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 Table of Contents  
REVIEW ARTICLE
Year : 2017  |  Volume : 1  |  Issue : 2  |  Page : 59-64

Neuropsychocardiology – Evolution and advancement of the heart-mind field


Neuropsychocardiology Laboratory; Duke Heart Mind Center; Duke University Medical Center, Durham, NC 27710, USA

Date of Web Publication16-Nov-2017

Correspondence Address:
Wei Jiang
Professor of Psychiatry and Behavioral Sciences, Professor of Medicine, Director, Neuropsychocardiology Laboratory Medical Director, Duke Heart Mind Center, Duke University Medical center, Durham, NC 27710
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/hm.hm_13_17

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  Abstract 


While humans have known that the health of their heart is linked to the health of their mind since ancient times, scientifically evaluating the relationship of the heart and mind has only emerged within the last century. A relevantly new field has developed over the past several decades with names such as “Psychocardiology,”[1] “Behavioral Cardiology,”[2] and/or “Neuropsychocardiology”[3] that designate effort to systematically investigating the interactions of the heart and mind to identify clinical impacts, the underlying mechanisms, and interventions alleviating the adverse interaction of heart and mind. Over a relatively very short period, these investigations have contributed positively to the medical literature elucidating the significant role of mind in cardiovascular health overall, and specifically in several particular clinical entities. The author of this article aims at briefly summarize what has been achieved and shares opinions regarding future directions in this field.

Keywords: Behavioral cardiology, neuropsychocardiology, psychocardiology


How to cite this article:
Jiang W. Neuropsychocardiology – Evolution and advancement of the heart-mind field. Heart Mind 2017;1:59-64

How to cite this URL:
Jiang W. Neuropsychocardiology – Evolution and advancement of the heart-mind field. Heart Mind [serial online] 2017 [cited 2019 Jul 16];1:59-64. Available from: http://www.heartmindjournal.org/text.asp?2017/1/2/59/218516




  Introduction Top


The idea that patients with cardiovascular diseases (CVD) might have increased abnormal mental conditions appeared in the medical literature at the turn of 19–20th century. A cardiologist [4] and a psychiatrist [5] published their retrospectively observed findings in 1937 which indicated that patients with depression and other mental problems might have increased adverse CV consequences, including death. A large amount of more scientifically and systematically conducted investigations were published in the later decades of 20th century and studies examining psychosocial risk factors for coronary heart disease (CHD) have increased exponentially since the millennium. These investigations can be categorized as the following: (1) prospectively conducted longitudinal cohort studies examining the prevalence and prognostic impact of negative emotions in patients with CVD, (2) experimental and/or field studies searching for mechanistic signatures that may underpin the adverse interaction between and heart and mind, and (3) formal clinical trials identifying therapeutic agents that may alleviate the adverse interaction between heart and mind.

Findings of epidemiological studies suggest negative psychological conditions impact cardiovascular diseases adversely

Findings of meta-analyses of longitudinal cohort studies have consistently demonstrated that several negative psychological conditions are, not only highly prevalent in patients with CVD, but also these negative emotions are associated with an increased risk of adverse prognosis. These negative psychological conditions or emotions are depression,[6],[7],[8] anxiety, hostility, pessimism, and feeling of chronically over stressed.[9]

Depression has been the longest and most commonly studied of these psychological attributes. In one meta-analysis of cohort studies consisting of 146,538 CHD patients with 6362 significant adverse events, the authors found the pooled relative risk of future CHD associated with depression was 1.81 (95% confidence interval (CI) 1.53–2.15) and the pooled relative risk of mortality associated with depression was 1.80 (1.50–2.15).[6] Another recent meta-analysis, limited to patients with myocardial infarction, reported unadjusted effects of 2.3 for all-cause mortality, 2.7 for cardiac mortality, and 1.6 for a composite outcome that included fatal and nonfatal events.[10] Furthermore, depression leads to the development of CHD [8] and aggravation of heart failure.[11] The estimated prevalence of depression in CHD and heart failure patients may range from 20% to above 40%, which is 2–3 times higher than the general population.[7],[12],[13],[14],[15] The variation in prevalence was related to size and particular populations studied and whether interview-based depression instruments or self-report questionnaires used.[8] The adverse associations of depression with CV prognosis were however generally stable over time, with only a small decline observed for the composite outcome. Being pessimistic, whether it is part of or independent of depression, has been found to increase the risk of CVD and all-cause mortality.[16],[17]

