Social stress and vascular diseases

Haomeng Zhu; Chris R Stone; Xiaokun Geng; Yuchuan Ding

doi:10.4103/ed.ed_4_17

REVIEW ARTICLE

Year : 2017 | Volume : 2 | Issue : 1 | Page : 1-4

Social stress and vascular diseases

Haomeng Zhu¹, Chris R Stone², Xiaokun Geng³, Yuchuan Ding³
¹ China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China
² Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA
³ China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA

Date of Submission	09-Mar-2017
Date of Acceptance	19-Mar-2017
Date of Web Publication	19-Apr-2017

Correspondence Address:
Yuchuan Ding
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ed.ed_4_17

Abstract

Both in China and abroad, the modern era of medicine and biomedical science has provided substantial improvements to the heath and quality of life of populations across many parameters. Concomitant with these improvements, however, the deleterious consequences of modern social production must also be investigated if we wish to produce a full account of how it has modified health. One such deleterious consequence is mental illness, which currently accounts for a substantial proportion of the disease burden worldwide. In this paper, we present one prominent component of this burden: the association of mental disorders with cerebrovascular disease. It has been established in the literature that cerebrovascular disease and mental illness are reciprocally aggravating; by discussing what is currently known about the mechanisms that mediate this relationship, we hope to stimulate future investigation into what is still unknown. We believe that further understanding in this area would not only improve our ability to treat patients with mental and cerebrovascular disease but also yield valuable insight into what factors, whether psychosocial, biological, or both, might constitute their common origin, and thus present a target for prevention.

Keywords: Intracranial atherosclerosis, stroke, stress

How to cite this article:
Zhu H, Stone CR, Geng X, Ding Y. Social stress and vascular diseases. Environ Dis 2017;2:1-4

How to cite this URL:
Zhu H, Stone CR, Geng X, Ding Y. Social stress and vascular diseases. Environ Dis [serial online] 2017 [cited 2023 Jun 5];2:1-4. Available from: http://www.environmentmed.org/text.asp?2017/2/1/1/204791

Introduction

The modern era has undeniably borne witness to tremendous progress in the fields of medicine and public health. In China, this progress is made manifest by an impressive catalog of epidemiologic changes achieved in recent decades. Between 1970 and 2010, male life expectancy increased by over 10 years, female life expectancy by over 15; the under-five mortality rate has decreased by nearly a factor of 10; age-standardized years of life lost from infectious diseases, neonatal causes, and injuries to children declined substantially; and so on.^[1] Nevertheless, the full account of changes in health and wellness wrought by modernity is not one of the unfettered progress. Industrialization and the ascent of information technology have brought unprecedented productive and analytic power to bear on the task of shoring up patients and populations against all causes of mortality. At the same time, however, they have created new ones. The frenetic pace, constant competition, and pressure to perform demanded by the modern mode of social production have been multifariously detrimental to the mental health of populations. Mental and psychological factors are currently considered to constitute the fourth largest cause of disease worldwide. In China, neuropsychiatric disorders are the most significant cause of illness, representing a disease burden in excess even of what is posed by cardiovascular, infectious, and neoplastic causes.^[2]

Psychological Disorders and Disease

Cardiovascular disorder

While this trend is deeply troubling on its own right, the frequent coexistence of mental and psychological disorders with cardiovascular disease magnifies its significance even further. Cardiovascular disease, a category that includes both heart disease and stroke, is currently the world's leading cause of death and disability. In 2008, it caused 17.3 million deaths, or 30% of all deaths that year. If, moreover, the current trends continue, that number is projected to rise to 23.3 million per year by 2030.^[3] Medical research on the coexistence of mental illness with overall cardiovascular disease is very well-developed,^[4],[5] and contains numerous and detailed investigations of the many possible mediating biological mechanisms.^[6] Not all aspects of cardiovascular disease are represented equally in this literature, however; cerebrovascular disease and stroke occupy relatively very little of it, and experimental work designed to directly investigate mechanisms intervening between mental illness and cerebrovascular disease occupies still less.^[7]

