Effect of Acute Psychological Stress on Prefrontal GABA Concentration Determined by Proton Magnetic Resonance Spectroscopy

Objective Impaired function of the central gamma-aminobutyric acid (GABA) system, which provides the brain’s major inhibitory pathways, is thought to play an important role in the pathophysiology of anxiety disorders. The effect of acute psychological stress on the human GABA-ergic system is still unknown, however. The purpose of this study was to determine the effect of acute stress on prefrontal GABA levels. Method A recently developed noninvasive magnetic resonance spectroscopy method was used to measure changes in the GABA concentration of the prefrontal cortex in 10 healthy human subjects during a threat-of-shock condition and during a safe condition (two sessions on different days). The main outcome measure was the mean GABA concentration within a 3×3×2-cm3 voxel selected from the medial prefrontal cortex. Results Prefrontal GABA decreased by approximately 18% in the threat-of-shock condition relative to the safe condition. This reduction was specific to GABA, since the concentrations of N-acetyl-aspartate, choline-containing compounds, and glutamate/glutamine levels obtained in the same spectra did not change significantly. Conclusions This result appeared compatible with evidence from preclinical studies in rodents, which showed rapid presynaptic down-regulation of GABA-ergic neurotransmission in response to acute psychological stress. The molecular mechanism and functional significance of this reduced inhibitory effect of acute psychological stress in relation to impaired GABA-ergic function in anxiety disorders merit further investigation.

Effects of aspirin and propranolol on the acute psychological stress response in factor VIII coagulant activity: a randomized, double-blind, placebo-controlled experimental study

Activity of clotting factor VIII has been shown to acutely increase with sympathetic nervous system stimulation. We investigated whether aspirin and propranolol affect the responsiveness of plasma clotting factor VIII activity levels to acute psychosocial stress. We randomized 54 healthy subjects double-blind to 5-day treatment with a single daily oral dosage of either 100 mg aspirin plus 80 mg propranolol combined, 100 mg of aspirin, 80 mg of propranolol, or placebo medication. Thereafter, subjects underwent a 13-min standardized psychosocial stressor. Plasma levels of clotting factor VIII activity were determined immediately before, immediately after, 45 min and 105 min after stress. Controlling for demographic, metabolic, and life style factors repeated measures analysis of covariance showed that the change in clotting factor VIII activity from prestress to 105 min poststress differed between medication groups (P = 0.023; partial eta = 0.132). The clotting factor VIII activity level decreased from prestress to immediately poststress in the aspirin/propranolol group relative to the placebo group (P = 0.048) and the aspirin group (P < 0.06). Between 45 min and 105 min poststress, clotting factor VIII levels increased in the aspirin/propranolol group relative to the placebo group (P = 0.007) and the aspirin group (P = 0.039). The stress response in clotting factor VIII activity levels was not significantly different between the aspirin/propranolol group and the propranolol group. Propranolol in combination with aspirin diminished the acute response in clotting factor VIII activity to psychosocial stress compared with placebo medication and aspirin alone. The effect of single aspirin on the acute clotting factor VIII stress response was indistinguishable from a placebo effect.

Longitudinal platelet reactivity to acute psychological stress among older men and women

Platelet reactivity to acute stress is associated with increased cardiovascular disease risk; however, little research exists to provide systematic methodological foundations needed to generate strong longitudinal research designs. Study objectives were: 1) to evaluate whether markers of platelet function increase in response to an acute psychological stress test among older adults, 2) to establish whether reactivity remains robust upon repeated administration (i.e. three occasions approximately 1 year apart), and 3) to evaluate whether two different acute speech stress tasks elicit similar platelet responses. The 149 subjects (mean age 71 years) gave a brief impromptu speech on one of two randomly assigned topics involving interpersonal conflict. Blood samples drawn at baseline and post-speech were assayed using flow cytometry for platelet responses on three outcomes (% aggregates, % P-selectin expression, and % fibrinogen receptor expression). Three-level hierarchical linear modeling analyses revealed significant stress-induced increases in platelet activation on all outcomes (p < 0.001). No significant habituation on any measure was found. Additional reactivity differences were associated with male gender, history of myocardial infarction, and use of aspirin, statins, and antidepressants. The results demonstrate that laboratory acute stress tests continued to produce robust platelet reactivity on three activation markers among older adults over 3 years.

