Examining the Use of Biomarkers in Establishing the Presence and Severity of Impairments Proceedings of a Workshop (2020) / Chapter Skim
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3 State of the Science for Specific Impairments
3 State of the Science for Specific Impairments
Pages 17-36
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From page 17... ...
. • There is no chronic pain condition where there is a good re lationship between anything peripherally measurable (e.g., radiograph or magnetic resonance imaging)
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. Trivedi also referenced a meta-analysis review on reward processing in depressed patients compared to healthy controls, which found consistent neural aberrations in imaging in the depressed patients (Keren et al., 2018)
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depression, but only if there is some elevation in inflammation, as measured in this study, at least through TNF-alpha." Brain-Based Biomarkers Trivedi shared a recently published EEG study he worked on with Amit Etkin, chief executive officer at Alto Neuroscience, which used a machine-learning approach to predict antidepressant response in major depression (Wu et al., 2020)
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. Etkin said EEG machine learning can help identify people who would be responsive to a particular intervention.
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can be a way to help patients achieve remission much faster. Etkin suggested that "You can train a machine-learning classifier to detect a certain subtype in one cohort and apply it to another with 90 percent accuracy, consistently." He added that replicability and robustness are important guiding factors for biomarker development and use.
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The only two exceptions are Alzheimer's disease and narcolepsy, he added. One of the first biomarkers associated with mental disorders was identified in 1967, when cerebral plaque findings in deceased patients were correlated with dementia severity and cognition (Roth et al., 1967)
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Neuromelanin can be detected using simpler imaging, and its presence in the mid-brain as a biomarker of dopamine has been validated in postmortem brains. Sulzer et al.
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From a biomarker standpoint, he said there are imaging modalities that can be used to detect this deterioration, but brain changes detected by imaging often come too late in the disease progression to have strong mitigation opportunities. Another method that is promising is using spectroscopy, Lieberman said, which involves comparing GABA peaks on spectroscopic resonance imaging between clinically high-risk patients who do not have the illness yet and healthy controls.
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But this assessment of negative symptoms is challenging and requires clinical experience, he said, so simply asking family members may not be enough. He shared some emerging strategies focused on "digital biomarkers" for negative symptoms in schizophrenia, and highlighted paging strategies.
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Previously, fibromyalgia was perceived "as a discrete illness characterized by focal areas of tenderness; now, it has really become the poster child for a third new mechanism of pain" called centralized or nociplastic pain, said Clauw. This mechanism also includes other pain conditions like irritable bowel syndrome, temporal mandibular joint disorder, tension headaches, and many others.
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Clauw said that even after patients with diagnosed fibromyalgia had surgery, the fibromyalgia score remained a powerful predictor, suggesting that the pain is coming more from the CNS than the actual surgical site. Other techniques, including imaging, can help researchers understand why opioids are not effective for fibromyalgia or other centralized pain states.
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Bathon explained that there is a genetic predisposition to RA. However, she said, the development of RA is a slowly evolving process where patients develop antibodies and an increased level of inflammatory cytokines, which eventually lead to joint pain and swelling.
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Treatment Response Biomarkers Treatment response biomarkers include composite scores, radiographic outcomes that can measure the effect of therapy, and patientreported outcomes, said Bathon. Many modalities used to assess damage or disability in RA do not always correlate with the patient's self-reported pain, but instead they indicate whether or not there is continued joint damage.
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. OA is often associated with pain, fatigue, sleep disturbance, walking disability and inactivity, as well as increased morbidity of heart disease, diabetes, and hypertension (Osteoarthritis Research Society International, 2016)
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LOW BACK PAIN Gwendolyn Sowa, chair of the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh, introduced low back pain as a multifactorial condition, similar to other conditions discussed, making it unlikely to use one single biomarker to tell the full story. She noted that the biggest component of disability for back pain comes when the patient transitions from acute to chronic pain.
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In addition to the association with pain scores, she said markers such as RANTES, which is a systemic inflammatory biomarker, have been shown to assess functions like gait speed and the Short Performance Physical Battery. Biomarkers for Treatment So, Sowa asked, how are biomarkers useful to guide treatment decisions?
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Brady asked about the next steps for biomarkers that have been identified to show early detection in order to develop learning algorithms for predictive treatment outcomes. Etkin said that the next step is validation, with a locked FDA compatible design.
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Once you have the equipment, he said, EEGs can be done by anyone, and cognitive tests and blood tests are also easy to conduct and cost-effective, so the main question is how good is the biomarker in addressing the value generated through that test. Another view Etkin suggested considering is the perspective of seeing psychiatric disease as a biological disease, and whether there are issues of stigma and compliance.
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From page 35... ...
She noted that she has seen this in RA where a patient has pain and after an MRI shows some small erosions, the patient is led down a path of medications and toxicities even if he or she never develops any other pain. Sowa agreed that the same occurs for the low back pain population, where patients "are horrified upon finding out they have degenerative disc disease, but the diagnosis does not give them an understanding of pain, function, or prediction of lifelong disease." From there, she said it is difficult to convince and empower patients that they can get back to work and their activities, and that they should not just rely on a radiographic diagnosis to define their condition.
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