EEG-Based Detection of Brain State Dynamics Associated with Auditory Hallucinations 2026 Award: $101,410 For many people with schizophrenia, hearing voices that aren't there is a daily reality, but existing treatments don't work for everyone. Our research uses brain activity recordings to map how the brain shifts between different states, and to pinpoint the moments when it becomes most vulnerable to producing hallucinations. This knowledge could transform brain stimulation therapy from a "where to stimulate" approach into a "where and when to stimulate" approach, one that acts at precisely the right moment to weaken the abnormal brain states that give rise to hallucinations. Need/Problem: Voices heard in the absence of a real sound are known as auditory verbal hallucinations. This symptom affects most people with schizophrenia, and for about 1 in 4 patients, hallucinations persist even with medication, increasing the [...]

Investigation of D2 and 5-HT2A Genetic Variants on Antipsychotic Responsiveness 2025 Award: $57,705 Many patients with schizophrenia endure months or even years of suboptimal treatment before finding an antipsychotic that works. This project aims to change that by identifying how individual genetic differences in brain receptors affect treatment response. The ultimate goal: a personalized tool that helps doctors choose the right antipsychotic the first time. Need/Problem: Antipsychotics are the cornerstone of schizophrenia treatment, yet patient responses vary widely. Many patients endure a lengthy trial-and-error process during medication selection, which often leads to prolonged symptoms and hospitalization, unnecessary side effects, and poor long-term outcomes. A precision-medicine approach is urgently needed to guide antipsychotic selection using a person’s unique genetic information. Grant Summary: This study will analyze how genetic variations in two key neuroreceptors—D2 and 5-HT2A—affect a patient’s long-term clinical stability [...]

Modeling genetic risk for schizophrenia in human-derived neurons 2025 Award: $60,000 Over 75% of the risk for developing schizophrenia is determined by the genes one inherits. In this project, the Mealer and Heinzen Labs plan to leverage recent advances in genetic studies of schizophrenia and neurons generated from human stem cells to better understand changes in brain development and function that could one day be used design better treatments for severe mental illness. Need/Problem: Antipsychotic medications, which are used to treat many different psychiatric conditions including schizophrenia, were not developed based on our knowledge of what is changed in the brain or how these disorders are inherited. As such, these treatments commonly provide limited symptom relief and do not appear to alter disease course or offer a chance at cure. Thus, there is incredible opportunity and need for rationally [...]

Development of Individual Differences in Adolescent Brain Structure and Risk 2024 Award: $150,989 Executive function is a critical ability that leads to better life outcomes, while low levels of executive function are a risk factor for mental illness. Therefore, characterizing neurocognitive trajectories of executive function and how they relate to future mental illness is a public health imperative. The main goal of this proposal is to identify aspects of neurocognitive trajectories from birth that predict the emergence of symptoms of mental illness in emerging adulthood. This research will move us closer to developing strategies for early identification and intervention by characterizing when and how neurocognitive trajectories related to executive function diverge to indicate risk for future mental illness. Need/Problem: High levels of executive function are associated with greater educational attainment, job success, and overall quality of life, while low [...]

White Matter Connectome and Behavior Relationships in Early Childhood 2023 Award: $27,044 Despite increasing research on the association between brain structure and cognition/behavior in adults, their relationship in early childhood remains largely unknown. We propose a new method to study how the brain’s networks relate to behavior in early childhood: connectome-based predictive modeling. Our prediction model will enable the early identification of children at high risk of developing psychiatric disorders. Need/Problem: There is strong evidence that white matter connectome computed from diffusion MRI is associated with cognition or behavior in adults and older children. However, little is known about their relationship in early childhood. Grant Summary: We will investigate how the brain’s networks relate to behavior. We will use the white matter connectome, which shows how different brain area connect to each other. We will develop a novel deep [...]

Randomized controlled trial of pyridoxine for tardive dyskinesia 2017 Award: $99,900 To date, the only effective medications to treat the symptoms associated with schizophrenia are the “antipsychotic” class of medications. Unfortunately, these medications have many possible side effects, including involuntary muscle movements known as tardive dyskinesia (TD). There is a small body of evidence, however, to suggest that pyridoxine (also known as Vitamin B6) may help alleviate the symptoms of TD; this study will build on that research, and test whether pyridoxine represents an effective treatment. Need/Problem: Involuntary muscle movements can emerge after long-term treatment with antipsychotic medications. This condition is called tardive dyskinesia (TD) and there are few treatments available for this debilitating and stigmatizing condition. Grant Summary: This project will test whether pyridoxine represents an effective treatment for tardive dyskinesia (TD). Goals and Projected Outcomes: Measure involuntary [...]