ABSTRACT: Depressive disorder (DD) or major depressive disorder (MDD) is a mental illness characterized by a persistently low mood, reduced activity, and diminished interest in life. It can manifest through mild to severe behavioral, emotional, and physical symptoms. Due to its complex etiology, depression cannot be fully explained by a single mechanism. This is evidenced by the high comorbidity of depression with various chronic physical conditions, including hypertension, coronary artery disease and cerebrovascular disease. According to follow-up research findings, MDD increases the risk of cardiovascular morbidity and mortality by approximately 80% [1]. The impact of DD on cardiovascular disorders may be explained in two ways: through mediating mechanisms such as unhealthy lifestyle choices, and through adverse pathophysiological disturbances.
I. Overview of Depression and Cardiovascular Disease
Depression or depressive disorder is a mental illness characterized by a persistently low mood, reduced activity, and diminished interest in life. It can manifest through mild to severe behavioral, emotional, and physical symptoms. About 280 million people worldwide suffer from depression, accounting for approximately 5% of the global adult population [2]. As a result of extensive exploration into the clinical pathogenesis of depression, numerous hypotheses have been proposed. The most significant among them are changes in monoaminergic neurotransmission, an imbalance of excitatory and inhibitory signaling in the brain, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and abnormalities of normal neurogenesis.
Over the past few years an increasing amount of research has highlighted a link between inflammation and depression as a possible important element in pathophysiology of condition. Similarly, circulating pro-inflammatory signals including cytokines and circulating leukocytes are also more prevalent in MDD patients [3].
Heart failure, hypertension, peripheral artery disease, coronary artery disease, stroke, and other conditions affecting the heart and blood vessels are all included in the category of cardiovascular disease (CVD). It accounts for almost one-third of all deaths annually, making it the leading cause of death worldwide. Along with elements like inflammation, thrombosis, and arrhythmias, atherosclerosis is primarily responsible for the development of CVD. In addition to non-modifiable factors like age, sex, and genetic predisposition, risk factors also include modifiable ones like smoking, poor diet, physical inactivity, high blood pressure, diabetes, and high cholesterol. Although results have improved due to advancements in medical care and preventative measures, CVD is still a significant global health concern, especially in low- and middle-income nations. The need for integrated care approaches is further highlighted by growing research on the role of mental health, particularly depression, in raising the risk and degrading the prognosis of cardiovascular conditions.
II. Pathophysiological and Behavioral Mechanisms
HPA AXIS
Stress is known as a risk factor for CVD. Constant stress over-stimulates the HPA axis [4]. Studies show that in depression, the HPA axis is constantly in a hyperactive state, which leads to deterioration and homeostasis disorders. At the same time, it is reported that this axis has an equally significant impact on cardiovascular disease, which links these two conditions together. This is all a neuroendocrine center that coordinates physiological responses to external stimuli, with a crucial function in maintaining internal homeostasis. The activation of the HPA axis begins with the release of corticotropin-releasing hormone by the hypothalamus, which triggers the secretion of adrenocorticotropic hormone (ACTH). In response ACTH stimulates the synthesis and secretion of GH (cortisol in humans and corticosterone in rodents), mineralocorticoids (aldosterone) and adrenal androgens into the blood. Increased glucocorticoid levels are known to negatively impact blood pressure and cause hypertension. Prolonged impact of high cortisol levels may result in overeating and weight gain. It leads to abdominal obesity which is one of the main risk factors for CVD [5].
AUTONOMIC NERVOUS SYSTEM
The autonomic nervous system (ANS) also plays an important role in cardiovascular disorders [6]. It is composed of two systems: the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). The activation of the fight-or-flight response, which results in the production of catecholamines (noradrenaline and norepinephrine), is an example of how the SNS is the predominant mechanism in reaction to stressful events. An activation of ANS result in different physiological changes such as an increase in heart rate and blood pressure [7]. ANS dysfunction is marked by elevated circulating catecholamines (mainly norepinephrine), an increased resting heart rate, reduced heart rate variability (HRV), impaired baroreflex sensitivity [8], and greater QTc interval variability.
INFLAMMATION AND NEUROINFLAMMATION
The term "neuroinflammation" was originally used to describe the inflammatory responses of microglia in pathological situations, but it is now used to refer to all immunologic activity in the central nervous system in connection with both acute and chronic illnesses. In fact, an increased levels of pro-inflammantory cytokines are reported in patients with depression. Cytokines, such as IL-1 β, IL-6 and TNF- α, which are typical for neuroinflammation in depression case are also involved in the progression of chronic heart failure cause of the remodeling and increased fibrosis [9] and this changes can further lead to the vulnerability of ventricular tissue to arrhythmias.
