Science Friday

Why Aren’t There Biomarkers For Mental Illness?

February 23, 2026

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  • The primary difficulty in finding biomarkers for mental illness stems from the inability to directly sample brain tissue for molecular analysis, unlike solid tumors. 
  • Molecular analysis of donated post-traumatic stress disorder (PTSD) and depression brain tissue reveals distinct, though overlapping, underlying molecular signatures for each disorder. 
  • The inclusion of biomarkers in the next *Diagnostic and Statistical Manual of Mental Disorders (DSM)* is currently aspirational, intended to set the stage for future diagnostic precision analogous to cancer diagnosis. 

Segments

Introduction to Biomarker Challenge
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(00:01:19)
  • Key Takeaway: Mental illnesses like depression and PTSD currently lack confirming blood tests or brain scans despite biological understanding.
  • Summary: Despite advances in biology, there is no definitive blood test or brain scan to confirm psychiatric illnesses such as depression, anxiety, or PTSD. The next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) will incorporate biomarkers, prompting questions about diagnostic readiness. Host Flora Lichtman introduces guest Dr. John Krystal to discuss the complexity of pinpointing these biological markers.
Difficulty of Psychiatric Biomarkers
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(00:02:09)
  • Key Takeaway: Psychiatric biomarker identification is challenging because researchers cannot biopsy the living brain tissue of interest.
  • Summary: The problem of finding biomarkers for mental illness is enormously challenging because researchers cannot analyze the exact tissue of interest (the living brain) as they would with a tumor biopsy. Precision medicine in psychiatry requires molecular signatures without invasive brain sampling. Researchers analyze donated post-mortem brain tissue to identify molecular signatures in specific brain circuits.
PTSD vs. Depression Signatures
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(00:04:26)
  • Key Takeaway: Molecular analysis shows that depression and PTSD have distinct underlying signatures, even though both share depressive symptoms.
  • Summary: Molecular analysis comparing PTSD and depression, conducted at the VA Connecticut Health Center, revealed that their underlying molecular signatures differ in important ways, despite both illnesses featuring depression as a symptom. This highlights that different disorders may have unique biological bases.
Symptom Overlap and Heterogeneity
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(00:05:06)
  • Key Takeaway: The vast number of ways to meet diagnostic criteria for a single condition, like major depression, suggests many underlying biological subtypes exist.
  • Summary: The heterogeneity within mental health disorders significantly complicates biomarker searches; for instance, the DSM-5 allows for around 270 different ways to meet the criteria for major depression. This suggests that a single diagnosis likely encompasses many biologically different subtypes of problems. This complexity mirrors how breast cancer is now understood to have many distinct forms.
Alzheimer’s as a Biomarker Success
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(00:06:09)
  • Key Takeaway: Alzheimer’s disease serves as a successful model where PET scans identify chemical accumulation, enabling precise diagnosis and treatment intervention.
  • Summary: Alzheimer’s disease is cited as a success story in psychiatry broadly, where a PET scan can identify accumulated chemicals associated with the disease to aid diagnosis. This precision is crucial because effective treatments now exist to slow the progression of memory problems in Alzheimer’s patients. Understanding the biological basis empowers patients to prepare for the future.
Current Research Avenues
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(00:07:50)
  • Key Takeaway: Psychiatry is currently utilizing blood tests, genetics, fMRI, structural scans, and granular behavioral data to subtype diagnoses.
  • Summary: The field of psychiatry is currently in its most exciting moment, employing every available data collection method, including blood tests, genetic analyses, and various brain scans, to better understand and subtype diagnoses. Researchers are also beginning to integrate granular behavioral data, such as daily activity patterns and social interaction levels, with biological information.
Genetic Complexity in Schizophrenia
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(00:09:02)
  • Key Takeaway: Schizophrenia risk is driven by a combination of rare, high-impact mutations and hundreds of common variants with trivial individual contributions.
  • Summary: Genetics in mental illness is complex because risk is conferred in multiple ways. For schizophrenia, a small percentage of cases involve rare mutations that increase vulnerability 50 to 100-fold. The majority of risk comes from approximately 450 common genetic variants, each contributing only a trivial amount individually, leading to significant heterogeneity.
DSM Incorporation Status
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(00:12:00)
  • Key Takeaway: Incorporating biological findings into the next DSM is mostly aspirational, as most discoveries are not yet ready for average clinical practice.
  • Summary: The move to include biomarkers in the DSM is largely aspirational because few biological findings are mature enough for implementation in the average doctor’s office. The American Psychiatric Association is setting the stage to anticipate the emergence of these biomarkers so that psychiatric practice is ready to incorporate them as they mature.