Precision Psychiatry2022-03-19

The empires of the future are the empires of the mind.

Winston Churchill

The current diagnosis in oncology is based on clinical symptoms, imaging, and biopsies with molecular profiling. The current treatment approaches often use molecular biomarkers to match the patient to specific drugs or combinations of drugs that may work best in that patient. Those biomarkers are used for new drug development clinical trials as companion diagnostics. “Liquid biopsies”, where molecular profiling is conducted in the blood, are now being rolled out for early detection and prevention approaches. The term “precision” does not need to be put in front of oncology anymore, it is a given. It took decades of work, but the field has arrived there.

My early graduate work was in cancer molecular biology. When I moved over to brain research and psychiatry almost 25 years ago, I set as a long-term goal for my research group to catch up with oncology. Psychiatry is in many ways harder than oncology. The symptoms part needed to be organized in a more quantitative way that we called (neuro)phenomics. For the molecular profiling, the brain cannot be biopsied in live individuals so we had to triangulate between human postmortem brain data, animal model data, and blood biomarker studies in live individuals, and approach we called Convergent Functional Genomics (CFG). To address the issue of power to detect reproducible signals, we focused on gene expression, not genetics, and developed longitudinal within- subject designs, over many years, as part of a multi-step process to discover, validate and test in independent cohorts blood biomarkers. For that, we relied not only on our human and animal model clinical research and experimental studies, but also manually curated all the relevant literature in the field in large databases, that permit Bayesian prioritization approaches as part of CFG. We are very grateful to all our colleagues and groups in the field who conducted such work, and view it as a de facto field-wide collaboration.

I am happy to see that our work and discoveries over the years, described in a series of comprehensive papers by my group and collaborators, is now available for practical use. The neurophenomics part has become an app. “Liquid biopsy” tests to help doctors assess patients and suggest possible matching treatments are available as well. While we are very mindful of privacy and confidentiality, we hope that their widespread adoption will generate additional normative data, contributed as an opt-in (not by default) and in a de-identified fashion, that will permit improved versions of the tests to be rolled out in the years ahead. In the meantime, the immediate concern is providing some relief to those suffering from mental health challenges. We are at the stage where the term “precision” still needs to be added in front of psychiatry, not removed as redundant like in oncology. But we are catching up as a field. I am confident than in the next 25 years, likely much sooner, it will be dropped.

Live. Happier. Longer.