About

Leanne M. Williams, PhD, is the Vincent V.C. Woo Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine and the Founding Director of the Stanford Center for Precision Mental Health. She directs the PanLab for Personalized and Translational Neuroscience and serves as Associate Chair of Translational Neuroscience within Stanford Psychiatry. Additionally, she holds a joint appointment as Director of the Precision Medicine Core at the VA Palo Alto Health Care System MIRECC. Her work focuses on transforming psychiatry through the development and clinical translation of a brain circuit–based platform for patient stratification, addressing the biological heterogeneity within diagnostic categories that contributes to prolonged trial-and-error treatment. Over the past 25 years, she has established and validated a taxonomy of brain-circuit 'biotypes' for depression, anxiety, attentional, and related disorders, utilizing standardized neuroimaging and behavioral paradigms to quantify circuit function at the individual level. Her team’s stratification approach has demonstrated the capacity to identify subgroups with significantly higher remission rates when treatments are aligned to circuit profiles, effectively doubling treatment success compared to non-stratified care. Dr. Williams has published over 400 scientific papers and authored the first book on Precision Psychiatry. Her research aims to accelerate the translation of neuroscience insights into new models of mental disorder and improve mental health treatment outcomes through personalized intervention strategies.

Research topics

• Psychiatry
• Psychology
• Medicine
• Clinical psychology
• Neuroscience
• Engineering
• Pathology
• Virology
• Biology
• Cognitive psychology
• Environmental health
• Genetics

Selected publications

• Integrative learning of individualized treatment rules from multiple studies with partially overlapping treatments

  arXiv (Cornell University) · 2026-04-12

  preprintOpen access

  An individualized treatment rule (ITR) tailors treatments to a patient's specific characteristics. However, randomized controlled trials (RCTs) are often underpowered to detect the treatment effect heterogeneity needed for reliable ITR estimation. To address this limitation, there is growing interest in leveraging information from multiple studies to improve statistical power and support individualized decision-making. A key challenge in this context is that available RCTs may not evaluate the same set of treatments. In this paper, we propose an integrative learning framework that synthesizes evidence across multiple RCTs that share a common comparator but differ in their alternative treatment arms. Our method integrates information through a regularized weighted misclassification risk function and adaptively determines the contribution of each study to the ITRs of the others. We rigorously study the excess risk of the resulting estimator. Simulation studies demonstrate that the proposed approaches improve the estimation of both value functions and benefit functions. We illustrate the utility of our methodology using data from two landmark studies of major depressive disorder: the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study and the International Study to Predict Optimized Treatment in Depression (iSPOT-D) study, both of which include a selective serotonin reuptake inhibitor as a common treatment arm. We find that the separate learning method outperforms one-size-fits-all methods, and our integrative methods further improve performance.

  PublisherDOI

• Polygenic score for C-reactive protein is linked to faster cortical thinning and psychopathology risk in adolescents

  Nature Mental Health · 2026-02-16

  articleOpen access

  Adolescence is a sensitive period of brain development marked by rapid cortical thinning and increased risk for psychiatric disorders, yet the biological drivers of atypical trajectories remain unclear. Here, using longitudinal data from the Adolescent Brain Cognitive Development Study, we examined whether genetic predisposition to systemic inflammation, indexed by polygenic scores for C-reactive protein (PGS-CRP), influences brain development and psychopathology. Higher PGS-CRP was associated with accelerated cortical thinning, particularly in medial temporal and insular regions, and with increased externalizing symptoms. Early-life infections independently predicted greater depressive and externalizing symptoms but did not interact with genetic risk. Mediation analyses indicated that cortical thinning partially accounted for the association between PGS-CRP and externalizing psychopathology. Biological annotation further identified the regional similarity between cortical effects of PGS-CRP and several neurotransmitter systems. Together, these findings suggest that genetic susceptibility to inflammation may shape adolescent brain maturation and contribute to mental health vulnerability via neuroimmune pathways.

