Combining a novel framework for psychopathology with a precision medicine approach to understand the heterogeneous response to abstinence from alcohol
Combining a novel framework for psychopathology with a precision medicine approach to understand the heterogeneous response to abstinence from alcohol
批准号:
10473770
负责人:
Eva Argyriou
金额:
$4.54万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-09-01 至 2023-08-31
关键词:
ARHGEF5 geneAbstinenceAddressAlcohol abuseAlcohol consumptionAlcoholsAnimalsBehavioralCategoriesCharacteristicsClinicalComplementComplexDataDecision MakingDevelopmentDimensionsElectrophysiology (science)Family history ofFellowshipFemaleFundingGeneticGoalsGrantGuidelinesHeterogeneityHumanIndividualIndividual DifferencesInterventionLaboratoriesLifeMeasurementMentorshipMethodologyMethodsModelingModernizationNeurobiologyPatientsPatternPopulationPsychopathologyRecommendationRelapseReportingResearchRisk FactorsSecondary toSubgroupSubstance Use DisorderSymptomsSyndromeTaxonomyUnited States National Institutes of HealthWomanalcohol abstinencealcohol abuse therapyalcohol researchalcohol responsealcohol seeking behavioralcohol use disorderbasecareerclinical decision-makingclinical practicecomorbiditycostdesigndrinkingfollow-uphospital readmissionindividualized medicineinnovationmenneurobiological mechanismnovelpersonalized medicineprecision medicinepredicting responserelating to nervous systemresponsesextraittreatment choicetreatment effecttreatment planningtreatment response
中文摘要
项目总结
英文摘要
Project Summary
Although abstinence-oriented interventions remain the typical treatment choice for alcohol use disorder
(AUD), relapse is common. Research in animals and humans shows that, in certain groups, short-term
abstinence followed by reinstatement of drinking escalates, instead of reduces, subsequent alcohol use. This
heterogeneity in response can in part explain poor AUD treatment effects, warranting personalized treatment
rules for when to prescribe abstinence-oriented interventions. Co-occurring psychopathology complicates AUD,
making it a prime factor on which to base clinical decision-making. The overall goal of this project is to utilize
a novel psychopathology framework, the Hierarchical Taxonomy of Psychopathology (HiTOP), to predict the
heterogeneous response to short-term abstinence and to examine shared neurobiological and genetic
mechanisms underlying this response. The specific aims of this application are to 1) characterize individuals
who benefit from, or are harmed by, short-term enforced abstinence based on HiTOP dimensions and
underlying neurobiological and genetic mechanisms in a well-controlled laboratory paradigm and 2)
Characterize individuals who show escalating patterns of alcohol consumption after natural periods of
abstinence over a one-year period based on HiTOP dimensions and underlying neurobiological and genetic
mechanisms. Modern cutting-edge subgroup discovery methodology will be leveraged which enables
simultaneously modeling a large number of treatment-moderator interactions with complex, nonlinear
moderation effects, to accurately estimate abstinence response. This cutting-edge methodology directly
informs clinical decision making, enabling the creation of guidelines for predicting response to abstinence in
practice. The proposed project is innovative and significant as it 1) studies heterogeneity in abstinence
response, which might explain escalation in alcohol use, a highly significant and costly problem; 2) leverages
the novel HiTOP framework for personalized alcohol treatment recommendations, which is easily assessed
and can be easily applied to clinical settings; 3) applies cutting edge modern statistical methodology that
addresses limitations of traditional methods in precision medicine and the urgent need for individualized
treatment planning; 4) complements data-driven approaches with potential underlying neurobiological and
genetic mechanisms; and 5) integrates a novel, well-controlled human laboratory paradigm with ecologically
valid longitudinal follow-up of real-world reported alcohol patterns to further provide rich and robust findings.
The long-term goal of this line of research is to develop guidelines to facilitate clinical practitioners’ decision-
making concerning when to utilize abstinence-based interventions.
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Combining a novel framework for psychopathology with a precision medicine approach to understand the heterogeneous response to abstinence from alcohol
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批准号:10259703
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项目类别:
-
资助金额:$4.47万
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财政年份:2020
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负责人:Eva Argyriou
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依托单位:
海外基金