Abnormal stress reactions as a general risk factor of disease development, manifestation and progression

Voice disturbances under stress overload
Voice perturbations under the stress overload is considered a useful biomarker to identify individuals in suboptimal health conditions potentially vulnerable to related pathologies developed later on in life.

Lasting vasospastic reactions
Under stress conditions, lasting vasospasm is caused by  high blood plasma level of the vasoconstrictor endothelin-1 (ET-1) strongly associated with systemic ischemic-hypoxic effects. In turn, ET-1 axes regulate a myriad of processes involved in a modulation of physical and mental well-being, female and male health, senses, pain, stress reactions, drug sensitivity and healing processes, amongst others. Imbalanced ET-1 overproduction modulates individual outcomes in the development and progression of communicable infections such as COVID-19 and non-communicable disorders such as metabolic impairments with cascading complications, accelerated ageing and related pathologies, cardiovascular diseases, neurodegenerative pathologies, and aggressive malignancies.

Psycho‑immunologic axis
Imbalanced stress reactions in a long-term manner may cause mood disorders such as depression strongly associated with compromised functionality and auto-regulation of the immune system. Chronic activation of the hypothalamic–pituitary–adrenal (HPA) axis in the stress response overload evidently impairs the immune response leading to the development and progression of related diseases such as cardiovascular and cerebrovascular pathologic conditions, metabolic and autoimmune disorders, cancers, amongst others.

Sleep deprivation
Caused by abnormal stress reactions, sleep shortage and  disturbances are per evidence risk factors and facilitators of a broad spectrum of disorders, including mood disorders, stroke, chronic inflammation, immune defence insufficiency and cancers. The reciprocal interrelationship between the abnormal stress, sleep quality and individual outcomes became evident under extreme circumstances such as the COVID-19 pandemic.

Mitochondrial dysfunction
Stress overload is a well-acknowledged risk factor of mitochondrial injury. In turn, mitochondriopathies play a key role in the aetiopathology of multifactorial diseases exhibiting a “vicious circle” characteristic for multi-organ damage and failure in the long run.

Systemic inflammation
Under imbalanced stress conditions, there are evident cumulative systemic effects leading to chronic inflammation including but not restricted to the lasting vasospastic reactions with systemic ischemic-hypoxic effects and involvement of ET-1 and neuro-immune axes, mitochondrial impairments and increased infection susceptibility with poor outcomes such as caused by the cytokine storm reported for
COVID-19-infected individuals. Chronic systemic inflammation is a key risk factor in several non-communicable diseases such as cancers .

Impaired healing
Delayed and impaired healing is a multifactorial condition frequently associated with both abnormal body weight and stress overload. In turn, impaired healing is indicative and predictive for a development and progression of many related pathologies such as an aggressive metastatic disease, which is considered a “non-healing wound”.