Post-traumatic stress in Crohn's disease and its association with disease activity.

OBJECTIVE: Violence, accidents and natural disasters are known to cause post-traumatic stress, which is typically accompanied by fear, suffering and impaired quality of life. Similar to chronic diseases, such events preoccupy the patient over longer periods. We hypothesised that post-traumatic stress could also be caused by Crohn's disease (CD), and that CD specific post-traumatic stress could be associated with an increased risk of disease exacerbation. METHODS: A cohort of CD patients was observed over 18 months in various types of locations providing gastroenterological treatment in Switzerland. The cohort included 597 consecutively recruited adults. At inclusion, CD specific post-traumatic stress was assessed using the Post-traumatic Diagnostic Scale (range 0-51 points). During follow-up, clinical aggravation was assessed by combining important outcome measures. Patients with post-traumatic stress levels suggestive of a post-traumatic stress disorder (≥ 15 points) were compared with patients with lower post-traumatic stress levels as well as with patients without post-traumatic stress. Also, the continuous relation between post-traumatic stress severity and risk of disease exacerbation was assessed. RESULTS: The 88 (19.1%) patients scoring ≥15 points had 4.3 times higher odds of exacerbation (95% CI 2.6 to 7.2) than the 372 (80.9%) patients scoring <15 points, and 13.0 times higher odds (95% CI 3.6 to 46.2) than the 45 (9.8%) patients scoring 0 points. The odds of exacerbation increased by 2.2 (95% CI 1.6 to 2.8) per standard deviation of post-traumatic stress. CONCLUSIONS: CD specific post-traumatic stress is frequent and seems to be associated with exacerbation of CD. Thus gastroenterologists may want to ask about symptoms of post-traumatic stress and, where relevant, offer appropriate management according to current knowledge.

Change over time in posttraumatic stress caused by myocardial infarction and predicting variables.

OBJECTIVE: The traumatic experience of a heart attack may evolve into symptoms of posttraumatic stress disorder, which can be diagnosed at the earliest 1 month after myocardial infarction (MI). While several predictors of posttraumatic stress in the first year after MI have been described, we particularly sought to identify longer-term predictors and predictors of change in posttraumatic stress over time. METHODS: We studied 274 post-MI patients with complete data (mean 61+/-10 years, 84% men). After a median of 60 days (range 30-365) following the index MI (study entry), they were asked to rate MI-related posttraumatic stress as well as psychological distress perceived during MI. After a median of 32 months (range 19-45) later, all patients were asked to rate posttraumatic stress again (follow-up). RESULTS: Female gender (P=.038) as well as greater helplessness (P<.001) and pain (P=.049) during MI predicted greater posttraumatic stress at study entry. Greater posttraumatic stress at follow-up was predicted by greater posttraumatic stress at study entry (P<.001), shorter duration of follow-up (P=.046), and greater pain during MI (P=.030). The decrease in posttraumatic stress over time (P<.001) was greater in patients with greater posttraumatic stress at study entry (P<.001) and in those with less pain during MI (P=.032). CONCLUSIONS: Demographic characteristics and perceived distress during MI were predictors of shorter-term posttraumatic stress. Although posttraumatic stress decreased over time and strongest in patients showing the greatest levels initially, greater short-term posttraumatic stress predicted maintenance of posttraumatic stress. Intense pain during MI adversely impacted both longer-term posttraumatic stress and its recovery.

Posttraumatic stress disorder and soluble cellular adhesion molecules at rest and in response to a trauma-specific interview in patients after myocardial infarction.

Posttraumatic stress disorder (PTSD) and circulating cellular adhesion molecules (CAMs) predict cardiovascular risk. We hypothesized a positive relationship between PTSD caused by myocardial infarction (MI) and soluble CAMs. We enrolled 22 post-MI patients with interviewer-rated PTSD and 22 post-MI patients with no PTSD. At 32±6months after index MI, all patients were re-scheduled to undergo the Clinician-Administered PTSD Scale (CAPS) interview and had blood collected to assess soluble CAMs at rest and after the CAPS interview. Relative to patients with no PTSD, those with PTSD had significantly higher levels of soluble vascular cellular adhesion molecule (sVCAM)-1 and intercellular adhesion molecule (sICAM)-1 at rest and, controlling for resting CAM levels, significantly higher sVCAM-1 and sICAM-1 after the interview. Greater severity of PTSD predicted significantly higher resting levels of sVCAM-1 and soluble P-selectin in patients with PTSD. At follow-up, patients with persistent PTSD (n=15) and those who had remitted (n=7) did not significantly differ in CAM levels at rest and after the interview; however, both these groups had significantly higher sVCAM-1 and sICAM-1 at rest and also after the interview compared to patients with no PTSD. Elevated levels of circulating CAMs might help explain the psychophysiologic link of PTSD with cardiovascular risk.

