As soon as the word depression is mentioned, we tend to think of a mental problem that may need treatment with antidepressant drugs, with all their risk of side-effects such as weight gain and loss of libido.
But what if it actually has a physical cause that could be treated with anti-inflammatory drugs such as aspirin and ibuprofen, or even antibiotics?
This is the fascinating possibility being explored by scientists at Cambridge University. Their research suggests that, in a significant number of cases, depression could be caused by long-term inflammation in the body.
The idea has been gathering credibility over the past few years among researchers worldwide. Indeed, the association between low mood and bodily inflammation caused by infections should be familiar to anyone who has ever had a cold and felt miserable, listless and tired.
Evolutionary psychology suggests that this may once have aided survival, by keeping us safe in our caves because we felt too low to go out when illness was making us both vulnerable to attack and at risk of spreading infection to our tribal fellows.
Now, a growing body of research has linked depression with inflammation.
In 2013, for example, investigators at Aarhus University, in Denmark, examined the health records of nearly 3.6 million people and found that those who had inflammation caused by autoimmune conditions, such as arthritis or Crohn’s disease (inflammation of the lining of the digestive system) were 45 per cent more likely to suffer from a depressive condition.
Furthermore, those who had ever been in hospital for a serious inflammatory infection, such as sepsis or hepatitis, were 62 per cent more likely than normal to suffer from a depressive disorder, according to the study published in the journal JAMA Psychiatry.
Earlier that year, another team of Danish researchers published a study in the same journal which found that raised levels of C-reactive protein — a substance the body produces in response to inflammation — were associated with an ‘increased risk for psychological distress and depression in the general population’.
Results such as these presented scientists with a crucial question: do people get depressed simply because an inflammatory illness is making their lives miserable, or is there a hidden physical process that makes inflammation cause depression?
The latter may be more likely to be true, according to an Australian study reported in the journal BMC Medicine in 2013. This found that giving healthy people drugs that cause inflammation can cause them to suffer all the typical symptoms of depression, such as low mood and lack of motivation.
Indeed, a quarter of patients who take interferon — a medication used to treat the viral liver infection hepatitis C that, as a side-effect, causes inflammation — develop major depression. Now this link is being investigated in much greater depth by Cambridge University scientists.
They have been following up on 4,500 children born in the Bristol area in the 1990s. They took blood samples when the children were aged nine to see if they showed evidence of raised levels of inflammation — testing for interleukin-6, a protein that the body releases in response to infections.
The investigators then followed up the children nine years later, when they were 18, to see if they had suffered from episodes of depression.
The results, which were published in the journal JAMA Psychiatry last August, showed that the nine-year-olds with high levels of inflammation in their bodies were nearly twice as likely as those with low inflammation levels to become depressed as teenagers.
Some of us constantly have higher levels of inflammation than others, explains Dr Golam Khandaker, the neuroscientist who led the study. ‘Our immune system acts like a thermostat, turned down low most of the time but cranked up when we have an infection,’ he says.
‘In some people the thermostat is always set slightly higher, behaving as if they have a persistent low-level infection — these people appear to be at higher risk of developing depression.’
The Cambridge team is also investigating the question of just how chronic inflammation could cause depression. Studies of mice suggest the answer may lie in the vagus nerve, which connects the brain to the abdomen.
When activated by inflammation in the gut, the vagus nerve sends signals to the brain that trigger an increase in toxic chemicals such as nitric oxide, quinolinic acid and kynurenic acid, which are bad for the functioning of nerve cells in the brain — which, in turn, could lead to depression symptoms.
So what might prompt some people to have high inflammation from childhood, and thus a greater risk of depression in later life?
Another of the Cambridge investigators, Peter Jones, a professor of psychiatry, told the Mail: ‘We are looking at what influences inflammation in children, such as genetics and low birthweight and also trauma early in life.
‘We don’t have the answers yet, but so far the results are looking very interesting.’
The research also hints at a new way to treat depression — with anti-inflammatory drugs such as ibuprofen or aspirin.
These might provide a less harmful alternative to commonly used anti-depressant pills such as selective serotonin reuptake inhibitors (SSRIs) like Prozac.
Prescriptions for antidepressants in Britain have doubled in the past ten years, according to figures published in January. A study by the pollsters YouGov found that nearly one adult in ten is taking pills to help with anxiety or depression.
Common side-effects include weight gain, loss of sexual desire, insomnia and fatigue. In rarer cases the drugs are believed to raise the risk of suicide, coronary disease and defects in unborn children if taken during pregnancy.
The conventional thinking is that SSRIs work by increasing levels of the chemical serotonin in the brain. Serotonin is a neurotransmitter, which means it carries signals between different cells in the brain, and is thought to help mood, emotions and sleep.
But Professor Jones says some of the benefit of anti-depressants may come from the fact that SSRI drugs appear to reduce inflammation in the body as a side-effect.
The Cambridge scientists are testing whether the antibiotic minocycline might be able to stave off damage resulting from chronic inflammation in the gut by directly reducing the level of toxic chemicals that this causes in the brain.
Minocycline, usually used to treat acne, has the rare ability to penetrate the brain’s defensive wall, the ‘blood-brain barrier’, and affect the brain’s chemistry.
The Cambridge team’s hope is that by teasing out the link between inflammation and depression, they may be able to help prevent thousands of deaths among those who suffer from the mood disorder — and prevent people needlessly being on antidepressant drugs.
‘Many people with depression die early, and it is widely assumed this is down to suicide,’ says Professor Jones. ‘But only a small proportion of the deaths are suicides. A huge proportion are caused by heart disease, which can also be caused by inflammation.
‘It looks as if inflammation could be the common cause, and we need to explore this.’
By revealing drug therapies for depression that are a far cry from anti-depressants, it may not just be mental distress that the Cambridge team helps to alleviate, but physical conditions such as damaged hearts as well.
by John Naish
May 11, 2015
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Can Aspirin Banish Depression? The Illness Could Be Caused By Inflammation