  PublisherOA PDFDOI

• Integrative learning of individualized treatment rules from multiple studies with partially overlapping treatments

  arXiv (Cornell University) · 2026-04-12

  articleOpen access

  An individualized treatment rule (ITR) tailors treatments to a patient's specific characteristics. However, randomized controlled trials (RCTs) are often underpowered to detect the treatment effect heterogeneity needed for reliable ITR estimation. To address this limitation, there is growing interest in leveraging information from multiple studies to improve statistical power and support individualized decision-making. A key challenge in this context is that available RCTs may not evaluate the same set of treatments. In this paper, we propose an integrative learning framework that synthesizes evidence across multiple RCTs that share a common comparator but differ in their alternative treatment arms. Our method integrates information through a regularized weighted misclassification risk function and adaptively determines the contribution of each study to the ITRs of the others. We rigorously study the excess risk of the resulting estimator. Simulation studies demonstrate that the proposed approaches improve the estimation of both value functions and benefit functions. We illustrate the utility of our methodology using data from two landmark studies of major depressive disorder: the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study and the International Study to Predict Optimized Treatment in Depression (iSPOT-D) study, both of which include a selective serotonin reuptake inhibitor as a common treatment arm. We find that the separate learning method outperforms one-size-fits-all methods, and our integrative methods further improve performance.

  PublisherOA PDF

• Emotional scars: limbic brain processing alterations in adults with childhood abuse across mental health disorders

  Molecular Psychiatry · 2026-03-05

  articleOpen access

  Abuse experienced during childhood and adolescence significantly influences brain development and increases the risk of psychiatric disorders later in life. However, its long-term impact on emotion processing across psychiatric conditions remains underexplored. In this functional MRI study, we examined a sample of 635 individuals with and without childhood abuse, including people with depression, anxiety disorders, PTSD, and healthy controls, to investigate differences in brain activation during conscious and non-conscious emotional face processing. Brain activation across regions involved in emotional regulation was compared in response to negative (anger, fear, disgust, sadness), happy and neutral facial expressions. Individuals exposed to abuse before age 13 showed heightened hippocampal activation during non-conscious negative emotion processing compared to non-abused individuals, an effect absent in those exposed to abuse between ages 13 and 18. Additionally, amygdala activation during conscious emotion processing was elevated across all emotions in individuals who experienced adolescent abuse (13-18 years), compared to both abuse-free individuals and those exposed to early childhood abuse. This transdiagnostic approach highlights distinct vulnerability windows in brain development, with differential effects on emotion processing depending on the timing of abuse. Our study provides novel insights into how early life adversities shapes emotional processing, advancing our understanding of its transdiagnostic impact on brain function.

  PublisherOA PDFDOI

• The 12-year longitudinal impact of risk and resilience trajectories on adult health following childhood trauma.

  American Psychologist · 2026-03-05

  articleOpen access

  While adverse childhood experiences (ACEs) are known to increase mental illness risk, their longterm impact on comprehensive mental well-being-and resilience from a strengths-based lenshas been less explored.This study examined well-being trajectories in individuals with and without ACEs and their ability to predict functional outcomes over 12 years.The TWIN-10 longitudinal study followed 1,668 healthy Australian adults at four time points (2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020)(2021)(2022)(2023)(2024).ACE exposure was measured at baseline, with participants stratified into ACE and non-ACE groups.Well-being was assessed longitudinally using the Composure, Own-Worth, Mastery, Positivity, Achievement, Satisfaction-Wellbeing (COMPAS-W) scale, a composite measure of mental wellbeing which encompasses happiness, self-worth, and purpose.To capture the real-world impacts of well-being, subsequent functional outcomes-covering mental and physical health, lifestyle behaviors, and social and psychological functioning-were captured at 10-and 12-year followups.Using growth mixture modeling, distinct higher and lower well-being trajectories were found in both groups.Fewer individuals with ACEs were in the higher well-being trajectory (66%) compared to those without ACEs (85%).However, those with ACEs who maintained higher wellbeing experienced broad long-term health benefits, including lower risk of psychiatric illness, obesity, and sleep or alcohol problems, and higher odds of good social, occupational, and lifestyle functioning.While similar trends were seen in the non-ACE group, effects were less pronounced.These findings highlight that individuals exposed to ACEs can still achieve and maintain moderateto-high well-being and associated health benefits.Promoting mental well-being may therefore offer an important complementary pathway to mitigate the long-term impacts of early adversity. Public Significance StatementLooking beyond mental ill health, how adverse childhood experiences influence positive health and well-being over the course of adulthood remains unclear.The present findings suggest that, while exposure to adverse childhood experiences may increase classification of having lower well-being over the long term, those who do sustain positive well-being are at decreased risk for diverse negative health outcomes, with significant benefits apparent across far-reaching health and lifestyle domains.

