Biomarkers for Mental Illness: Can They Transform Psychiatric Diagnosis?

Science Friday examines why there is no simple blood test or brain scan to diagnose depression, anxiety, PTSD, or other psychiatric illnesses, and how the next DSM might begin to include biomarkers as research matures. Flora Lichtman talks with Dr. John Crystal of Yale about the strides and the hurdles, from postmortem brain analysis to PET and MRI, and how biology could eventually inform diagnosis and treatment. They discuss why mental health conditions are diverse and overlapping, the genetics of schizophrenia, and the Alzheimer’s example as a current biomarker success story. The conversation also covers what it would take for biomarkers to move from aspirational research to routine clinical practice.

Overview: The Promise and Challenge of Psychiatric Biomarkers

Despite major advances in understanding the biology of mental health disorders, there is still no blood test or brain scan that confirms conditions like depression, anxiety, or PTSD. Flora Lichtman talks with Dr. John Crystal, a Yale psychiatrist and neuroscientist, about how the Diagnostic and Statistical Manual of Mental Disorders (DSM) may begin to incorporate biomarkers as the science matures. The discussion underscores that psychiatry faces unique hurdles: the brain is highly complex, living brain tissue cannot be biopsied in most cases, and diagnostic criteria are built on behavior, which can be variable and overlapping across disorders.

"The most exciting moment in the history of the field of psychiatry, literally" - Dr. John Crystal

Biomarkers Across Modalities: From Tissue to Tech

Crystal explains that to pursue precision medicine in psychiatry we would ideally sample the brain tissue itself, but since that is not feasible in living patients, researchers rely on other data streams. Donated brain tissue allows researchers to map molecular signatures of individual cells across neural circuits, contributing to what may become a molecular understanding of psychiatric illnesses. In parallel research centers, such as the VA Connecticut Health Center, have begun molecular analyses comparing PTSD to depression, showing that while these conditions share symptoms, their molecular signatures can differ in important ways. The field is also leveraging imaging methods like PET scans, functional MRI, and blood-based measures, combining signals from multiple modalities to refine subtypes within broad diagnoses.

"In psychiatry, because we're diagnosing today based on behavior, it's analogous to diagnosing breast cancer based on the lump" - Dr. John Crystal

Genetics, Subtypes, and Heterogeneity

The genetic architecture of mental illness adds another layer of complexity. Crystal notes that schizophrenia has a few large-risk factors, including rare mutations that can raise risk dramatically for a subset of individuals. Yet most people with schizophrenia carry a constellation of common variants, of which hundreds have small effects. Approximately 450 common variants contribute to risk, and the combination of these variants differs from person to person, driving substantial heterogeneity within a single diagnostic category. This diversity suggests there may be multiple biologically distinct subtypes that manifest as similar clinical symptoms, complicating the search for universal biomarkers.

"The DSM-5 has something like 270 or so different ways that you can make the criteria for major depression" - Dr. John Crystal

Lessons from Alzheimer's: A Biomarker Success Story

Among psychiatric disorders, Alzheimer's disease is highlighted as a relative success story where biomarkers guide diagnosis and treatment decisions. A PET scan measuring amyloid burden helps to diagnose Alzheimer’s disease with specificity, and when memory problems begin to emerge, there are now interventions that can slow progression. This contrast illustrates what psychiatry hopes to achieve: a diagnostic process that uses objective biological signals to tailor treatment plans and set expectations for patients and families. The Alzheimer’s example also reinforces the empowering potential of clearer prognoses when biomarkers are integrated into clinical care.

DSM, Practice, and the Road Ahead

Despite the readiness of some biomarkers in other fields, Crystal emphasizes that most biomarker findings are not yet ready for everyday clinical use. The American Psychiatric Association is trying to stage the arrival of biomarkers in a way that prepares practitioners to incorporate them as they mature. Lichtman and Crystal agree that the field should continue to collect diverse data—genetics, imaging, blood-based signals, and granular behavioral information—from digital sources and daily life patterns. The goal is to move beyond diagnosing by behavior toward a precision diagnosis with corresponding, targeted treatments. The discussion closes by acknowledging the aspirational nature of current findings and the careful, stagewise work required to translate research into routine care.

In sum, the episode frames a pivotal transition in psychiatry: biomarkers are inching toward the clinic, but the path requires robust validation, integration across data streams, and thoughtful alignment with clinical workflows. The promise is clear, and the steps to get there are being laid out now by researchers, clinicians, and professional societies.

"It's mostly aspirational in the sense that few of the biological findings that we have are really ready to implement in the average doctor's office" - Dr. John Crystal