• MARIAM AHMED School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, United Kingdom
  • HANA MORRISSEY School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, United Kingdom
  • PATRICK ANTHONY BALL School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, United Kingdom



Neuroplasticity, Heart Failure, Depression, Anxiety, Primary Care


This review aims to understand the co-existence of mental ill-health and heart failure and if this comorbidity affects patient self-care motivation and overall health outcomes. Databases searched were; PubMed®, Google® scholar and Science Direct® for studies related to heart failure, heart failure and mental health, depression and anxiety. Eleven articles were identified and reviewed. There were two studies disagreed with the theory that the mental ill-health and heart failure has disease modification and worsen patient health outcomes, three studies concluded that only anxiety has effect, five studies concluded that both anxiety and depression have effect, six studies concluded that depression only has effect but all eleven stated that more research is required. Recent theories on depression and cardiovascular disease comorbidity and the effect mental ill-health have on medication adherence in heart failure patients was discussed. People with long-term physical illnesses may suffer further complications to their health if they develop mental illness; increasing the cost of their care by an average of 45%, however, in the majority of these cases, the mental issues neither diagnosed nor treated. This review explored the link between cardiovascular disease (CVD) and mental ill health; and how comorbidity of the two conditions affects patients’ adherence to therapy behaviour. It was concluded that while the link between mental ill health and heart failure (HF) is recognized, studies that may be used as a basis of evidence to confirm this link are scarce.


Download data is not yet available.


