Reading time: 8 minutes
Colette Bilynsky
The number of people who will be diagnosed with cancer in their lifetime is growing, with estimates saying that by 2030, more than 26 million people worldwide will be affected by some type of cancer [1]. However, as noted throughout Oncobites, treatments are continually improving, resulting in increased patient survival. This means that more and more people will be living with the trauma of their diagnosis and treatments. Additionally, rigorous follow-ups with oncologists–which are standard for cancer survivors–can continuously expose patients to related stressors.
Unsurprisingly, considering the reasons listed above, many cancer patients will end up developing mental health conditions, including depression, anxiety, or post-traumatic stress disorder (PTSD) [1]. One German study in 2017 found that one in four cancer patients is depressed, with brain and thyroid cancer patients being the most affected [2]. Furthermore, cancer patients are five times more likely to be depressed than the general population [2]. The exact prevalence of depression in cancer patients is variable depending on the study, though the range is between 5% and 60% [1]. Patients also demonstrated post-traumatic stress symptoms, with the reported rates of PTSD in cancer patients being between 3% and 35%, depending on the reporting author [3]. When the demographics from over 6,000 breast cancer patients were analyzed, it was found that around 38% of patients had some sort of psychiatric disorder diagnosis. The most common diagnoses were anxiety (27.7%), depression (21.9%), and stress reaction/adjustment disorders (6%) [4].
In addition to the added physical and mental burden of mental health disorders, cancer patients with a psychiatric diagnosis have significantly higher healthcare costs than those without [4]. In the breast cancer study referenced previously, the researchers found that patients with a psychiatric disorder were significantly more likely to see their primary care provider, visit the emergency room, or need an inpatient admission than those without a psychiatric disorder [4]. Numerous studies have demonstrated that depression relating to a cancer diagnosis causes a delay in the start of treatment (which can lead to worse outcomes), a lowered quality of life, and an increase in suicide attempts [1]. This highlights the need for a mental health hygiene regime that can adequately support cancer patients.
The causes of both cancer and mental health disorders are complex and intricate; however, there are some biological links between the two that could contribute to the increased prevalence of these disorders in cancer patients [1], [5], [6]. While the psychological stress related to cancer diagnosis is a large factor in the comorbid (simultaneous) psychiatric conditions, there are other overlapping factors. For depression, both cancer patients and people with depression will experience sleep disruption, inflammation, an imbalance in the gut microbiome, and abnormal neurotransmission (how the cells in your brain communicate with each other) [1]. The mouthful of a term psychoneuroimmunoendocrinology (PNIE) refers to the signaling that occurs between the nervous, immune, and endocrine (glands that release hormones) systems along with the gut microbiome and the psychological functioning of the person [1]. PNIE is considered to be the link between complex conditions like cancer and mental health conditions [1]. Below is an introduction to some of the underlying biology for some of these overlapping factors between cancer and psychiatric conditions:
- Sleep Disruption
As mentioned, cancer is a huge psychological stressor. This type of high stress leads to the hyperactivation (abnormally high activation) of the hypothalamic-pituitary-adrenal axis (HPA), which is a signaling cascade that begins in the hypothalamus in the brain that goes to the pituitary and adrenal glands [1], [6]. This leads to an increase in cortisol levels. Hyperactivation of the HPA is associated with the development of major depressive disorder [1]. Furthermore, having the HPA abnormally activated leads to cortisol being released at incorrect times, disrupting the circadian rhythm [1]. Typically, cortisol concentrations should be high in the morning and low in the evening. Cancer patients however, will often see a spike in cortisol concentration at both 8 AM and 8 PM [1]. Furthermore, cancer patients with depression will see less normal variation in their cortisol levels than those without the psychiatric disorder, which implies an increasingly distributed circadian rhythm [1], [6]. Besides cortisol, melatonin (another hormone that regulates a person’s circadian rhythm) has been found to be dysregulated in both cancer and major depressive disorder [1]. Your circadian rhythm is the internal 24-hour clock that tells your body when it should be alert or sleepy, affected by hormones as well as light changes around you [7]. Because of this, when a patient’s circadian rhythm is being dysregulated, they will experience trouble sleeping or interrupted sleep.
