Connection Between Brain, Depression and Effectiveness of Chemotherapy

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Chemotherapy is a type of therapy that uses various, rather aggressive, medicines to eliminate cancer cells from the body or slow down the growth of tumors. Cancer cells are different from normal cells as they reproduce a lot faster. Chemotherapy specifically targets the fast dividing cells and thus affects cancer cells the most. However, chemotherapy is a systemic therapy and therefore can be harmful for all other cells in the body. It has the largest negative effect on normal tissues that are quickly generated (e.g., blood cells, hair follicles, and sperm cells). Despite the disadvantages, chemotherapy remains one of the most important approaches to cancer treatments.

People with the same type of cancer can react very differently to the same chemotherapy regiments. In some patients, chemotherapeutic drugs demonstrate much stronger effect on cancer cells, while in the others the tumor continues to grow unaffected.

The list of factors that influence the effectiveness and outcomes of chemotherapy is in the hundreds at least. Tumors of the same type are never exactly the same, as they might be caused by different mutations and influenced through different regulatory mechanisms and pathways. The individual sensitivity to chemotherapeutic agents can also differ widely depending on the patient’s sensitivity to drugs, and their ability to metabolize them and remove the metabolites.  Chemotherapeutic agents rarely kill all cancer cells but they can weaken the disease and thus allow the natural immune response to cleanse the body of cancer cells. However, immune system strength can vary greatly and depends on the patient’s age, general health status and presence of other chronic diseases and comorbidities. Therefore, predicting the outcome of chemotherapy is never an exact science, and practitioners only compare treatments in terms of their statistical chances of success.

Novel studies have added a new dimension to the complexity of chemotherapy: it turns out that its success is also linked to the psychological state of patient’s brain.

A few months ago at the end of 2016, researchers from Henan Cancer Hospital, Zhengzhou, China, lead by Yufeng Wu, published results that claim that depression plays an important role in the effectiveness of chemotherapy. The study was conducted on 186 patients with small cell lung cancer who underwent chemotherapeutic treatment. The mental health status of patients and their depression level were evaluated before the beginning of treatment. Patients with more severe depression had a lot more side effects associated with chemotherapy and spent more time in hospital. It was noted that patients at later stages of cancer had more severe symptoms of depression. Also, the body mass index (BMI) played an important role in depression development in cancer patients. Patients with lower BMI experienced more severe depression.

Researchers found that the level of brain-derived neurotrophic factor (BDNF) was strongly linked with depression level. In patients with more severe depression, the level of a brain-derived neurotrophic factor was much lower than in patients with less severe depression. The results demonstrate that depression influences cancer prognosis by lowering the level of the brain-derived neurotrophic factor.

BDNF reduces tissue sensitivity to chemotherapy medicines. This, in turn, reduces the effect of drugs on cancer cells. Thus, the level of BDNF indirectly influences how many tumor cells are killed by chemotherapy.

BDNF is a protein that can be found in human brain and peripheral nervous tissue. BDNF is known to increase the survival of neurons and peripheral neurons in the brain and induce the differentiation of new neurons. It also helps neurons to create new connections. BDNF plays one of the most important roles in the formation of long-term memory, and therefore plays an important role in the development of some diseases and chronic conditions such as schizophrenia, Alzheimer’s disease, depression and epilepsy.

BDNF is reduced after extended periods of severe stress associated with high cortisone levels. Lower levels of BDNF cause atrophy of parts of the brain. In case of depression, degenerative processes in the hippocampus were reported. The long-term use of depression medication does protect the hippocampus from atrophy and thus helps in the management of depression.

The reported link between depression, BDNF level, and the effectiveness of chemotherapy certainly gives scientists some food for thought and may direct further research to investigate this phenomenon. It would be interesting to see if the BDNF level in cancer patients can be elevated by using antidepressants, and if this intervention can influence the outcomes of chemotherapeutic treatments. Potentially, treatment of depression may give cancer patients a better chance in fighting the disease.

Being optimistic about health was always considered helpful in fighting various illnesses. It appears that researchers have finally uncovered the actual molecular mechanism behind the will power.  The findings point out to the importance of paying attention to the mental state of patients, as depression may seriously reduce their chances of defeating cancer.

References

Acheson, A., Conover, J.C., Fandl, J.P., DeChiara,T.M., Russell,M., et. al. (1994) A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature 374, 450 – 453. doi: 10.1038/374450a0

Huang, E.J.,  Reichardt, L.F. (2001) Neurotrophins: Roles in Neuronal Development and Function. Annual Review of Neuroscience, 24: 677-736. doi: 10.1146/annurev.neuro.24.1.677

Warner-Schmidt, J.L. and Duman, R.S. (2006) Hippocampal neurogenesis: Opposing effects of stress and antidepressant treatment. Hippocampus, 16: 239–249. doi: 10.1002/hipo.20156

Wu, Y., Si, R., Yang, S., Xia, S., He, Z., Wang, L., He, Z., Wang, Q., & Tang, H. (2016) Depression induces poor prognosis associates with the down-regulation brain derived neurotrophic factor of serum in advanced small cell lung cancer. Oncotarget, 7(52): 85975-85986. doi: 10.18632/oncotarget.13291

Image via cristhianelouback0 / Pixabay.

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