|Year : 2017 | Volume
| 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 Publication||16-Nov-2017|
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
Source of Support: None, Conflict of Interest: None
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,” “Behavioral Cardiology,” and/or “Neuropsychocardiology” 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
| Introduction|| |
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  and a psychiatrist  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,,, anxiety, hostility, pessimism, and feeling of chronically over stressed.
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). 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. Furthermore, depression leads to the development of CHD  and aggravation of heart failure. 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.,,,, The variation in prevalence was related to size and particular populations studied and whether interview-based depression instruments or self-report questionnaires used. 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.,
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.,, 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. 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. On the other hand, anxiety has been found to be greatly associated with various symptoms of CVD, such as arrhythmia , 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, pessimism, 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. 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., 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. 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. 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.
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., 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. 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. 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. 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., 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.
|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.,, 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.,, Over a couple of decades, we have learned that mental stress-induced myocardial ischemia occurs more frequently than exercise stress-induced ischemia  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. 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.,, 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, 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. It may be more effective for CHD patients who have had depression before CHD onset 
- 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 
- 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 
- 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])
- 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.,
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.,, Furthermore, being optimistic is associated with enhanced immune, endothelial, and autonomic function., 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. 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. 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.,,, 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.
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Conflicts of interest
There are no conflicts of interest.
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