Diagnostic and prognostic biomarkers for subtypes of addiction-related circuit dysfunction
成瘾相关回路功能障碍亚型的诊断和预后生物标志物
基本信息
- 批准号:10177987
- 负责人:
- 金额:$ 60.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-01 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAmygdaloid structureAnhedoniaAnimal ModelAnteriorAnxietyAnxiety DisordersArousalBehaviorBiological MarkersBrainBrain scanCardiovascular DiseasesCategoriesClinicalCocaineCocaine DependenceCognitionCognitiveCommunitiesCorpus striatum structureData AnalysesData SetDiagnosisDiagnosticDiseaseDorsalFunctional Magnetic Resonance ImagingFunctional disorderHabitsHeterogeneityImpairmentIndividualIndividual DifferencesLateralLeadLearningMalignant NeoplasmsMapsMeasuresMedialMediatingMedicalMental DepressionMolecularMood DisordersMotivationNegative ReinforcementsNeurobiologyNicotinePatient CarePatientsPatternPharmaceutical PreparationsPharmacologyPhysiciansPrediction of Response to TherapyPrevalenceProcessPrognostic MarkerPsychiatric DiagnosisRegulationRelapseResearchResearch PersonnelRestRewardsRiskScanningSubgroupSubstance Use DisorderSymptomsSyndromeTestingTranscendTreatment outcomeVentral StriatumWithdrawaladdictionanimal dataanxiousbasebiobankbiomarker validationcocaine usecomorbid depressioncomorbiditycravingdiagnostic biomarkerdiagnostic platformdisabilitydisease classificationdisease diagnosisdrug seeking behaviorindividual patientindividualized medicineinterestlarge scale datamachine learning methodnegative affectnegative emotional statenetwork dysfunctionneuroimagingneurophysiologyneuropsychiatrynovelnovel therapeutic interventionnovel therapeuticspatient subsetsreinforcerresponsespecific biomarkerssubstance misusetool
项目摘要
Project Summary
Substance use disorders (SUDs) are increasing in prevalence and are already a leading cause of disability,
due in part to the fact that our understanding of the underlying pathophysiology is incomplete. Like most
neuropsychiatric syndromes, SUDs are highly heterogeneous, and distinct mechanisms may be operative in
some individuals but not in others, even within a single diagnostic category. Furthermore, SUDs frequently co-
occur with depression, anxiety, and other psychiatric syndromes, complicating efforts to identify molecular and
circuit-level mechanisms, and disentangle them from those involved in mood and anxiety disorders. Diagnostic
heterogeneity is thus a fundamental obstacle to developing better treatments, identifying biomarkers for
quantifying risk for different forms of addiction, and predicting treatment response and relapse. Recently, we
developed and validated an approach to discovering and diagnosing subtypes of depression using fMRI
measures of functional connectivity, which in turn predicted subtype-specific clinical symptom profiles and
treatment outcomes. Here, in response to PAR-18-062, we propose a secondary data analysis that would
extend this approach to SUDs, leveraging multiple deeply characterized and large-scale neuroimaging
datasets. Our central hypothesis is that individual differences in mechanisms underlying impairments in
response inhibition and salience attribution (iRISA) are mediated by distinct forms of dysfunctional connectivity
in addiction-related circuits, which in turn interact and give rise to distinct neurophysiological addiction
subtypes. In Aim 1, we will use statistical clustering and machine learning methods to delineate these subtypes
and optimize classifiers (fMRI biomarkers) for diagnosing them in individual patients, focusing initially on
cocaine addiction. In Aim 2, we will validate these subtype-specific biomarkers by first replicating them in a
new dataset and then evaluating their longitudinal stability and predictive utility. In Aim 3, we will test whether
subtype-specific circuit mechanisms generalize to mediate iRISA functions in other forms of addiction, and
define their interactions with distinct mechanisms mediating anhedonia and anxious arousal in patients with
comorbid depression and anxiety.
