Page 81 - JCBP-2-2

Journal of Clinical and
Basic Psychosomatics Stress versus placebo effects

The discourse on mind-body interaction is inherently the oxidative deamination of amines, such as the
entwined with the concept of stress. The term “stress,” neurotransmitters dopamine and serotonin. In contrast,
being common in clinical scenarios, usually refers to 5-HTT is an integral membrane protein that can terminate
personal experiences encompassing perception, appraisal, the action of serotonin by transporting serotonin from
and response to external or internal noxious stimuli. synaptic spaces into presynaptic neurons. Moreover,
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The interplay between external noxious stimuli and the hormone signaling pathways also contain common
an individual’s psychosomatic state can influence the molecules, such as glucocorticoids and nuclear receptor
perception and appraisal of stress and subsequently induce subfamily 3 group c member 1 (NR3C1). Glucocorticoids
4,9
varying responses. Some instances result in eustress and are steroid hormones that regulate immune reactions,
lead to positive achievements and outcomes. However, and their secretion by the adrenal cortex is controlled by
stress would more often manifest as negative stress, thereby adrenocorticotropic hormone. NR3C1 is a glucocorticoid
resulting in low plasticity and persistent homeostatic receptor and acts as a transcription factor that binds to
dysregulation. In the study, the psychosomatic state glucocorticoid response elements within the promoter
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denotes the amalgamation of biological, psychological, regions of glucocorticoid-responsive genes to activate
and social factors that encompass the responses from their transcription. Findings from brain imaging research
physiological and emotional aspects, cognitive appraisal, indicated that both periaqueductal gray (PAG) and
and the influences of the social and environmental milieu, prefrontal cortex (PFC) are related to stress and placebo
suggesting that stress responses may integrate biological, effects. 9,11,12 PAG may play a role in integrating a multitude of
social, and psychological components, usually resulting in sensory signals and serve as a control center for behavioral
the non-specific response of the body to any demand. 4 modulation. Conversely, PFC is implicated in working
Interestingly, the placebo effects are also dependent memory as well as in self-regulatory and goal-directed
on the interactions of social, psychological, and biological behaviors. Given the extensive research conducted on
factors. Besides an individual’s genetic predispositions, stress responses and placebo effects, the exact mechanism
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the personality traits, beliefs, expectations, and prior of the biological factors involved in both stress and placebo
experiences of the individual also influence both stress effects is expected to be elucidated sooner than later.
and placebo responses. 3,5,6 The term “placebo” refers to The present study proposed that stress and placebo
a matter without a pharmacologically active effect that responses may represent two sides of the same coin when
is believed to possess therapeutic benefits. The placebo for external stimuli. When an external matter is perceived
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effects observed after placebo treatments are the body’s as beneficial, it can trigger placebo effects; conversely,
responses to the improvement of physical or psychological when perceived as harmful, it may elicit stress responses.
symptoms induced by the action of a placebo. Placebo Moreover, adopting the dialectical perspective from
effects typically have three characteristics: (i) Instigating traditional Chinese medicine, a substance possesses the
autonomic alterations and improving certain symptoms but potential to facilitate therapy but also can induce non-
not impacting underlying pathophysiological processes; therapeutic, even harmful effects, the effects of which
(ii) varying in different contextual factors, whereby the depend on the individual’s body constitution or physique.
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placebo effect may markedly differ among diverse subjects In other words, stress and placebo responses, triggered by
or even within the same subject undergoing different suffers external factors, may represent two imbalanced states in
or undergoing the same treatment methodology at different the mind-body interaction.
time slots; and (iii) yielding adverse consequences, i.e., the Furthermore, contemporary methodologies and
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“nocebo effect,” which arises from negative psychosocial concepts employed in the study of stress responses are
factors. In some disorders, a placebo may induce changes extensive and can be extrapolated to investigate placebo
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in the immune system and trigger physiological responses effects. A recently proposed framework for delineating
but not affect the underlying pathophysiological processes stress responses involves a four-phase cycle: (i) The resting
of the particular disorder. 10 ground phase, (ii) the tension phase, (iii) the response

There are several common biological factors phase, and (iv) the relief phase. A comparable four-phase
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between stress and placebo effects despite the limited cycle may exist for placebo effects, namely, (i) the receiving
research on placebos. Association studies, based on the external matter phase, (ii) the accepting internalization
genome or proteome, proposed that some molecules in phase, (iii) the response phase, and (iv) the relief phase.
neurotransmitter signaling pathways are shared between Parameters of each phase, such as frequency, duration, and
stress and placebo effects, such as monoamine oxidase A intensity, can serve as valuable tools for understanding both
(MAOA) and 5-hydroxytryptamine transporter (5-HTT). stress and placebo effects. Through a further investigation
MAOA is a mitochondrial enzyme that catalyzes of the comprehensive molecular biological components

Volume 2 Issue 2 (2024) 2 https://doi.org/10.36922/jcbp.1860