hypertension, coronary heart disease, psychoneurobiological mechanisms, emotion processing, biological CHD risk factors, prospective CHD risk, acute mental stress, physiological hyperreactivity, oxytocin, imaging, essential hypertension, stress reactivity
Nedeljkovic M., Webfer V., Ausfeld-Hafter B., Wirtz P.H., Streitberger K. (2013), Influence of general self-efficacy as a mediator in Taiji-induced stress reduction - results from a randomized controlled trial, in European Journal of Integrative Medicine
, 5(3), 284-290.
Nedeljkovic M. Wirtz P.H. Ausfeld-Hafter B. (2012), Effects of Taiji Practice on Mindfulness and Self-Compassion in Healthy Participants—A Randomized Controlled Trial, in Mindfulness
, 3(3), 200-208.
Kuebler Ulrike, Trachsel Manuel, von Känel Roland, Abbruzzese Elvira, Ehlert Ulrike, Wirtz Petra H. (2014), Attributional styles and stress-related atherogenic plasma lipid reactivity in essential hypertension, in J Psychosom Res
, 77(1), 51-56.
Kuebler Ulrike, von Känel Roland, Heimgartner Nadja, Zuccarella-Hackl Claudia, Stirnimann G., Ehlert Ulrike, Wirtz Petra H. (2014), Norepinephrine infusion with and without alpha-adrenergic blockade by phentolamine increases salivary alpha amylase but not cortisol levels in healthy men, in Psychoneuroendocrinology
, 49, 290-298.
von Känel Roland, Meister Rebecca, Stutz Monika, Kummer Petra, Arpagaus Angela, Huber Susanne, Ehlert Ulrike, Wirtz Petra H. (2014), Effects of dark chocolate consumption on the prothrombotic response to acute psychosocial stress in healthy men, in Thromb Haemost
, 112(6), 1151-1158.
Kuebler Ulrike, Wirtz Petra H., Sakai Miho, Stemmer Andreas, Meister Rebecca E. (2015), Anticipatory cognitive stress appraisal modulates suppression of wound-induced macrophage activation by acute psychosocial stress, in Psychophysiology
, 52(4), 499-508.
Kuebler Ulrike, Zuccarella-Hackl Claudia, Arpagaus Angela, Wolf Jutta M., Fahramand Firouzeh, von Känel Roland, Wirtz Petra H. (2015), Stress-induced modulation of NF-κB activation, inflammation-associated gene expression, and cytokine levels in blood of healthy men, in Brain Behav Immun
, 46, 87-95.
Zuccarella-Hackl Claudia, von Känel Ronald, Thomas Livia, Hauser Mark, Kuebler Ulrike, Widmer Hans-Ruedi, Wirtz Petra H. (2016), Macrophage Superoxide Anion Production in Essential Hypertension: Associations With Biological and Psychological Cardiovascular Risk Factors, in Psychosom Med
, 78(6), 750-757.
Zuccarella-Hackl Claudia, von Känel Roland, Thomas Livia, Kuebler Peggy, Schmid Jean-Paul, Mattle Heinrich P, Mono Marie-Louise, Rieben Robert, Wiest Roland, Wirtz Petra H (2016), Higher macrophage superoxide anion production in coronary artery disease (CAD) patients with Type D personality, in Psychoneuroendocrinology
, 68, 186-193.
Wirtz Petra H, Ehlert Ulrike, Kottwitz Maria U, La Marca Roberto, Semmer Norbert K (2013), Occupational role stress is associated with higher cortisol reactivity to acute stress., in Journal of occupational health psychology
, 18(2), 121-131.
Wirtz Petra H, Siegrist Johannes, Schuhmacher Anna, Hoefels Susanne, Maier Wolfgang, Domes Gregor, Schwab Sibylle, Zobel Astrid W (2013), The association between overcommitment to work and depressive symptoms is moderated by the polymorphic region of the 5-HTT gene., in Psychiatry research
, 208(2), 199-200.
Kuebler Ulrike, Wirtz Petra H, Sakai Miho, Stemmer Andreas, Ehlert Ulrike (2013), Acute stress reduces wound-induced activation of microbicidal potential of ex vivo isolated human monocyte-derived macrophages., in PloS one
, 8(2), 55875-55875.
Austin Anthony W, Wirtz Petra H, Patterson Stephen M, Stutz Monika, von Känel Roland (2013), Challenges in controlling for the effects of hemoconcentration reply, in Psychosomatic medicine
, 75(2), 223-226.