项目摘要
物质使用障碍(SOD)的患病率正在上升,已经成为导致残疾的主要原因,
部分原因是我们对潜在的病理生理学的理解是不完整的。像大多数人一样
神经精神综合征,sod是高度异质性的,不同的机制可能在
一些个体,但不是在其他人,甚至在一个单一的诊断类别。此外,肥皂水经常与
与抑郁、焦虑和其他精神症状一起发生,使识别分子和
电路水平的机制,并将它们与那些涉及情绪和焦虑症的人分开。诊断性
因此,异质性是开发更好的治疗方法、识别生物标记物和
量化不同形式成瘾的风险,并预测治疗反应和复发。最近,我们
开发并验证了一种使用功能磁共振成像发现和诊断抑郁症亚型的方法
功能连通性的测量,这反过来又预测特定亚型的临床症状和
治疗结果。在这里,为了响应PAR-18-062,我们提出了一个二次数据分析,它将
将这种方法扩展到SODS,利用多种深度特征化和大规模的神经成像
数据集。我们的中心假设是,在损伤发生机制上的个体差异
反应抑制和显著归因(IRSA)由不同形式的功能障碍连接所介导
在与成瘾相关的回路中,这反过来又相互作用并引起不同的神经生理学成瘾
子类型。在目标1中,我们将使用统计聚类和机器学习方法来描述这些子类型
并优化分类器(fMRI生物标记物)用于个别患者的诊断,最初重点放在
可卡因成瘾。在目标2中,我们将通过首先将这些亚型特定的生物标记复制到
新的数据集,然后评估其纵向稳定性和预测效用。在目标3中,我们将测试
亚型特有的电路机制一般用于在其他形式的成瘾中调节IRSA功能,以及
明确它们与介导快感缺乏和焦虑唤醒的不同机制之间的相互作用
抑郁和焦虑并存。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Rita Z Goldstein其他文献
Oral Methylphenidate Normalizes Cingulate Activity and Decreases Impulsivity in Cocaine Addiction During an Emotionally Salient Cognitive Task
在一项情感显著的认知任务中,口服哌甲酯可使扣带回活动正常化,并降低可卡因成瘾者的冲动性
- DOI:
10.1038/npp.2010.145 - 发表时间:
2010-11-30 - 期刊:
- 影响因子:7.100
- 作者:
Rita Z Goldstein;Nora D Volkow - 通讯作者:
Nora D Volkow
Rita Z Goldstein的其他文献
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{{ truncateString('Rita Z Goldstein', 18)}}的其他基金
Brain-to-brain neurofeedback during naturalistic dynamic stimuli to reduce craving in heroin addiction
自然动态刺激期间的脑对脑神经反馈可减少海洛因成瘾的渴望
- 批准号:
10725836 - 财政年份:2023
- 资助金额:
$ 60.4万 - 项目类别:
Targeting neural, behavioral and pharmacological mechanisms of drug memories in cocaine addiction
针对可卡因成瘾药物记忆的神经、行为和药理学机制
- 批准号:
10447976 - 财政年份:2022
- 资助金额:
$ 60.4万 - 项目类别:
Targeting neural, behavioral and pharmacological mechanisms of drug memories in cocaine addiction
针对可卡因成瘾药物记忆的神经、行为和药理学机制
- 批准号:
10707903 - 财政年份:2022
- 资助金额:
$ 60.4万 - 项目类别:
Sex differences in the neural correlates underlying impairments in response inhibition and salience attribution in cocaine addiction
神经系统中的性别差异与可卡因成瘾的反应抑制和显着性归因的潜在损伤相关
- 批准号:
9913128 - 财政年份:2020
- 资助金额:
$ 60.4万 - 项目类别:
Sex differences in the neural correlates underlying impairments in response inhibition and salience attribution in cocaine addiction
神经系统中的性别差异与可卡因成瘾的反应抑制和显着性归因的潜在损伤相关
- 批准号:
10561729 - 财政年份:2020
- 资助金额:
$ 60.4万 - 项目类别:
Sex differences in the neural correlates underlying impairments in response inhibition and salience attribution in cocaine addiction
神经系统中的性别差异与可卡因成瘾的反应抑制和显着性归因的潜在损伤相关
- 批准号:
10358597 - 财政年份:2020
- 资助金额:
$ 60.4万 - 项目类别:
Neuroimaging response inhibition and salience attribution changes during mindfulness-based treatment of human heroin addiction
基于正念的人类海洛因成瘾治疗过程中神经影像反应抑制和显着性归因的变化
- 批准号:
9763882 - 财政年份:2019
- 资助金额:
$ 60.4万 - 项目类别:
Diagnostic and prognostic biomarkers for subtypes of addiction-related circuit dysfunction
成瘾相关回路功能障碍亚型的诊断和预后生物标志物
- 批准号:
10414018 - 财政年份:2019
- 资助金额:
$ 60.4万 - 项目类别:
Neuroimaging response inhibition and salience attribution changes during mindfulness-based treatment of human heroin addiction
基于正念的人类海洛因成瘾治疗过程中神经影像反应抑制和显着性归因的变化
- 批准号:
10188440 - 财政年份:2019
- 资助金额:
$ 60.4万 - 项目类别:
Neuroimaging response inhibition and salience attribution changes during mindfulness-based treatment of human heroin addiction
基于正念的人类海洛因成瘾治疗过程中神经影像反应抑制和显着性归因的变化
- 批准号:
10646215 - 财政年份:2019
- 资助金额:
$ 60.4万 - 项目类别: