Stress and stress-related disease states as topics of multi-approach research

As time passes, we realize that everything changes including scientific approaches to stress research. In the seventies, the main focus of stress research was studying the response itself. At that time, stress research was focused on attempts to understand the nature of stress response and discover its control mechanisms. Primary attention was given to main stress hormones, particularly catecholamines (Kopin, 1976; Kvetnansky, 1980). Evaluated parameters included brain tissue and plasma catecholamine concentrations, activities of catecholamine-related enzymes (namely catecholamine synthesizing and degrading enzymes) and binding characteristics of adrenergic receptors. Soon it became evident that important roles were being played by other neurotransmitters and by the interactions with other stress hormones (Axelrod, 1984). Thus, the focus of the field was extended to include a variety of amines, neuropeptides and other neuroactive substances, which regulate and, in turn, are regulated by stress mechanisms (Van Loon, 1989). Pharmacological modulation of central and peripheral neurotransmitters as well as other regulatory factors was an additional research focus (Porter & Jezova, 1990).

Different aspects of stress theory have fueled a continuous (and ongoing) long-term debate among stress researchers. Stress is an inferred state (such as anxiety, pleasure, fear, etc), and attempts to identify it as a biological construct have suffered the same fate as other such discussions. The basic concept is attributed to Hans Selye (1974), who posited that stress is the nonspecific response of the body to any demand upon it. In subsequent years, many experimental approaches brought forth new evidence that the neuroendocrine response is in fact stressor-specific. Results on various intensities of different stressors and multiple central and peripheral neurochemical parameters demonstrated a marked heterogeneity of neuroendocrine responses (Goldstein et al., 1996). More recent debate has centered around balancing the positive and negative aspects of stress, as well as consideration of whether the definition of stress should be limited to its negative connotations (Koolhaas et al., 2011). A consensus definition of stress still eludes the field. With respect to intensity of stressors and potential negative consequences for the body, the current focus is directed toward unpredictability and inescapability of stress experience as well as individual differences in resilience and susceptibility.

With the development of new techniques, researchers went more in depth, working to elucidate the molecular mechanism involved in the control and execution of humoral responses to different stressors. Of particular importance were, and still are, the studies on gene expression of individual components of the stress system. One example is the proper transcriptomic analysis of adrenal medulla in acute and repeated stress (Liu et al., 2008). Of course, the molecular mechanisms of the central regulatory systems remained among the hot topics of the stress research (DeKloet, 2004).

Currently scientists are focusing primarily on physiological and pathophysiological consequences of stress exposure. There are a number of serious diseases or disorders which are directly or indirectly related to stress (see the “cross-word” diagram in Figure 1). While the association of these and several other disease states with stress exposure is evident, the underlying mechanisms remain to be elucidated. An understanding of causal links between stress-induced neurochemical and behavioral alterations and onset of pathological changes in the body is needed to achieve better prevention, diagnosis and treatment of stress-related disease states.

Figure 1. Selected stress-related disease states.

The above-mentioned historical premise provided a springboard for the scientific program of the 12th Symposium on Catecholamines and Other Neurotransmitter in Stress held in Smolenice Castle, Slovakia on 15–19 June 2019. Consistent with the evolution of the field, there were a number of changes from previous conferences in this series (Jezova & Herman 2016). The historical topics of Smolenice meetings, such as catecholamines, other neurotransmitters and neuroendocrine factors were not forgotten, but the program was shifted toward the evaluation of pathophysiological mechanisms of stress-related disease states. The symposium had nine oral sessions and five of them were directly devoted to stress-related pathologies, namely to Stress, Catecholamines and Cardiovascular Diseases; Stress and Cancer; Stress and Mental Health; Catecholamines and Cognitive Impairment; Stress and Metabolic Diseases. The majority of articles in this Special Issue are on topics related to stress and mental health (Dygalo et al., 2020; Fazekas et al., 2020; Goldstein, 2020; Hadad et al., 2020; Jezova et al., 2020; Shishkina et al., 2020; Sipos et al., 2020).

As highlighted by the speaker of the Introductory Kvetnansky Lecture, James P. Herman, and other international experts, the symposium series on Catecholamines and Other Neurotransmitters in Stress continues to provide for high-level high scientific, educational and social interaction for its participants, from students to senior reseachers. Three young scientists (Francesca Mottarlini, Italy; Charlotte Steenblock, Germany; Monika Zavodska, Slovakia) were recipients of the Irwin Kopin Award and many other young scientists and students from different countries presented their research work. The success of the 12th Symposium in 2019 was based on past initiatives (starting in 1975) of the founders of this symposium series, I.J. Kopin and R. Kvetnansky, well-known pioneers in the field of stress and catecholamines. Although they are not among us anymore, their presence was clearly felt at the 12th Symposium together with strong feelings of honor and thanks expressed by the organizers and participants of the meeting.