Trier Social Stress Test (TSST)

Based on the ‘Mason’ factors (1968 Psychosom Med) A situation is perceived as stressful if it contains… novelty unpredictability uncontrollability ambiguity anticipation (of negative consequences) ego-involvement Recent metaanalysis (Dickerson & Keneny 2004 Psychol Bull) situations inducing HPA axis responses do often combine Uncontrollability and Social-Evaluative Threat

Meanwhile  well over 4.000 TSST sessions performed world-wide (for recent reviews see Kudielka et al., 2007a, 2007b) TSST versions for children and older adults healthy populations patients (psychiatric disorders, CFS, PTSD, pain, immunological disorders, etc.) Studies on effects of: age, gender, sex hormones genetics, polymorphisms social support, social hierachy personality factors intervention / stress management training oxytocin, pregnancy, lactation & breast-feeding nicotine, alcohol & coffee consumption, food/dietary energy supplies medication (psychoactive drugs, aspirin, beta-blocker etc.) habituation […] The TSST protocol can also be employed to test children and older adults after changing the instructions slightly for the respective age group. In elderly adults, subjects are instructed to apply for a (voluntary) part-time job (e.g., child caring, house keeping, technical assistant, etc). To help a retired subject to take over the role of a job applicant, a fabricated newspaper advertisement can be presented (tested age range 59-91 years). adapted TSST for children (TSST-C´)

Only a very few findings with TSST …

Do men and women show different stress responses? Kudielka et al. (1998) Journal of Clinical Endocrinology & Metabolism Kudielka et al. (2004) Psychoneuroendocrinology Yes ! Role of menstrual cycle phase: Kirschbaum, Kudielka et al. (1999) Psychosomatic Medicine

Role of menstrual cycle phase Kirschbaum, Kudielka et al. (1999) Psychosomatic Medicine

DEX-CRH-Feedback-Test: Yes Age effects TSST: No DEX-CRH-Feedback-Test: Yes Kudielka et al. (2004) Psychoneuroendocrinology Kudielka et al. (1999) Neuroendocrinology Kudielka et al. (2000) Stress Dex-premedication Time (min) 20 40 60 80 100 120 2 4 6 8 10 12 14 Younger men (n=12) older men (n=15) 100 µg hCRH Free Salivary Cortisol (nmol/l) younger women (N=15) older women (N=15) N=102 30 Alte 41 Jüngere 31 Kinder

Methodological aspects: time of day increase area under the curve Kudielka et al. (2004) Psychoneuroendocrinology N=180 Vormittag: N=109 Nachmittag: N=71

Variables that show increases after the TSST salivary free cortisol (2-3fold rise in about 70-80% of subjects) total plasma cortisol, ACTH adrenaline, noradrenaline, growth hormone, prolactin, testosterone blood pressure, heart rate, α-amylase immune parameters (e.g., lymphocytes, IL-6, TNF-α) blood coagulation markers (e.g., fibrinogen, D-dimer, vWF, clotting factors) measures of hemoconcentration (e.g., hematocrit, haemoglobin, plasma volume) endogenous inhibitor of monoamine oxidase (MAO-AI) […] altered well-being, pain sensitivity, alcohol consumption, drug effects etc. With this protocol, salivary cortisol levels rise two to threefold in about 70-80% of all subjects with peak levels around 10-20 minutes after cessation of the stress task. In addition to free cortisol, the levels of total plasma cortisol, ACTH, catecholamines (adrenaline, noradrenaline), growth hormone, prolactin, testosterone, systolic and diastolic blood pressure, heart rate, immune parameters (e.g., neutrophils, eosinophils, basophils, lymphocytes, interleukin-6, TNFα), glucose, alpha-amylase, endogenous inhibitor of monoamine oxidase (MAO-AI) as well as measures of hemoconcentration (e.g., hematocrit, haemoglobin, plasma volume) and blood coagulation (fibrinogen, von Willebrand factor antigen, D-dimer, clotting factors) increase significantly.

Final Remarks Identifying the determinants of HPA axis regulation and dysregulation is, particularly in humans, a very challenging task. An extensive phenotyping with markers of basal as well as stimulated HPA axis activity is required in order to elucidate the mechanisms mediating stress related disorders and to develop new therapeutic strategies

Future Challenges What is a normal range?  huge interindividual variability  HPA axis = highly adaptive system many aspects not directly observable in humans (brain, earlier adaptive processes) sensitivity of target tissue low correlation across tests cortisol level is not a stable attribute of a subject influenced by situational factors  extent to which trait components can be detected depends significantly on the quality of the used measures