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Stress and morphine autoregulation. The general neurobiological principle of autoregulatory stress response mechanisms, i.e., endogenous stress management, is to terminate the initial stress response and recover the systems, i.e., secondary back-up; references: [Cannon, 1914; Esch, 2008b; Esch & Stefano, 2002e; Esch & Stefano, 2007b; Esch et al. 2002a; Esch et al. 2009a; Kream et al. 2009; McCarty & Gold, 1996; Salamon et al. 2006; Stefano et al. 1995c; Stefano et al. 1996b; Stefano et al. 2005d].

Stress and morphine autoregulation. The general neurobiological principle of autoregulatory stress response mechanisms, i.e., endogenous stress management, is to terminate the initial stress response and recover the systems, i.e., secondary back-up; references: [Cannon, 1914; Esch, 2008b; Esch & Stefano, 2002e; Esch & Stefano, 2007b; Esch et al. 2002a; Esch et al. 2009a; Kream et al. 2009; McCarty & Gold, 1996; Salamon et al. 2006; Stefano et al. 1995c; Stefano et al. 1996b; Stefano et al. 2005d].

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Stress is natural and belongs to life itself. To sustain it and even grow with it biology invented different mechanisms, since stress resistance is obligatory. These pathways, we surmise, can be activated and learned intentionally, through professional stress management training or 'mind-body medicine', or endogenously and automatically through aut...

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... mor- phinergic signalling, since this latter opiate alkaloid has only recently been found in human tissues (e.g., [Atmanene et al. 2009;Bilfinger et al. 2002;Boettcher et al. 2005;Fricchione et al. 2008;Olsen et al. 2005;Poeaknapo, 2005;Poeaknapo et al. 2004;Stefano & Kream, 2009c;Zhu et al. 2005a;Zhu et al. 2007]) and linked to stress regulation (Fig. 4). Indeed, the catecholamine pathway may have arisen from endogenous MO biosynthesis, coupling these signalling processes in an even more intimate relationship as also made evident by common enzymes in the synthesis of these chemical messengers Neri et al. 2008;Stefano & Kream, 2007b;Stefano & Kream, 2009c]. The results that we now ...
Context 2
... of a successful strategy that helped to fight the stressor in mind, and somehow accessible afterwards, so that after the fight is over, this success- ful strategy can become endogenously evaluated and, if positive, memorized (learned). MO seems to play a critical role in this process, for example, as a recovery or secondary back-up molecule (Fig. 4 and ...

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... The intentional directing of attention to a previously learned (conditioned)-and positively anticipated (expected), in a suitable situation-favorable outcome activates self-healing processes (Esch, 2014). It is undisputed that there can also be specific effects within the framework of MBM and MBIs, just as the individual pillars of the BERN framework also present specific components in addition to overlapping signaling paths (see Esch and Stefano, 2010; Figure 2). In addition to the anticipation and motivation systems involved, other CNS networks also come into play, such as the salience network, which is closely linked to the reward system, the resting state network (default mode network), or parts for self-processing and self-reference, and finally, frontal CNS networks for executive functions (Lee et al., 2018;Gothe et al., 2019;Esch, 2021b;Esch, 2021, 2022;Zhang et al., 2021). ...
... In a sense, we can understand MBM and related behavioral self-healing rituals as practical anchors of the neurobiological and psychological connections presented (Esch and Stefano, 2010). Thus, MBM can be viewed as an ''applied placebo effect'', and self-healing as a type of ''placebo medicine'' (Stefano et al., 2001). ...
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Background : Mind-body medicine (MBM) focuses on improving our understanding of how the interactions between the brain, mind, body, and behavior can be used to promote health. In this narrative review, we present the basic principles of MBM, including the introduction of a rational framework for the implementation of MBM-based interventions. We also discuss the contributions of MBM to motivation and reward systems in the brain including those that may specifically involve the mitochondria. Results : MBM can be used to promote health in patients with chronic diseases, especially conditions identified as lifestyle-related. MBM builds on salutogenesis, which is a paradigm that focuses on health (as opposed to disease) determinants and the development of individual resilience and coherence factors as a means to reduce stress, decrease the burden of disease, and improve the quality of life. This approach involves several well-known principles of self-healing and self-care. MBM interventions typically include behavioral modification techniques in conjunction with cognitive work focused on stress regulation, exercise, relaxation, meditation, and nutrition. We suggest the use of the acronym “BERN” (Behavior, Exercise, Relaxation, and Nutrition) to summarize the operational framework of this approach. Discussion : Different BERN techniques act via shared autoregulatory central nervous system (CNS) reward and motivation circuitries. These systems rely on numerous neurobiological signaling pathways with overlapping effector molecules that converge, e.g., on nitric oxide (NO) as a common effector molecule. NO is critically coupled to reward physiology, stress reduction, and self-regulation as it modulates the responses of various mitochondrial, nuclear, and chromosomal processes within brain cells. NO has also been implicated in relevant outcomes (e.g., the placebo response). Conclusions : MBM interventions typically follow the BERN model and aim to strengthen health and resilience, and reduce stress. The mechanisms of action of these processes involve the CNS reward systems and correlate with placebo and self-healing pathways.
