Chemotherapy linked to increased risk of depression in cancer patients

A chemotherapy drug used to treat brain cancer may increase the risk of patients developing symptoms of depression, scientists have said. It may do so by preventing neurogenesis – the birth of new brain cells.

Cognitive impairments and mental health problems – depression and anxiety in particular – have often been observed in cancer patients. However, a poor integration of mental health services and oncology services in the UK means that these needs are not always well addressed.

Dr Annabel Price, a psychiatrist on the executive committee of the faculty of liaison psychiatry at the Royal College of Psychiatrists, told IBTimes UK: "There is a growing recognition that people have both physical and emotional needs at different point throughout their cancer journey. But at present, there is a lack of integration between physical and psychological care, some patients struggle to access the metal health services that they need as part of their cancer care.

"If we are going to manage cancer care in the way that is most helpful to patients, then we need to think about psychological care and support as part of their cancer treatment".

It's not exactly clear what makes cancer patients more vulnerable to depression – and learning more about this may be important to improve care.

Mental health problems may arise as a result of the diagnosis and the stress of having cancer, but chemotherapy treatment and its effects on the brain may also be to blame.

A study now published in the journal Translational Psychiatry is the first to show, in mice, that chemotherapy can induce depression symptoms.

Chemotherapy and neurogenesis

A majority of cancer patients are treated with chemotherapy, which stops cells in the body from dividing, including brain cells. Although this contributes to killing cancer cells, the treatment has a number of significant side-effects, such as hair loss.

The team from King's College London investigated the impact of chemotherapy on neurogenesis, and how it could leave people more vulnerable to depression.

They gave healthy mice chemotherapy drug known as Temozolomide (TMZ) which is often administered as a treatment for brain cancer in humans. The scientists observed a reduction in the growth of new neurons in the hippocampus – the brain region associated with emotion and memory.

They also discovered that the more neurogenesis was prevented by the drug, the greater the increase in stress hormones when exposed to stress.

Finally, they noted changes in the behaviours of mice who had undergone chemotherapy. Some of their behaviours appeared to mimic some of the symptoms of depression that are seen in humans, such as a lack of pleasure seeking or behavioural despair (which mimics how depression patients easily give up or are less motivated).

The findings suggest that chemotherapy may stop the growth of new brain cells, with biological and behavioural consequences that may leave people less able to cope with the stress of having cancer and more at risk of depression.

Although this is a mouse model, and therefore does not entirely represent what is going on with depression patients, it is the first to show this link between chemotherapy, neurogenesis and depression. Other chemotherapy drugs acting on cell division, like TMZ, would likely have the same effect.

"What is important about this paper is that it develops the evidence base for what we see in clinical practice – that people can struggle with mood during and after cancer treatment. This potential mechanism is an important area for further research", Price, who is also a Consultant liaison Psychiatrist at Addenbrooke's Hospital, commented.

Brain training

The researchers believe these findings could help improve the care and the quality of life of cancer patients.

"It may be important to inform patients before chemotherapy of the potential side-effects. Just as clinicians inform people about hair loss, they might also inform them about the fact that they might develop depression symptoms. It does not mean that they will get depression but it will make them more vulnerable", senior author Dr Sandrine Thuret told IBTimes UK.

The scientists are also keen to validate these findings in humans, although at present they have no way to observe neurogenesis directly in the brains of live patients.

On the long-term, they would like to test if certain interventions in cancer patients, such as cognitive training, can increase their neurogenic reserve before they go on to chemotherapy – and thus protect them better against depression.

"We would like to boost the pool of stem cells in the hippocampus that give way to neurons before chemotherapy treatment. We can't do anything during treatment, but maybe could we do cognitive training before, or give people antidepressants as preventive measures, if they agree to it", explained Thuret.

Selecting the participants to conduct such a study will not be an easy task as it will require a large number of patients and scientists will be constrained by timing to carry out their interventions, as some people may urgently need to receive chemotherapy.

"We will have to determine when is the best time to intervene and how much time we have. Treating the cancer is the priority of course. However, if we can improve the quality of life of the patient, it can also be a step forward and may reduce their vulnerability to mental health problems", she concluded.