein (CRP), and D-dimer belong to the biological alterations of the "frailty syndrome," defining increased vulnerability for diseases and mortality with aging. We hypothesized that, compatible with premature frailty, chronic stress and age are related in predicting inflammation and coagulation activity in Alzheimer caregivers. METHODS: Plasma IL-6, CRP, and D-dimer levels were measured in 170 individuals (mean age 73 +/- 9 years; 116 caregivers, 54 noncaregiving controls). Demographic factors, diseases, drugs, and lifestyle variables potentially affecting inflammation and coagulation were obtained by history and adjusted for as covariates in statistical analyses. RESULTS: Caregivers had higher mean levels of IL-6 (1.38 +/- 1.42 vs 1.00 +/- 0.92 pg/mL, p =.032) and of D-dimer (723 +/- 530 vs 471 +/- 211 ng/mL, p <.001) than controls had. CRP levels were similar between groups (p =.44). The relationship between caregiver status and D-dimer was independent of covariates (p =.037) but affected by role overload. Age accounted for much of the relationship with IL-6. After controlling for covariates, the interaction between caregiver status and age was significant for D-dimer (beta =.20, p =.029) and of borderline significance for IL-6 (beta =.17, p =.090). Post hoc regression analyses indicated that, among caregivers, age was significantly correlated with both D-dimer (beta =.50, p <.001) and IL-6 (beta =.38, p =.001). Among controls, however, no significant relationship was observed between age and either D-dimer or IL-6. CONCLUSIONS: The interaction between caregiving status and age for D-dimer and IL-6 suggests the possibility that older caregivers could be at risk of a more rapid transition to the frailty syndrome and clinical manifestations of cardiovascular diseases.

Delayed response and lack of habituation in plasma interleukin-6 to acute mental stress in men

Acute mental stress induces a significant increase in plasma interleukin (IL)-6 levels as a possible mechanism for how psychological stress might contribute to atherosclerosis. We investigated whether the IL-6 response would habituate in response to a repetitively applied mental stressor and whether cortisol reactivity would show a relationship with IL-6 reactivity. Study participants were 21 reasonably healthy men (mean age 46+/-7 years) who underwent the Trier Social Stress Test (combination of a 3-min preparation, 5-min speech, and 5-min mental arithmetic) three times with an interval of 1 week. Plasma IL-6 and free salivary cortisol were measured immediately before and after stress, and at 45 and 105 min of recovery from stress. Cortisol samples were also obtained 15 and 30 min after stress. Compared to non-stressed controls, IL-6 significantly increased between rest and 45 min post-stress (p=.022) and between rest and 105 min post-stress (p=.001). Peak cortisol (p=.034) and systolic blood pressure (p=.009) responses to stress both habituated between weeks one and three. No adaptation occurred in diastolic blood pressure, heart rate, and IL-6 responses to stress. The areas under the curve integrating the stress-induced changes in cortisol and IL-6 reactivity were negatively correlated at visit three (r=-.54, p=.011), but not at visit one. The IL-6 response to acute mental stress occurs delayed and shows no adaptation to repeated moderate mental stress. The hypothalamus-pituitary-adrenal axis may attenuate stress reactivity of IL-6. The lack of habituation in IL-6 responses to daily stress could subject at-risk individuals to higher atherosclerotic morbidity and mortality.

Anger, hostility, and posttraumatic stress disorder in trauma-exposed adults: A meta-analysis

This meta-analysis synthesizes the available data on the strength of association between anger and posttraumatic stress disorder (PTSD) and between hostility and PTSD, covering 39 studies with trauma-exposed adults. Effect sizes did not differ for anger and hostility, which could therefore be combined; effect sizes for anger expression variables were analyzed separately. The analyses revealed large effects. The weighted mean effect size (r) was .48 for anger–hostility, .29 for anger out, .53 for anger in, and -.44 for anger control. Moderator analyses were conducted for anger–hostility, showing that effect sizes were substantially larger with increasing time since the event and that effect sizes were larger in samples with military war experience than in samples that had experienced other types of traumatic events.

[Spontaneous and post-therapeutic cartilage repair: evaluation criteria.]

Articular cartilage has poor reparative capacities, and once damaged cartilage lesions remain chronic and can lead to osteoarthritis. Over the last decade, several innovative therapies have been introduced to promote the regeneration of articular cartilage while sustaining sufficient mechanical stress and permitting a pain free motion. An important measure of outcome is the morphological characterization of the repair tissue in order to allow for cross-study evaluation. The International Cartilage Repair Society has developed a analogue visual scale to quantify repair tissue, which is described in this paper.