... It provides inner guidelines, i.e., directions, and lets us humans plan or implement behaviors from which we hope to derive a desired (beneficial) outcome [2,5,6,8]. Therefore, the feeling of happiness-if based on an experience that has already been made before (i.e., memorized, conditioned, and also linked to it: a positive expectation for the future)-is an efficient way of integrating or automating experiences made earlier into behavioral or treatment concepts that can be quickly implemented and activated (i.e., short-cut) [8,11,12]. ...
... Happiness as a biological concept was passed on genetically and further developed in evolution [4,7,[13][14][15]. It has a biomolecular basis yet is used for autoregulation and survival (of the individual and of the species) [5,7,12,16,17]. Happiness can thus be measured (e.g., in the brain, blood; see below) and is associated with biophysiological changes in the body [7,[18][19][20][21][22][23][24]. At its core, happiness, as is the case with the entire body (the living organism), is dynamic by nature and is subject to cyclical or internal "maturation processes" (see below). ...
... Underlying the concepts of motivation are physiological mechanisms that occur in brain areas distinct from other sensory or cognitive areas [5,7,49]. An integral part of the central nervous system (CNS), approach motivation and reward systems are neurons that have their principal origin in the ventral tegmental area (VTA), located in the midbrain [5,12]. These neurons send projections, e.g., to the frontolimbic brain, mostly to the nucleus accumbens (NAcc) [50,51]. ...
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Happiness is a feeling, an immediate experience, not a cognitive construct. It is based on activity in the brain’s neurobiological reward and motivation systems, which have been retained in evolution. https://encyclopedia.pub/entry/24683 (accessed on 30 June 2022)
... Dopamine receptors are involved in a variety of biological processes, which are primarily the CNS [37][38][39][40], including cognition, memory, learning, and motor control, as well as neuroendocrine signaling modulation [41], and are thus associated with a variety of psychiatric and neurological disorders. DRD4 is a target for the most common neuroleptic medications [42]. ...
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Objective: The aim of this present study is to find flavonoids that can be potential drug lead compounds targeting the human D(4) Dopamine receptor (DRD4). Thirty-nine flavonoids were collected from the literature survey, and 23 of them were predicted by SwissTargetPrediction to have bioactivity toward DRD4. Methods: ADME properties were evaluated, and molecular docking was executed. Among the flavonoids studied, Isovitexin, Glabridin, and Glabrone have shown better binding energy than the native ligand, Nemonapride. However, ADME analysis has demonstrated that Isovitexin has low GI absorption and is in the grey zone of the BOILED-egg. Glabridin is a BBB permeant but is a P-gp substrate. Glabrone has high GI absorption, and a P-gp non-substrate but not a BBB permeant. Results and Conclusion: The experimental investigations and clinical evaluations are recommended to examine the mechanisms of their actions and other pharmacological effects and to validate the results of this in silico study. The scaffolds of these compounds can also be optimized to improve the few lapses and have better attributes as CNS drug lead candidates.
... It provides inner guidelines, i.e., directions, and lets us humans plan or implement behaviors from which we hope to derive a desired (beneficial) outcome [2,5,6,8]. Therefore, the feeling of happiness-if based on an experience that has already been made before (i.e., memorized, conditioned, and also linked to it: a positive expectation for the future)-is an efficient way of integrating or automating experiences made earlier into behavioral or treatment concepts that can be quickly implemented and activated (i.e., short-cut) [8,11,12]. ...
... Happiness as a biological concept was passed on genetically and further developed in evolution [4,7,[13][14][15]. It has a biomolecular basis yet is used for autoregulation and survival (of the individual and of the species) [5,7,12,16,17]. Happiness can thus be measured (e.g., in the brain, blood; see below) and is associated with biophysiological changes in the body [7,[18][19][20][21][22][23][24]. At its core, happiness, as is the case with the entire body (the living organism), is dynamic by nature and is subject to cyclical or internal "maturation processes" (see below). ...
