The amygdala is located deep inside the brain
Thursday January 12 2017
"The effect of constant stress on a deep-lying region of the brain explains the increased risk of heart attack, a study in The Lancet suggests," BBC News reports.
Research suggests that stress stimulates the amygdala. The amygdala is, in evolutionary terms, one of the oldest areas of the brain and has been linked to some of the most primal types of emotion, such as fear and stress. It is thought to be responsible for triggering the classic "fight or flight" response in situations of potential danger.
Researchers in the US, using medical imaging, found that higher levels of activity in the amygdala predicted how likely people were to have a heart attack or stroke.
People with an over-active amygdala were also likely to show more activity in their bone marrow, which makes blood cells, and to have inflamed blood vessels. The researchers think their findings are linked – that stress activates the amygdala, which prompts the bone marrow to produce more cells, causing inflammation of the arteries, which in turn, raises risk of heart attacks and strokes.
While the theory is plausible, the study was quite small and due to its design, can't prove cause and effect.
A final interesting point, raised in the study, is evidence that mindfulness-based meditation has been shown to reduce amygdala activity. It may be possible that meditation could reduce the risk of stress-based heart attack or stroke.
Read more about how mindfulness can improve wellbeing.
Where did the story come from?
The study was carried out by researchers from Massachusetts General Hospital, Weil Cornell Medical College, Icahn School of Medicine and Tufts University, all in the US. The researchers say the study had no specific funding, although they acknowledge grants from the US National Institutes of Health.
The study was published in the peer-reviewed medical journal The Lancet.
The Sun and the Daily Mirror headlines both suggested this was the first time stress had been linked to cardiovascular disease (specifically heart attacks and stroke), but the link has actually been known for over a decade.
Other media outlets correctly identified that the possible mechanism behind the link is the real newsworthy issue.
However, most reports presented the mechanism as if it was fact, rather than a theory that still needs further research.
What kind of research was this?
The researchers did two types of study.
The first was a longitudinal cohort study in which 293 people who'd had full body scans (mostly due to a suspected cancer diagnosis) were followed up for up to four years, to see whether they developed cardiovascular disease.
The second was a cross-sectional study of just 13 people, all of whom had previously had post-traumatic stress disorder (PTSD), in which the participants filled in a stress questionnaire and underwent body scans.
Neither study is able to show whether one factor (such as amygdala activity or stress) causes another, such as cardiovascular disease. However, they can flag up factors which are linked in some way, suggesting theories that can be tested in further research.
What did the research involve?
In the first study, researchers used data from body scans of 293 people, most of whom had been tested for cancer (although they did not have cancer at the time of the scan). The scan showed areas of activity and inflammation in the body and brain.
Researchers looked for links between activity in the amygdala of the brain, bone marrow, the spleen, and blood vessel inflammation. They then followed the people up for at least three years, to see if they developed cardiovascular disease.
In the second study, they asked 13 people with previous PTSD to fill in questionnaires about their perceived levels of stress. They then gave them body scans to look for evidence of activity in the amygdala, an inflammatory chemical called C-reactive protein, and levels of inflammation in the blood vessels. They looked to see whether these measures were linked to their stress scores.
The scanning technique used, F-fluorodexoyglucose positron emission tomography (F-FDG PET), involves injecting people with a type of sugar that shows up on scans, so the scan can show where it's being taken up by cells, and therefore which areas of the body are active or inflamed.
People in the first study weren't asked about their stress levels. They were only included if they had no history of cardiovascular disease, no active cancer, no inflammatory or autoimmune disease, and were over 30 years old.
They weren't checked directly for cardiovascular disease during the three to four years follow up. Instead, researchers looked at their medical records to see if any cardiovascular events such as stroke had occurred.
Researchers adjusted figures in the first study to take account of known risk factors for cardiovascular disease, including:
- age
- smoking
- cardiovascular risk score
- body mass index (BMI)
- diabetes
What were the basic results?
Twenty-two people had one or more events of cardiovascular disease (including heart attack, stroke, unstable angina, first episode of angina, heart failure and peripheral arterial disease).
Higher activity in the amygdala was linked to an increased chance of having a cardiovascular event. The researchers calculated that each unit increase (standard deviation of amygdala activity increased the risk of cardiovascular disease 1.6 times – hazard ratio 1.6, confidence intervals not given). This link remained true after taking account of cardiovascular risk factors.
Activity in the amygdala was also linked to higher activity in the spleen and the bone marrow, which produce blood cells, and with higher inflammation of artery walls. Activity in the bone marrow was reflected in more white blood cells in the blood.
By analysing the statistics, researchers said bone marrow activity could account for almost half the link between amygdala activity and artery inflammation, and that artery inflammation accounted for 39% of the link between amygdala activity and cardiovascular events.
In the second study, activity in the amygdala was linked to people's perceived stress levels, artery inflammation and C-reactive protein levels.
How did the researchers interpret the results?
The researchers say they have shown "for the first time in human beings" that activity in the amygdala of the brain predicts the development of cardiovascular disease in years to come. They say this is linked to blood cell production and artery inflammation, and to perceived stress.
They say that clinicians treating people with stress related illnesses "could reasonably consider the possibility that alleviation of stress might result in benefits to the cardiovascular system," and that "eventually, chronic stress could be treated as an important risk factor for cardiovascular disease," which could be screened for and managed in the way high cholesterol or blood pressure are managed.
Conclusion
This intriguing study sets out a possible pathway by which the effects of stress on the brain could translate into inflammation in the blood vessels, and so raise the risks of cardiovascular disease. This would help to explain why people living in stressful situations, or with illnesses such as depression and anxiety, are more at risk of heart attacks and strokes.
However, there are important limitations to the study which mean we should treat the findings with caution. The main study of 293 people was relatively small for a long-term study looking at cardiovascular disease, and only 22 people had a cardiovascular event. That means there's more likelihood of the results being down to chance.
The study mainly used patients being tested for cancer (either because they'd had it in the past, or were suspected of having it). That could mean their stress levels, amygdala activity and so on are not typical of people in the wider population. They were almost all white, so results may not apply to other ethnic groups.
Also, people in this group didn't have their stress levels tested, so we don't know whether raised amygdala activity in this group was a result of stress. That means we don't know whether people who had heart attacks or other cardiovascular events were more stressed – only that their amygdalae showed more activity on one occasion.
The cross-sectional study, which linked stress to amygdala activity, was very small. It only included people with a history of PTSD, so again we can't be sure these results would apply to a wider population.
So we need to see larger, longer-term studies to test this theory that stress causes cardiovascular disease via amygdala, bone marrow and arteries.
However, we already know that long-term stress is linked to poor health, both in terms of mental and physical health, so lack of evidence about the pathway should not stop us from trying to alleviate stress.
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