A partnership to provide comprehensive perinatal mental health and parenting support for the first 1,000 days
The Raising Washington Initiative seeks to develop an evidence-based fully integrated perinatal support program that will offer mental health care, parent training and support services for the first 1,000 days of a baby’s life (conception through child’s 2nd birthday) for every high-risk baby born in Washington. This will include creating care pathways informed by the needs of patients and providers, navigators to help guide families through the many care transitions in the perinatal period and accessible information to keep parents and babies healthy.
To learn more this work, please contact Project Manager Lori Ferro, MHA at ljf9@uw.edu.
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 of African ancestry, who also show reduced neuropathologic burden. We hypothesize that ancestry-specific regulatory variation at the APOE locus alters risk allele dosage and contributes to these differences. Single-nucleus RNA-seq studies show reduced APOE ε4 expression in astrocytes of African carriers, but the underlying regulatory variants remain unknown. This proposal aims to define the APOE transcript repertoire in human brain (Aim 1) and functionally evaluate ancestry-enriched APOE variants for effects on transcription, splicing, and RNA processing (Aim 2) using targeted long-read RNA sequencing and multiplex reporter assays. This work will generate a regulatory map of APOE and identify variants that lower APOE expression and protect against AD.
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, while biallelic loss-of-function variants cause early-onset dementia. TREM2 undergoes alternative splicing, but its transcript repertoire and regulation in human brain remain poorly defined. We identified a novel splice isoform lacking exon 2 (Δe2) that encodes a truncated protein with altered activity. Preliminary data show that AD- and dementia-associated variants shift splicing toward Δe2, reducing functional TREM2 dosage. We will define TREM2 isoforms in human brain, functionally assess regulatory variants affecting splicing, and analyze interactions between cis-variants and trans-acting splicing factors altered in AD, using long-read RNA sequencing and high-throughput functional assays.
Death by suicide is the 2nd leading cause of death among young adults in the United States. While most patients who die by suicide have had recent contact with their health care providers, the medical delivery system is poorly equipped to address this preventable issue. EMA (ecological momentary assessment) systems show promise as indicators of suicide risk and as a means of enhancing existing resources. However, little is known about how to apply these methods in the context of clinical care. The AMPERE study leverages existing work on EMAs and human-centered design principles to develop and pilot a prototype suicide risk monitoring system to support suicide risk management for adolescents and young adults (ages 16-30) within the UW Medicine Primary Care system.
Our project will seek to identify factors associated with gaps in transitions of care for psychiatric inpatients who presented with substance-induced psychosis (SIP) for the first time. We will analyze historical electronic health record data of patients who were treated for psychosis at Harborview Medical Center. We will test the hypotheses that (1) treatment with long-acting injectable antipsychotics (LAI) and referrals to outpatient behavioral health are lower for patients diagnosed with first-episode SIP compared to those diagnosed with first-episode psychosis and that (2) patients diagnosed with first-episode SIP will have worse post-discharge outcomes (rehospitalization, ED utilization), in part due to lower use of LAI.
Improved financial literacy among people living with serious mental illness (SMI) is associated with a higher quality of life, fewer hospitalizations, and better treatment adherence. Yet people living with SMI frequently express how their lack of financial knowledge has negative personal consequences and that they don’t know where to turn for assistance. This project will gather qualitative and quantitative data from people admitted to the Center for Behavioral Health and Learning, a psychiatric hospital, to understand the need and desire for a financial skills intervention and its role in discharge planning. The assessment will also seek input from family members/caregivers, representative payees/fiduciaries and experts in the community. Ultimately, we hope to create a replicable, standardized intervention that can be evaluated and implemented in inpatient settings and modified as necessary for outpatient settings.
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 (GLP-1R) agonists. Endogenous GLP-1 is released in response to food intake, but GLP-1Rs are present in many tissues throughout the body, including brain regions involved in addiction. Early studies have shown GLP-1R agonists may reduce drug seeking. Here, we aim to determine if the long acting GLP-1R agonist dulaglutide, given once weekly, can reduce fentanyl SA for a substantial period of time (3 weeks), even after SA has been established.
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 responsible for motivating avoidance of withdrawal, and processing reward cues, we may be able to produce targeted pharmacotherapies or genetic therapies to improve the rate of voluntary abstinence.
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 we will characterize the large scale brain network impairment in comorbid SAD and CUD given commonly overlapping symptoms and population prevalence