BEHAVIORAL MECHANISM
Behavioral mechanisms for CVD include inactivity, obesity, poor diet, poor adherence to medication and smoking cessation. Carney et al. found that patients with depression and CVD are substantially less adherent to a daily routine of aspirin than patients with CVD but without depression. This observation is important is our case because non adherence to medications such as aspirin is associated with morbidity and mortality in patients with CVD [10].
Many studies noticed that for patients with depression is typical to be less active than without it. An inactivity is associated with a high risk of CVD mortality independently of age, sex and other factors. Moreover, a lack of physical activity leads to feelings of sadness, suppression, etc., which ultimately leads to the initiation of depressive disorders. At the same time, depression is typified by a constant feeling of sadness and lack of energy, motivation, etc., which leads to a decrease in physical activity. In addition, decreased levels of neurotransmitters such as dopamine, serotonin, and acetylcholine can also lead to a decrease in physical activity in patients. All of this highlights the correlation between depression and cardiovascular disease.
IV. Conclusion
Heart disease and depression are intimately associated. Depression is three times more common in people with CVD than in the general population, and the condition can generate depressed symptoms [11]. Hundreds of observations have been performed on depression as a risk factor for the initiation or progression of CVD. For now CVD are still the leading cause of death. Depression is linked to higher mortality and morbidity among patients with CVD. It is important to understand that both diseases require a multifaceted approach. A better comprehension of the individual mechanisms and the connection between the two conditions will improve treatment tactics and the prognosis of patients.
References
1. Penninx B. W. J. H. Depression and cardiovascular disease: Epidemiological evidence on their linking mechanisms. Neuroscience & Biobehavioral Reviews. 2017. Vol. 74. P. 277–286. URL: https://doi.org/10.1016/j.neubiorev.2016.07.003 (date of access: 19.04.2025).
2. GBD Results. Institute for Health Metrics and Evaluation. URL: https://vizhub.healthdata.org/gbd-results (date of access: 19.04.2025).
3. Neurobiology of resilience in depression: immune and vascular insights from human and animal studies / K. A. Dudek et al. European Journal of Neuroscience. 2019. URL: https://doi.org/10.1111/ejn.14547 (date of access: 19.04.2025).
4. Hassamal S. Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories. Frontiers in Psychiatry. 2023. Vol. 14. URL: https://doi.org/10.3389/fpsyt.2023.1130989 (date of access: 19.04.2025).
5. Iob E., Steptoe A. Cardiovascular Disease and Hair Cortisol: a Novel Biomarker of Chronic Stress. Current Cardiology Reports. 2019. Vol. 21, no. 10. URL: https://doi.org/10.1007/s11886-019-1208-7 (date of access: 19.04.2025).
6. Bernardi J., Aromolaran K. A., Aromolaran A. S. Neurological Disorders and Risk of Arrhythmia. International Journal of Molecular Sciences. 2020. Vol. 22, no. 1. P. 188. URL: https://doi.org/10.3390/ijms22010188 (date of access: 19.04.2025).
7. Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis / G. A. Alvares et al. Journal of Psychiatry & Neuroscience. 2016. Vol. 41, no. 2. P. 89–104. URL: https://doi.org/10.1503/jpn.140217 (date of access: 20.04.2025).
8. Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post-traumatic stress disorder / J. Park et al. The Journal of Physiology. 2017. Vol. 595, no. 14. P. 4893–4908. URL: https://doi.org/10.1113/jp274269 (date of access: 20.04.2025).
9. Inflammatory Cytokines in Heart Failure: Mediators and Markers / L. Gullestad et al. Cardiology. 2012. Vol. 122, no. 1. P. 23–35. URL: https://doi.org/10.1159/000338166 (date of access: 20.04.2025).
10. Carney R. M., Freedland K. E. Depression and coronary heart disease. Nature Reviews Cardiology. 2016. Vol. 14, no. 3. P. 145–155. URL: https://doi.org/10.1038/nrcardio.2016.181 (date of access: 20.04.2025).
11. Bernardi J., Aromolaran K. A., Aromolaran A. S. Neurological Disorders and Risk of Arrhythmia. International Journal of Molecular Sciences. 2020. Vol. 22, no. 1. P. 188. URL: https://doi.org/10.3390/ijms22010188 (date of access: 20.04.2025).
|
Голосування 
Ця робота ліцензується відповідно до Creative Commons Attribution 4.0 International License
Знайшли помилку? Виділіть помилковий текст мишкою і натисніть Ctrl + Enter