  PublisherOA PDFDOI

• A genome-wide association study of brain function across multiple cognitive domains

  Pharmacopsychiatry · 2025-04-30

  article

  Task-based fMRI is widely used to study the neurobiological basis of behavior, cognition, and emotion. Previous studies disagree on whether statistics derived from task-based fMRI are heritable – estimates range from approximately five percent to more than forty percent. Here we present the largest and most diverse genome-wide association study of task-based fMRI to date that uses a single, harmonized data analysis pipeline across all contributing sites. This abstract reports the SNP-based heritability results obtained from the current sample.We invited researchers with access to relevant data to contribute through the ENIGMA consortium and public postings on social media. We chose three tasks that have been widely used for inclusion in the study. These are emotional faces, working memory, and reward tasks.SNP-based analyses of seven datasets show moderate heritability across a wide range of brain regions for emotional faces and reward tasks. The amygdala is known to have a large effect size in the emotional faces task. However, we find greater heritability in cortical regions not commonly associated with the task. For reward, we found the maximum heritability in the striatum, which is consistent with brain maps found by imaging-only studies. We did not find significant heritability for working memory, likely due to a lack of statistical power. At time of writing, not all sites planned for inclusion in the meta-analysis have completed data analysis. We expect to increase statistical power by including these datasets.Our results are consistent with previous findings of SNP-based heritability for the amygdala in the emotional faces task. This demonstrates the feasibility of genome-wide association studies for investigating individual differences in task-based fMRI. The results presented here will inform secondary analyses including genetic correlations and annotation. These may provide important insights into the relation of genes, molecules, cells, and circuits to psychological domains.

  PublisherDOI

• Negative Affect Circuit Subtypes and Neural, Behavioral, and Affective Responses to MDMA

  JAMA Network Open · 2025-04-30 · 8 citations

  articleOpen accessSenior authorCorresponding

  Importance: Rapidly acting therapeutics like 3,4-methylenedioxymethamphetamine (MDMA) are promising treatments for disorders such as posttraumatic stress disorder (PTSD). However, understanding who benefits most and the underlying neural mechanisms remains a critical gap. Stratifying individuals by neural circuit profiles could help differentiate neural, behavioral, and affective responses to MDMA, enabling personalized treatment strategies. Objective: To investigate whether baseline stratification of individuals based on negative affect circuit profiles, particularly in response to nonconscious threat stimuli, can differentiate acute responses to MDMA. Design, Setting, and Participants: This randomized clinical trial, implementing a double-blinded, within-participant, placebo- and baseline-controlled design, was conducted at Stanford University School of Medicine between November 2, 2021, and November 9, 2022, for wave 1 data collection. Participants had used MDMA on at least 2 prior occasions, but not in the past 6 months, and had subthreshold PTSD symptoms and early life trauma but no current psychiatric disorders. Data were analyzed from March 1, 2023, to January 1, 2024. Interventions: Participants completed 4 visits: 1 baseline session followed by 1 placebo session and 2 MDMA sessions in a randomized order, totaling 64 visits. Baseline functional magnetic resonance imaging (fMRI) assessed the negative affect circuit using a nonconscious threat processing task (NTN). Main Outcomes and Measures: Primary outcomes included activity and connectivity of amygdala and subgenual anterior cingulate cortex (sgACC) defining the negative affect circuit. Secondary outcomes were behavioral measures of implicit threat bias, likability of threat expressions, and affective assessments. Results: Sixteen participants (10 [63%] female; mean [SD] age, 40.8 [7.6] years) were stratified into subgroups with high and low levels of NTN activity in the amygdala (NTNA+ [n = 8] and NTNA- [n = 8], respectively), based on a median split of baseline nonconscious threat-evoked fMRI responses. Following administration of the 120 mg of MDMA vs placebo, the NTNA+ subgroup showed significant reductions in amygdala (contrast estimate [CE], -1.43; 95% CI, -2.60 to -0.27; Cohen d, -1.22; P = .02) and sgACC activity (CE, -1.48; 95% CI, -2.42 to -0.54; Cohen d, -1.56; P = .004), increased sgACC-amygdala connectivity (CE, 0.65; 95% CI, 0.02-1.28; Cohen d, 1.02; P = .04), and increased likability of threat expressions (CE, 14.38; 95% CI, 1.46-27.29; Cohen d, 0.86; P = .03) compared with the NTNA- subgroup. Conclusions and Relevance: In this randomized clinical trial of MDMA's acute profiles, 120 mg of MDMA acutely normalized negative affect circuit reactivity in participants stratified by heightened amygdala reactivity at baseline, demonstrating the potential of neuroimaging to identify prospective biomarkers and guide personalized MDMA-based therapies. Trial Registration: ClinicalTrials.gov Identifier: NCT04060108.