Effects of depressive and anxious symptoms on norepinephrine and platelet P-selectin responses to acute psychological stress among elderly caregivers

BACKGROUND: Caring for a spouse with Alzheimer's disease is associated with increased psychological distress, impaired immunity, and heightened cardiovascular risk. Hyperreactivity of sympathetic and platelet activation responses to acute psychological stress, or the failure to recover quickly from stressful events, may constitute an important pathway linking stress and negative affect with cardiovascular disease (CVD). OBJECTIVES: (1) To evaluate associations between negative affect (i.e., depressive and anxious symptoms) with increased norepinephrine and P-selectin responses to an acute psychological stress task. (2) To establish whether these associations are augmented among elderly spousal caregivers (CG) compared to non-caregivers (NC). METHODS: Depressive (DEP) and anxious (ANX) symptoms from the Brief Symptom Inventory were assessed among 39 CG and 31 NC. Plasma norepinephrine levels (NE) and percent platelet P-selectin (PSEL) expression were assayed at three time-points: rest, immediately following a laboratory speech test (reactivity), and after 14 min of recovery. Results: Among CG, but not NC, increased symptoms of depression and anxiety were associated with delayed NE recovery (DEP: beta=.460, p=.008; ANX: beta=.361, p=.034), increased PSEL reactivity (DEP: beta=.703, p<.001; ANX: beta=.526, p=.002), and delayed PSEL recovery (DEP: beta=.372, p=.039; ANX: beta=.295, p=.092), while controlling for age, gender, aspirin use, antidepressant use, and preexisting CVD. Bivariate correlations showed delayed NE recovery was also associated with increased PSEL reactivity (r=.416) and delayed PSEL recovery (r=.372; all ps<.05) among CG but not NC. DISCUSSION: Among chronically stressed caregivers, increased levels of depressive and anxious symptoms are associated with prolonged sympathetic activation and pronounced platelet activation. These changes may represent one pathway linking caregiving stress to cardiovascular risk.

The role of psychological stress in inflammatory bowel disease: quality assessment of methods of 18 prospective studies and suggestions for future research

BACKGROUND: Enquiries among patients on the one hand and experimental and observational studies on the other suggest an influence of stress on inflammatory bowel diseases (IBD). However, since this influence remains hypothetical, further research is essential. We aimed to devise recommendations for future investigations in IBD by means of scrutinizing previously applied methodology. METHODS: We critically reviewed prospective clinical studies on the effect of psychological stress on IBD. Eligible studies were searched by means of the PubMed electronic library and through checking the bibliographies of located sources. RESULTS: We identified 20 publications resulting from 18 different studies. Sample sizes ranged between 10 and 155 participants. Study designs in terms of patient assessment, control variables, and applied psychometric instruments varied substantially across studies. Methodological strengths and weaknesses were irregularly dispersed. Thirteen studies reported significant relationships between stress and adverse outcomes. CONCLUSIONS: Study designs, including accuracy of outcome assessment and repeated sampling of outcomes (i.e. symptoms, clinical, and endoscopic), depended upon conditions like sample size, participants' compliance, and available resources. Meeting additional criteria of sound methodology, like taking into account covariates of the disease and its course, is strongly recommended to possibly improve study designs in future IBD research.

