Have you ever had the flu, and along with the physical symptoms a temporary feeling of being low and fed up? Though most of us would shrug these feelings off as a result of not being able to go out with friends or play sport, they are beginning to attract some serious attention from neuroscientists and psychiatrists.
The interest stems from the similarities between these sickness symptoms and those of depression: low mood, apathy and loss of interest in activities we previously enjoyed. Both are also associated with poor concentration, slowing of thoughts and actions, and a loss of motivation, particularly to engage socially.
When it comes to sickness, of course, the symptoms are much less severe than in depression and fortunately only last a few days. However, their remarkable similarity has led psychiatrists to ask whether depression is perhaps an unusually severe or prolonged sickness response.
To test this hypothesis, researchers have begun to look at the blood markers of inflammation in people who are depressed. More than 100 studies of this type have been completed, and the general consensus is that people with depression do appear to have higher levels of bodily inflammation.
While this data is important, it doesn’t tell us whether inflammation actually causes depression and has led to some controversy. For example, it is perfectly possible that depression causes inflammation by making us less attentive of our physical health.
So scientists have needed to find ways to safely induce inflammation in otherwise healthy volunteers.
In a study we carried out, volunteers were given a clinical typhoid vaccination. This produces mild inflammation that is gone within 24 hours. After being given the vaccination, volunteers reported a slight lowering of their mood and some concentration difficulties.
Depression: a response to sickness?
However, it’s what is happening in the brain that is so exciting. Inflammation rapidly triggers a change in the responsiveness of a critical mood-regulating network and the way that it connects to other areas of the brain. Remarkably, this is the same network that is impaired in depression. This suggests that depression - at least in some cases - could well be some type of aberrant sickness response.
Although this finding shows that mood changes induced by inflammation use the same brain network as depression, it doesn’t tell us whether inflammation could be a factor in clinical depression, which leads to more prolonged periods of feeling down.
To study this further, depression researchers teamed up with a surprising group of patients – those with chronic hepatitis-C. The disease doesn’t cause particularly high levels of inflammation but if left untreated it slowly causes liver damage that can lead to cirrhosis and ultimately liver failure. To prevent this, and to potentially cure the hepatitis-C, most people are advised to take a six to 12-month course of antivirals and an immune-system boosting drug called interferon, which helps regulate inflammation.
But interferon injections not only induce sickness symptoms but can also result in clinical depression. About one in three patients treated with interferon develop depression, typically within six to eight weeks of starting treatment. The depression presents in a similar way to other people suffering with depression, and shows a similar response to anti-depressant medication. This suggests that chronic immune stimulation can cause depression.
An inflammatory suggestion
It remains uncertain how many patients with depression may have an inflammatory cause. It is also unclear whether anti-inflammatory drugs would help. Recent data suggests that they may, though it is still too early to be sure of this.
For example, in a paper published last year researchers gave patients with depression an anti-inflammatory drug originally designed to treat rheumatoid arthritis. Even though these people had severe and hard to treat depression, some of them showed a significant improvement in their symptoms, particularly those who already had high levels of inflammation where the treatment worked on both the inflammation and the depression. A similar finding has also been found in patients with psoriasis who had milder depressive symptoms.
These discoveries are causing considerable excitement within psychiatry, an area of medicine where there has been no new class of medication for nearly 20 years. If this early promise is continued they may also open up an important new therapeutic options for the millions of people worldwide who suffer from depression, a condition that can often have a profound and devastating impact on their lives.