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Journal of Clinical and
Basic Psychosomatics Somatic symptom disorder etiology

maintenance of SSD. For example, in studies of patients made in the adrenal glands. PAMP downregulates
with FSDs, some initially develop pain from increased SNS further catecholamine release, likely as part of the HPA
activity caused by hypercortisolism, yet almost all FSD axis feedback loop, eventually returning the system to
patients present with a dysfunctional PNS, which disrupts normal response. 84-87 MR-PAM has recently been shown
allostasis and sustains pain. 71 to significantly reduce cortisol synthesis and secretion
in both human infants and mice. CRH then excites
87
Methodology discrepancies explain the few examples
that counter the hypercortisolism connection in pain adrenocorticotropin hormone (ACTH) production in
the pituitary gland. ACTH triggers the adrenal glands
patients. For example, women in Heim et al.’s study 79 80,88,89
revealed hypocortisol and PTSD symptomology (an to produce cortisol. Cortisol travels to numerous
parts of the body. In the brain, it steroidally depotentiates
expected correlation), but they also suffered with chronic ACh that has already bound with its receptors in the
pelvic pain. However, finding hypocortisolism in some hippocampus, blocks further ACh from binding with ACh
of patients with pain should be cautiously evaluated receptors and binds with glucocorticoid receptors. 59,89 The
because cortisol measurements were collected in vastly hippocampus contains more glucocorticoid binding sites
different ways, at different times of day, and calculated than anywhere else in the brain, though the amygdala
differently, so making conclusions regarding a trend also contains many glucocorticoid receptors. Roozendaal
toward hypocortisolism, hypercortisolism, or no effect, et al. discovered that high levels of cortisol binding with
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in maintenance of SSD is premature. 71,79 A hypercortisol its receptors in the basolateral amygdala led to stronger
condition is linked both to traumatic amnesia and emotional and kinesthetic memories of trauma, providing
initiation of SSD, through disruption of the PNS. During further evidence that while the hippocampus is the
maintenance of the disorders, cortisol levels sometimes seat of declarative memory, the amygdala is the seat of
vary. The next section illustrates the chain of neurological emotional memory. It is very important to note that each
events that connects amnesia and pain through the action is differentially affected by cortisol; the hippocampus has
of the HPA axis and provides a new formulation of the a curvilinear relationship with cortisol – failing to encode
etiology of SSD. The model also indicates how procedural memory when cortisol levels are very low and very high,
memories of trauma are cemented at the same time that but indelibly or normally recording memory when levels
declarative memories are prevented. are low to moderate. The amygdala has a linear relationship

6.4. Cortisol and the HPA axis with cortisol – low levels lead to less emotional memory
and high levels lead to more emotional memory. 10,52,81
Cortisol’s role in the HPA axis as it responds to stress is
mapped in Figure 1. Trauma and stress are first perceived A complex algorithm dictates the normal storage of
by the sensory thalamus, which quickly sends input to the long-term declarative memories. Electrical theta and
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amygdala, or possibly simultaneously to the amygdala gamma oscillations that are potentiated by ACh as it binds
and locus coeruleus, depending on the emotional content with mAChRs and nAChRs are depotentiated by GABA and
and level of arousal of the stressor. 5,67,80-83 The amygdala has allow for continuous feedforward and feedback mechanisms
been observed to release corticotropin-releasing hormone between the hippocampus and other brain areas which
(CRH)/factor directly to the pituitary, but in most HPA store long-term memories, based on the strength and
55
82,88,90
axis models, CRH release occurs after the amygdala prior use of pathways. The same neurotransmitters
and receptors identified as affected during the HPA axis
is stimulated by the locus coeruleus. The action of
catecholamines released directly from the locus coeruleus response to trauma – ACh and GABA, nAChRs, and
to the hypothalamus triggers CRH production. 67,82,83 Some muscarinic AChRs, respectively – influence how or whether
91,92
hypothesize that fear-related stress would tend to trigger any new memory is encoded. If the delicate rhythm is
interrupted, as in the case of hypercortisol, then memory
amygdala-mediated CRH release (and the less perceived is disrupted. Among nAChR inhibitors, cortisol shows
control, the more fear, therefore the more CRH release), moderate strength. Furthermore, cortisol’s blocking of
59
whereas physiological stress/trauma would tend to elicit nAChRs triggers GABAergic overstimulation, 72,88,93 as does
hypothalamus-mediated CRH release. 55,81,83
cortisol’s ability to bind with glutamate receptors, leaving
Once the catecholamines (epinephrine, norepinephrine, more glutamate circulating. Excessive glutamate also
and dopamine) are triggered in the locus coeruleus, overstimulates GABA’s inhibitory role. The hippocampus
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two relevant analog peptides in the traumatic-amnesia- provides a feedback system for the HPA axis through
pain equation are co-secreted: proadrenomedullin N the inhibition of further CRH production by both
terminal-20 peptide (PAMP) and mid-regional pro- cortisol interference with hippocampus excitation, and
adrenomedullin (MR-PAM), two of the four peptides overproduction of GABA. GABA has a calming effect on
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Volume 3 Issue 1 (2025) 9 doi: 10.36922/jcbp.4254