1. Cook C, Cole G, Asaria P, Jabbour R, Francis D. The annual global economic burden of heart failure. Int J Cardiol 2013;171:368-76.
2. National Institute for Health and Care Excellence (NICE). Chronic heart failure in adults: diagnosis and management. NG106. London: NICE; 2018. Available from: https:// [Last accessed on 27 Apr 2019].
3. Aston Medication Adherence Study (AMAS); 2013. Available from: [Last accessed on 27 Apr 2019]
4. Tan L, Williams G, Tan K, Cohen Solal A. So many definitions of heart failure: are they all universally valid? A critical appraisal. Expert Rev Cardiovasc Ther 2010;8:217-28.
5. Mayet J, Hughes A. Cardiac and vascular pathophysiology in hypertension. Heart 2003;89:1104-9.
6. Merrill A. Mechanisms of salt and water retention in heart failure. AJM 1949;6:357-67.
7. Watson R, Gibbs C, Lip G. Clinical features and complications. Br Med J 2000;320:236–9.
8. Tamargo J, Lopez Sendon J. Novel therapeutic targets for the treatment of heart failure. Nat Rev Drug Discovery 2011;10:536–55.
9. Morton G, Masters J, Cowburn P. Multidisciplinary team approach to heart failure management. Heart 2018;104:1376-82.
10. Khan S, Khan R. Chronic stress leads to anxiety and depression. Ann Psychiatry Ment Health 2017;5:1091.
11. The International Society for Affective Disorders (ISAD). Available from: [Last accessed on 27 Apr 2019]
12. Frank E, Prien F, Jarrett B, Keller B, Kupfer J, Lavori W, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiat 1991;48:851-5.
13. Ferguson J. Depression: diagnosis and management for the primary care physician. Prim Care Companion J Clin Psychiatry 2000;2:173-8.
14. Tolentino J, Schmidt S. DSM-5 criteria and depression severity: implications for clinical practice. Front Psychiatry 2018;9:450.
15. Stahl M. Regulation of neurotransmitter receptors by desipramine and other antidepressant drugs: the neurotransmitter receptor hypothesis of antidepressant action. J Clin Psychiatry 1984;45:37–45.
16. Liu W, Ge T, Leng Y, Pan Z, Fan J, Yang W, et al. The role of neural plasticity in depression: from the hippocampus to prefrontal cortex. Available from: 2017/6871089. [Last accessed on 27 Apr 2019].
17. Cramer C, Sur M, Dobkin H, O’Brien C, Sanger D, Trojanowski Q, et al. Harnessing neuroplasticity for clinical applications. Brain 2011;134:1591–609.
18. Serafini G. Neuroplasticity and major depression, the role of modern antidepressant drugs. World J Psychiatry 2012;22:49-57.
19. Bailey H, Kandel R. Structural changes accompanying memory storage. Annu Rev Physiol 1993;55:397-426.
20. Pearson Fuhrhop K, Kleim J, Cramer S. Brain plasticity and genetic factors. Top Stroke Rehabil 2009;16:282-99.
21. Chen H, Lombes M, Menuet D. Glucocorticoid receptor represses brain-derived neurotrophic factor expression in neuron-like cells. Mol Brain 2017;10. Doi:10.1186/s13041-017-0295-x.
22. Phillips C. Brain-derived neurotrophic factor, depression, and physical activity: making the neuroplastic connection. Neural Plast 2017.
23. Levine S, Dreyfus F, Black B, Plummer R. Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors. Proc Natl Acad Sci USA 1995;92:8074-7.
24. Vedder C, Savage M. BDNF regains function in hippocampal long-term potentiation deficits caused by diencephalic damage. Learning Memory 2017;24:81-5.
25. Sartorius N, Ustün B, Lecrubier Y, Wittchen U. Depression comorbid with anxiety: results from the WHO study on psychological disorders in primary health care. Br J Psychiatry 1996;30:38-43.
26. Bubier J, Drabick D. Co-occurring anxiety and disruptive behavior disorders: the roles of anxious symptoms, reactive aggression, and shared risk processes. Clin Psychol Rev 2009;29:658-69.
27. Engel G. The clinical application of the biopsychosocial model. Am J Psychiatry 1980;137:535–44.
28. Davis M. The role of the amygdala in fear and anxiety. Annu Rev Neurosci 1992;15:353-75.
29. Janak P, Tye K. From circuits to behavior in the amygdala. Nature 2015;517:284-92.
30. Bucher D, Marder E. Snapshot: neuromodulation. Cell 2013;155:482–2.
31. Craske M. Anxiety. Lancet 2016;388:3048-59.
32. DSM-V. American psychiatric association. Diagnostic and Statistical Manual of Mental Disorders (5th edition.). Washington, DC; 2016.
33. Taylor C. Panic disorder. Br Med J 2006;332:951-5.
34. Ohlin B, Nilsson P, Nilsson L, Berglund G. Chronic psychosocial stress predicts long-term cardiovascular morbidity and mortality in middle-aged men. Eur Heart J 2004;10:867-73.
