R01MH127571

Clinical and Biomarker-Based Trajectories of Psychosis-Risk Populations in Kenya - Project Summary

Worldwide, up to 3% of people will experience psychosis, a heterogeneous neurodevelopmental and neurodegenerative brain disorder typically characterized by delusions, hallucinations, and functional decline.

Currently, clinicians can identify adolescents and young adults who are at clinical high risk (CHR) for developing psychosis. However, as the mechanisms leading to the development of psychosis are not fully known, we have limited ability to predict who will develop psychosis. Safe intervention in this population requires high confidence in predictive biomarkers that can stratify individuals into likely clinical trajectories and match them with effective treatments.

Africa has a very limited early psychosis research effort, resulting in a substantial gap in our knowledge about the ethnic heterogeneity of the high-risk state. Recently, a multi-site international effort, the Psychosis-Risk Outcomes Network (PRONET), was funded by the NIH to analyze variation in a diverse set of biomarkers to predict individual CHR clinical trajectories. However, while countries in North America, Europe, and Asia are included in this landmark effort, it includes no African country. This is relevant, as risk genes for psychosis as well as the clinical and cultural presentation of psychosis often differ across ethnic groups.

This proposal aims to build research capacity in Kenya, using state-of-the-art multimodal methods in Kenya identical to that applied in the PRONET study, in order to map clinical outcomes in CHR populations (Aim 1). This involves building ERP/EEG infrastructure in Nairobi, by acquiring research-grade acquisition equipment and software; MRI upgrades, including advanced diffusion and fMRI BOLD imaging capability; and elaborate research training.

In Aim 2, we will collect multi-modal biomarkers over 24 months (eight timepoints) from 100 CHR participants (aged 15-22), including brain MRI, ERP/EEG, psychopathology, cognition, genetics, and cortisol. Healthy volunteers (N=50) will complete baseline assessment to quantify typical variation.

Aim 3 will test the hypothesis that psychosis outcomes in Kenyan CHR populations will differ from the international PRONET CHR cohort, including a lower rate of psychosis conversion and improved functioning. MRI and ERP analyses are expected to find orbitofrontal cortical thinning and reduced P300 (auditory P3b) amplitude with psychosis progression.

Together, this work would address key existing knowledge gaps in global CHR research and provide insights into the ethnic heterogeneity of outcomes among CHR patients. By building capacity in CHR clinical and biomarker-based research in Kenya, we will facilitate Sub-Saharan Africa joining future international research efforts.

Washington University

THE MISSION OF THE NATIONAL INSTITUTE OF MENTAL HEALTH (NIMH) IS TO TRANSFORM THE UNDERSTANDING AND TREATMENT OF MENTAL ILLNESSES THROUGH BASIC AND CLINICAL RESEARCH, PAVING THE WAY FOR PREVENTION, RECOVERY, AND CURE. WE FULFILL THIS MISSION BY SUPPORTING AND CONDUCTING RESEARCH ON MENTAL ILLNESSES, HEALTH SERVICES, AND THE UNDERLYING BASIC SCIENCE OF THE BRAIN AND BEHAVIOR; SUPPORTING THE TRAINING OF SCIENTISTS TO CARRY OUT BASIC AND CLINICAL MENTAL HEALTH RESEARCH; AND COMMUNICATING WITH SCIENTISTS, PATIENTS, PROVIDERS, AND THE PUBLIC ABOUT MENTAL HEALTH RESEARCH ADVANCES AND PRIORITIES. IN MAY 2024, NIMH RELEASED ITS STRATEGIC PLAN FOR RESEARCH. THE STRATEGIC PLAN BUILDS ON THE SUCCESSES OF PREVIOUS NIMH STRATEGIC PLANS BY PROVIDING A FRAMEWORK FOR SCIENTIFIC RESEARCH AND EXPLORATION, AND ADDRESSING NEW CHALLENGES IN MENTAL HEALTH.THE NEW STRATEGIC PLAN OUTLINES FOUR HIGH-LEVEL GOALS: GOAL 1: DEFINE THE BRAIN MECHANISMS UNDERLYING COMPLEX BEHAVIORS GOAL 2: EXAMINE MENTAL ILLNESS TRAJECTORIES ACROSS THE LIFESPAN GOAL 3: STRIVE FOR PREVENTION AND CURES GOAL 4: STRENGTHEN THE PUBLIC HEALTH IMPACT OF NIMH-SUPPORTED RESEARCH THESE FOUR GOALS FORM A BROAD ROADMAP FOR THE INSTITUTES RESEARCH PRIORITIES OVER THE NEXT FIVE YEARS, BEGINNING WITH THE FUNDAMENTAL SCIENCE OF THE BRAIN AND BEHAVIOR, AND EXTENDING THROUGH EVIDENCE-BASED SERVICES THAT IMPROVE PUBLIC HEALTH OUTCOMES.

93.242 - Mental Health Research Grants

National Institute of Mental Health (NIMH) [HHS - NIH]

Saint Louis, Missouri 631101010 United States

Single Zip Code

Global Brain and Nervous System Disorders Research Across the Lifespan (R01 Clinical Trials Optional) (PAR-18-835)

Amendment Since initial award the total obligations have increased 449% from $606,105 to $3,330,526.