RESEARCH WEEKLY: Developing Neuroimaging Biomarkers for Schizophrenia
By Elizabeth Hancq
Biomarkers are powerful clinical and public health tools. They can be diagnostic, inform treatment decisions, or help determine disease risks if prevention measures are needed. At a population-level, these objective biological measures are extremely useful to researchers who are analyzing groups of people and can also inform public health metrics such as disease prevalence. However, biomarkers for schizophrenia currently do not exist.
Biomarkers are defined by the Food and Drug Administration and the National Institutes of Health as “a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions.” Examples of biomarkers can range from blood pressure as a measure of cardiovascular health to cancer antigen 125 blood levels to understand risk and treatment monitoring for ovarian cancer.
In an article published in The American Journal of Psychiatry earlier this month, researchers from the American Psychiatric Association Workgroup for Biomarkers and Novel Treatments argue there is a tremendous need for biomarkers in schizophrenia and that neuroimaging techniques for biomarkers are a promising development. “Imaging can capture phenotypic variations in molecular and cellular disease targets or in brain circuits that are a unique representation of gene-environment interactions and are associated with behavioral alterations,” the authors write. “It offers versatility in terms of measuring multiple pathophysiological mechanisms, including brain structural integrity deficits, functional dysconnectivity, and altered neurotransmitter systems.” In other words, using neuroimaging as biomarkers allows to measure multiple things at the same time while also capturing changes in the measurements during the observation. Neuroimaging also offers more detail into the differences within particular subsets of patients that have the potential to provide more information into what is underlying particular symptoms of the illness.
There are a variety of criteria that a potential biomarker must meet for it to be useful, including measuring something that is clinically relevant, while having sensitivity, meaning it is measuring what it is supposed to, and specificity, that the measurement is due to the biological target of interest. A good biomarker is also ideally easy to measure and cost-effective.
The authors review six different possible biomarker targets that could meet the above criteria and be measured via neuroimaging:
- Dopamine hyperactivity – Dopamine is a neurotransmitter found in the brain that is known to be dysregulated in schizophrenia; many antipsychotic medications work to reduce dopamine signaling in the brain.
- NMDA receptor hypofunction – NMDA receptors and their glutamate signaling are important for a variety of neurological processes, including learning and memory function. Glutamate levels in different areas of the brain have been shown to correlate with treatment response in patients with schizophrenia.
- Hippocampal hyperactivity – Increased activity in the hippocampus region of the brain is a downstream effect of the NMDA receptor hypofunction and has been shown to correlate with psychosis severity in patients.
- Immune dysregulation/Neuroinflammation – There is a demonstrated link between immune system activation and the development of psychosis. Biomarkers related to immune system regulation may capture early illness progression or psychosis exacerbation events, according to the authors.
- Dysconnectivity – Changes in the balance of excitation and inhibition of brain cells may impact the way brain cells are connected in patients with schizophrenia. Measuring these disturbances in connections could correspond with symptom severity and treatment response.
- Cortical gray matter loss – Gray matter in the brain is what is responsible for processing information. Individuals with schizophrenia are known to have cortical gray matter volume loss, especially in their front-temporal regions of the brain. Cortical gray matter loss is often found to be already present at the onset of the illness.
The authors call on the need for a largescale nationwide initiative to advance biomarker development for individuals with schizophrenia, using the Alzheimer’s Disease Neuroimaging Initiative as a roadmap. Advances toward objectively measuring disease processes, validating new treatments, predicting treatment response and moving towards more personalized treatment rely on some investment into the future of biomarkers for schizophrenia.
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