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Determination of the association between BDNF, a potential biomarker, and depression in patients with cancer

Principal Investigator
Name
Lei Zhang
Degrees
M.D.
Institution
Uniformed Services University
Position Title
Associate professor
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
PLCO-1021
Initial CDAS Request Approval
Aug 22, 2022
Title
Determination of the association between BDNF, a potential biomarker, and depression in patients with cancer
Summary
Depressive disorder is the leading cause of disability worldwide. Its economic burden was over 83.1 billion USD in the year 2000. People with multiple chronic conditions (MCCs), including comorbid depression and cancer, now comprise over one-quarter of the U.S. population, and that percentage continues to grow. The depression rate in cancer patients is twice more than the prevalence in the general population. Cancer patients with depression could feel low energy, decreased drive, trouble making decisions, and uselessness/helplessness, showing a significantly higher risk of adverse outcomes and complications, more clinic visits, and more medication intake. Although depression in cancer patients ominously results in a poorer Quality of Life (QOL), interferes with medical care, compromises patient outcomes, and leads to higher mortality rates, it is sometimes overlooked. A primary challenge for early identification of depression in cancer patients is the lack of an objective assessment or biomarker for depression. Its diagnosis is currently reliant on the description of symptoms and medical history. The lack of an objective assessment impedes patients from choosing the best treatment option and results in a poorer QOL. Our long-term goal is to study the possible molecular mechanism and to identify biological diagnostic markers for depression, particularly in cancer patients. Recent studies have highlighted that depression has been associated with several potential protein markers, including Brain-derived neurotrophic factor (BDNF), which might constitute a translational study to develop an assessment predicting depression in cancer patients.
The BDNF is a neurotrophic factor that regulates neuronal survival and synaptic plasticity. Several pieces of evidence show that BDNF plays a vital role in depression. For example, depressive/suicide risk is associated with the dysregulation of the BDNF receptor. BDNF up-regulation is observed in patients with depression treated with antidepressants. The investigators of this proposal have pioneered biomarker studies of BDNF in mental disorders and found that BDNF is associated with suicide ideation in 3,889 US service members deployed to Iraq and Afghanistan. The immediate objective of this study is to examine our evidenced hypothesis that BDNF is associated with depression using existing PLCO data cost-effective. It has not been tested elsewhere previously. To achieve this objective, we will request the data on Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) to determine or validate the original discovery showing the association between BDNF and depression in the military population. We will examine the relationships between BDNF and depression and the sensitivity and specificity of BDNF in the diagnosis of depression in cancer patients; Moreover, we will analyze the effect of the BDNF gene and environment (G x E) interaction on depression in cancer patients. Environmental factors include education, sleep, smoking, pain, etc. The proximate expected outcome of this work is that it may provide a new approach for identifying depression and significantly positively impact mental health, particularly in cancer patients.
Aims

We would like to request existing PLCO data from the study titled Multiplexed Assay of Serum Biomarkers for Pancreatic Cancer to determine the association between BDNF (a depression-relevant molecule) and cancer. Our objective is to examine if BDNF is associated with depression in patients with cancer in PLCO.
Previously we found that BDNF was associated with depression in the military population by using a sample of Service members who deployed during the Iraq and Afghanistan wars. Like deployment, a cancer diagnosis is traumatic life stress. It often results in non-pathological sadness and even comorbid depression. In the U.S., over 25% of 1.2 million cancer patients annually may be diagnosed with depression. This depression rate is twice more of the general population. Our long-term goal is to study the possible molecular mechanism, identify new biomarkers for the development of diagnostic approaches and, therefore, help antidepressant planning. Our hypothesis is that BNDF is associated with depression in cancer patients. This hypothesis is based on synthesizing our own and others’ published work. We will test our central hypothesis and attain our objective via using PLCO data. The data include:
• BDNF levels in the blood
• Demographic data
• Addition variables: Such as smoking, pain, and stressful life events.
• Supplement intake (calcium and vitamin D).
• Diagnosis: Depression or non-depression, the stage of cancer.
• Depression may be associated with many conditions, such as vitamin D, excise, age, sex, education, and traumatic stress. Therefore, we will examine the relationships between BDNF and the variables to understand better the gene and environment interactions (G x E).
To achieve our objective, the following Specific Aims are proposed: 1. Characterize the relationships between BDNF and depression in cancer patients, including the association between BDNF, diagnostic sensitivity, specificity, and the severity of depression in cancer patients. 2. Study the effect of the BDNF gene and environment (G x E) interaction on depression in cancer patients. Environmental variables include age, sex, education, smoking, pain, race, etc. Impact: Our study may generate not only feasible results to better understand the mechanisms of depression but also to identify an innovative target for prevention and treatment in cancer patients, which may have a significant positive impact on improving their quality of life.

Related Publications
1 Spiegel, D. Cancer and depression. Br J Psychiatry Suppl, 109-116 (1996).
2 Colucci-D’Amato, L., Speranza, L. & Volpicelli, F. Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. International Journal of Molecular Sciences 21, 7777 (2020).
3 Fiedler, D. et al. Brain-Derived Neurotrophic Factor/Tropomyosin Receptor Kinase B Signaling Controls Excitability and Long-Term Depression in Oval Nucleus of the BNST. J Neurosci 41, 435-445, doi:10.1523/jneurosci.1104-20.2020 (2021).
4 Lee, B.-H. & Kim, Y.-K. The Roles of BDNF in the Pathophysiology of Major Depression and in Antidepressant Treatment. Psychiatry Investig 7, 231-235, (2010).
5. Zhang L. et al., Genetic predictor of current suicidal ideation in US service members deployed to Iraq and Afghanistan. Journal of Psychiatric Research. 2019, 65-71

Collaborators

Collaborators
Xianzhang Hu (USUHS)
Robert Ursano (USUHS)
David M. Benedek (USUHS)