... Underlying the concepts of motivation are physiological mechanisms that occur in brain areas distinct from other sensory or cognitive areas [5,7,49]. An integral part of the central nervous system (CNS), approach motivation and reward systems are neurons that have their principal origin in the ventral tegmental area (VTA), located in the midbrain [5,12]. These neurons send projections, e.g., to the frontolimbic brain, mostly to the nucleus accumbens (NAcc) [50,51]. ...
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Background: Happiness is a feeling, an immediate experience, not a cognitive construct. It is based on activity in the brain's neurobiological reward and motivation systems, which have been retained in evolution. This conceptual review provides an overview of the basic neurobiological principles behind happiness phenomena and proposes a framework for further classification. Results: Three neurobiologically distinct types of happiness exist: (A) wanting, (B) avoiding, and (C) non-wanting. Behind these types lies a dynamic gradation, ranging from the more youthful anticipation, pleasure and ecstasy (A), to stress processing, escape and relief (B) as we find them accentuated in the middle-aged, to deep satisfaction, quiescence and inner joy (C), which is particularly attributed to older people. As a result, the development of happiness and satisfaction over the course of life typically takes the form of a U-curve. Discussion: The outlined triad and dynamic of happiness leads to the paradoxical finding that the elderly seem to be the happiest-a phenomenon that is termed "satisfaction paradox". This assumed change in happiness and contentment over the life span, which includes an increasing "emancipation" from the idea of good health as a mandatory prerequisite for happiness and contentment, can itself be changed-it is trainable. Conclusions: Programs for mindfulness, contemplation, or stress reduction, including positive psychology and mind-body/behavioral medicine training, seem to be capable of influencing the course happiness over time: Happiness can be shaped through practice.
... They could choose how they usually behave when confronted with stress from 11 different items. Some of those items represent "adaptive" mechanisms, like "working out", "spending time with family" or "communication with friends", since studies have shown a positive connection between such constructs and favorable psychological outcomes [40][41][42]. In addition, some others can be considered as "maladaptive" mechanisms, since they are connected to negative mental health outcomes in time ("eating food", "smoking", "drinking alcohol") [40][41][42]. ...
... Some of those items represent "adaptive" mechanisms, like "working out", "spending time with family" or "communication with friends", since studies have shown a positive connection between such constructs and favorable psychological outcomes [40][41][42]. In addition, some others can be considered as "maladaptive" mechanisms, since they are connected to negative mental health outcomes in time ("eating food", "smoking", "drinking alcohol") [40][41][42]. ...
... In order to assess the type of mechanisms by which FPs cope with daily stress, we offered them to choose from 11 different items, with the possible selection of multiple answers. Results have shown that the most commonly chosen mechanisms were working out (47%) and spending time with family (48%), which both can be considered as adaptive, positive coping mechanisms according to the available literature [40][41][42]66]. Moreover, these mechanisms were more represented in the group with a negative MHD history, and associated with lower burnout scores, which further emphasizes their commendatory, adaptive features. ...
Article
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Family physicians (FPs) are exposed to high amounts of stress, and could be susceptible to the development of mental health disorders (MHD), especially after the emergence of the COVID-19 pandemic. The aim of the current study was to assess MHD history, attitudes toward MHDs and stress‑coping strategies in FPs. An additional goal was to estimate their comprehensive well-being and investigate connections with resilience and a healthy lifestyle. A total of 483 FPs submitted their responses via online survey. MHD attitudes were assessed with the according questionnaires, while burnout levels, healthy lifestyle, resilience, job and life satisfaction were estimated with validated scales. Results have shown that 32.5% of FPs disclosed positive MHD history, while 68.7% used professional help. Resilience and healthy lifestyle levels were significantly higher in MHD negative FPs (p < 0.001), while burnout levels were lower (p < 0.001). Moreover, healthy lifestyle (β = 0.03, p < 0.001) was an independent correlate of resilience, while healthy lifestyle (β= −0.35, p < 0.001, and resilience (β= −1.82, p < 0.001) were of burnout levels. Finally, resilience (OR = 0.387, p < 0.001) and healthy lifestyle (OR = 0.970, p = 0.021) were shown as independent predictors of positive MHD history status. Strong promotion and education of FP population regarding resilience and healthy lifestyle should be utilized in practice in order to alleviate the possibility of mental health disturbances and the according consequences.
