More Brain, Body Connection Data

The relationship between stress, anxiety, depression and physical health is complicated. Recent advances in neuroscience, medicine and psychiatry have changed how we look at illness. The emergence of “behavioral medicine” over the past 10-15 years has attempted to bridge this gap as it has become increasingly clear that emotional stressors are associated with physical health, especially cardiovascular disease.

It makes sense. All human experience is processed and interpreted by the brain where meaning is encoded. This process is central in how we respond to our world and to individual stressors. When we are injured, for example, the brain creates natural painkillers called endorphins. To keep us healthy and prevent disease, the brain produces gamma globulin to bolster our immune system. The brain also produces catecholamines that regulate our heart rate, blood pressure and mood, and interferon for combating infections, viruses and even cancer. Stress, depression and anxiety affect the brain which, in turn, impacts our physical health and well-being.

Stress on The Body

During times of acute stress our brain releases powerful hormones, including adrenalin and cortisol, to heighten senses and boost our strength, alertness and energy via the amygdala, an almond shaped structure in the midbrain. This healthy stress response serves us well when we face real, acute threat. However, this stress response was never intended to handle the chronic stressors of modern life.

Simply stated, persistent, chronic stress affects our brain first, which in turn affects everything else. For example, stress suppresses our ability to produce and maintain lymphocytes (the white blood cells necessary for killing infection) and other natural killer cells, which seek out and destroy foreign invaders. When our immune system is compromised, we are more susceptible to infection and disease. Researchers now suspect that mental stress cause the endothelium (the lining on the inner wall of our blood vessels) to constrict, which can raise blood pressure and cause a myriad of cardiovascular problems. Previously reported mortality data reveal that women who report high levels of mental stress are twice as likely to die from stroke or heart disease than those with low stress levels. Men who report moderate or high levels of mental stress are nearly twice as likely to suffer a heart attack compared to men with lower stress. It is not surprising that most visits to the doctor are for stress-related and stress-induced illnesses. Recently (January 2018) an excellent study and analysis by Tawakol, et al, recruited 293 patients (median age 55 years [IQR 45·0-65·5]) for a longitudinal study. The team imaged the amygdala via PET/CT scans to determine whether its resting metabolic activity would be predictive of subsequent cardiovascular events. In addition to measuring amygdalar activity, bone-marrow changes and arterial inflammation were assessed using validated methodology. In addition, a concurrent cross-sectional study analyzed the association between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. The results were robust. Increased amygdalar activity was significantly associated with arterial inflammation (r=0·70; p=0·0083). Perceived stress was also associated with amygdalar activity (r=0·56; p=0·0485), arterial inflammation (r=0·59; p=0·0345) and altered levels of C-reactive protein (r=0·83; p=0·0210).

This novel investigation showed that amygdalar activity independently and robustly predicted cardiovascular disease events are mediated, in part, by increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease and mortality in humans.

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Why Does This Matter?

The findings are the result of the largest-ever longitudinal study comparing brain imaging of resting amygdalar activity and disease outcomes in human subjects. The robust outcome reveals that the heart and brain are connected by psycho-biological processes. The finding of a sequential pathway, triggered by stress, followed by increased bone marrow activity and elevated arterial inflammation, and lastly elevated circulating inflammatory markers—all conditions that are known risk factors for a cardiovascular event.

This information supports the concept of multimodal clinical practice within cardiology, psychiatry and especially addiction medicine, where co-occurring stress disorders, trauma, anxiety and depression are the norm, rather than the exception.


Tawakol A. et al. Relation between resting amygdalar-activity and cardiovascular events: a longitudinal and cohort study. Lancet. 2017 Feb 25;389(10071):834-845. doi: 10.1016/S0140-6736(16)31714-7. Epub 2017 Jan 12.