Page 29 - JCBP-2-1

Journal of Clinical and
Basic Psychosomatics The endocannabinoid system

Individual differences and genetic factors further add realm of PSD, intensifying sensations of pain, fatigue, and
complexity to this relationship, influencing the variability other somatic manifestations [47-50] .
in stress responses among individuals. In essence, The persistent activation of the HPA axis, a hallmark
serotonin’s involvement in the HPA axis underscores its feature of PSD, carries profound repercussions for immune
broader significance in maintaining both emotional well- dynamics, resulting in a state of immunosuppression.
being and the physiological response to stress. Negative This prolonged activity disrupts immune cell function,
emotional states and stress are implicated in the disruption rendering them less effective while concurrently elevating
of serotonergic function [42,43] . susceptibility to inflammatory events. This immune
2.2. Immune dysregulation dysregulation is posited as a driving force behind the
emergence and aggravation of physical symptoms within
The immune system, tasked with safeguarding the the PSD spectrum [51,53] .
organism against pathogens and preserving tissue
homeostasis, undergoes profound modulation by the HPA During stress, the sympathetic nervous system
axis. The multifaceted role of cortisol in orchestrating the activates, releasing neurotransmitters and neuropeptides
stress response encompasses its potent anti-inflammatory that exert influence over blood flow, immune function, and
capacity, a mechanism designed to curb immune reactions, the integrity of the skin barrier. The ensuing neurogenic
and forestall excessive inflammation [44-46] . inflammation, an intricate interplay between the nervous
system and the skin, alters cutaneous physiology, giving
While adaptive in the short term, persistent activation rise to manifestations such as redness, itching, and the
of the HPA axis, a characteristic feature of individuals formation of rashes. Psychological stressors modulate this
grappling with PSD, yields deleterious consequences. interaction, disrupting the normal functioning of skin cells
Cortisol, a glucocorticoid steroid hormone, diffuses and immune responses. Therefore, leads to vulnerability to
through the cell membrane and binds to cytoplasmic skin rashes over individuals grappling with PSD [53-55] .
glucocorticoid receptors (GRs). On binding, these
receptors undergo conformational changes, allowing 2.3. Alterations of cardiovascular and
them to translocate into the cell nucleus, where they gastrointestinal systems
function as transcription factors. Within the nucleus, Elevated cortisol levels, stemming from HPA axis
activated GRs modulate gene expression by binding to dysregulation in individuals with PSD, have significant
glucocorticoid response elements (GREs) in the promoters implications for the cardiovascular system, dysregulating
of target genes. This transcriptional regulation influences blood pressure and heart rate, and contributing to
the synthesis of various anti-inflammatory proteins, such symptoms such as palpitations and chest pain [56-61] .
as lipocortin-1 and IκB, and inhibits the expression of
proinflammatory cytokines such as interleukin-1 alpha The activation of cortisol receptors, specifically
(IL-1α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), mineralocorticoid receptors (MRs) and GRs, plays
and tumor necrosis factor-alpha (TNF-α). In addition, a pivotal role in mediating the molecular responses
cortisol-activated GRs interfere with the activation of associated with elevated cortisol levels. These responses
transcription factors like nuclear factor-kappa B (NF-κB), result from HPA axis dysregulation in individuals with
crucial for the initiation of inflammatory responses. PSD, leading to cardiovascular manifestations. Cortisol’s
Consequently, cortisol exerts an immunosuppressive binding to MR predominantly influences vascular smooth
effect, dampening immune cell activation, and the release muscle cells, promoting sodium retention and potassium
of inflammatory mediators. While this anti-inflammatory excretion. This leads to vasoconstriction, contributing
action is essential for resolving acute inflammation and to increased systemic vascular resistance and elevated
maintaining immune homeostasis, chronic or excessive blood pressure, hallmark features in PSD. Simultaneously,
cortisol exposure may lead to immunosuppression, cortisol’s interaction with GR in cardiac muscle cells
contributing to increased susceptibility to infections, and enhances myocardial contractility, augmenting the force of
alterations in immune function observed in conditions cardiac contractions. This effect contributes to palpitations
associated with dysregulated cortisol levels, including and altered cardiac function observed in individuals with
[62-64]
stress-related disorders and psychosomatic manifestations. PSD .
This sustained activation induces immune dysregulation Moreover, GR activation modulates the autonomic
marked by compromised immune cell functionality and nervous system, impacting the balance between
heightened vulnerability to inflammatory processes. Such sympathetic and parasympathetic activity. Increased
immune dysregulation plays a pivotal role in both the sympathetic activity, a consequence of GR activation,
genesis and exacerbation of physical symptoms within the further intensifies the cardiovascular response, resulting

Volume 2 Issue 1 (2024) 5 https://doi.org/10.36922/jcbp.2288