Prothrombotic changes with acute psychological stress: combined effect of hemoconcentration and genuine coagulation activation

INTRODUCTION: Acute psychosocial stress accelerates blood coagulation and elicits hemoconcentration which mechanisms are implicated in acute coronary thrombotic events. We investigated the extent to which the change in prothrombotic measures with acute stress reflects hemoconcentration and genuine activation of coagulation. MATERIAL AND METHODS: Twenty-one middle-aged healthy men underwent three sessions of a combined speech and mental arithmetic task with one-week intervals. Coagulation and plasma volume were assessed at baseline, immediately post-stress, and 45 min post-stress at sessions one and three. Measures of both visits were aggregated to enhance robustness of individual biological stress responses. Changes in eight coagulation measures with and without adjustment for simultaneous plasma volume shift were compared. RESULTS: From baseline to immediately post-stress, unadjusted levels of fibrinogen (p=0.028), clotting factor VII activity (FVII:C) (p=0.001), FVIII:C (p<0.001), FXII:C (p<0.001), and von Willebrand factor (VWF) (p=0.008) all increased. Taking into account hemoconcentration, fibrinogen (p=0.020) and FVII:C levels (p=0.001) decreased, activated partial prothrombin time (APPT) shortened (p<0.001) and prothrombin time (PT) was prolonged (p<0.001). Between baseline and 45 min post-stress, unadjusted (p=0.050) and adjusted (p=0.001) FVIII:C levels increased, adjusted APTT was prolonged (p=0.017), and adjusted PT was shortened (p=0.033). D-dimer levels did not significantly change over time. CONCLUSIONS: Adjustment for stress-hemoconcentration altered the course of unadjusted levels of several prothrombotic factors. After adjustment for hemoconcentration, APPT was shortened immediately post-stress, whereas 45 min post-stress, FVIII:C was increased and PT was shortened. Procoagulant changes to acute stress may reflect both hemoconcentration and genuine activation of coagulation molecules and pathways.

Association Between Posttraumatic Stress Disorder Following Myocardial Infarction and Liver Enzyme Levels: A Prospective Study

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.

Mood and nonmood components of perceived stress and exacerbation of Crohnʼs disease

BACKGROUND: Diverse psychological factors are involved in the pathophysiology of stress. In order to devise effective intervention strategies, it is important to elucidate which factors play the most important role in the association between psychological stress and exacerbation of Crohn's disease (CD). We hypothesized that the association between perceived stress and exacerbation of CD would remain after removal of mood and anxiety components, which are largely involved in stress perception. METHODS: In all, 468 adults with CD were recruited and followed in different hospitals and private practices of Switzerland for 18 months. At inclusion, patients completed the Perceived Stress Questionnaire and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. During the follow-up, gastroenterologists assessed whether patients presented with a CD exacerbation. By means of binary logistic regression analysis, we estimated the factor by which one standard deviation of perceived stress would increase the odds of exacerbation of CD with and without controlling for anxiety and depression. RESULTS: The odds of exacerbation of CD increased by 1.85 times (95% confidence interval 1.43-2.40, P < 0.001) for 1 standard deviation of perceived stress. After removing the anxiety and depression components, the residuals of perceived stress were no longer associated with exacerbation of CD. CONCLUSIONS: The association between perceived stress and exacerbation of CD was fully attributable to the mood components, specifically anxiety and depression. Future interventional studies should evaluate the treatment of anxiety and depression as a strategy for potential prevention of CD exacerbations. (Inflamm Bowel Dis 2011;).

Hemoconcentration and hemostasis during acute stress: interacting and independent effects

Acute psychological stress can produce significant hemoconcentration as well as prothrombotic changes in blood, both of which may have potentially harmful effects on the cardiovascular system. It is unclear whether these effects are independent or have influence on each other.

Stress-induced alterations in coagulation: assessment of a new hemoconcentration correction technique

For the examination of psychological stress effects on coagulation, the Dill and Costill correction (DCC) for hemoconcentration effects has been used to adjust for stress-induced plasma volume changes. Although the correction is appropriate for adjusting concentrations of various large blood constituents, it may be inappropriate for time-dependent or functional coagulation assays. Two new plasma reconstitution techniques for correcting hemoconcentration effects on stress-induced changes in coagulation were compared with the DCC.

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.