The etiological and prognostic links between anxiety disorders and CVD are only recently emerging, although anxiety has been concerned in hypertension, CHD, arrhythmia, and open heart surgery outcomes for greater than a century.[18],[19],[20] A recent meta-analysis comprised 1,565,699 patients from 37 publications with the follow-up ranged from 1 to 24 years. Anxiety was associated with a 52% increased incidence of CVD (hazard ratio = 1.52, 95% CI 1.36–1.71), and the risk seemed independent of traditional risk factors and depression.[21] The prognostic impact of anxiety disorders in patients with CVD may not be as straight forward as what has been seen with depression. Tully et al. conducted a meta-analysis of studies reporting the association of anxiety disorders according to structured interview with major adverse CV events (MACE) that are myocardial infarction, left ventricular failure, coronary revascularization procedure, and stroke in CHD patients. Of the five anxiety disorders, i.e., generalized anxiety, panic disorder, agoraphobia, social phobia, and obsessive-compulsive disorders, generalized anxiety disorder in outpatients was found to be significantly associated with almost two-fold increase of MACE (adjusted hazard ratio = 1.94, 95% CI 1.45–2.60). Jiang et al. have noted that anxiety and depression were highly correlated in heart failure patients. However, depression, but not anxiety, was associated with increased risk of heart failure mortality.[22] On the other hand, anxiety has been found to be greatly associated with various symptoms of CVD, such as arrhythmia [23],[24] chest pain/discomfort, and dizziness making the clinical management of those CVD conditions highly challenging among those patients with anxiety disorders or high levels of anxiety (Cohen 2015).

Anger or hostility,[25] pessimism,[26] and being chronically stressed, and/or having posttraumatic stress disorder, feeling socially lonely or not receiving enough support, and/or having high job demand with little latitude, have been shown to have adverse impact on development and/or prognosis of CVD.[9] These psychological conditions are also considered attitudes that are highly associated with depression and anxiety. However, the majority of the attitudes' studies did not provide results regarding whether their adverse impact on CVD was independently from depression and/or anxiety.

One clinical entity representative of the heart-mind adverse interaction that has been increasingly recognized over the past 2–3 decades is “Takotsubo” or “stress” cardiomyopathy.[27],[28] Stress is the main factor in Takotsubo cardiomyopathy, with more than 85% of cases set in motion by either a physically or emotionally stressful event that prefaces the start of symptoms.[29] Examples of emotional stressors include grief from the death of a loved one, fear of public speaking, arguing with a spouse, relationship disagreements, betrayal, and financial problems. Physical stressors included acute asthma, surgery, chemotherapy, and stroke.[29] Although it used to be thought a benign condition, a recent study using data collected from the International Takotsubo Registry (www. takotsubo-registry.com) demonstrates that, during long-term follow-up, the rate of MACE was 9.9%/patient-year, and the rate of death was 5.6%/patient-year. Women, particularly postmenopause, are highly susceptible. Of the 1750 patients collected from the registry, 89.8% were women with a mean age of 66.8 years.[30]

Mechanistic investigations uncover biomarkers underpinning the adverse interaction between heart and mind