Stress hormones in patients with posttraumatic stress disorder caused by myocardial infarction and role of comorbid depression.

BACKGROUND: Chronic posttraumatic stress disorder (PTSD) has been associated with perturbed hypothalamic-pituitary-adrenal (HPA) axis function and a hyperadrenergic state. We hypothesized that patients with PTSD attributable to myocardial infarction (MI) would show peripheral hypocortisolemia and increased norepinephrine levels, whereby taking into account that depressive symptoms would affect this relationship. METHODS: We investigated 15 patients with interviewer-rated PTSD caused by myocardial infarction (MI) and 29 post-MI patients with no PTSD. Patients also completed the depression subscale of the Hospital Anxiety and Depression Scale and had blood collected to determine plasma cortisol and norepinephrine levels. RESULTS: In bivariate correlation analysis PTSD and depressive symptoms were not significantly associated with cortisol levels. However, patients with PTSD had lower mean+/-SEM cortisol levels than patients with no PTSD when controlling for depressive symptoms (77+/-11 vs. 110+/-7 ng/ml, p=.035). In turn, depressive symptoms correlated with cortisol levels when taking PTSD into account (r=.36, p=.019). In all patients cortisol levels correlated with total PTSD symptoms (r=-.43, p=.005) and hyperarousal symptoms (r=-.45, p=.002) after controlling for depressive symptoms. Depression correlated with cortisol levels after controlling for total PTSD symptoms (r=.45, p=.002). Posttraumatic stress disorder and depressive symptoms were not significantly associated with norepinephrine levels. CONCLUSIONS: In post-MI patients we found peripheral hypocortisolemia related to PTSD, respectively hypercortisolemia related to depressive symptoms, when taking joint effects of PTSD and depression into account. No evidence was found for a hyperadrenergic state. Comorbid depressive symptoms ought to be considered to disentangle the unique associations of PTSD with HPA axis dysfunction in cardiac patients.

Inflammatory biomarkers in patients with posttraumatic stress disorder caused by myocardial infarction and the role of depressive symptoms.

OBJECTIVE: Inflammation might link posttraumatic stress disorder (PTSD) with an increased risk of cardiovascular events. We explored the association between PTSD and inflammatory biomarkers related to cardiovascular morbidity and the role of co-morbid depressive symptoms in this relationship. METHODS: We investigated 15 patients with interviewer-rated PTSD caused by myocardial infarction (MI) and 29 post-MI patients with no PTSD. All patients completed the depression subscale of the Hospital Anxiety and Depression Scale and had blood collected to determine inflammatory markers of increased cardiovascular risk. RESULTS: Controlling for demographic and medical covariates, patients with PTSD had higher leptin levels than patients with no PTSD (p = 0.038, explained variance 10.4%); this difference became nonsignificant when controlling for depressive symptoms. After controlling for depressive symptoms, PTSD patients had higher interleukin-6 (p = 0.041; explained variance 10%), lower C-reactive protein (p = 0.022, explained variance 12.1%), and lower soluble CD40 ligand (p = 0.016, explained variance 13.4%) than patients without PTSD. After controlling for PTSD status, depressive symptoms correlated with soluble CD40 ligand (r = 0.45, p = 0.002) and with C-reactive protein (r = 0.29, p < 0.07). CONCLUSIONS: The findings provide further evidence for altered inflammation in PTSD. Comorbid depressive symptoms ought to be considered to disentangle the unique associations of PTSD caused by MI and systemic inflammation.

Association between posttraumatic stress disorder following myocardial infarction and liver enzyme levels: a prospective study.

BACKGROUND: Research in rodents demonstrated that psychological stress increases circulating levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase reflecting liver injury. Moreover, chronic posttraumatic stress disorder and transaminases predicted coronary heart disease. AIMS: To investigate the hypothesis that severity of posttraumatic stress disorder following myocardial infarction would prospectively relate to liver enzymes. METHODS: Study participants were 24 patients (mean 59+/-7 years, 79% men) with an interviewer-rated diagnosis of posttraumatic stress disorder caused by an index myocardial infarction 3+/-3 months before. After a mean follow-up of 26+/-6 months, patients had a clinical interview to reassess posttraumatic stress disorder severity, a medical history, and blood collected to determine liver enzymes. RESULTS: Total posttraumatic stress disorder symptoms assessed at study entry prospectively predicted plasma levels of alanine transaminase (r=.47, p=.031) and alkaline phosphatase (r=.57, p=.004), but not of aspartate transaminase (p=.15), controlling for follow-up duration and antidepressant use. Total posttraumatic stress disorder symptoms assessed at follow-up were associated with alanine transaminase (r=.72, p=.004), aspartate transaminase (r=.60, p=.018), and alkaline phosphatase (r=.64, p=.001) in the 16 patients who had maintained diagnostic posttraumatic stress disorder, but not in all 24 patients. CONCLUSIONS: The severity of posttraumatic stress disorder following myocardial infarction was associated with mild increase in liver enzyme levels, suggesting that chronic psychological stress relates to hepatic damage in humans. This might help to explain the previously observed increased cardiovascular risk in chronically traumatized individuals.