- Inflammation and the gut microbiome
Cancer patients will often have both a disrupted immune system (leading to chronic inflammation) and an abnormal gut microbiome composition [1]. I’ve discussed in a previous article how chronic (long-lasting) inflammation can lead to an altered gut microbiome and to colorectal cancer. This chronic inflammation seen in cancer patients can affect the brain, which is called neuroinflammation. Inflammation, particularly neuroinflammation, is also commonly seen in major depressive disorder [1]. Psychological stressors can cause chronic inflammation due to the constant activation of the sympathetic nervous system, leading to the release of pro-inflammatory cytokines (or proteins that tell cells how they should function in a given scenario) [5]. These cytokines can cause the activation of the HPA, which, as we discussed in the previous section, can lead to depressive symptoms. Cancer patients with depression have been found to have an increased level of IL-6 (one of these cytokines) [1]. IL-6 is considered to be a major indicator of major depressive disorder.
People with depression often will also have an altered gut microbiome as well as increased bacterial translocation, which is when bacteria from the gut microbiome makes its way into sterile tissues where it does not belong [1]. One study of colorectal cancer patients found specific families of microbiota that correlated with depression, while other microbiota correlated with a lack of psychiatric disorder [8]. In patients with breast cancer or gastrointestinal cancer, a decreased diversity of gut microbiome leads to an increased likelihood of depression and anxiety [9], [10].
- Abnormal neurotransmission
Monoamines (dopamine, norepinephrine, and serotonin) are neurotransmitters (signaling molecules that allow the cells of your nervous system to communicate) that play a central role in many psychiatric disorders [1]. Many typical antidepressants, including SSRIs (serotonin selective reuptake inhibitors), target these monoamines. Monoamines affect a person’s mood, thoughts, attention, behavior, and senses, and so, it’s probably not surprising that if the levels of these monoamines are altered, people will often experience negative mental health symptoms [1]. Some tumors are able to affect a patient’s monoamines. For example, some tumors can affect how the body is able to break down serotonin, leading to its increased concentration at the tumor. This will cause a decrease in serotonin reserves in the brain, which can cause depressive symptoms [1]. Furthermore, some tumors will activate an enzyme that converts a precursor to serotonin into kynurenine (KYN) [1]. This has two big effects. Firstly, it will reduce serotonin synthesis [1]. Secondly, the KYN can enter the brain and be broken down in quinolinic acid and kynurenic acid. Quinolinic acid then causes toxic effects on the cells within the brain [1].
There are some challenges associated with treating psychiatric disorders in cancer patients. As we discussed in the previous sections, cancer patients will often exhibit lots of inflammation. However, depressive symptoms that are associated with inflammation do not respond as well to typical pharmacological therapies (like anti-depressants), meaning that we need to find different, more effective therapies for these patients [5]. One of the challenges with treating stress disorders in cancer patients is that most studies of individuals with post-traumatic stress symptoms have focused on disaster victims, where a singular catastrophic event was the stressor [3]. Cancer patients, however, are exposed to an ongoing series of traumatic events that act as stressors: diagnosis, active medical treatment, post-treatment recovery, and long-term monitoring [3].
There have been a few studies on how best to treat psychiatric disorders in cancer patients. A meta-analysis of 14 clinical trials (which includes 1,364 patients) looked at the effectiveness of using different antidepressants [11]. They found that none of the antidepressants were more effective than the others, and even that the antidepressants were no more effective than the placebo [11]. These results have been confirmed in an observational study on hospice patients with cancer [12]. Furthermore SSRIs, a type of antidepressants, can worsen nausea, which is already a huge problem for cancer patients receiving chemotherapy or radiation [6]. A COX-2 inhibitor (which would cause decreased inflammation) was found to decrease depressive symptoms in colorectal cancer patients [5]. Some non-pharmaceutical therapies have also been tried. A mindfulness approach that aimed to reduce stress, was able to reduce both depressive symptoms and inflammation in breast cancer patients [5]. Group therapy was similarly effective [5]. The major problem with these approaches is the limited data available on their effectiveness. Besides therapies, oncologists need better tools to be able to recognize mental health disorders in their patients. It’s estimated that around 60% of depressed cancer patients go undetected, with elderly patients at particular risk of being unrecognized [5]. Because of the overlap between the physical symptoms of depression and cancer (lack of appetite, sleep disturbance, fatigue, cognitive difficulties), and some patients’ unwillingness to “burden” their oncologists with their emotional symptoms, it can be very difficult to recognize depression in these patients [5], [6], [11].
While the research into new methods to treat and diagnose cancer is exciting and necessary, it is important that we also psychologically support these patients. There are not adequate studies into the best methods to treat or diagnose psychiatric conditions in cancer patients, and this is a vital and underserved research area.
Edited by Karli Norville
Works Cited:
OncoBites 
Leave a comment