Cerebrovascular disorder

Fortunately, what we do know of the comorbidity between mental illness and cerebrovascular disease is just as important as what we still do not know. It is certainly enough to warrant more work in this field. We know that a wide variety of psychological problems are associated with cerebrovascular disease. These include anxiety and depression, hostility, anger, social isolation, low socioeconomic status (SES), pessimism, job stress, and perception of unfair treatment.^{[7],[8],[9],[10],[11],[12]} We also know that cerebrovascular disease and psychological disease are reciprocally aggravating; that is, we know that the possession of one can lead to the other.^[13],[14] The mental disease known to follow stroke has attracted significant scholarly attention, including a search for treatments that has yielded preliminary success.^[15] The reverse relationship, whereby psychological disease precipitates cerebrovascular disease, has been confirmed epidemiologically,^[16] but research regarding the mechanism of this causality is still too new to have produced viable interventions. Nevertheless, depression is one of the most common symptoms of mental disorders associated with cerebrovascular disease and is considered an independent risk factor for stroke.

Possible Biological Mechanisms

As is the case with psychological disease generally, the biological mechanism whereby depression increases the risk of cerebrovascular disease is not yet fully understood. Several plausible candidates for a mechanism appear in the literature, however, representing several promising directions for research in this field. They will be presented separately in what follows, but this should not be taken to imply their mutual exclusivity; on the contrary, all of them converge on the endothelial pathology common to many cerebrovascular disease modalities.

Neuroendocrine factors, including hyperactivity of the hypothalamic–pituitary–adrenal axis and sympathetic nervous system

Many studies have shown that patients with untreated hypercortisolism are afflicted with severe depression. Cortisol may also lead to hypertension and dyslipidemia, both of which are risk factors for stroke,^[17] and cause vascular endothelial and intimal injury to a degree greater than is required to precipitate atherosclerosis.^{[18],[19],[20]} Regarding sympathetic hyperactivity, it has been reported that the elevated norepinephrine concentration in the plasma of patients with depression, coupled with the increased adrenal catecholamine activity also observed in depression, yields effects on the vasculature and heart that can lead to the occurrence of cerebrovascular disease.^[21]

Cerebrovascular disease is influenced by the platelet system

Musselman and Nemeroff, in a study of 12 patients with depression and 8 normal subjects, showed that baseline platelet activation was higher in the depressed cohort compared with normal subjects.^[22] Ariyo et al.^[23] also found that patients with depression exhibited increased platelet activity and aggregation, rendering them prone to thrombosis. Because of platelet system abnormalities common to depressed patients, as well as the relevance of platelet pathology in the etiology of cerebrovascular disease, this is generally accepted as a possible mediating mechanism.

Drug-related factors

Because of the blood glucose and lipid metabolism abnormalities they produce, a causative role has been proposed for some drugs, including antidepressants and second-generation antipsychotics. Due, however, to the independent association between depression and elevated fasting glucose and triglyceride levels,^[24],[25] research has not yet been able to isolate the influence of the drugs.^[26]

Genetic factors in the comorbidity between depression and cerebrovascular disease

In 2015, the American Heart Association (AHA) released a statement ^[27] that discusses major depressive disorder and bipolar disorder in youth, implicating both disorders in the accelerated development of atherosclerosis and early cardiovascular disease. Because atherosclerosis is also a risk factor for the development of cerebrovascular disease, cerebrovascular disease incidence is elevated in this population. When discussing mechanisms that may account for the mental-physical comorbidity it reported, the statement invokes twin and molecular genetic findings that suggest genetic pathways common to the two types of disorder. According to this research, there is preliminary evidence of a familial association between depression and cardiovascular disease in adolescents. Parents with major depressive disorder give birth to offspring with increased aortic stiffness and blood pressure and decreased insulin sensitivity. In addition, parents of children with major depressive disorder have been shown to have an increased risk of cerebrovascular disease. Other genetic factors may also be relevant. One study that suggests as much reports on apolipoproteins (derangements in the metabolism of which are a risk factor for atherosclerosis), showing that apolipoprotein-associated disease may also be associated with depression.^[28]