The role of stress hormones in the relationship between resting blood pressure and coagulation activity

BACKGROUND: Systemic hypertension confers a hypercoagulable state. We hypothesized that resting mean blood pressure (MBP) interacts with stress hormones in predicting coagulation activity at rest and with acute mental stress. METHODS: We measured plasma clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, epinephrine and norepinephrine, and saliva cortisol in 42 otherwise healthy normotensive and hypertensive medication-free men (mean age 43 +/- 14 years) at rest, immediately after stress, and twice during 60 min of recovery from stress. RESULTS: At rest, the MBP-by-epinephrine interaction predicted FVII:C (beta = -0.33, P < 0.04) and D-dimer (beta = 0.26, P < 0.05), and the MBP-by-cortisol interaction predicted D-dimer (beta = 0.43, P = 0.001), all independent of age and body mass index (BMI). Resting norepinephrine predicted fibrinogen (beta = 0.42, P < 0.01) and D-dimer (beta = 0.37, P < 0.03), both independent of MBP. MBP predicted FVIII:C change from rest to immediately post-stress independent of epinephrine (beta = -0.37, P < 0.03) and norepinephrine (beta = -0.38, P < 0.02). Cortisol change predicted FVIII:C change (beta = -0.30, P < 0.05) independent of age, BMI and MBP. Integrated norepinephrine change from rest to recovery (area under the curve, AUC) predicted D-dimer AUC (beta = 0.34, P = 0.04) independent of MBP. The MBP-by-epinephrine AUC interaction predicted FVII:C AUC (beta = 0.28) and fibrinogen AUC (beta = -0.30), and the MBP-by-norepinephrine AUC interaction predicted FVIII:C AUC (beta = -0.28), all with borderline significance (Ps < 0.09) and independent of age and BMI. CONCLUSIONS: MBP significantly altered the association between stress hormones and coagulation activity at rest and, with borderline significance, across the entire stress and recovery interval. Independent of MBP, catecholamines were associated with procoagulant effects and cortisol reactivity dampened the acute procoagulant stress response.

Oxidative stress in lungs of mice infected with influenza A virus

As oxidative stress has been implicated in the pathogenesis of certain viral diseases we determined antioxidant and prooxidant parameters in lungs and bronchoalveolar lavage fluid (BALF) of mice infected with a lethal dose of influenza A/PR8/34 virus. Viral infection was characterized by massive infiltration of leukocytes, mainly polymorphonuclear leukocytes, into the alveolar space. The total number of BALF cells increased up to 8-fold (day 3 post-infection) and these cells appeared activated as judged by their increased rates of superoxide anion radical (O2-.) generation upon stimulation. Maximal rates of radical generation by BALF cells during the early stages of infection were 15- or 70-fold higher than those of cells from control animals when expressed per cell or total BALF cells, respectively. At the terminal stages of infection the total capacity of BALF cells to release O2-. declined to approximately 35-fold the control values. Infection also resulted in increased in vivo formation of hydrogen peroxide (H2O2) within the lungs at a time that coincided with the maximal capacity of BALF cells to release O2-.. Whereas pulmonary activities of glutathione peroxidase and reductase remained unaltered, levels of ascorbate in the cell-free BALF decreased significantly during the early stages of the infection and then returned to normal levels and above, late in infection. The oxidation state of the dehydroascorbic acid/ascorbate couple increased concomitantly with the decrease in ascorbate concentrations early in infection and remained elevated throughout the infection. As assessed by the prevention of peroxyl radical-induced loss of phycoerythrin fluorescence, the total antioxidant capacity present in lung tissue homogenate from terminally ill animals was not diminished when compared to that prepared from lungs of control mice. We conclude that although early stages of influenza infection are associated with the presence of oxidative stress in the lung tissue and alveolar fluid lining the epithelial cells, this stress does not appear to overwhelm local antioxidant defenses. The results therefore do not support a direct causative role of oxidative tissue damage in the pathogenesis of influenza virus infection.

