FACULTY LEADERSHIP

From trial-and-error to precision mental health

For too long, mental health care has relied on diagnoses based primarily on symptoms and treatments selected according to what works for the average patient. Yet two people with the same diagnosis can have very different underlying biology, and respond very differently to the same treatment.

Precision mental health offers a different path.

At the Stanford Center for Precision Mental Health, our goal is to understand the biological and behavioral differences that matter for each person and translate them into better decisions about prevention and treatment.

This has been the vision behind our work for more than two decades. What has changed is that we are increasingly able to put it into practice.

Measuring what matters for the individual

A major focus of our Center is understanding the brain circuits that shape how we think, feel and behave, and how differences in these circuits contribute to mental health conditions and treatment response.

Our work has progressed from developing standardized ways to measure emotion and cognition, to identifying reproducible patterns of circuit dysfunction, quantifying these differences at the individual level, defining brain circuit “biotypes,” and testing how these differences relate to response across treatments.

A central framework we have developed through this work is Precision Circuit Mapping (PCM). PCM combines standardized resting-state and brief task-based functional MRI with automated, norm-referenced measurement of brain circuit function at the individual-patient level. The resulting Personalized Circuit Scores quantify each individual's circuit function relative to established reference ranges, providing interpretable measures for identifying circuit profiles, biologically meaningful subgroups and informing personalized treatment selection.

It was designed from the outset for clinical translation. Our standardized imaging protocol can be completed in under 30 minutes, with end-to-end automated quality control, processing and Personalized Circuit Scores generated in under 15 minutes. 

Importantly, we measure the brain not only at rest, but while circuits involved in emotion and cognition are engaged. These task-based measures have been critical for identifying treatment-relevant differences that may not be apparent from resting-state connectivity alone.

From brain circuits to treatment decisions

Our goal is more than creating better brain maps. It is to determine which biological differences matter for which treatment decisions, and use that information to personalize treatment with the goal of improving outcomes.

We use Personalized Circuit Scores and circuit-based stratification across antidepressant medications, behavioral treatments and neuromodulation, as well as mechanistically selective repurposed treatments and emerging therapeutics including ketamine, MDMA-assisted therapy and psilocybin. Precision Circuit Mapping provides a framework for determining who is most likely to benefit and moving beyond one-size-fits-all treatment indications.

Across these different treatments, we are asking a simple question:

Which treatment is most likely to work for which person, and how can we know sooner?

That question matters because trial-and-error has consequences. Every unsuccessful treatment costs time, prolongs suffering and can erode hope. Our aim is to give clinicians and patients better information at the point when a treatment decision is being made.

Human-centered AI for precision care

The next challenge is turning increasingly sophisticated neuroscience into information that is actually useful in a clinical encounter.

We are developing explainable, human-centered AI and clinical decision support that integrate Personalized Circuit Scores with treatment-relevant evidence to translate complex neuroscience into transparent and interpretable information for individuals, researchers and clinicians.

We believe AI should augment, not replace, clinical judgment. Clinicians should be able to understand a patient's Personalized Circuit Scores and treatment-relevant Circuit Markers, see the evidence connecting those measures with potential treatment outcomes, and decide how that information applies to the person in front of them.

For us, the goal of AI is therefore not prediction alone. It is better human decision-making.

From evidence to use

Precision mental health will not be transformed by another biomarker that remains in a research paper.

Translation has therefore been built into our work from the outset. We are developing standardized measurement approaches, automated pipelines, prospective clinical studies, and the implementation and regulatory pathways needed to determine how validated neuroscience can work in real clinical settings.

Functional brain imaging provides one of our most advanced platforms for precision measurement, but our vision for precision mental health extends beyond any single modality. Across the Center, we integrate brain circuit measures with clinical and behavioral data, digital biomarkers, AI and other patient-level measures to determine which information—and which combinations of information—are most useful for individual clinical decisions.

Our work spans three interconnected goals: 

•  defining biologically meaningful differences within and across traditional diagnoses; 
•  personalizing treatment selection with Personalized Circuit Scores and other precision measures to              improve outcomes; and 
•  identifying which individuals are most likely to benefit from new and emerging therapeutics through            Precision Circuit Mapping and biologically informed stratification.

Building the future of precision mental health together

The next phase requires more than any one laboratory or discipline.

Our Center brings together scientists, clinicians, engineers, data scientists and innovators across Stanford and the VA Palo Alto Health Care System, together with collaborators nationally and internationally. We work across disciplines because moving precision mental health into practice requires advances in measurement, therapeutics, computation, clinical trials, implementation and health care delivery to come together.

The question for our field is no longer simply whether people with the same diagnosis are biologically different. We know that they are.

The challenge now is to determine which differences are actionable, for which decisions, with what level of evidence, and how we can make that knowledge useful to patients and clinicians.

That is the transformation we created the Stanford Center for Precision Mental Health to accelerate.

Our goal is both ambitious and practical: to replace prolonged trial-and-error with better information, better treatment decisions and a faster path to recovery.

Leanne M. Williams, PhD
Vincent V.C. Woo Professor of Psychiatry and Behavioral Sciences
Founding Director, Stanford Center for Precision Mental Health