Objective Measures in Mental Health2023-06-25

If you can’t measure it, you can’t manage it.

—Peter Drucker

Blood biomarkers for mental health offer real-world clinical practice advantages. As the brain cannot be readily biopsied in live individuals, and CSF is less easily accessible than blood, we have endeavored over the years to identify blood biomarkers for neuropsychiatric disorders. A whole–blood approach facilities field deployment of sample collection. The assessment of gene expression changes focuses our approach on immune cells. The ability to identify peripheral gene expression changes that reflect brain activities is likely due to the fact that the brain and immune system have developmental commonalities, marked by shared reactivity and ensuing gene expression patterns. There is also a bi-directional interaction between the brain and immune system. Not all changes in expression in peripheral cells are reflective of or germane to brain activity. By carefully tracking a phenotype with our within-subject design in the discovery step, and then using convergent functional genomics prioritization, we are able to extract the peripheral changes that do track and are relevant to the brain activity studied, in this case anxiety state, and its disorders. Subsequent validation and testing in independent cohorts narrow the list to the best markers. In the end, we do not expect to recapitulate in the blood all that happens in the brain. We just want to have good accessible peripheral biomarkers-“liquid biopsies”, as they are called in cancer.

These biomarkers can be used as polygenic panels of biomarkers in clinical studies and practical clinical applications in the field. They may permit to distinguish, upon an initial clinical presentation, whether the person is in fact severely ill and at chronic risk. The integration of phenomic data, such as repeated measures on a phone app, can further substantiate and elucidate the diagnosis.

Biomarkers may also be useful for matching patients to medications and measuring response to treatment (pharmacogenomics), as well as new drug discovery and repurposing.

Our work is a step forward towards better understanding, diagnosing, and treating mental health disorders. We hope that our biomarkers will eventually be used in preventive primary care approaches, before the full-blown disorder manifests itself. Prevention could be accomplished with social, psychological, or biological interventions (i.e., early targeted use of medications or nutraceuticals).

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