Buying Us Time: The Search for Neuro Biomarkers

We all recall going to the doctor and getting our arm squeezed for what seemed like forever by a surprisingly tight black Velcro cuff. Believe it or not, the doctor wasn’t doing this to make us uncomfortable; this test was done to check our blood pressure, which means making sure our blood was pumping with a healthy amount of force. As the doctor let the air out, she reported “120/80 mmHg” a normal blood pressure. Whew! We can all breathe a sigh of relief. A high reading, like 140/90 mm Hg, would be bad and require medical interventions. In this case, the measurements that the doctor obtained were serving as a biological marker, or biomarker, for problems with our circulatory system.

Biomarkers are extremely important in medicine and because they are ways to measure how well inner parts of the body are working from the outside. Biomarkers are helpful for doctors because they are accurate and reproducible, meaning they can trust the results [1]. Imagine you were going to your favorite restaurant. You would want the food to be made with all the correct ingredients (accurate) and the peace of mind that it would taste the same the next time you come (reproducible)! 

Almost any disease you can think of, like cancer, COVID-19, or heart failure, have distinct biomarkers that are classified as predictive (show your risk for disease), diagnostic (show if you have a disease), monitoring (measure symptoms of a disease), and therapeutic (find the best treatment for a disease) [2]. Detecting biomarkers is essential for our doctors to monitor our current health, decide the most appropriate treatments for diseases, and help researchers better understand the mechanisms that cause a disease.

The brain has always been a fascinating organ. When the brain works correctly, we can do many amazing things like playing a musical piece on the piano entirely by memory or balancing on a surfboard. However, with a complex composition of 100 billion neurons and 60 trillion connections between them, there is the unfortunate flip side of our brains: disease [3]. Neurological and psychiatric diseases can be devastating and hard to understand because patients with the same disease can have very different symptoms [4]. Researchers use many techniques and technologies to understand brain illnesses to try to find  new neuro biomarkers that are the same in all patients, which could help save lives.

Cerebral Spinal Fluid Biopsy

Some of the most prominent neuro biomarkers have been seen in the neurodegenerative Parkinson’s disease and Alzheimer’s disease. Parkinson’s disease is notable for changes in an individual’s movement. The disease is due to the loss of dopamine neurons in a brain region called the substantia nigra. Unfortunately, you cannot know for sure if someone had Parkinson’s until after they have died, because there is no way to measure dopamine neurons directly in the brain without performing an autopsy [5]. Instead, doctors measure levels of proteins, like alpha-synuclein, in cerebral spinal fluid, clear fluid that flows in and around your brain and spinal cord, as biomarkers to diagnose Parkinson’s [6]. A similar method is used to diagnose Alzheimer's, a disease that causes extensive memory loss, by measuring levels of tau and Aβ42 proteins in the CSF [7].

Electroencephalogram

Other types of biomarkers use measurements from electroencephalograms (EEG), a noninvasive clinical tool to monitor brain activity. EEGs are extremely useful to diagnose epilepsy and seizure disorders and more recently are used as another tool to diagnose Alzheimer’s [8]. Additionally, EEG abnormalities are currently being explored as possible biomarkers for the neurodevelopmental disorder Autism Spectrum Disorder [9]. 

Blood Draw

Elsewhere in the world of psychiatric biomarkers, researchers are learning more about the brain’s interaction with the rest of the body via the blood. Numerous research labs have found biomarkers like short non-coding RNAs and cytokine proteins released from immune cells in patients with depression [10, 11]. These unique findings provide us with more insights into the possible mechanisms of a highly complex disorder.

Functional MRI Scan and Machine Learning

Just like we get an MRI if we have knee pain, we cannot ignore the importance of brain imaging. Researchers use a version of MRI called fMRI (functional magnetic resonance imaging) to measure activity between connected regions across the whole brain, by tracking changes in blood-oxygen levels. Measurements from fMRIs may be promising biomarkers to diagnose Post-Traumatic Stress Disorder (PTSD) from understanding how the hippocampus (memory storage) and amygdala (emotion center) communicate in patients with PTSD [12]. Exciting developments in Artificial intelligence (AI) and Machine learning (ML) are helping researchers better understand complicated fMRI measurements to potentially predict the onset of neurological and psychiatric diseases in an unbiased and reproducible way [13].

Studying neuro biomarkers is very exciting because there are countless promising biomarkers and many more that are still being discovered. Only some neuro biomarkers have actually been approved for doctors to use, which shows the importance of understanding neurological and psychiatric diseases. Discovering more neuro biomarkers will help diagnose patients earlier to extend and save their lives. I am always excited to go to lab, hoping that my research will contribute to new discoveries!

References:

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9. Bosl WJ, Tager-Flusberg H, Nelson CA. EEG Analytics for Early Detection of Autism Spectrum Disorder: A data-driven approach. Scientific Reports. 2018; 8(1): 6828.

10. Kargbo RB. Pioneering Changes in Psychiatry: Biomarkers, Psychedelics, and AI. ACS Medicinal Chemistry Letters. 2023; 14(9): 1134-7.

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12. Yuval Neria, Ph.D. Functional Neuroimaging in PTSD: From Discovery of Underlying Mechanisms to Addressing Diagnostic Heterogeneity. American Journal of Psychiatry. 2021; 178(2): 128-35.

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Edited by Alexandra Fink