Deciphering Developmental Origin of Neural Connectivity Associated with Substance Use Disorder by Learning Natural Trajectory of Functional Connectivity 2026 Award: $59,939 Substance use disorder is often rooted in early brain changes that remain hidden until clinical symptoms emerge. Using our “digital bridge” framework, we reconstruct brain maturation trajectories to trace adult neural patterns back to adolescence and identify early precursors of addiction. Our goal is to support proactive, precision-based prevention before substance use problems fully develop. Need/Problem:Substance use disorder (SUD) research is limited by a major gap between adolescent development and adult clinical outcomes. This makes it hard to separate early vulnerability from substance-related brain changes and slows progress toward proactive, precision-based prevention. Grant Summary:SUD is a major public health crisis, but early intervention is limited by the gap between adolescent brain development and adult clinical outcomes. This project [...]

Adolescent Binge Drinking Persistently Shifts Microglia to a Proinflammatory Phenotype through Reversible Epigenetic Reprogramming 2023 Award: $98,592 In addition to increasing risk for later development of an alcohol use disorder, adolescent binge drinking increases neuroinflammation in brain that persists into adulthood contributing to neuropathology. In this project, we will investigate the mechanism underlying persistent neuroinflammation in brain using a preclinical rat rodent model of adolescent binge drinking. Findings from the preclinical rat studies will provide an initial step toward understanding molecular mechanisms underlying persistent neuroinflammation in brain and mechanisms of reversal. Need/Problem: Alcohol use disorder (AUD) is a chronic relapsing disease characterized by uncontrolled drinking and preoccupation with alcohol despite adverse life and health consequences. An early adolescent age of alcohol binge drinking is highly predictive of developing an AUD and other psychiatric disorders later in life. For instance, [...]

Investigation of the GLP-1 receptor agonist semaglutide on alcohol effects: relevance for the treatment of alcohol use disorder 2023 Award: $70,152 Alcohol use disorder (AUD) is a devastating disease that affects many individuals and families. There is an urgent need to identify medications to help with the treatment of AUD. The goal of the present work is to determine whether semaglutide (an FDA-approved antidiabetic and weight management medication) blunts the subjective/interoceptive effects of alcohol. This is an important question as these effects have the capability to influence alcohol drinking behavior and relapse. Need/Problem: Alcohol use disorder (AUD) is a significant health and societal burden. However, there are only three FDA-approved medications for treating AUD and while these medications work well for some, they do not work for all individuals. Therefore, there is the need to identify new medications to [...]

A novel glutamatergic mechanism for the treatment of cocaine and opioid use disorders, and co-occurring anxiety 2022 Award: $39,565 Substance Use has steadily risen over the past decade and COVID-19 has exacerbated these trends. More than 50% of people diagnosed with Substance Use Disorders, are also diagnosed with co-occurring psychiatric disorders. There is a need for targeted treatments to simultaneously address these co-occurring mental health conditions. This project will systematically investigate whether a novel brain protein called TARP γ-8 could be a novel target for therapeutic interventions for substance use and anxiety. Need/Problem: Despite tremendous need, effective pharmacotherapies for the treatment of Substance Use Disorders and co-occurring psychiatric conditions are lacking. Repeated drug use dysregulates key neurotransmitter systems in the brain and leads to enduring changes in strength and function of brain pathways that regulate reward and pleasure. It [...]

Biomarkers of Systemic Inflammation in Alcohol Use Disorder 2022 Award: $98,500 Studies of post-mortem brains of people who suffered from Alcohol Use Disorders show abnormal activation of inflammatory immune signals that are proposed to underlie addiction to alcohol. We propose to determine if serum levels of inflammatory markers are biomarkers of excessive alcohol drinking. Such a biomarker could provide a useful diagnostic tool and indicate if patients might respond to novel treatments that inhibit the same inflammatory pathways. We will test this idea in men and women who meet criteria for AUD in hopes of discovering a biomarker of AUD drinking severity and to facilitate study of new ways to treat alcohol use disorders. Need/Problem: The burden of alcohol use disorders (AUDs) in our society is greater than any other addictive drug, but, there is no reliable diagnostic biomarker [...]