... However, the triggering of stress reactions does not presuppose the conscious perception of stressors and the possibility of coping with them. Complementing the theory of Folkman et al. (1986), it is also possible in exceptional cases to be (physiologically) stressed without perceiving it and/or without feeling incompetent Benson and Stefano, 2005;McEwen, 2007McEwen, , 2017Esch and Stefano, 2010;Werdecker and Esch, 2018). In this respect, it would also be possible to experience burnout without noticing that there is, e.g., a coping problem. ...
... Given extensive research in the field of stress and stress physiology, burnout and its underlying causes are numerous and complex (e.g., Esch, 2002Esch, , 2003Esch and Stefano, 2010;Esch, 2018, 2021). The symptoms can occur in the case of overload due to accumulation of demands, lack of job resources (Demerouti et al., 2001), as well as inappropriate and insufficient health resources and resistance factors (individual resilience and coherence factors) (Gillespie et al., 2007). ...
... Something that will still be there before and after oneself and that is beyond everyday experience, e.g., God or nature (Esch, 2011). The relationship between spirituality, faith, belief and burnout or stress was examined in several general population studies (Van Dierendonck et al., 2005;Esch, 2008aEsch, ,b, 2010Esch, , 2011Esch, , 2017Esch, , 2019Doolittle et al., 2013;Daniel, 2014;Ho et al., 2016;Yang et al., 2017;Watson et al., 2019). Initial evidence points to the direction that individuals who are more religious or spiritual than others tend to possess higher resilience levels and are therefore less likely to be affected by burnout (Carneiro et al., 2019). ...
Article
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Background: Burnout is a widespread, multifactorial, and mainly psychological phenomenon. The pathogenesis of burnout is commonly described within the bio-psycho-social model of health and disease. Recent literature suggests that the phenomenon of burnout may be broader so that the three dimensions might not reflect the multifaceted and complex nature of the syndrome. Consequently, this review aims to identify the diversity of factors related to burnout, to define overarching categories based on these, and to clarify whether the bio-psycho-social model adequately describes the pathogenesis of burnout—holistically and sufficiently. Method: Five online databases (PubMed, PubPsych, PsychARTICLES, Psychology and Behavioral Sciences Collection, and Google Scholar) were systematically searched using defined search terms to identify relevant studies. The publication date was set between January 1981 and November 2020. Based on the selected literature, we identified factors related to burnout. We aggregated these factors into a comprehensible list and assigned them to overarching categories. Then, we assigned the factors to the dimensions of an extended model of health and disease. Results: We identified a total of 40 burnout-related factors and 10 overarching categories. Our results show that in addition to biological, psychological, and socio-environmental factors, various factors that can be assigned to a spiritual and work cultural dimension also play an important role in the onset of burnout. Conclusion: An extended bio-psycho-socio-spirito-cultural model is necessary to describe the pathogenesis of burnout. Therefore, future studies should also focus on spiritual and work cultural factors when investigating burnout. Furthermore, these factors should not be neglected in future developments of diagnosis, treatment, and prevention options.
... Psychological research shows that chronic stress can result in disorders, such as depressive symptoms, anxiety, sleep, and cardiovascular disorders, neurological and immunological diseases, or burnout (Esch et al., 2002a,b,c;Hapke et al., 2013;Kivimäki et al., 2018;Koutsimani et al., 2019). Following the model of allostatic load/allostatic stress response (McEwen, 1998), which combines both biomedical models, i.e., auto regulatory reaction model of the organism and psychological theories (perception, processing, and coping with potentially stressful stimuli) (Esch, 2003;Esch and Stefano, 2010;Werdecker and Esch, 2018), current research focuses on the self-regulation aspect of the organism (maintaining stability through changes), i.e., allostasis. According to the theory of allostatic load, a permanent or long-lasting stimulation (chronic excitation) by a stressor without sufficient recovery phases can lead to an overstrain of the organism. ...
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Apart from biological, psychological, and social factors, recent studies indicate that spirituality and work culture also play an important role in the onset of burnout. Hence, the commonly applied bio-psycho-social model of health and disease might not be sufficient to comprehensively explain and describe burnout. This study empirically investigates the relationship between spirituality (operationalized by perceived meaningfulness of work) and work culture (operationalized by sense of homeliness of the working environment) with burnout risk and work engagement. For this purpose, an anonymous cross-sectional data collection with fully standardized questionnaires and selected socio-demographic and work-related items was conducted among working adults ( n = 439) from different industries via social media and local health service centers. For all scales and subscales, we found significant moderate to strong correlations. Furthermore, positive meaning within the perceived meaningfulness of work scale was the largest beta coefficient for burnout (β = −0.65) and work engagement (β = 0.62). Within sense of homeliness, the largest beta coefficient for burnout was needs fulfillment (β = −0.34) and work engagement emotional connection (β = 0.36). The strong associations suggest that the current health and disease model needs to be expanded to a bio-psycho-socio-spirito-cultural model to be able to sufficiently describe burnout. The perceived meaningfulness of work and a sense of homeliness should be adequately considered when examining the onset of burnout, describing burnout as a concept, and explaining work engagement.
