Loneliness is bad for your health—certainly as bad as being obese, and possibly as bad as being a moderate smoker.
So, in these days of plague, when enforced solitude is the order of the day in many places,
how to stop solitude turning into loneliness is a pressing medical question.
One part of the answer is to try to understand the physiology of the change.
And that has, for the past few years, been the objective of Steven Cole of the University of California, Los Angeles.
Dr Cole began his work with a study he published in 2015, in collaboration with John Cacioppo of the University of Chicago.
The pair led a team of psychologists, neuroscientists and immunologists who found that
the pattern in people's blood of immune cells called myeloid cells is notably different in those who score as "very lonely" on loneliness tests compared with those who do not.
Lonely people have unusually low numbers of a type of myeloid cell that generates what are known as interferon responses, which hamper viral replication.
This makes them particularly vulnerable to viral infections. They also have an abundance of a second type of myeloid cell,
one that promotes the activity of genes which drive inflammation—
and it has been known for years that those who feel lonely experience more inflammation than those who do not.
These correlations are intriguing, but do not explain which comes first, the loneliness or the myeloid response.
Dr Cole and Dr Cacioppo addressed that question by repeatedly measuring perceptions of social isolation in individual volunteers,
while simultaneously tracking, from blood samples, their gene-expression patterns and other changes in their physiology.
They found that, initially, volunteers' feelings of isolation coincided with an increase in their inflammation genes' activity
and a concomitant increase in the circulation of immature immune cells, called monocytes, that are involved in inflammation—
and which are also known to travel into the brain and promote anxiety.
They noted, too, increased levels in the brain of signalling molecules associated with both inflammation and behaviours such as social withdrawal,
feelings of suspicion towards the outside world and a tendency to act more defensively by making decisions that involve few risks.
That, of course, promotes further feelings of loneliness. Which, in turn, trigger a further myeloid response. And so on.
It seems, therefore, that though loneliness starts with solitude, it can quickly take on a physiological life of its own.
Dr Cole thus worries that the enforced isolation, brought about by current circumstances,
of those who are already living alone may create in many people a state of chronic loneliness that is difficult to escape from when things start returning to normal.