The mechanisms underpinning the adverse interaction of heart and mind are bio-psycho-socially intertwined and appealing. Numerous investigations focusing on the biological mechanisms have uncovered that CVD and the negative emotions share multiple systems and/or pathways that have been perturbed [Figure 1]. For instance, sympathetic hyperactivity has been implicated in increased CV morbidity and mortality in people suffering major depression.[31],[32] The cardiac sympathetic activity in patients with major depressive disorder follows a bimodal distribution, with values being very high in some patients and very low in others. Those with panic disorder have shown to have higher mean noradrenaline spillover compared to those without panic disorder. It has also been shown that sympathetic nervous activity is regionalized in depressed patients in that cardiac and total sympathetic activity is raised while muscle sympathetic activity is not. It is suggested that reduced removal of noradrenaline from the sympathetic synapse after its release in the heart, subsequently augmenting the sympathetic neural signal, could be an important causal factor in generating cardiac risk.[33] Elevated platelet reactivity that can cause increased thrombosis, arterial occlusion, and vasoconstriction has been proposed as a mechanism underlying the association between major depression and increased risk of ischemic heart disease.[34] Inflammatory processes have been posited as another common causal pathway responsible in part for both the development of depressive symptoms and for adverse cardiac outcomes.[35] Patients with major depression have been shown to have elevated levels of inflammatory cytokines and C-reactive protein (CRP). Elevated levels of pro-inflammatory markers have been reported in depression, CHD, and heart failure, specifically pro-inflammatory cytokines such as tissue necrosis factor, interleukin-1, interleukin-2, and interleukin-6.[36],[37] Studies in depressed patients with CHD and heart failure suggest that elevated markers of inflammation predict poor response to treatment. Inflammation is speculated as a cause of atherosclerosis as well.[38]
Figure 1: Underlying pathomechanisms shared by depression and cardiovascular diseases

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Investigations using mental stress tasks in provoking mental stress-induced myocardial ischemia or left ventricular dysfunction (MSILVD) in the laboratory have considerably enhanced the heart-mind research by increasing our understanding of the underlying mechanisms of heart-mind interaction and identifying individuals who have greater susceptibility to such adversity.[39],[40],[41] Mental stress tasks such as doing a serial subtraction of 7 mentally, tracing a star by looking at the mirror reflection, and/or giving a 3-minute speech talking about recent upsetting events in a laboratory setting trigger occurrence of MSILVD in approximately 50% of patients who have clinically stable CHD. MSILVD has been found consistently to be a significant and independent predictor for adverse CVD outcomes in clinical stable CHD patients.[3],[40],[41] Over a couple of decades, we have learned that mental stress-induced myocardial ischemia occurs more frequently than exercise stress-induced ischemia [39] in clinically stable CHD patients, and mental stress testing induces a greater reduction of left ventricular ejection fraction (LVEF) than exercise testing, which on average, increases LVEF.[39] Such a mental stress-induced, LVEF reduction is a paradox of fight or flight responses of CV system. Mental stress has been found to cause coronary vasculature constriction in the context of having injured endothelium in contrast to healthy individuals who show a dilation of coronary vasculature in response to stress.[42],[43],[44] Being a female, living alone as a man, being depressed, and/or having resting diastolic dysfunction, increases the risk of having MSILVD. More intriguingly, investigations identifying circulating biomarkers that predict or are associated with MSILVD have yielded little evidence for measures obtained during resting phase. However, stress-induced alterations of several circulating biomarkers, such as platelet aggregation,[45] CRP and cortisol, and fuel energy metabolites, induced by mental stress testing have been associated with MSILVD (data pending for publications).

MSILVD investigations have revealed a critical and complex interwoven mechanism underlying the adversity of CVD with negative emotions. Such investigations, in addition, remind us that, certain patients' CV systems respond to commonly encountered mental stressors more adversely than others. The presence of these adverse changes during mental stress indicates that application of mental stress testing is necessary in eliciting certain pathological processes that cannot be detected during the resting state, and therefore may be an effective measure to identify individuals who are more susceptible to emotional stressful experiences.

Interventions that may alleviate the heart-mind adverse interaction

Many investigations of bio-psycho-behavioral interventions have been applied to alleviate the adverse interaction of heart and mind. The majority of the well-designed, randomly controlled, clinical trials have targeted on depression, social isolation, chronically stressed, MACE, and MSILVD.