Myocardial infarction and post-traumatic stress disorder: frequency, outcome, and atherosclerotic mechanisms.

BACKGROUND: Post-traumatic stress disorder (PTSD) may develop in the aftermath of an acute myocardial infarction (MI). Whether PTSD is a risk factor for cardiovascular disease (CVD) is elusive. The biological mechanisms linking PTSD with atherosclerosis are unclear. DESIGN: A critical review of 31 studies in the English language pursuing three aims: (i) to estimate the prevalence of PTSD in post-MI patients; (ii) to investigate the association of PTSD with cardiovascular endpoints; and (iii) to search for low-grade systemic inflammatory changes in PTSD pertinent to atherosclerosis. METHODS: We located studies by PubMed electronic library search and through checking the bibliographies of these sources. RESULTS: The weighted prevalence of PTSD after MI was 14.7% (range 0-25%; a total of 13 studies and 827 post-MI patients). Two studies reported a prospective association between PTSD and an increased risk of cardiovascular readmission in post-MI patients and of cardiovascular mortality in combat veterans, respectively. In a total of 11 studies, patients with PTSD had increased rates of physician-rated and self-reported cardiovascular diseases. Various cytokines and C-reactive protein were investigated in a total of seven studies suggesting that PTSD confers a pro-inflammatory state. CONCLUSIONS: Increasing evidence suggests that PTSD specifically related to MI develops considerably frequently in post-MI patients. More research is needed in larger cohorts applying a population design to substantiate findings suggesting PTSD is an atherogenic risk factor and to understand better the suspected behavioural and biological mechanisms involved.

Health-related quality of life measured by the SF12 in working populations: associations with psychosocial work characteristics.

This study investigated the contribution of psychosocial work characteristics (decision latitude, job demand, social support at work, and effort-reward imbalance) to health-related quality of life. Data were derived from 2 aircraft manufacturing plants (N=1,855) at the start of a longitudinal study. Regression analysis showed that work characteristics (1st model) explained 19% of the variance in the mental summary score of the Short Form-12 Health Survey. R2 change for work characteristics decreased to 13%, accounting for demographics, socioeconomic status, body mass index, and medical condition (5th model). Including health behavior and personality factors (full model), R2 change for work characteristics remained significant. Psychosocial work characteristics account for relevant proportions in the subjective perception of mental health beyond a wide array of medical variables and personality factors.

The interrelationship of psychosocial risk factors for coronary artery disease in a working population: do we measure distinct or overlapping psychological concepts?

There is growing evidence that psychosocial factors contribute to the risk of coronary artery disease. Commonly used psychometric scales share several features leading to questions about whether they reflect distinguishable concepts. Study participants were 822 employees of the Augsburg Cohort Study (mean age 40 years, 89% men). The authors analyzed the interrelationship between the following psychosocial measures by applying Pearson correlations and factor analysis to the Hospital Anxiety and Depression Scale (HADS), Type D Personality (DS14), the Maastricht Vital Exhaustion Questionnaire (VE), Social Support (F-SozU), the SF12 Health Survey, and Effort-Reward Imbalance. Although the full correlation matrix revealed low to medium associations supporting the notion that the applied psychometric scales show some conceptual overlap, factor analyses resulted in 13 distinguishable and interpretable factors, considerably reflecting the original psychometric scales. This strengthens the assumption that the psychometric scales used constitute distinct psychological concepts, in particular, depressive symptomatology and negative affectivity versus vital exhaustion.

Hypercoagulability in working men and women with high levels of panic-like anxiety.