Kuebler Ulrike, Linnebank Michael, Semmler Alexander, Stoffel-Wagner Birgit, La Marca Roberto, Ehlert Ulrike, Wirtz Petra H (2013), Plasma homocysteine levels increase following stress in older but not younger men., in Psychoneuroendocrinology
, 38(8), 1381-1387.
Nedeljkovic Marko, Bürgler Christina, Wirtz Petra H, Seiler Roland, Streitberger Konrad M, Ausfeld-Hafter Brigitte (2012), Getting started with taiji: investigating students expectations and teachers appraisals of taiji beginners courses., in Evidence-based complementary and alternative medicine : eCAM
, 2012, 595710-595710.
Wirtz Petra H, Thomas Livia, Domes Gregor, Penedo Frank J, Ehlert Ulrike, Nussbeck Fridtjof W (2013), Psychoendocrine validation of a short measure for assessment of perceived stress management skills in different non-clinical populations., in Psychoneuroendocrinology
, 38(4), 572-586.
Austin Anthony W, Wirtz Petra H, Patterson Stephen M, Stutz Monika, von Känel Roland (2012), Stress-induced alterations in coagulation: assessment of a new hemoconcentration correction technique., in Psychosomatic medicine
, 74(3), 288-295.
Nedeljkovic Marko, Ausfeld-Hafter Brigitte, Streitberger Konrad, Seiler Roland, Wirtz Petra H (2012), Taiji practice attenuates psychobiological stress reactivity--a randomized controlled trial in healthy subjects., in Psychoneuroendocrinology
, 37(8), 1171-1180.
Nedeljkovic M., Ausfeld-Hafter B., Seiler R., Wirtz P.H. (2012), Minderung physiologischer Reaktivität auf psychosozialen Stress durch Taiji-Training – wer profitiert besonders?, in Z Med Psychol
, 21(4), 161-169.
Kuebler Ulrike, Ehlert Ulrike, Zuccarella Claudia, Sakai Miho, Stemmer Andreas, Wirtz Petra H (2013), An in vitro method to investigate the microbicidal potential of human macrophages for use in psychosomatic research., in Psychosomatic medicine
, 75(9), 841-848.
Thomas Livia, Schwaninger Adrian, Heimgartner Nadja, Hedinger Patrik, Hofer Franziska, Ehlert Ulrike, Wirtz Petra H. (2014), Stress-induced cortisol secretion impairs detection performance in airport security x-ray baggage screening for hidden weapons by screening novices, in Psychophysiology
, 51(9), 912-920.
Wirtz Petra H., von Känel Roland, Meister Rebecca, Arpagaus A., Treichler S., Kuebler U., Huber S., Ehlert U. (2014), Dark chocolate intake buffers stress reactivity in humans, in J Am Coll Cardiol
, 63(21), 2297-2299.
Kuebler Ulrike, Arpagaus Angela, Meister Rebecca E, von Känel Ronald, Huber Susanne, Ehlert Ulrike, Wirtz Petra H (accepted), Dark chocolate attenuates intracellular pro-inflammatory reactivity to acute psychosocial stress in men: A randomized controlled trial, in Brain Behav Immun
The present proposal aims to elucidate psychoneurobiological mechanisms in essential hypertension and CHD.
It combines assessment of psychological parameters and intermediate biological risk factors for CHD, both in prospective CHD assessment as well as in cross-sectional mechanistic neuroimaging and psychopharmacological intervention studies in hypertensive subjects, in patients with overt CHD, and in normotensive healthy controls.
Specific scientific aims are:
(A) To investigate emotion processing in essential hypertension and coronary heart disease (CHD).
(B) To determine the prospective association between psychological factors including emotion processing, intermediate biological CHD risk factors, and future CHD in patients, essential hypertensives, and healthy controls.
(C) To evaluate the effect of social support and oxytocin administration on reducing physiological hyperreactivity to stress in essential hypertension.
(D) To identify the neural basis of physiological hyperreactivity to stress in essential hypertension and its association with emotion processing.
Coronary heart disease (CHD) is a leading cause of premature death in industrialized countries and arterial hypertension is a major risk factor for CHD. 90% of hypertensive patients are diagnosed as “essential hypertensives” as the cause for their chronically elevated arterial blood pressure is unknown. The psychoneurobiological mechanisms underlying essential hypertension, its association with increased incidence of CHD, and heightened morbidity and mortality among CHD patients are still poorly understood.
