Clinical Biomarkers Associated with Depressive Symptoms in Chronic Liver Disease Patients

Patients with chronic illnesses often report feelings of anxiety, depression, or worry associated with their condition. Brain-derived neurotrophic factor (BDNF) levels have been shown to fluctuate in the presence of chronic liver disease, psychiatric conditions, and alcohol use. This study focuses on the associations between BDNF, its related biochemical compounds, and depressive symptoms in a sample of patients from the Beatty Liver and Obesity Research Program at Inova Fairfax Hospital. The sample consists of healthy controls and patients with either non-alcoholic fatty liver disease (NAFLD) or hepatitis C virus (HCV). Patients will be evaluated for depressive symptoms based on responses to the chronic liver disease questionnaire (CLDQ), medical history of depression, and/or regular use of prescription anti-depressant medications. While laboratory work has been postponed to the spring semester, it is expected that patients with chronic liver diseases and a history of depression will have lower BDNF levels than patients with either liver disease or depression.

Hello and thank you for coming to my presentation. My name is Natalie VanderNoot and I’m presenting my study on depressive symptoms and blood analytes in chronic liver disease patients and are processed to find if there’s an association between these things. My mentor is Dr Ali Weinstein from the Department of Global and Community Health at George Mason University.

Some background from how we got to this question is focused on brain-derived neurotrophic factor. So in my first URSP project in fall of 2020, BDNF stood out as an analyte of interest based on its association with human activity, which was in turn associated with fatigue in our patient population at that time. Brain derived neurotrophic factor is a neurotransmitter in the brain that is associated with neuroplasticity and brain growth in adults, and it is also operating in the rest of the body as myokine which is a compound released from skeletal muscle but its function in the rest of the body is still under investigation. Previous studies have found that patients who have alcohol use disorder and a coinciding liver disease had a lower serum BDNF (this is the BDNF tested in their blood) than those without a liver disease, and that patients who have psychiatric conditions and mood disorders also have lower BDNF but that this can be raised by treating those patients with antidepressants.

So this led me to ask questions about our patient population at Inova Fairfax Hospital which consists of patients without liver disease, patients with non-alcoholic fatty liver disease, and patients with hepatitis c virus. And I’m wondering if the patients who have either of those two liver diseases but who don’t have significant fatigue or depressive symptoms have different levels of BDNF in their blood than the controls which might be associated with the presence of the liver disease itself. I’m also wondering if a history of depression in the patient’s medical history correlates with BDNF or any of the other blood analytes that we’ll be testing. I also have to incorporate the use of psychiatric medications because previous research has indicated that those can have an effect on BDNF concentrations so I’m wondering if the use of any sort of psychiatric medications like antidepressants or anti-anxiety medications will affect BDNF levels in NAFLD and and hepatitis c patients and I’m also curious to return to our original focus of self-reported activity and fatigue and I’m wondering if activity will affect BDNF independent of the fatigue and depressive symptoms since we did not consider any history of depression or depressive symptoms in our past analysis.

However this process led to more questions throughout the semester. The questions that I originally proposed were not as easy to answer as they seemed. I learned a lot this semester about how we can accurately answer clinical questions and what needs to go into study design that i hadn’t considered when writing my research proposal. I have to consider how we’re going to define depressive symptoms, and what surveys i’ll take those from, and since patients with different liver diseases take different surveys at our research center I have to figure out how to combine those. I have to figure out what other things I might want to test in the blood that could be associated with mental health, fatigue, or the muscle loss and activity that the research group focuses on. I have to figure out how to actually group the hundreds of medications that the patients in our sample are taking and then I have to look at all of the patients in the research studies at Inova Fairfax at the Betty liver and obesity research program and decide which of those patients are eligible and what criteria I will use to narrow down the sample and what would exclude a patient from the study.

This has been my focus for much of the semester and now going forward with this process I’m almost done my plans for the break and the upcoming semester will be to finalize the patient data set, complete the medication groupings, actually conduct laboratory testing to find the BDNF concentrations in our patient blood samples, to analyze the data, and answer the research questions and then share the results at a conference or in a publication.

Thank you for listening and I would like to also thank my mentors at George Mason Iniversity and Inova Fairfax: Dr Ali Weinstein, Dr. Lynn Gerber, Dr. Michael Estep, Dr. Jillian Kallman-Price, and Dr. Zobair Younossi. And of course a big thanks to Dr. Karen Lee and the undergraduate research scholars program for funding my work this semester.