Overall, the results yielded from these studies are quite mixed; some showed no effects on improving these negative emotions, some did, and few showed benefit in alleviating MACE. The various discrepancies are likely related to ways the emotional statuses were assessed, particular populations were studied along with various sample sizes, duration of intervention and follow-up. How these bio-psycho-behavioral interventions were delivered was also a critical matter. Findings support the bio-psycho-behavioral interventions are beneficial for CVD patients can be summarized as the followings:

  • Selective serotonin reuptake inhibitors are effective in reducing depression in patients postacute coronary syndrome patients.[46] It may be more effective for CHD patients who have had depression before CHD onset [47]
  • Cognitive behavioral therapy improved psychosocial outcomes at 6 months with a greater reduction in depressive symptoms and increases in social support, compared to control group [48]
  • Centralized depression care with patient preference for problem-solving treatment given through the telephone or the Internet, pharmacotherapy, both, reduced depressive symptoms measured by Beck Depression Inventory, relative to usual care control [49]
  • Escitalopram is effective in reducing MSILVD after 6-week escitalopram treatment compared to placebo (65.8% vs. 82.5%, odds ratio = 2.62 [95% CI, 1.06–6.44])[50]
  • Stress management has been shown to significantly improve chest pain, negative emotions, perceived health, well-being, and MSILVD. Furthermore, stress management improved longer term CVD outcomes.[51],[52]


Critical matters with future directions

Despite the significant progress in the heart-mind field, there are still several critical issues that need to be addressed.

One critical issue related to the massive epidemiological findings is that majority of previous investigations have focused on the impact of negative psychological conditions on CVD. Only recently the role of positive psychological conditions in CVD has emerged. One notable example is the study in optimism that has been shown, compared to pessimism, to be associated with a greater experience of positive emotions, enhanced social functioning, and better outcome postmyocardial infarction and cardiac procedures.[16],[53],[54] Furthermore, being optimistic is associated with enhanced immune, endothelial, and autonomic function.[55],[56] This evidence suggests that our mental outlook may be a substantial contributor of our health. With it, we need to answer many questions. For example, what are the bio-psycho-social determinants of optimism? How can we reserve and/or promote optimism and other positive emotions? Will promoting optimism and other positive psychological functions be superior to reducing depression, anxiety, and other negative emotions?

Another critical area that has been poorly studied in the heart-mind field is the role of the brain in the heart and mind interaction. For example, a question that needs to be answered urgently is whether or not the above mentioned negative psychological conditions or emotions reflect the brain reaction to various external stimuli from a more unified pathway or multiple complex pathways, and whether these pathways have a particular impact on various CV functions. In studies examining activities of brain regions using imaging studies, i.e., positron emission tomography, functional magnetic resonance imaging, and single photon emission computerized tomography, a complex series of areas of the brain implicated in the pathophysiology of depression. This included a network of regions such as the frontal and temporal cortex as well as the insula and cerebellum that are hypoactive in depressed subjects and in which there is an increase in activity with treatment.[57] A meta-analysis of the available data concluded that the most consistently identified regions related to depression included areas of the anterior cingulate, dorsolateral, medial and inferior prefrontal cortex, insula, superior temporal gyrus, basal ganglia, and cerebellum. Activities of the amygdala and hippocampus are well known to be abnormal with anxiety conditions but were not discussed in the study of Fitzgerald et al.[57] Advanced neuroimaging studies along with molecular research permit more sophisticated investigations in differential specific regions or pathways with special peripheral activities, and evaluate temporal changes of the brain between acute and chronic stimulations.

The third critical area is that we now know multiple systems of bodies are similarly perturbed in individuals suffering from depression and other negative emotions and in CVD patients. Molecular research has recently brought the dysfunction of mitochondria, the key organelle responsible for cellular energy production, to attention as a newly recognized system that is perturbed under the conditions that have been discussed so far in this article. Since mitochondrial dysfunction was first described in the 1960s, medicine has advanced in its understanding the role mitochondria play in health, disease, and aging. A wide range of seemingly unrelated disorders, such as schizophrenia, bipolar disease, dementia, depression, anxiety, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, diabetes, have underlying pathophysiological mechanisms in common, namely, reactive oxygen species production, the accumulation of mitochondrial DNA damage, and resulting in mitochondrial dysfunction.[58],[59],[60],[61] One recent investigation has demonstrated mitochondrial respiration in peripheral blood mononuclear cells to be correlated with depressive symptoms. Advancement in mitochondrial research will no doubt facilitate the investigations of the heart-mind field. Further investigations focusing on mitochondrial responses to various emotions will most likely advance the discovery of crucial mechanisms underpinning the brain-mind-heart interactions and facilitate interventional targets.

