Psychologist researches impact of depression and circadian disruption to head and neck cancer patients
Tue, 06/04/2019 - 12:32
Liz Cash

Elizabeth Cash, Ph.D., works with and researches the unique experiences of head and neck cancer patients at UofL James Graham Brown Cancer Center. She is a psychologist specializing in helping patients cope with stressful diagnoses like cancer. With a research background centered on cancer biology, she and her team have examined how psychological and social aspects of a diagnosis of head and neck cancer contribute to treatment outcomes and survivorship. An important aspect of her work is making sure it is rapidly translatable, so that findings offer information that can immediately be used to benefit our current head and neck cancer patients as they navigate treatment.

Read more about Dr. Cash’s research below, including the impact of depression and circadian disruption:

Research Target: The Impact of Depression
When I began my position in 2014, I quickly learned that many head and neck cancer patients were experiencing symptoms of depression, and this seemed to make it more difficult for them to navigate treatment. We began carefully assessing depressive symptoms with patients near the time of diagnosis and treatment planning. We discovered that patients who reported more depressive symptoms at their initial appointments were more likely to miss scheduled chemotherapy and/or radiation treatments. We also learned that patients who start treatment with more depressive symptoms have tumors that were more likely to persist after treatment.

The continued support of the Karman Bush gift fund allowed us to extend this research in an innovative way that, to our knowledge, no other group has done for head and neck cancer patients. By observing patients for two years after their diagnosis, we have shown that patients who were depressed at the time of their diagnosis also suffered higher mortality rates. To better understand how this might be, we examined patients with persistent tumors to see if biological processes might explain the connection between depression and cancer survival. We found that, at least in part, this was the case. Intriguingly, depression seems to play a unique role in the outcomes of our head and neck patients that coincides with, but is not fully explained by, the activities of the tumor. These findings have recently been published in a high-impact, rigorous cancer research journal, where we hope they may be of benefit to head and neck cancer care providers and patients on a more national level.

Research Target: Circadian Disruption 
This work laid the foundation for expanding our focus to more closely examine biological pathways that might explain how depression influences head and neck cancer treatment outcomes. We know that patients who are depressed have often lost interest in daytime activities and have trouble sleeping at night. These shifts in daily (circadian) rhythms have demonstrated importance in prior cancer research. The 2017 Nobel Prize in Physiology or Medicine honored scientists who discovered the molecular mechanisms of circadian rhythms. We applied this information to extend our work with our head and neck cancer patients. 

From the work of pioneering scientists, we have learned that human biology is deeply entwined with the rotation of the earth: Our physical activities – even the activity of our individual cells – follow the earth’s circadian rhythms. Even subtle shifts of our own biological rhythms away from regular circadian patterns can place us at increased risk for the initiation of cancer or faster growth of tumors. 

It is also clear that circadian biology can alter the response of tumors to medical treatment. It is not clear how circadian disruption influences cancer outcomes. With complementary funds from a University of Louisville research incentive grant, my team and I have been collecting circadian disruption measures from our head and neck cancer patients using non-invasive wrist-worn devices (similar to a Fitbit) to measure sleep and physical activity. We found that patients who were experiencing more depressive symptoms at the time of diagnosis were also suffering from more sleep disruption at night, and both of these features were significantly associated with shorter two-year overall survival. Notably, depression and nighttime sleep disruption also predicted whose tumors were more likely to persist after treatment. 

We believe our work is some of the first to observe the phenomenon of circadian disruption among head and neck cancer patients. So far, our findings have been presented at national and international research meetings and published in top-tier cancer scientific journals. Given that our culture increasingly disconnects human activity from the earth’s day/night cycles, we are continuing this work to illuminate how a complex, understudied, and potentially harmful interaction of humans with their circadian environment may be a determinant of success in medical treatment for head and neck cancer. We are expanding our assessments in future studies to measure other factors under circadian control and with proven cancer influence, including stress hormones and body temperature fluctuations. We are also planning to study how circadian disruption may drive tumor progression by studying relationships to growth receptors that are expressed on tumor surface. 

Benefit to Patients
Because of our increased understanding on how depressive symptoms may play a role in treatment success, my team and I have a better understanding how best to help our patients. For example, we may be able to offer suggestions that may lessen the impact of depression, such as strategies for getting good sleep, keeping physically active, talking about pain with their physicians, and doing things they enjoy to brighten their mood. Medications like anti-depressants and sleep-aids may also be beneficial. Because both depression and circadian disruption can be altered by behavioral and pharmacological interventions, we feel these are promising targets for enhancing cancer treatment and extending life expectancy in patients with head and neck cancer.