Chronic stress is a burden of modern societies and is known to be a risk factor for numerous somatic and affective disorders, including cardiovascular dysfunction, inflammatory bowel disease, gastric ulceration, general and/ or social anxiety- and depression-related diseases, as well as systemic immunological dysfunctions. Although many of these disorders are paralleled by either hypocorticism, glucocorticoid (GC) resistance, or a combination of both, resulting in a decreased GC signalling, the underlying aetiology of these disorders is still poorly understood, at least partly due to a lack of appropriate and clinically relevant animal models.

Importantly, not all people are equally affected by chronic stressors. While some individuals subjected to severe adverse life events develop pathologies, others do not. But again, the underlying mechanisms engendering resilience and vulnerability are also far from being understood and, thus, the possibility to clinically benefit from these observations is currently still limited.

A failure of immunoregulation, attributable to reduced exposure to the microbial environment within which the mammalian immune system evolved ("Old friends hypothesis"), is thought to be one factor contributing to recent increases in stress-related chronic inflammatory disorders, as well as mood disorders for which chronic low-grade inflammation is a risk factor ("cytokine theory of depression") (Lowry et al., 2016 Curr Environ Health Rep; Reber et al., 2016 PNEC).

Therefore, the main research aims of the Laboratory for Molecular Psychosomatics are to extend the current knowledge on the mechanisms underlying 1i) stressor-induced development of somatic and mental pathologies and 1ii) individual differences in stress resilience and 2) to use this mechanistic knowledge for the development of novel strategies in terms of stress protection (Fig. 1).

To investigate our research hypotheses stated above, we employ several preclinically validated rodent models of chronic psychosocial stress and study in detail their effects on behavioral, physiological, neuroendocrine, and immunological parameters, thereby considering individual differences in the stress coping strategy. Our main paradigm in this context to induce chronic psychosocial stress during adulthood is the chronic subordinate colony housing (CSC) paradigm (Reber et al., 2007 PNEC; Reber, 2012 PNEC; Langgartner et al., 2015 Frontiers in Psychiatry; Reber et al., 2016 PNEC). The CSC model is based on repeated psychosocial traumatization (social defeat, Days 1, 8, and 15) and prolonged (19 d) social subordination of male experimental mice to a larger dominant male and results in many behavioral, endocrine and immunological changes known from posttraumatic stress disorders patients (for review see Reber et al., 2016 PNEC). The value and clinical relevance of this stress model has recently been acknowledged with the "Curt P. Richter Award" by the International Society for Psychoneuroendocrinology (ISPNE). To induce chronic psychosocial stress in mice during early life we employ the maternal separation (MS) paradigm (Veenema et al., 2008 Endocrinology). Here, the pubs are separated from the mother for 3h per day between postnatal days (PND) 1-14. MS negatively affects the behavior (i.e. increases anxiety-related behavior), alters HPA axis (re)activity, and promotes immune activation, which is in line with what has been reported in humans exposed to early life trauma/stress.

To induce acute psychosocial stress in human volunteers under standard laboratory conditions for investigating its effects on mood, physiology and the immune system, we employ a slightly modified version of the "Trier Social Stress Test (TSST)", originally described earlier (Kirschbaum et al., 1993 Neuropsychobiology). TSST exposure reliably activates the two main stress axes, namely the sympathetic nervous system (SNS) and the hypothalamus-pituitary-adrenal (HPA) axis, as well as the cardiovascular and the immune system.