ARE we programmed for depression? People with overactive immune systems appear to be primed for the condition. The finding could allow doctors to distinguish between different types of depression, offer help earlier and prescribe more personalised treatments.
鈥淭hat would be a real game changer for us,鈥� says , a psychiatrist at Emory University in Atlanta, Georgia. 鈥淩ight now we鈥檙e so non-specific in choosing a treatment, it鈥檚 pot luck,鈥� he says. 鈥淚 will ask patients which drugs they鈥檝e heard of, or what their friends are taking, when prescribing.鈥�
鈥淚f you could predict the course of depression, you could tailor treatment,鈥� says at King鈥檚 College London. When a person suffers a period of sadness, it is near impossible to predict whether it is likely to simply pass with time or spiral into severe depression, leading to shattered lives and perhaps even suicide. 鈥淭he problem is that you only realise when it鈥檚 too late.鈥�
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Now Pariente鈥檚 team have found that some people may be more biologically sensitive to triggers for depression, and that this heightened sensitivity could be spotted using a blood test.
They discovered this by studying people who were taking a drug called interferon alpha. Used to treat hepatitis, it is thought to work by ramping up immune system activity.
One side effect of the drug is that between 30 and 40 per cent of those who take it go on to develop depression. The drug can have an effect similar to experiencing a stressful life event, says Pariante 鈥� some who take it will develop depression, while others will be resilient.
Pariante鈥檚 team monitored 58 people who took the drug for six months for hepatitis C. The researchers took blood samples before and after this period, and assessed the participants鈥� mental health using questionnaires.
By the end of the period, 20 of them had experienced a major depressive episode, with symptoms such as persistent fatigue, sadness, hopelessness, and loss of appetite.
When Pariente鈥檚 team looked at the blood samples, they found that these individuals had altered patterns of gene expression before they even started taking the drug. These people seemed naturally to make more proteins that are involved in inflammation, oxidative stress and the death of neurons, and fewer proteins involved in brain cell growth (Neuropsychopharmacology, ). 鈥淥verall, this has a toxic effect on brain function,鈥� says Pariante.
Immune link
Inflammation is usually a result of the healing response, caused by the immune system targeting and protecting damaged tissue. But there is mounting evidence that elevated levels of inflammation are linked to a number of disorders (see 鈥�An aspirin a day?鈥�), including depression.
Previous work has shown that around half of people with depression have heightened levels of immune cells and compounds that cause inflammation in their blood 鈥� and that it is this group of people who see little or no benefit from , such as drugs that affect serotonin or other brain signalling chemicals.
The discovery that changes in gene expression are detectable before the onset of depression could help predict how badly someone is likely to respond to particularly stressful life events, such as a bereavement. This information could warn doctors to monitor at-risk patients, and help them decide when medication might be helpful.
鈥淚 agree that identifying gene expression signatures could be used as risk biomarkers for the prediction of depression,鈥� says at Deakin University in Geelong, Australia. 鈥淚f we can identify at-risk individuals and the pathways involved, we know in whom we can or should intervene.鈥�
The finding could also improve treatments. Blood tests could be used to see if a person with symptoms of depression has an overactive immune system. Those who show signs of significant inflammation could then take drugs that target the immune system instead of medicines like Prozac, which act on serotonin.
Once upon a time, being biologically sensitive to stress would have been a useful adaptation, says Pariante. He thinks that in our evolutionary past, the biggest sources of stress would have been things that put us at risk of injury or infection, such as an attack from a predator. It would make sense to ramp up the immune system to respond to such events.
But now, when much of our stress stems from relationships or work, this response is causing unnecessary and potentially harmful inflammation. 鈥淭oday, the price we pay for the response is too high,鈥� Pariante says.
An aspirin a day?
Inflammation鈥檚 telltale fingerprints are increasingly showing up in a range of conditions. People who develop schizophrenia have more active immune cells in their brain even before their symptoms appear, for example. And although heart attacks are caused by arteries getting physically blocked, there is now evidence that the inflammation of blood vessel walls is also an important factor.
At least three types of tumours often form at sites of inflammation. Some studies suggest that low doses of aspirin might .
Inflammation may also be part of the root cause of Alzheimer鈥檚 disease. A powerful anti-inflammatory drug usually used for arthritis has shown promise in tackling the condition in a trial. Clare Wilson
This article appeared in print under the headline 鈥淧rimed for depression鈥�
