Hello. I’m Leanne Williams, Professor of Psychiatry and Behavioral Sciences and Director of the Stanford Center for Precision Mental Health and Wellness.

Text onscreen: How can novel frameworks such as the Research Domain Criteria (RDoC) inform research?
RDoC provides a new basis for understanding neuropsychiatric disorders across the lifespan. Different types of symptoms and brain circuits may also cut across our traditional disease categories. These are prime targets for transdiagnostic research.

Text onscreen: What does precision medicine mean to you in psychiatry?
My vision for precision medicine in psychiatry is to optimize treatment for each and every patient. I focus on direct measures of brain circuitry as targets for the development of more precise treatment strategies. Not only is the brain the organ of interest for psychiatric disorders of the central nervous system, but brain circuits are directly impacted by the treatments we deliver. Currently, disorders such as schizophrenia or depression are diagnosed based on broad subjective categories of signs and symptoms. Measuring underlying brain circuits gives us a more objective means to disentangle the different subtypes that underlie the variability of these signs and symptoms. We can then connect circuits to other measures of physiology, genetics, and behavior. These brain circuits give us biological targets for more precisely matching treatments to individual disease profiles. We can then optimize treatment outcomes for each individual.

Over the past 2 decades, I have led interrelated studies that have developed and tested the foundations for precision medicine in psychiatry. An innovation in my approach was to use a common core set of assessments so that data and insights could be linked across studies. The multiple thousands of patients who have taken part in my research span major depressive disorder, bipolar disorder, anxiety disorders, early-onset psychosis, first-episode psychosis, chronic schizophrenia, ADHD, anorexia nervosa, and conversion disorders. A common focus across these disorders is the alteration in cognitive and behavioral circuits that govern negative and positive emotional processes.

Text onscreen: What has been the focus of your research?
I have focused on six circuits that contribute to the cognitive and emotional functions that give us our human experience, and that also go awry in different mental disorders. Advances in brain imaging technologies make it possible to quantify these circuits, at rest, and while performing tasks. I have characterized at least eight ways that brain circuits can become maladaptive. For example, under activation of the striatal region of the positive affect circuit, shown here in purple, implicates symptoms of anhedonia. Under activation of the brain’s frontal regions and their interaction with parietal regions, shown here in red, is related to cognitive impairments across disorders.

Text onscreen: How might your research impact on clinical practice in the future?
The complexity of mental illnesses will always require a holistic approach. Our evolving toolkit of data and treatments now puts us in a position to align our approaches with those in the fields of cardiology, oncology, and infectious disease. In these fields, treatment selection is routinely based, not on preference or expediency, but on explicit imaging and biological markers. In all of its complexity, I believe this is the future of psychiatry.