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INNOSC Theranostics and
Pharmacological Sciences The Takotsubo syndrome: A gender disparity

which is linked to sympathetic dominance and causes the with the levels of stress experienced. Of note, increased NE
heart rate to rise and pressor responses to rise. Along with synthesis is believed to occur in chronic stress situations
1,2
its reciprocal connections to other brain regions such as the when there is a sustained increase in the excitability of
limbic system, the IC is also linked to autonomic, sensory, the adrenal-medullary axis and the HPA. The issue of
12
and motor functions. In a series of studies investigating the whether decreased GC self-regulation in the pituitary and
functional neuroanatomy of sustained fear, defined as a PVH is a major factor in poor stress management emerges.
situation of unpredictable threat over a period of time, the The disruption of negative GC feedback and the resulting
IC was co-activated together with the bed nucleus of the prolonged activation and maintenance of elevated systemic
stria terminalis, anterior and posterior cingulate cortex, GC levels account for the loss of GC self-regulation. The
and the periaqueductal gray in healthy controls as well increased availability of these hormones causes alterations
3
as anxiety disorder patients. According to our current in behavior and normal physiology, as well as enhanced
4,5
understanding about the cortical modulation network, activation of the HPA axis in brain structures such as the
sympathovagal balance is essential for homeostasis and LC and amygdala. 13-15 Prolonged elevation of systemic GC
involves major portions of the IC. An imbalance resulting levels can lead to immunosuppression, as well as facilitate
from a damaged IC affects the cardiovascular system, the onset of autoimmune diseases and mood disorders. 16
promoting the development of Takotsubo syndrome In consideration of the above, it is appropriate to
(TTS). A middle cerebral artery hemorrhage stroke, sexual discuss the condition of chronic unpredictable mild stress
hormones such as estrogen or emotional processing are (CUMS). This well-established model explains mood
some of the various factors that can cause an interruption disorders and stress-induced brain plasticity, which are
of the IC. psychological and physical stressors brought on by a brain’s
Different brain nuclei are known to be activated in inability to adapt to a variety of stressful stimuli that are
response to both physical and psychological stressors. comparable to stressors encountered in daily life. 17,18 In
Actually, the neuroendocrine and autonomic nervous this context, the connection between loss of HPA self-
systems (CAN) are primarily activated, which results regulation and NE release is discussed. Using blood
19
in alterations in behavior. Research utilizing brain samples from TTS patients, a recent study1 was able to
6
functional magnetic resonance imaging to track brain demonstrate that patients in various stages of the disease
functional connectivity during resting states revealed showed several validated biological and psychological
hypoconnectivity of limbic and central brain regions’ indicators of chronic stress, as defined by the trier social
parasympathetic and sympathetic associated subnetworks stress test. The authors consistently demonstrated the
20
in TTS patients when compared to group controls. 7 presence of elevated levels of interleukin 6, tumor necrosis
factor-α, nuclear factor “kappa-light-chain-enhancer” of
Stress becomes a deleterious factor, in the case of
compromised of self-regulation, subjecting the body more activated B-cells, blood cortisol, dehydroepiandrosterone,
susceptible to immune system disease, psychiatric disorder, aldosterone, adrenaline, NE, and dopamine. As a result,
8,9
and cardiovascular disease. The paraventricular nucleus chronic psychosocial stress as an underlying factor driving
21
of the hypothalamus (PVH), amygdala nuclei, septal- the development of TTS must be recognized.
hippocampal complex, parabrachial and raphe nuclei, 2. Pathophysiology involving physical and
prefrontal and cingulate cortexes, and locus coeruleus emotional triggers
(LC) all play significant roles in the stress response. The
hypothalamic-pituitary-adrenal (HPA) axis is stimulated TTS is believed to be primarily caused by physical and
by the signals that follow. The anterior pituitary gland emotional triggers, but psychological and psychosocial
releases adrenocorticotropin hormone (ACTH) in response stress factors may have a greater influence than previously
to the release of the corticotropin-releasing factor (CRF), thought. TTS is associated with several major risk factors.
which is triggered by the PVH in the signaling chain. The
adrenal glands then begin secreting glucocorticoid (GC) 2.1. TTS triggers
as a result of ACTH. 10,11 For the coordination of certain Almost universally, TTS is associated with stress as a major
physiological systems, CRF is essential because it can be feature of its development. In most cases, an emotional
produced both in the peripheral and central nervous or physical trigger precedes such an event. There is some
systems (CNS). In fact, during stressful situations, CRF evidence to suggest that emotional triggers are more
plays a crucial role in regulating the sympathetic response prevalent than physical stressors, with the prevalence
brought on by stress and in the peripheral and central distribution of these triggers showing gender-specific
release of norepinephrine (NE). It is crucial to note the characteristics. In general, men seem to be more likely to
connection of the alterations in behavior and physiology respond to physical events, whereas women are more likely

Volume 7 Issue 4 (2024) 2 doi: 10.36922/itps.3142