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Principal Investigator: Sarah Yip
Organization: YALE UNIVERSITY
Fiscal Year: 2024
Award: $722,366
Funding agency: National Institute on Drug Abuse
Abstract
Opioid use disorder (OUD) is a significant public health problem with opioid-associated overdoses and deaths
reaching epidemic levels in recent years. Methadone and buprenorphine are widely used and generally effective
medications for OUD (MOUDs). However, relapse and nonadherence rates remain high and average treatment
retention is suboptimal (e.g., <6 months in 30-50% of cases). As risk of overdose is highest following relapse
and treatment dropout, improved mechanistic understanding of risk and resilience factors in individuals in early
MOUD (i.e., <6 months) is urgently needed. This application uses network-based analysis, with built-in cross-
validation, to identify brain networks associated with (i) patterns of illicit opioid use during early MOUD and (ii)
medication adherence during early MOUD in a diverse sample of individuals (N=240, 50% female, 50% male,
50% receiving methadone, 50% receiving buprenorphine). This is critical to improve understanding of
mechanisms and predictors of MOUD response and is an essential precursor to development of improved,
evidence-based interventions grounded in known neurobiology. This work builds on our prior work identifying
brain connections prospectively associated with future relapse to illicit opioids during sustained MOUD. The
identified ‘opioid abstinence network’ included connections between frontoparietal, salience, sensorimotor and
default mode regions and was robust to analyses controlling for relevant clinical variables (e.g., MOUD dose,
years of opioid use). In AIM 1, we seek to externally validate and extend this finding via collection of
neuroimaging data from a larger, more diverse sample of individuals early in MOUD treatment. In AIM 2, we
propose to collect additional, multi-task neuroimaging data to determine the impact of different, task-induced
brain states on network identification. Finally, in AIM 3, we will use our recently developed approach, in which
variation in model accuracies are assessed as a function of core sources of clinical diveristy (e.g., sex,
medication dose, co-occurring disorders), to identify sources of model bias and neurobiological heterogeneity.
Assessing sources of model bias and neurobiological heterogeneity embraces the clinical complexity that is
inherent to the current opioid epidemic. These clinical sources of variance have typically either been excluded
for or ignored (e.g., treated as covariates of no interest) in prior neuroimaging studies of MOUD. All acquired
data will be shared via the NIMH Data Archive.
Terms: <Abstinence><Achievement><Achievement Attainment><Actiq><Adanon><Adherence><Affective Disorders><Althose><Basic Research><Basic Science><Behavior><Biological><Brain><Brain Nervous System><Buprenorphine><Cessation of life><Clinical><Collection><Complex><Cues><Data><Death><Development><Dolophine><Dose><Dropout><Drugs><Duragesic><Educational Achievement><Educational Status><Encephalon><Epidemic><Evidence based intervention><Exclusion><Female><Fentanest><Fentanyl><Fentyl><Functional MRI><Functional Magnetic Resonance Imaging><Future><Generations><HCV Transmission><HCV/HIV><HIV and HCV><HIV and hepatitis C><HIV-HCV><HIV/HCV><HIV/Hepatitis C><Hepatitis C Transmission><Heterogeneity><Individual><Individual Differences><Intelligence><International><Link><Liquid substance><Medical><Medication><Mental disorders><Mental health disorders><Methadone><Methadose><Methods><Modeling><Mood Disorders><NIDA><NIMH><National Institute of Drug Abuse><National Institute of Mental Health><National Institute on Drug Abuse><Nature><Network-based><Neurobiology><Opiates><Opioid><Outcome><Overdose><Overdose reduction><Participant><Pattern><Performance><Pharmaceutical Preparations><Phentanyl><Protocol><Protocols documentation><Psychiatric Disease><Psychiatric Disorder><Public Health><Publishing><Race><Races><Recovery><Relapse><Rest><Risk><Risk Factors><Sampling><Source><Testing><United States><Validation><Variant><Variation><Work><biologic><brain based><brain behavior><chronic pain><clinical relevance><clinically relevant><co-occurring disorders><cocaine use><cognitive control><cognitive reappraisal><cognitive regulation><computer based prediction><criminal behavior><data archive><data archives><developmental><drug adherence><drug compliance><drug/agent><dual diagnosis><educational level><effective therapy><effective treatment><fMRI><fMRI scan><fluid><functional MRI scan><functional magnetic resonance imaging scan><hepatitis C virus transmission><heroin intake><heroin use><illicit opiate><illicit opioid><improved><insight><interest><liquid><male><medication adherence><medication compliance><medication for opioid use disorder><mental illness><mortality><multi-task><multitask><negative affect><negative affectivity><neural imaging><neuro-imaging><neurobiological><neurobiological mechanism><neuroimaging><neurological imaging><opiate consumption><opiate crisis><opiate drug use><opiate intake><opiate use><opiate use disorder><opioid consumption><opioid crisis><opioid drug use><opioid epidemic><opioid intake><opioid use><opioid use disorder><overdose risk><patient retention><predictive modeling><programs><prospective><psychiatric illness><psychological disorder><racial><racial background><racial origin><reduce overdose><reduction in overdose><resilience factor><resiliency factor><response><sex><synthetic opiate><synthetic opioid><training achievement><training level><training status><validations>