This project aims to identify genetic causes of heritable movement disorders and define pathogenic mechanisms to improve diagnosis and enable targeted therapies. Parkinson’s disease, ataxias, spastic paraplegias, and dystonic or choreiform disorders are highly genetically heterogeneous, and many causative genes remain unknown. We will (1) recruit and characterize individuals and families with genetically unexplained movement […]
Variants in the apolipoprotein E (APOE) gene strongly influence Alzheimer’s disease (AD) risk, neuropathology, and longevity. The APOE ε4 allele confers the greatest genetic risk for AD in Europeans and Japanese populations and is associated with reduced lifespan, whereas the protective ε2 allele is enriched among centenarians. Notably, APOE ε4 risk is attenuated in individuals […]
Alzheimer’s disease (AD) risk is strongly influenced by genetic variation, much of which lies in noncoding regions that regulate gene expression and RNA splicing. Protein-coding variants explain only ~30% of AD heritability, highlighting the need to functionally characterize regulatory variants. TREM2 is a microglia-specific immune receptor in which heterozygous missense variants increase late-onset AD risk, […]
Fentanyl overdose is responsible for nearly 75,000 deaths each year in the U.S. and causes severe psychological, physical, financial, and social harm. Despite existing treatments, fentanyl addiction remains difficult to overcome due to the chronic and complex nature of fentanyl addiction which contributes to patterns of chronic use and high relapse rates. This is partly […]
Many psychiatric disorders involve an abnormality in movements, termed ‘psychomotor’dysfunction, that reflects aberrant activity of the brain circuits producing behavior. Nevertheless,psychomotor mechanisms remain poorly understood. One possible source of psychomotor dysfunction is alterations in neuromodulatory transmitters, such as norepinephrine (NE), which is broadcast throughout the brain from a small brainstem region called locus coeruleus (LC). […]
We have developed – and are currently conducting a large-scale randomized trial of – at teacher-focused version of the Beliefs and Attitudes for Successful Implementation in Schools (BASIS) implementation strategy. BASIS-T is being tested in context of Positive Greetings at the Door (PGD) implementation. Details are available in a study protocol published in Implementation Science.
Current pharmacological treatments for fentanyl use disorder, primarily opioid replacements, have proven insufficient to stem the tide of fentanyl related suffering and deaths. Novel pharmacotherapies are desperately needed, ideally ones that are non-opioid, highly convenient, and produce minimal side effects. One promising class of drugs that meets these criteria are glucagon-like peptide 1 (GLP-1) receptor […]
Fentanyl abuse has reached epidemic proportions in the United States and is responsible for more than 70,000 overdose deaths each year. Avoidance of significant physical and emotional turmoil during withdrawal and exposure to drug-associated cues are two key deterrents to voluntary abstinence in those suffering from substance abuse disorder. By investigating the localized neuronal projections […]
Social anxiety disorder (SAD) is characterized by maladaptive self-focused attention (SFA), which itself is correlated with large scale brain network connectivity impairments. Cannabis use disorder (CUD) is commonly conceptualized as impaired reward processing within the ventral dopaminergic network, however, it is also implicated in connectivity disturbances in other critical cortical circuits. In the current study […]
The overall aim of the REACT Study is to create and assess smartphone-based cognitive tasks to examine how acute alcohol intoxication affects attention. First, we will adapt laboratory-based cognitive tasks for use on smartphones. To maximize usability, feedback will be gathered in rapid prototyping interviews with young adults. Then, we will evaluate the adapted smartphone […]
