A chemotherapy drug used to treat brain cancer may increase vulnerability to depression by stopping new brain cells from growing, according to a new King's College London study out today in Translational Psychiatry.
Depression is thought to be the least recognised symptom in people with cancer. It has previously been difficult to determine if some people with cancer develop depression as a result of chemotherapy or the stress of having cancer itself.
Although an early animal study, these findings are the first to suggest that chemotherapy causes behavioural and biological brain changes related to depression that are separate from the psychological distress resulting from a cancer diagnosis.
Recent research has shown that depression is most common in cancer patients who have brain cancer. Studies show that around 30 per cent of patients with brain cancer experience depression and the disorder is thought to be highly under-diagnosed. For example, one recent study pointed out that 90 per cent of patients self-reported symptoms of depression, whereas only 20 per cent were classified as having clinical depression.
Most cancer patients are treated with chemotherapy as a lifesaving intervention that stops all cells in the body from dividing. The primary outcome of this treatment is to kill rapidly dividing cancer cells, but disrupting this process can have potential side effects related to cell division, such as hair loss. Researchers now know from animal studies that chemotherapy may similarly stop the growth of new brain cells (neurogenesis).
In their new study, scientists from King's College London set out to examine whether the effects of chemotherapy on neurogenesis could alter biological brain mechanisms which increase vulnerability for depression.
They administered a chemotherapy drug to mice called Temozolomide (TMZ), using the same procedure that human patients would experience in a clinic. Mice receiving the chemotherapy drug showed a significant reduction in growth of new brain cells in the hippocampus – a region associated with emotion and memory. Results from the study show that the more the drug decreased neurogenesis, the greater the increase in stress hormones when exposed to stress.
When researchers looked at the mice's behaviour following treatment, they observed several changes related to depression, including robust deficits in novelty processing and a decrease in preference for a rewarding sugar solution. A lack of pleasure seeking, as observed in mice that received the chemotherapy drug, is a core diagnostic symptom of depression.
Dr Martin Egeland, first author of the study, from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London, said: 'Although these preliminary findings are based on mice, our results suggest that chemotherapy may stunt the growth of new brain cells, which has biological and behavioural consequences that may leave people less able to cope with the stress of having cancer.
'Despite the potential side effects, chemotherapy is essential for increasing survival rates in cancer patients. However, understanding the specific effects of chemotherapy on mood could lead to improved treatments and increase quality of life for those affected by cancer.'
Dr Sandrine Thuret, senior author of the study also from the IoPPN at King's College London, said: 'Our study highlights the importance of protecting brain stem cells or building up a reserve of cells before cancer treatment. This could help to preserve the mood and cognitive functions these cells are known to regulate, and could also improve quality of life for people with cancer.
'We now need to explore whether neurogenesis enhancing interventions or drugs, such as antidepressants, can alleviate this deficit in new brain cells after chemotherapy takes place.'
This study was funded principally by an EU-FP7 Marie Curie fellowship.
Notes to editors
High-quality research images available on request.
For further media information please contact Jack Stonebridge, Senior Press Officer, Institute of Psychiatry, Psychology & Neuroscience, King's College London [email protected]/ 07718697176.
About King's College London
King's College London is one of the top 25 universities in the world (2016/17 QS World University Rankings) and among the oldest in England. King's has more than 26,500 students (of whom nearly 10,400 are graduate students) from some 150 countries worldwide, and nearly 6,900 staff. The university is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
King's has an outstanding reputation for world-class teaching and cutting-edge research. In the 2014 Research Excellence Framework (REF) King's was ranked 6th nationally in the 'power' ranking, which takes into account both the quality and quantity of research activity, and 7th for quality according to Times Higher Education rankings. Eighty-four per cent of research at King's was deemed 'world-leading' or 'internationally excellent' (3* and 4*). The university is in the top seven UK universities for research earnings and has an overall annual income of more than £600 million.
King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar.
King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: http://www.kingshealthpartners.org