Last, but not the least, another critical matter is the very slow progress in integrating evidenced-based bio-psycho-behavioral interventions in everyday clinical practice. Multifactorial reasons are impeding the progress. Primary care clinicians and cardiologists are either too busy to, not confident enough, or not able to make mental health care a priority. Mental health providers, on the other hand, are either too far from reaching these patients or poorly reimbursed from their services. Anticipating that CVD patients will visit mental health providers separately from visiting their primary care clinicians and/or cardiologists shows a lack of awareness to the increased burden on the patient in terms of the time, the effort, and financial burden. Engaging and mobilizing stakeholders of global and national health policy makers, patients, and their loved ones, and many other health-care promotion organizations and individuals will be a significant dimension to proceed.

In summary, the heart-mind field has grown into a recognizable professional entity. Further advancement will be based on advancements in multiple layers in research, education, and clinical practice, and require broadly diversified collaborations from not only medical professions of medicine, cardiology, mental health, neuroscience, and basic research but also the involvement of many stakeholders.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jordande J, Bardé B, Zeiher AM. editors. Contributions Toward Evidence-Based Psychocardiology: A Systematic Review of the Literature. USA: The Free Library, Book News, Inc.; 2006. Available from: https://www.thefreelibrary.com/Contributions+toward+evidence-based+psychocardiology%3b+a+systematic.-a0155203252. [Last retrieved on 2017 Jun 23].  Back to cited text no. 1
    
2.
Rozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: The emerging field of behavioral cardiology. J Am Coll Cardiol 2005;45:637-51.  Back to cited text no. 2
    
3.
Jiang W, Babyas M, McNulty S, Coleman RE, Waugh RA, Hanson MW, et al. Mental stress-induced myocardial ischemia predicts cardiac events in patients with CAD. JAMA 1996;275:1651-6.  Back to cited text no. 3
    
4.
Gordon AH. Mental complications of heart disease. Trans Am Clin Climatol Assoc 1937;53:53-65.  Back to cited text no. 4
    
5.
Malzberg B. Mortality among patients with involution melancholia. Am J Psychiatry 1937;93:1231-8.  Back to cited text no. 5
    
6.
Nicholson A, Kuper H, Hemingway H. Depression as an aetiologic and prognostic factor in coronary heart disease: A meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J 2006;27:2763-74.  Back to cited text no. 6
    
7.
Jiang W, Alexander J, Christopher E, Kuchibhatla M, Gaulden LH, Cuffe MS, et al. Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure. Arch Intern Med 2001;161:1849-56.  Back to cited text no. 7
    
8.
Jiang W, Krishnan RR, O'Connor CM. Depression and heart disease: Evidence of a link, and its therapeutic implications. CNS Drugs 2002;16:111-27.  Back to cited text no. 8
    
9.
Rozanski A. Behavioral cardiology: Current advances and future directions. J Am Coll Cardiol 2014;64:100-10.  Back to cited text no. 9
    
10.
Meijer A, Conradi HJ, Bos EH, Thombs BD, van Melle JP, de Jonge P, et al. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: A meta-analysis of 25 years of research. Gen Hosp Psychiatry 2011;33:203-16.  Back to cited text no. 10
    
11.
Ghosh RK, Ball S, Prasad V, Gupta A. Depression in heart failure: Intricate relationship, pathophysiology and most updated evidence of interventions from recent clinical studies. Int J Cardiol 2016;224:170-7.  Back to cited text no. 11
    
12.
Hemingway H, Marmot M. Evidence based cardiology: Psychosocial factors in the aetiology and prognosis of coronary heart disease. Systematic review of prospective cohort studies. BMJ 1999;318:1460-7.  Back to cited text no. 12
    