... Building personal sustainability requires individuals to be aware of the stress, manage the stress, and also thrive from it [4,15]. This means that individuals will have to demonstrate consistent stress management behavior in various contexts. ...
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Research about stress management has traditionally focused on reducing possible stressors. However, more recent studies have highlighted the importance of renewal as an antidote to stress. The purpose of this paper is to provide a theoretical explanation of how renewal activities can invoke a psycho-physiological response that enhances personal sustainability. By drawing upon recent evidence from the fields of medicine, psychology, and management, we developed a conceptual understanding of how renewal activities are characterized by the movement of the individual from a negative to a positive psycho-physiological state. Such a transition happens over a tipping point, which people can enact in themselves and in others through emotional and social intelligence competencies. We illustrate this proposition with the specific case of ideal self-based coaching in the workplace that can enhance personal sustainability among both leaders and their team members.
... Music therapy is a complementary approach by using music to help someone with various health conditions that can affect their physiology, psychology, and emotion [8,9,15,16]. This therapy can manage stress problems of people of different ages with minimal side effects and a small amount of money. ...
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Stress is a physiological and psychological response to the perception of danger and threat. Stress can occur due to a physical injury, mechanical disturbance, chemical change, or emotional factor. Stress can occur at all ages, including children and adolescents. Various physical and psychological events can cause stress in children, for example suffering from an illness, injury/trauma, parental divorce, parental death, sexual abuse, natural disasters, war, etc. Various exposures to physical and psychological stress harmful to the body can cause it to carry out defense mechanisms against these threats, one of which is changes in the cortisol hormone. Cortisol hormone is used as a biochemical marker for acute and chronic stress. The increase in this hormone as an indicator of stress can be changed through psychosocial interventions, one of which is by the provision of music therapy. Music therapy can manage stress problems of people at various ages with minimal side effects and a small amount of money. It is also easy to apply and does not require any intellectual ability to interpret. There are no limitations for users to use music therapy.
... The former (e.g., cognitive behavioral therapy) primarily aims to resolve emerging issues related to living with the disease (Wenzel, 2017). On the other hand, emotion-focused interventions (e.g., stress management and relaxation techniques) try foremost to alleviate MS-related stress and facilitate emotional adjustment to the disease (Esch & Stefano, 2010). Although the problem-versus emotion-focused distinction is not always clear in the literature, there is now cogent proof indicating that multidisciplinary interventions are more likely to improve psychological adjustment to the disease, than less integrative interventions (Amatya, Khan, & Galea, 2019;Fiest et al., 2016;Kidd et al., 2017;Sánchez-Lastra, Martínez-Aldao, Molina, & Ayán, 2019;Simpson et al., 2019;van den Akker et al., 2016). ...
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Objective Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system affecting patients’ well-being and quality of life. Pythagorean Self-Awareness Intervention (PSAI) is a novel non-pharmaceutical intervention with significant benefits both in MS and other chronic diseases. In this study, the longstanding effectiveness of PSAI was investigated. Method This was a two-arm quasi-experimental pragmatic trial in relapsing–remitting MS patients (23 in the PSAI and 21 in the control group). PSAI patients received an 8-week training period and then they performed PSAI at home for another 16 weeks. Assessments took place at baseline, 8 weeks, and 24 weeks. These included cognition, fatigue, perceived stress, and hair cortisol. Results Significant group × time interactions favoring PSAI were found during the first 8-week period for information processing speed, fatigue, and perceived stress. However, only verbal memory was found to be significantly improved in the PSAI group during the 24-week follow-up period. There were no significant group × time differences with respect to hair cortisol. No side effects were noted and compliance was excellent. Conclusions PSAI was mostly effective during the first 8-week training period. Its benefits worn out during the non-training period, albeit we observed a delayed significant improvement of verbal memory. Our findings will help to further refine the technique, either by extending the training period and/or by including booster sessions, throughout the PSAI treatment. This study provided Class III evidence for PSAI.