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Inflammation, the possible link between heart disease and depression
People with heart disease are more likely to suffer from
depression, and the opposite is also true. Now, scientists at
the University of Cambridge believe they have identified a
link between these two conditions: inflammation – the body’s
response to negative environmental factors, such as stress.
While inflammation is a natural response necessary to
fight off infection, chronic inflammation, which may result
from psychological stress as well as lifestyle factors such as
smoking, excessive alcohol intake, physical inactivity and
obesity, is harmful.
The link between heart disease and depression is well
documented. People who have a heart attack are at a
significantly higher risk of experiencing depression. Yet
scientists have been unable to determine whether this is due
to the two conditions sharing common genetic factors or
whether shared environmental factors provide the link.
‘It is possible that heart disease anddepression share common
underlying biological mechanisms, which manifest as two
different conditions in two different organs, the cardiovascular
system and the brain,’ says Dr Golam Khandaker, a Wellcome
Trust intermediate clinical fellow at the University of
Cambridge. ‘Our work suggests that inflammation could be a
shared mechanism for these conditions.’
Khandaker and colleague Dr Stephen Burgess led a
team of researchers from Cambridge who examined this
link by studying data relating to almost 370 000 middle-
aged participants of UK Biobank. First, the team looked
at whether family history of coronary heart disease was
associated with risk of major depression. They found that
people who reported at least one parent having died of heart
disease were 20% more likely to develop depression at some
point in their life.
Next, the researchers calculated a genetic risk score for
coronary heart disease, ameasure of the contributionmade by
the various genes known to increase the risk of heart disease.
Heart disease is a so-called ‘polygenic’ disease – in other
words, it is caused not by a single genetic variant, but rather
by a large number of genes, each increasing an individual’s
chances of developing heart disease by a small amount.
Unlike for family history, however, the researchers found
no strong association between the genetic predisposition for
heart disease and the likelihood of experiencing depression.
Together, these results suggest that the link between heart
disease and depression cannot be explained by a common
genetic predisposition to the two diseases. Instead, it implies
that something about an individual’s environment, such as
the risk factors he/she is exposed to, not only increases the
risk of heart disease, but at the same time increases the risk
of depression.
This finding was given further support by the next
stage of the team’s research. They used a technique known
as Mendelian randomisation to investigate 15 biomarkers
– biological ‘red flags’ – associated with increased risk
of coronary heart disease. Mendelian randomisation is a
statistical technique that allows researchers to rule out the
influence of factors that otherwise confuse, or confound, a
study, such as social status. Of these common biomarkers,
they found that triglycerides and the inflammation-related
proteins interleukin-6 (IL-6) and C-reactive protein (CRP)
were also risk factors for depression.
Both IL-6 and CRP are inflammatory markers that are
produced in response to damaging stimuli, such as infection,
stress or smoking. Studies by Khandaker and others have
previously shown that people with elevated levels of IL-6
and CRP in the blood are more prone to develop depression,
and that levels of these biomarkers are high in some
patients during acute depressive episodes. Elevated markers
of inflammation are also seen in people with treatment-
resistant depression. This has raised the prospect that anti-
inflammatory drugs might be used to treat some patients
with depression.
Khandaker is currently involved in a clinical trial to
test tocilizumab, an anti-inflammatory drug used for the
treatment of rheumatoid arthritis that inhibits IL-6, to see if
reducing inflammation leads to improvement in mood and
cognitive function in patients with depression.
While the link between triglycerides and coronary heart
disease is well documented, it is not clear why they, too,
should contribute to depression. The link is unlikely to be
related to obesity, for example, as this study has found no
evidence for a causal link between body mass index and
depression.
‘Although we don’t know what the shared mechanisms
between these diseases are, we now have clues to work with
that point towards the involvement of the immune system,’
says Burgess. ‘Identifying genetic variants that regulate
modifiable risk factors helps to find what is actually driving
disease risk.’
Dr Sophie Dix, director of research at MQ, says: ‘This
study adds important new insight into the emergence and risk
of depression, a significantly under-researched area. Taking
a holistic view of a person’s health, such as looking at heart
disease and depression together, enables us to understand
how factors like traumatic experiences and the environment
impact on both our physical and mental health.
‘This research shows clearly the shared biological changes
that are involved. This not only opens opportunities for earlier
diagnosis, but also creates a solid foundation for exploring
new treatments or using existing treatments differently. We
need to stop thinking about mental and physical health in
isolation and continue this example of bringing sciences
together to create real change.’
Source:
Medical Brief 2019