Animal model for percutaneous creation of traumatic thoracic aortic transection

PURPOSE: This study was conducted to create an animal model for thoracic aortic transection that is suitable for thoracic endograft research. MATERIALS AND METHODS: Percutaneous aortic transection creation was attempted in 12 sheep. A custom collapsible circumferential cutting device was inserted into the proximal descending thoracic aorta via a femoral approach with an 11-F delivery catheter. The device was deployed 2 cm distal to the left subclavian artery origin and rotated 20 times to create aortic transection. Aortic diameters, mean aortic pressures, and heart rates were tested for degrees of difference between measurements before and after the creation of transection. On necropsy, the extent of aortic damage was classified as none, nontransmural, or transmural, and aortic transection was classified as none, partial, or circumferential. RESULTS: On angiography, creation of transmural thoracic aortic transection was successful in 91.7% (11/12) of animals. Aortic transection was circumferential in 54.4% (6/11) of animals and partial in 45.6% (5/11) of animals. Mean aortic diameter was 19.6 +/- 3.4 mm (range 12-24 mm) pre-transection and 25.8 +/- 4.5 mm (range 17.8-33 mm) post-transection (P = .0003). Pre-transection, mean aortic pressure was 79 +/- 13.8 mmHg, and 64.6 +/- 15.8 mmHg 15 min post-transection (P = .041). Pre-transection, mean heart rate was 94.5 +/- 17.2 beats per minute (bpm), and 105.8 +/- 17.2 bpm 15 min post-transection (P = .0057). CONCLUSIONS: Thoracic aortic transection was successfully created percutaneously in most animals. The animals remained in hemodynamically stable condition for as long as 240 minutes after the creation of aortic injury. This percutaneous animal model is straightforward and may be of potential value for future thoracic endograft research.

Prevalence and predictors of posttraumatic stress disorder in patients with acute myocardial infarction

OBJECTIVE: We estimated the prevalence of posttraumatic stress disorder (PTSD) and identified predictors of self-rated PTSD symptoms in patients post-myocardial infarction (MI). METHODS: We recruited 400 patients (mean age 60 +/- 12 years, 79% were men) with a previous acute index MI who were referred to a tertiary cardiology clinic. PTSD was assessed by the Clinician-administered PTSD Scale, and self-rated severity of PTSD symptom levels were assessed by the Posttraumatic Diagnostic Scale. RESULTS: Of the 190 patients who completed the Posttraumatic Diagnostic Scale, 34 met the cutoff for clinically significant PTSD symptomatology and 32 agreed to be interviewed. Among these patients, the Clinician-administered PTSD Scale interview yielded a prevalence of full and subsyndromal PTSD of 9.5% (95% confidence interval 7.4-11.6). Retrospectively rated feelings of helplessness (beta = .47, P < .001) and pain intensity during MI (beta = .15, P = .019) independently predicted PTSD symptom level. CONCLUSIONS: Approximately 10% of patients post-MI had full or subsyndromal PTSD. Subjective perception of MI predicted self-rated PTSD symptom level.

Omega-3 fatty acids and the neurovascular responses to mental stress in humans

Hypertension is the most prevalent form of cardiovascular disease (CVD) in the world, and is known to increase the risk for developing other diseases. Recently, the American Heart Association introduced a new classification of blood pressure, prehypertension (PHT). The criteria for PHT include a systolic of 120-139 mmHg and/or a diastolic blood pressure of 80-89 mmHg. It has been observed that individuals with PHT have a higher risk of developing hypertension later in life. Therefore, it is important to understand the mechanisms contributing to PHT in order to possibly prevent hypertension. Omega-3 fatty acids found in fish oils have been suggested as a means of lowering blood pressure. However, little is known on the effects of fish oil in PHT humans. Therefore we conducted two studies. In Study 1 we investigated PHT and normotensive (NT) individuals during a mental stress task. Mental stress is known to contribute to the development of hypertension. In Study 2 PHT and NT subjects were placed in an eight week double-blind placebo controlled study in which subjects consumed 9g/day of either fish oil or placebo (olive oil) in addition to their regular diets. Subjects were tested during a resting baseline (seated and supine), 5 minutes of a mental stress task, and 5 minutes of recovery both pre and post supplementation. We measured arterial pressure (AP), heart rate (HR), muscle sympathetic nerve activity (MSNA), and forearm and calf vascular responses. In Study 1 PHT demonstrated augmented AP and blunted vasodilation during mental stress, but MSNA did not change. In Study 2, fish oil did not directly influence blood pressure, MSNA or vascular responses to mental stress. However, it became clear that fish oil had an effect on some but not all subjects (both PHT and NT). Specifically, subjects who experienced a reduced blood pressure response to fish oil also demonstrated a decrease in MSNA and HR during mental stress. Collectively, the investigations in this dissertation had several novel findings. First, PHT individuals demonstrate an augmented pressor and blunted vascular response to mental stress, a response that may be contributing to the development of hypertension. Second, fish oil does not consistently lower resting blood pressure, but the interindividual responses may be related to MSNA. Third, fish oil attenuated the heart rate and MSNA responses and to mental stress in both PHT and NT. In conclusion, we found that there are both similarities and differences in the way PHT and NT individuals respond to mental stress and fish oil.