35. Jiang W, Kuchibhatla M, Cuffe M, Christopher E, Alexander J, Clary G, et al. Prognostic value of anxiety and depression in patients with chronic heart failure. Circulation 2004;110:3452-6.
36. Rutledge T, Reis V, Link S. Depression in heart failure: a meta-analytic review of prevalence, intervention effects and associations with clinical outcomes. J Am Coll Cardiol 2006; 48:1527–37.
37. Lett H, Blumethal J, Babyak M, Sherwood A, Strauman T, Robins C, et al. Depression as a risk factor for coronary artery disease: evidence, mechanisms, and treatment. Psychosomatic Med 2004;66:305-15.
38. Hu K, Gaudron P, Bahner U, Palkovits M, Ertl G. Changes of atrial natriuretic peptide in brain areas of rats with chronic myocardial infarction. Am J Physiol 1996;270:312–6.
39. Mbakwem A, Aina F, Amadi C. Expert opinion-depression in patients with heart failure: is enough being done? Card Fail Rev 2016;2:110-2.
40. Herrmann Lingen C, Binder L, Klinge M, Sander J, Schenker W, Beyermann B, et al. High plasma levels of N-terminal pro-atrial natriuretic peptide associated with low anxiety in severe heart failure. Psychosomatic Medicine 2003;65:517–22.
41. Weber M, Hamm C. Role of B-type natriuretic peptide (BNP) and NT-pro BNP in clinical routine. Heart 2006;92:843-9.
42. Carney R, Freedland K, Veith R. Depression, the autonomic nervous system, and coronary heart disease. Psychosomatic Med 2005;67:29-33.
43. Parissis J, Fountoulaki K, Paraskedvaidis I, Kremastinos D. Depression in chronic heart failure: novel pathophysiological mechanisms and therapeutic approaches. Expert Opin Investig Drugs 2005;14:567–77.
44. Musselman L, Tomer A, Manatunga K, Knight T, Porter R, Kasey S, et al. Exaggerated platelet activity in major depression. Am J Psychiatry 1996;153:1313–7.
45. Berthold Losleben M, Himmerich H. The TNF-? system: functional aspects in depression, narcolepsy and psychopharmacology. Curr Neuropharmacol 2008;6:193-202.
46. Orus J, Roig E, Perez Villa F, Pare C, Azqueta M, Filella X, et al. Prognostic value of serum cytokines in patients with congestive heart failure. J Heart Lung Transplant 2000;19:419–25.
47. Varghese F, Brown E. The hypothalamic-pituitary-adrenal axis in major depressive disorder: a brief primer for primary care physicians. Prim Care Companion J Clin Psychiatry 2001;3:151–5.
48. Smith S, Vale. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci 2006;8:383–95.
49. Golden S, Wand G, Malhotra S, Kamel I, Horton K. Reliability of hypothalamic–pituitary–adrenal axis assessment methods for use in population-based studies. Eur J Epidemiol 2011;26:511-25.
50. Holsboer F, Barden N. Antidepressants and hypothalamic-pituitary-adrenocortical regulation. Endocr Rev 1996;17:187–205.
51. Shen Q, Lal R, Luellen B, Earnheart J, A Bernhard, Andrews A, et al. GABAA receptor deficits cause HPA axis hyperactivity and antidepressant drug sensitivity reminiscent of melancholic forms of depression. Biol Psychiatry 2011;68:512-20.
52. Sale M, Ridding M, Nordstrom M. Cortisol inhibits neuroplasticity induction in human motor cortex. J Neuroimmune Pharmacol 2008;28:8285-93.
53. Gradin V, Pomi A. The role of hippocampal atrophy in depression: a neurocomputational approach. J Biol Phys 2008;34:107-20.
54. Jeanneteau F, Chao M. Are BDNF and glucocorticoid activities calibrated? Neuroscience 2013;239:173-95.
55. Pizzi C, Manzoli L, Mancini S, Bedetti G, Fontana F, Costa G. Autonomic nervous system, inflammation and preclinical carotid atherosclerosis in depressed subjects with coronary risk factors. Atherosclerosis 2010;212:292-8.
56. Zheng Z, Wu J, Wang R, Zeng Y. Diabetes mellitus may induce cardiovascular disease by decreasing neuroplasticity. Funct Neurol 2014;29:7-13.
57. Zheng Z, Zeng Y, Wu J. Increased neuroplasticity may protect against cardiovascular disease. Int J Neurosci 2013;123:599-608.
58. Almas A, Forsell Y, Iqbal R, Janszky I, Moller J. Severity of depression, anxious distress and the risk of cardiovascular disease in a swedish population-based cohort. PLoS One 2015. Doi:10.1371/journal.pone.0140742.



How to Cite

AHMED, M., H. MORRISSEY, and P. A. BALL. “MENTAL ILL-HEALTH AND HEART FAILURE COMORBIDITY”. International Journal of Current Pharmaceutical Research, vol. 11, no. 4, July 2019, pp. 11-17, doi:10.22159/ijcpr.2019v11i4.34931.



Review Article(s)

Most read articles by the same author(s)

1 2 > >>