13.
Kuper H, Marmot M, Hemingway H. Systematic review of prospective cohort studies of psychosocial factors in the etiology and prognosis of coronary heart disease. Semin Vasc Med 2002;2:267-314.  Back to cited text no. 13
    
14.
Frasure-Smith N, Lespérance F. Depression and cardiac risk: Present status and future directions. Heart 2010;96:173-6.  Back to cited text no. 14
    
15.
Gathright EC, Goldstein CM, Josephson RA, Hughes JW. Depression increases the risk of mortality in patients with heart failure: A meta-analysis. J Psychosom Res 2017;94:82-9.  Back to cited text no. 15
    
16.
Giltay EJ, Kamphuis MH, Kalmijn S, Zitman FG, Kromhout D. Dispositional optimism and the risk of cardiovascular death: The Zutphen elderly study. Arch Intern Med 2006;166:431-6.  Back to cited text no. 16
    
17.
Gruenewald TL, Karlamangla AS, Greendale GA, Singer BH, Seeman TE. Feelings of usefulness to others, disability, and mortality in older adults: The MacArthur study of successful aging. J Gerontol B Psychol Sci Soc Sci 2007;62:P28-37.  Back to cited text no. 17
    
18.
Miles HH, Cobb S. Neurocirculatory asthenia, anxiety and neurosis. N Engl J Med 1951;245:711-9.  Back to cited text no. 18
    
19.
Fish F. The psychiatric aspects of paroxysmal tachycardia. Br J Psychiatry 1964;110:205-10.  Back to cited text no. 19
    
20.
Weiss E, Dolin B, Rollin HR, Fischer HK, Bepler CR. Emotional factors in coronary occlusion. I. Introduction and general summary. AMA Arch Intern Med 1957;99:628-41.  Back to cited text no. 20
    
21.
Batelaan NM, Seldenrijk A, Bot M, van Balkom AJ, Penninx BW. Anxiety and new onset of cardiovascular disease: Critical review and meta-analysis. Br J Psychiatry 2016;208:223-31.  Back to cited text no. 21
    
22.
Jiang W, Kuchibhatla M, Cuffe MS, Christopher EJ, Alexander JD, Clary GL, et al. Prognostic value of anxiety and depression in patients with chronic heart failure. Circulation 2004;110:3452-6.  Back to cited text no. 22
    
23.
Thompson TS, Barksdale DJ, Sears SF, Mounsey JP, Pursell I, Gehi AK, et al. The effect of anxiety and depression on symptoms attributed to atrial fibrillation. Pacing Clin Electrophysiol 2014;37:439-46.  Back to cited text no. 23
    
24.
Cohen BE, Edmondson D, Kronish IM. State of the art review: Depression, stress, anxiety, and cardiovascular disease. Am J Hypertens 2015;28:1295-302.  Back to cited text no. 24
    
25.
Chida Y, Steptoe A. The association of anger and hostility with future coronary heart disease: A meta-analytic review of prospective evidence. J Am Coll Cardiol 2009;53:936-46.  Back to cited text no. 25
    
26.
Pänkäläinen M, Kerola T, Kampman O, Kauppi M, Hintikka J. Pessimism and risk of death from coronary heart disease among middle-aged and older Finns: An eleven-year follow-up study. BMC Public Health 2016;16:1124.  Back to cited text no. 26
    
27.
Dote K, Sato H, Tateishi H, Uchida T, Ishihara M. Myocardial stunning due to simultaneous multivessel coronary spasms: A review of 5 cases. J Cardiol 1991;21:203-14.  Back to cited text no. 27
    
28.
Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E, et al. Apical ballooning syndrome or takotsubo cardiomyopathy: A systematic review. Eur Heart J 2006;27:1523-9.  Back to cited text no. 28
    
29.
Sharkey S, Lesser J, Maron B. Takotsubo (stress) cardiomyopathy. Am Heart Assoc 2011;124:e460-e462. Available from: http://www.circ.ahajournals.org/content/124/18/e460. [Last accessed on 2017 Nov 9].  Back to cited text no. 29
    
