Patient Population: Adults

Improving risk-stratification of substance-induced psychosis: incorporating stakeholder perspectives and implementing a standardized assessment of risk factors

First-episode substance-induced psychosis (SIP) presents a clinical challenge in which treatment decisions cannot rely on evidence-based guidelines and long-term outcomes are not well understood. Preliminary findings from our retrospective study of psychiatry inpatients at Harborview Medical Center (HMC) suggest that patients with first-episode SIP had similar rehospitalization rates to those with first-episode psychosis (FEP) but were less likely to receive long-acting injectable antipsychotics (LAIs) even though LAIs may reduce the risk of 30- and 180-day rehospitalization. Our study has also revealed inconsistent assessment of key risk factors for rehospitalization—such as family history of psychosis and patterns of cannabis use—that may be limiting informed decision-making, including appropriate LAI use. This project seeks to improve the risk stratification of first-episode SIP by addressing these gaps. Aim 1 will use qualitative interviews with inpatient attending psychiatrists, psychiatry residents, and patients to explore factors influencing the management of first-episode SIP. Aim 2 will evaluate the acceptability and feasibility of implementing a standardized assessment of cannabis use and family history of psychosis on HMC inpatient psychiatry units. This project will lay the groundwork for future clinical interventions that optimize treatment decisions and improve patient outcomes in psychiatric inpatient settings.

Unraveling the genetics of schizophrenia and bipolar disorder with large-language models

Schizophrenia (SCZ) and bipolar disorder (BPD) are among the most heritable psychiatric conditions, yet their genetic foundations remain poorly understood. Historically, unraveling these disorders’ genetic architectures was limited by inadequate technology. However, breakthroughs in next-generation sequencing have recently produced expansive genomic datasets—including those from the Psychiatric Genomics Consortium (PGC)—for SCZ and BD. Simultaneously, genomic foundation models—advanced large-language models (LLMs) trained on biological data rather than corpuses of text—have emerged as next-generation artificial intelligence platforms that offer unparalleled abilities to predict the functional effects of genetic variants, many of which were previously unclassified. This proposal harnesses these models to analyze publicly available PGC genomic datasets, aiming to annotate both common and rare genetic variants associated with SCZ and BD, pinpoint disease-associated genes, and map the biological pathways they influence. By bridging these recent advances in artificial intelligence with robust genomic data, this proposal seeks to illuminate the genetic underpinnings of SCZ and BPD. The anticipated insights promise to deepen our understanding of heritable psychiatric conditions, laying the groundwork for enhanced diagnostics and novel therapies aimed at biology, rather than nosology

Psychomotor function of Locus Coeruleus-Norepinephrine system during decision-making

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). LC-NE is implicated in psychiatric disorders including depression, PTSD, ADHD, and dementia, with behavioral neuroscience studies demonstrating roles in arousal and decision-making. LC-NE is often studied in psychiatry on the timescale of minutes to hours with a focus on NE drugs, leaving underexamined the precise temporal relationship between LC neural activity and discrete components of motivated behavior. This proposal aims to identify psychomotor functions of LC-NE in decision-making at the level of neural circuit activity in mice. We leverage powerful techniques to record LC neural activity with high spatiotemporal precision while simultaneously deploying advances in AI machine vision technology to quantify the mouse’s movements. By precisely quantifying movement patterns and LC-NE activity, we aim to characterize basic psychomotor functions related to cognition. In turn, our work will build a foundation for noninvasive, mechanistic biomarkers that enhance the diagnosis and management of psychiatric disorders.

Brain, Environment, and Alcohol Research (BEAR) Study

This project examines how brain responses to alcohol cues interact with everyday social contexts to shape drinking in young adult heavy drinkers. We pair multimodal neuroimaging (fMRI, EEG) with a 2-week ecological momentary assessment including transdermal alcohol monitoring and photo-based context capture. We test whether neural incentive salience predicts real-life intoxication, how social features (group size, familiarity, gender mix) influence drinking, and how perceived norms mediate these effects. We further assess whether incentive salience moderates context and norm influences. Findings will refine models of alcohol use disorder etiology and inform prevention and intervention strategies by linking precise brain markers with ecologically valid, context-rich assessments.

Evaluation of the VHA Acute Pain Service Expansion Program implementation and impact

The objective of the project is to evaluate the implementation and impact of the Acute Pain Services Expansion Program (APSEP), an expansion of the independent and formal set of services that provide comprehensive inpatient pain management consultative services and is designed to meet perioperative care needs of veterans receiving inpatient pain management.

Complementary and integrative health stepped care for co-occurring chronic pain and PTSD

The aim of the project is to conduct a pragmatic pilot trial of a CIH-based stepped care approach v. treatment as usual in two primary care settings (one rural and one urban). The pilot trial will focus on feasibility, acceptability, and appropriateness for providers and patients (e.g., randomization, retention, and treatment satisfaction) of the stepped care approach versus usual care (n=30 per site, N=60 total). Primary clinical outcomes are pain interference and PTSD symptoms at 6-months.

Improving treatment strategies and clinical outcomes in patients with first-episode psychosis and substance use disorders

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.

Strengthening financial literacy for people living with serious mental illness

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.