Acute alcohol ingestion and sympathetic neural responses during orthostatic stress in humans

Acute alcohol consumption has been reported to decrease mean arterial pressure (MAP) during orthostatic challenge, a response that may contribute to alcohol-mediated hypotension and eventually syncope. Muscle sympathetic nerve activity (MSNA) increases during orthostatic stress to help maintain MAP, yet the influence of alcohol on MSNA during orthostatic stress has not been determined. We hypothesized that alcohol ingestion would blunt arterial blood pressure and MSNA responses to progressive lower body negative pressure (LBNP). MAP, MSNA, and heart rate (HR) were recorded during progressive LBNP (-5, -10, -15, -20, -30, and -40 mmHg; 3 min/stage) in 30 subjects(age 24 ± 1 yrs). After an initial progressive LBNP protocol (pre-treatment), subjects were randomly assigned to consume alcohol (0.8g ethanol/kg body mass; n=15) or placebo (n=15) and then repeated the progressive LBNP protocol (post-treatment). Alcohol increased (drug × treatment, P ≤ 0.05) resting HR (59 ± 2 to 65 ± 2 beats/min) and MSNA (13 ± 3 to 19 ± 4 bursts/min) when compared to placebo. While alcohol increased MAP (83 ± 2 to 87 ± 2 mmHg), these increases were also observed with placebo (82 ± 2 to 88 ± 1 mmHg; treatment, P < 0.05; drug × treatment, P > 0.05). During progressive LBNP, a prominent decrease in MAP was observed after alcohol (drug × time × treatment, P < 0.05), but not placebo. There was also a significant attenuated response in forearm vascular resistance (FVR) during progressive LBNP (drug × time × treatment, P < 0.05). MSNA and HR increased during all LBNP protocols, but there were no differences between treatments or groups (drugs). In summary, acute alcohol ingestion induces an attenuation in blood pressure response during an orthostatic challenge, possibly due to the effect that alcohol has on impairing peripheral blood vessel constriction.

Effects of cognitive behavioral stress management on HIV-1 RNA, CD4 cell counts and psychosocial parameters of HIV-infected persons

OBJECTIVE: To determine the effects of cognitive-behavioral stress management (CBSM) training on clinical and psychosocial markers in HIV-infected persons. METHODS: A randomized controlled trial in four HIV outpatient clinics of 104 HIV-infected persons taking combination antiretroviral therapy (cART), measuring HIV-1 surrogate markers, adherence to therapy and well-being 12 months after 12 group sessions of 2 h CBSM training. RESULTS: Intent-to-treat analyses showed no effects on HIV-1 surrogate markers in the CBSM group compared with the control group: HIV-1 RNA < 50 copies/ml in 81.1% [95% confidence interval (CI), 68.0-90.6] and 74.5% (95% CI, 60.4-85.7), respectively (P = 0.34), and mean CD4 cell change from baseline of 53.0 cells/microl (95% CI, 4.1-101.8) and 15.5 cells/microl (95% CI, -34.3 to 65.4), respectively (P = 0.29). Self-reported adherence to therapy did not differ between groups at baseline (P = 0.53) or at 12 month's post-intervention (P = 0.47). Significant benefits of CBSM over no intervention were observed in mean change of quality of life scores: physical health 2.9 (95% CI, 0.7-5.1) and -0.2 (95% CI, -2.1 to 1.8), respectively (P = 0.05); mental health 4.8 (95% CI, 1.8-7.3) and -0.5 (95% CI, -3.3 to 2.2) (P = 0.02); anxiety -2.1 (95% CI, -3.6 to -1.0) and 0.3 (95% CI, -0.7 to 1.4), respectively (P = 0.002); and depression -2.1 (95% CI, -3.2 to -0.9) and 0.02 (95% CI, -1.0 to 1.1), respectively (P = 0.001). Alleviation of depression and anxiety symptoms were most pronounced among participants with high psychological distress at baseline. CONCLUSION: CBSM training of HIV-infected persons taking on cART does not improve clinical outcome but has lasting effects on quality of life and psychological well-being.