30.
Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al. Clinical features and outcomes of takotsubo (Stress) cardiomyopathy. N Engl J Med 2015;373:929-38.  Back to cited text no. 30
    
31.
Carney RM, Saunders RD, Freedland KE, Stein P, Rich MW, Jaffe AS, et al. Association of depression with reduced heart rate variability in coronary artery disease. Am J Cardiol 1995;76:562-4.  Back to cited text no. 31
    
32.
Brown AD, Barton DA, Lambert GW. Cardiovascular abnormalities in patients with major depressive disorder: Autonomic mechanisms and implications for treatment. CNS Drugs 2009;23:583-602.  Back to cited text no. 32
    
33.
Barton DA, Dawood T, Lambert EA, Esler MD, Haikerwal D, Brenchley C, et al. Sympathetic activity in major depressive disorder: Identifying those at increased cardiac risk? J Hypertens 2007;25:2117-24.  Back to cited text no. 33
    
34.
Musselman DL, Tomer A, Manatunga AK, Knight BT, Porter MR, Kasey S, et al. Exaggerated platelet reactivity in major depression. Am J Psychiatry 1996;153:1313-7.  Back to cited text no. 34
    
35.
Poole L, Dickens C, Steptoe A. The puzzle of depression and acute coronary syndrome: Reviewing the role of acute inflammation. J Psychosom Res 2011;71:61-8.  Back to cited text no. 35
    
36.
Kop WJ, Gottdiener JS. The role of immune system parameters in the relationship between depression and coronary artery disease. Psychosom Med 2005;67 Suppl 1:S37-41.  Back to cited text no. 36
    
37.
Xiong GL, Prybol K, Boyle SH, Hall R, Streilein RD, Steffens DC, et al. Inflammation markers and major depressive disorder in patients with chronic heart failure: Results from the sertraline against depression and heart disease in chronic heart failure study. Psychosom Med 2015;77:808-15.  Back to cited text no. 37
    
38.
Frasure-Smith N, Lespérance F. Reflections on depression as a cardiac risk factor. Psychosom Med 2005;67 Suppl 1:S19-25.  Back to cited text no. 38
    
39.
Jiang W, Samad Z, Boyle S, Becker RC, Williams R, Kuhn C, et al. Prevalence and clinical characteristics of mental stress-induced myocardial ischemia in patients with coronary heart disease. J Am Coll Cardiol 2013;61:714-22.  Back to cited text no. 39
    
40.
Wei J, Rooks C, Ramadan R, Shah AJ, Bremner JD, Quyyumi AA, et al. Meta-analysis of mental stress-induced myocardial ischemia and subsequent cardiac events in patients with coronary artery disease. Am J Cardiol 2014;114:187-92.  Back to cited text no. 40
    
41.
Sun JL, Boyle SH, Samad Z, Babyak MA, Wilson JL, Kuhn C, et al. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients. Eur J Prev Cardiol 2017;24:591-9.  Back to cited text no. 41
    
42.
Yeung AC, Vekshtein VI, Krantz DS, Vita JA, Ryan TJ Jr., Ganz P, et al. The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med 1991;325:1551-6.  Back to cited text no. 42
    
43.
Dakak N, Quyyumi AA, Eisenhofer G, Goldstein DS, Cannon RO 3rd. Sympathetically mediated effects of mental stress on the cardiac microcirculation of patients with coronary artery disease. Am J Cardiol 1995;76:125-30.  Back to cited text no. 43
    
44.
Ghiadoni L, Donald AE, Cropley M, Mullen MJ, Oakley G, Taylor M, et al. Mental stress induces transient endothelial dysfunction in humans. Circulation 2000;102:2473-8.  Back to cited text no. 44
    
45.
Jiang W, Boyle SH, Ortel TL, Samad Z, Velazquez EJ, Harrison RW, et al. Platelet aggregation and mental stress induced myocardial ischemia: Results from the responses of myocardial ischemia to escitalopram treatment (REMIT) study. Am Heart J 2015;169:496-5070.  Back to cited text no. 45
    