  PublisherOA PDFDOI

• Polygenic score for C-reactive protein is associated with accelerated cortical thinning and increased psychopathology in adolescents: a population-based longitudinal cohort study.

  Research Square · 2025-06-30

  preprintOpen access
  PublisherOA PDFDOI

• From Scanner to Bedside: Building Bridges in Translational Psychiatric Neuroimaging

  American Journal of Psychiatry · 2025-08-01

  letter
  PublisherDOI

• Topological data analysis reveals rigid brain-state dynamics during self-viewing in trait rumination

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-27

  articleOpen access

  Rumination-repetitive, negatively valenced, self-focused thought-is a maladaptive cognitive style linked to emotional dysregulation and psychiatric risk. To investigate its neural underpinnings in a naturalistic context, we developed an fMRI paradigm in which participants observed and reflected on videos of their own past group-based problem-solving sessions, a naturalistic self-relevant context rarely examined in fMRI studies. Thirty-two adults (mean age = 30.4 ± 5.4 years; 13 F) were recorded during collaborative design-thinking tasks in triads. In a subsequent scanning session, each participant viewed two self-relevant team videos and one control team video, followed by a structured reflection period. We assessed trait rumination using the Rumination-Reflection Questionnaire (RRQ) and applied Topological Data Analysis (TDA) via the Mapper algorithm to model individual-level whole-brain dynamics during the task. Mapper shape graphs captured temporal transitions between brain states, allowing us to quantify the similarity of timepoints across the session. Individuals with higher trait rumination showed significantly higher temporal similarity, indicating reduced brain-state variability, during self-relevant conditions (r = 0.46, p = 0.018). This effect was not observed during the control condition. These findings suggest that rumination is associated with rigid brain dynamics during self-observation and evaluative processing. Traditional GLM and inter-subject correlation (ISC) analyses confirmed task engagement of key self-referential and social-evaluative regions, while Mapper revealed dynamic features not captured by static or group-averaged methods. Together, these findings demonstrate that trait rumination is associated with rigid large-scale brain dynamics during self-relevant cognition and highlight the value of combining naturalistic paradigms with topological approaches to capture behaviorally meaningful signatures.

  PublisherDOI

Recent grants

• Engaging self-regulation targets to understand the mechanisms of behavior change and improve mood and weight outcomes

  NIH · $2.6M · 2015–2021

• Engaging self-regulation targets to understand the mechanisms of behavior change and improve mood and weight outcomes

  NIH · $2.6M · 2015–2018

• Mapping connectomes for disordered emotional states

  NIH · $3.1M · 2017–2022

• Neural Dimensions of Threat Reactivity and Regulation for Understanding Anxiety

  NIH · $2.3M · 2016–2018

• Mechanistic circuit markers of transcranial magnetic stimulation outcomes in pharmacoresistant depression

  NIH · $3.4M · 2019–2025

Frequent coauthors

• Evian Gordon

  Brain Resource Center

  694 shared

• Anthony Harris

  Westmead Institute for Medical Research

  463 shared

• Mayuresh S. Korgaonkar

  University of Sydney

  447 shared

• Justine M. Gatt

  388 shared

• Stuart M. Grieve

  University of Sydney

  309 shared

• Peter R. Schofield

  Neuroscience Research Australia

  289 shared

• Richard A. Bryant

  UNSW Sydney

  235 shared

• Michael Kohn

  Westmead Institute for Medical Research

  223 shared

Education

• Ph.D.

  Stanford University School of Medicine

• M.D.

  Sydney Medical School

Awards & honors

• The Gold Medal Award, Society of Biological Psychiatry (SOBP…
• The Perry Award (In memory of Samuel Wesley Perry III, MD),…
• Educator Award, Society of Biological Psychiatry (SOBP) (202…
• Chairman’s Senior Faculty Mentor Award, Stanford School of M…
• George Thompson Award to the Women’s Leadership Group of SOB…