Interdisciplinary research suggests a role for associations between emotion processing and future CHD risk. We previously found first evidence for poor emotion regulation in essential hypertensives compared to normotensive controls but emotion processing remains to be further elucidated, particularly in CHD. Project A is therefore intended to measure emotion processing in hypertension and CHD by assessing emotion recognition of facial affect in a representative sample size of hypertensive and normotensive individuals including women, and CHD patients.
Moreover, although recent meta-analyses document associations between anger and hostility with future CHD, both in healthy controls and CHD patients, the prospective association between emotion processing and future CHD has not yet been investigated. Project B therefore aims to determine the prospective association between emotion processing and other psychosocial risk factors with future CHD in a longitudinal study over a 3-year follow-up period in a sizable number of CHD patients, essential hypertensives, and healthy controls. In addition to the psychosocial factors (i.e. vital exhaustion, depressive symptom severity, overcommitment, hostility, anger, low social support, Type D personality) and emotion processing, intermediate biological CHD risk factors (i.e. inflammation markers, lipids, coagulation), as well as continuous CHD indicators (i.e. intima media thickness, six-minute walk test) will be assessed at baseline and after 18 and 36 months. This will allow complex assessment of the individual contribution of each psychological risk factor to future CHD indicators, while studying potential underlying biological pathways.
The testing of physiological reactivity to controlled challenges such mental stress, which is considered as a window into complex psychological and physiological processes involved in the development of cardiovascular disease, demonstrated prospective associations between greater physiological stress reactivity and poor cardiovascular risk status. The physiological hyperreactivity to stress in terms of sympathetic nervous system and hypothalamus-pituitary-adrenal axis activity, blood lipids, and coagulation activity that we and others observed in essential hypertension, has therefore been suggested to play a mechanistic role in the association between hypertension and heightened CHD risk. Moreover, we found lower perceived social support in hypertensives (which may suggest a potential deficit in social interaction abilities) as compared to normotensives with highest physiological stress responses in hypertensives with low perceived social support. Given that oxytocin and social support have been shown interact in reducing psychophysiological responses to stress in normotensive individuals and that oxytocin exerts positive social interaction in healthy humans, exogenous oxytocin administration may enable hypertensives to effectively take advantage of provided social support. Thereby, oxytocin may enhance the effect of social support on reducing the previously observed physiological hyperreactivity to stress in essential hypertensives. Project C therefore aims to evaluate a psychopharmacological intervention strategy intended to elucidate neuroendocrine pathways underlying the observed association between lower social support and heightened physiological stress reactivity in hypertensives: In a placebo-controlled, double-blind study design, hypertensive and normotensive men (subgroups of project B) will randomly be assigned to receive intranasal oxytocin (24 IU) or placebo 50 min before stress, and either social support from their best friend during the preparation period of the stress protocol or no social support. All participants will be exposed to a standardized social laboratory stressor (Trier Social Stress Test) and neuroendocrine reactivity will be measured repeatedly. As our recent findings suggests strong associations between social support and heightened coagulation activity in healthy subjects before and after social stress and as we found higher lipid and coagulation reactivity to social stress in hypertensives, biological risk factors for CHD will be assessed as well.
Finally, whereas attempts have been done to identify neural correlates of physiological stress reactivity in healthy persons, the neural mechanisms underlying the physiological hyperreactivity to stress in hypertension have been subject to speculation but are still unknown. Project D is therefore intended to study the neural basis of physiological hyperreactivity to acute stress in hypertension. Physiological reactivity will be assessed by repeated measurement of neuroendocrine reactivity as well as of reactivity of intermediate biological risk factors for CHD to psychosocial stress during functional magnetic resonance imaging in a subsample of hypertensive and normotensive men of project B. Psychosocial stress will be induced by the Montreal Imaging Stress Task (MIST) a standardized psychosocial stress paradigm developed for functional imaging studies. The project aims to investigate potential differences between hypertensive and normotensive men in their neural reactivity to the MIST and at finding associations between neural reactivity and peripheral reactivity of neuroendocrine parameters and intermediate biological risk factors. Given the observed association between poor emotion regulation and physiological hyperreactivity in our hypertensives, a potential modulation of neurophysiological stress reactivity by emotion processing (project A) will be additionally studied.
Taken together, the innovative and integrative approach of the proposal allows for a better understanding of psychoneurobiological mechanisms underlying the heightened stress reactivity and CHD risk in essential hypertension as well as the adverse disease outcomes in CHD patients. The implications of the proposed studies may provide important new information for the development of interdisciplinary intervention strategies for essential hypertension and CHD.