46.
Lespérance F, Frasure-Smith N, Koszycki D, Laliberté MA, van Zyl LT, Baker B, et al. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: The Canadian cardiac randomized evaluation of antidepressant and psychotherapy efficacy (CREATE) trial. JAMA 2007;297:367-79.  Back to cited text no. 46
    
47.
Glassman AH, O'Connor CM, Califf RM, Swedberg K, Schwartz P, Bigger JT Jr., et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002;288:701-9.  Back to cited text no. 47
    
48.
Berkman LF, Blumenthal J, Burg M, Carney RM, Catellier D, Cowan MJ, et al. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: The enhancing recovery in coronary heart disease patients (ENRICHD) randomized trial. JAMA 2003;289:3106-16.  Back to cited text no. 48
    
49.
Davidson KW, Bigger JT, Burg MM, Carney RM, Chaplin WF, Czajkowski S, et al. Centralized, stepped, patient preference-based treatment for patients with post-acute coronary syndrome depression: CODIACS vanguard randomized controlled trial. JAMA Intern Med 2013;173:997-1004.  Back to cited text no. 49
    
50.
Jiang W, Velazquez EJ, Kuchibhatla M, Samad Z, Boyle S, Kuhn C, et al. Responses of mental stress-induced myocardial ischemia to escitalopram treatment: Results from the REMIT trial. JAMA 2013;309:2139-49.  Back to cited text no. 50
    
51.
Blumenthal JA, Jiang W, Babyak MA, Krantz DS, Frid DJ, Coleman RE, et al. Stress management and exercise training in cardiac patients with myocardial ischemia. Effects on prognosis and evaluation of mechanisms. Arch Intern Med 1997;157:2213-23.  Back to cited text no. 51
    
52.
Blumenthal JA, Babyak M, Wei J, O'Connor C, Waugh R, Eisenstein E, et al. Usefulness of psychosocial treatment of mental stress-induced myocardial ischemia in men. Am J Cardiol 2002;89:164-8.  Back to cited text no. 52
    
53.
Kubzansky LD, Sparrow D, Vokonas P, Kawachi I. Is the glass half empty or half full? A prospective study of optimism and coronary heart disease in the normative aging study. Psychosom Med 2001;63:910-6.  Back to cited text no. 53
    
54.
Giltay EJ, Geleijnse JM, Zitman FG, Hoekstra T, Schouten EG. Dispositional optimism and all-cause and cardiovascular mortality in a prospective cohort of elderly Dutch men and women. Arch Gen Psychiatry 2004;61:1126-35.  Back to cited text no. 54
    
55.
Endrighi R, Hamer M, Steptoe A. Associations of trait optimism with diurnal neuroendocrine activity, cortisol responses to mental stress, and subjective stress measures in healthy men and women. Psychosom Med 2011;73:672-8.  Back to cited text no. 55
    
56.
Ikeda A, Schwartz J, Peters JL, Fang S, Spiro A 3rd, Sparrow D, et al. Optimism in relation to inflammation and endothelial dysfunction in older men: The VA normative aging study. Psychosom Med 2011;73:664-71.  Back to cited text no. 56
    
57.
Fitzgerald PB, Laird AR, Maller J, Daskalakis ZJ. A meta-analytic study of changes in brain activation in depression. Hum Brain Mapp 2008;29:683-95.  Back to cited text no. 57
    
58.
Einat H, Yuan P, Manji HK. Increased anxiety-like behaviors and mitochondrial dysfunction in mice with targeted mutation of the Bcl-2 gene: Further support for the involvement of mitochondrial function in anxiety disorders. Behav Brain Res 2005;165:172-80.  Back to cited text no. 58
    
59.
Pieczenik SR, Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol 2007;83:84-92.  Back to cited text no. 59
    
60.
Tobe EH. Mitochondrial dysfunction, oxidative stress, and major depressive disorder. Neuropsychiatr Dis Treat 2013;9:567-73.  Back to cited text no. 60
    
61.
Bansal Y, Kuhad A. Mitochondrial dysfunction in depression. Curr Neuropharmacol 2016;14:610-8.  Back to cited text no. 61
    


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