BACKGROUND: There is growing evidence that cardiovascular diseases are relatively more prevalent in subjects who feel anxious. An increased clotting diathesis might subject anxious individuals to an elevated arterial thrombotic risk. We investigated whether panic-like anxiety would relate to a hypercoagulable state. METHODS: Study participants with a complete data set were 691 employees (mean age +/- SD 40 +/- 11 years, 83% men) recruited from two German companies. Subjects were asked to self-rate the onset of sudden feelings of panic in the previous week on a 4-point Likert scale: 0=not at all (n=416), 1=not very often (n=179), 2=quite often (n=55), and 3=very often indeed (n=41). Levels of fibrinogen, of the antifibrinolytic enzyme type 1 plasminogen activator inhibitor (PAI-1), and of the hypercoagulability marker fibrin D-dimer were measured in plasma. RESULTS: While the level of D-dimer was significantly different across the 4 scores of panic feelings (F3, 687=6.49, p <0.001), the levels of fibrinogen and PAI-1 were not. After having controlled for a range of confounders of hemostatic function, the 96 subjects reporting panic feelings either 'quite often' or 'very often indeed' had higher D-dimer levels (mean +/- SEM 165 +/- 12.0 vs. 145 +/- 4.3 ng/ml, F20, 670= 4.78, p=0.030) and lower fibrinogen levels (259 +/- 6.9 vs. 274 +/- 2.5 mg/dl, F20, 670=4.71, p=0.030) than the 595 subjects reporting panic feelings either 'not at all' or 'not very often'. CONCLUSIONS: The findings suggest increased fibrin turnover with sudden feelings of panic. Prospective studies need to show whether such a procoagulant mechanism may contribute to the increased coronary risk with panic-like anxiety.

Effect of the G-308A polymorphism of the tumor necrosis factor (TNF)-alpha gene promoter site on plasma levels of TNF-alpha and C-reactive protein in smokers: a cross-sectional study.

BACKGROUND: Plasma levels of tumor necrosis factor (TNF)-alpha and of C-reactive protein (CRP) are elevated in smokers. Previous studies failed to show an association between the G-308A polymorphism in the promoter region of the TNF-alpha gene and coronary artery disease (CAD). We investigated whether smoking would interact with the TNF-alpha G-308A polymorphism in determining plasma levels of TNF-alpha and CRP. METHODS: Study participants with a complete data set in terms of smoking and the TNF-alpha G-308A polymorphism were 300 middle-aged male and female industrial employees. After excluding 24 irregular smokers, analyses were performed on 198 "non-smokers" (life-long non-smokers or subjects who quit smoking >6 months ago) as compared to 78 "regular smokers" (subjects currently smoking >3 cigarettes/day). All subjects had a fasting morning blood draw to measure plasma levels of TNF-alpha and CRP by high-sensitive enzyme-linked immunosorbent assays. RESULTS: The cardiovascular risk factor adjusted analysis regressing log-transformed CRP levels against smoking status, genotype, and smoking-status-genotype interaction revealed a significant main effect for smoking status (F1,250 = 5.67, p = .018) but not for genotype (F1,250 = 0.33, p = .57). The interaction-term between genotype and smoking status was not significant (F1,250 = 0.09, p = .76). The fully adjusted model with plasma TNF-alpha failed to show significant main effects for smoking and genotype, as well as for the smoking-status-genotype interaction. CONCLUSIONS: The findings suggest that the TNF-alpha G-308A polymorphism does not mediate the effect of smoking on plasma CRP levels. It remains to be seen whether other genetic polymorphisms along the inflammatory pathway may modulate vascular risk in smokers.

Relationship between overnight neuroendocrine activity and morning haemostasis in working men.

Sustained effects of SNS (sympathetic nervous system) and HPAA (hypothalamic-pituitary-adrenal axis) hyperactivity on haemostasis have not been investigated. In the present study, we tested for an association of overnight urinary catecholamine and cortisol excretion with morning plasma levels of fibrinogen, PAI-1 (plasminogen activator inhibitor-1) and D-dimer. Participants (639 male industrial employees) with a complete dataset were studied (age, 41+/-11 years; mean+/-S.D.). Subjects collected overnight urinary samples and had a fasting morning blood sample drawn. Measurement of urinary adrenaline (epinephrine), noradrenaline (norepinephrine) and cortisol were dichotomized to perform multivariate analyses of (co)variance. Haemostatic parameters were measured by ELISA. Fibrinogen was higher in men with high adrenaline (F(7,631)=5.68, P=0.018; where the subscripted value represents the degrees of freedom) and high noradrenaline (F(7,631)=4.19, P=0.041) compared with men with low excretion of the respective hormones. PAI-1 was higher in men with high cortisol than in men with low cortisol (F(7,631)=4.77, P=0.029). Interaction revealed that subjects with high cortisol/low noradrenaline had higher PAI-1 than subjects with low cortisol/high noradrenaline (P=0.038). Subjects with high adrenaline/high noradrenaline had higher D-dimer than subjects with high adrenaline/low noradrenaline (P=0.029), low adrenaline/high noradrenaline (P=0.022) and low adrenaline/low noradrenaline (not significant). When covariance for several confounders of haemostatic function was determined, the main effect of adrenaline on fibrinogen and the interaction between adrenaline and noradrenaline for D-dimer maintained significance. Although overnight SNS hyperactivity was associated independently with morning hypercoagulability, the relationship between the activity of HPAA and haemostasis was mediated by traditional cardiovascular risk factors.