Occupational factors

While it may be comparatively well-characterized, depression is far from the only modality of mental distress employed in research on the connection between psychological and cerebrovascular diseases. As noted above, factors as disparate as job stress, worry, anger, social isolation, low SES, and pessimism have all been shown to elevate blood pressure, disrupt metabolism, accelerate atherosclerosis, and change blood supply to the brain – thus, these also represent possible avenues to cerebrovascular disease.^{[29],[30],[31]} For instance, in a recent meta-analysis on this subject, Landsbergis et al. showed that occupational tension increased blood pressure, and should therefore be considered a risk factor for elevated blood pressure.^[32]

To understand how occupational factors might be causally connected to cerebrovascular disease, consider the case of hypertension among middle school teachers in Beijing. While the prevalence of hypertension in China overall is 18.8%,^[26] the rate among these teachers is 30.46% – nearly double. This is also a population among which mental stress is very high. Among other factors, pressure from administration to maintain an optimal enrollment rate and an exceptionally heavy workload may contribute to this stress. Burdened by these circumstances, the teachers become chronically stressed, predisposing them to hypertension,^[27] which they develop at the aforementioned very high rate. Since hypertension is the primary risk factor for the development of cardiovascular and cerebrovascular diseases, they then go on to develop these conditions at elevated rates.

Summary and Future Studies

Whatever the specific metrics used to analyze the relationship, the research is currently sufficient to conclude that cerebrovascular and mental disease are intimately intertwined. The literature we have summarized above has shown that the two types of disorder are reciprocally causative. We have also discussed several of the psychological symptoms with which the incidence and prognosis of cerebrovascular disease have been shown to be associated.

In addition, we have suggested that there is much that remains to be known in this area of research. This is partially due to the complexity and promiscuity of psychological disorders that render studying associations with them particularly difficult. That is, there is simply not enough yet known about the pathogenesis of such disorders to trace connections between them and better-characterized physiological disorders with satisfactory completeness and precision. For the same reason, the significance of the observed fact that psychological symptoms tend to cluster (depression, for example, is often accompanied by anxiety, fatigue often accompanies both depression and anxiety, and apathy accompanies both depression and cognitive disorders) for this type of research is also unknown. How should the relationship between research about the connection between psychosocial stress and stroke, on the one hand, and research about the connection between depression and stroke, on the other hand, be conceptualized? What about the relationship between studies that use subjective measures of stress, and those that use objective measures? These kinds of questions cannot presently be answered. Moreover, associated with cerebrovascular disease or otherwise, there is a general lack of large-scale clinical trials of high quality to provide a source of evidence for the treatment of psychiatric symptoms of all etiologies. This deficiency may push the possible therapeutic yield of any mechanistic insights obtained from the research described in this article further into the future.

In years to come, it is our hope that cross-disciplinary research, combining insights from psychiatry, pharmacology, cardiology neurology, neurological surgery, as well as the broad variety of other basic scientific pursuits relevant to the association between diseases of the mind and those of the body, continues to yield collaborative progress in this field. The pace, pressure, and general sacrifice of wellness for the sake of profit that characterizes modern social production are here to stay. Thus, this research must continue – lest we be compelled, one day in the near future, to say the same of heart attack and stroke.

Financial support and sponsorship

This work was partially supported by AHA grant-in-aid (14GRNT20460246), Merit Review Award (I01RX-001964-01) from the US Department of Veterans Affairs Rehabilitation, R & D Service, National Natural Science Foundation of China (81501141), Science and Technology Plan of Beijing Tongzhou District (KJ2016CX035) and Beijing New-star Plan of Science and Technology (xx2016061).

Conflicts of interest

There are no conflicts of interest.

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