Self-Regulation Failure: Identifying and Modifying a Risk Phenotype

自我调节失败：识别和修改风险表型

• 批准号: 8311035
• 负责人: AHMAD R HARIRI
• 金额: $ 58.35万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311035
• 关键词: Acute; Adolescent; Affect; Affective; Alcohol abuse; Alcoholism; Alleles; Behavior; Behavior Disorders; Behavioral; Behavioral Mechanisms; Behavioral Sciences; Catechol O-Methyltransferase; Cessation of life; Chronic; Cognitive; Cues; Development; Discipline; Distress; Dopamine; Drug Addiction; Eating Disorders; Emotional; Emotions; Environment; Enzymes; Failure; Feedback; Functional Magnetic Resonance Imaging; Functional disorder; Future; Genes; Genetic; Genotype; Goals; Health; Human; Image; Impulsivity; Individual; Individual Differences; Informal Social Control; Interdisciplinary Study; Intervention; Laboratories; Lead; Link; Modeling; Mood Disorders; Obesity; Pathway interactions; Phenotype; Preventive Intervention; Process; Public Health; Regulation; Research; Research Design; Risk; Risk Behaviors; Role; Sampling; Science; Series; Services; Smoking; Stimulus; Suicide; Techniques; Testing; Therapeutic Intervention; Thinking; Tobacco use; Translational Research; base; behavior change; cognitive neuroscience; coping; cost; disability; experience; extracellular; flexibility; frontal lobe; information processing; meetings; neuromechanism; novel; prevent; programs; psychologic; public health relevance; research study; response; social; success; theories; university student

DESCRIPTION (provided by applicant): Human behavior involves the unique capacities to regulate our own psychological states to pursue desired goals, bring our behavior in line with internal/external standards, manage our emotions, and cope with challenges and opportunities that arise. The term self-regulation denotes the processes through which people intentionally or automatically initiate, maintain, and terminate their own thoughts and behaviors in the service of pursuing personal goals. The importance of understanding self-regulation becomes obvious when one considers the array of public health problems that can be traced to problematic goal pursuit. Many behaviors that put people at increased risk for illness, disability, and death - such as obesity, eating disorders, smoking, alcohol abuse, suicidality, and drug addiction - involve difficulties with self-regulation. Thus, maladaptive self-regulation is an important contributory factor in a large number of psychological, social, and health-related problems. We believe that significant progress can be made in understanding and overcoming self- regulatory problems by combining existing theory and research in behavioral science with parallel findings in related disciplines. Recent developments in cognitive neuroscience (specifically, the role of the orbitofrontal cortex in self-regulation of goal pursuit) and imaging genetics (specifically, how heritable variability in the gene encoding catechol-O- methyltransferase [COMT], an enzyme that controls extracellular dopamine in the frontal cortex, influences processing of motivationally salient stimuli) offer synergistic perspectives on how failure in self-regulation could, for a particular subset of individuals, lead to chronically maladaptive behavior and increase vulnerability to a range of significant health problems. The aims of this R01 application are: (1) to validate a hypothesized gene/environment/self-regulation risk phenotype conferring vulnerability to failures of self- regulation, and (2) to test a novel set of cognitive/behavioral techniques that we predict will acutely reverse the dysfunctions that underlie self-regulatory failure. The proposed research will be conducted in two samples: adolescents, who are vulnerable to initiation of a number of health-risking behaviors and psychological problems, and college students, some of whom already engage regularly in such behaviors and manifest psychological difficulties. We predict that a combination of three contributory factors - individual differences in regulatory focus, COMT genotype, and chronic failure to attain a particular kind of personal goal - creates a self- regulation pathway to disordered behaviors with significant public health implications. PUBLIC HEALTH RELEVANCE: The aims of this R01 application are: (1) to conduct a program of translational research validating a hypothesized gene/environment/self-regulation risk phenotype conferring vulnerability to failures of self-regulation, and (2) to test a novel set of cognitive/behavioral techniques that we predict will acutely reverse the dysfunctions that underlie self-regulatory failure. We predict that we will observe, in both adolescent and college student samples, that a combination of three contributory factors - individual differences in regulatory focus, COMT genotype, and chronic failure to attain a particular kind of personal goal - creates a self- regulation pathway to a broad array of disordered behaviors and psychological states with significant public health implications, including tobacco use, alcoholism, mood disorders, obesity, eating disorders, and impulsivity. Based on this model, we anticipate that the theory- based brief change techniques will prove efficacious and will ultimately provide a basis for effective broader-scale therapeutic and preventive interventions in future studies.

描述（由申请人提供）：人类行为涉及调节我们自己的心理状态以追求预期目标的独特能力，使我们的行为符合内部/外部标准，管理我们的情绪，并科普出现的挑战和机遇。自我调节是指人们为了追求个人目标而有意或自动地启动、维持和终止自己的思想和行为的过程。当人们考虑到一系列可以追溯到有问题的目标追求的公共卫生问题时，理解自我调节的重要性变得显而易见。许多使人们面临疾病、残疾和死亡风险增加的行为--如肥胖、饮食失调、吸烟、酗酒、自杀和吸毒--都涉及自我调节的困难。因此，适应不良的自我调节是一个重要的促成因素，在大量的心理，社会和健康相关的问题。我们相信，通过将行为科学中现有的理论和研究与相关学科的平行发现相结合，可以在理解和克服自我调节问题方面取得重大进展。认知神经科学的最新进展（特别是眶额皮质在自我调节目标追求中的作用）和成像遗传学（具体来说，编码儿茶酚-O-甲基转移酶[COMT]（一种控制额叶皮质细胞外多巴胺的酶）的基因的遗传变异性如何影响动机显着刺激的处理）提供了关于自我调节失败如何的协同观点，对于特定的一部分人来说，这会导致长期适应不良的行为，并增加对一系列重大健康问题的脆弱性。该R 01应用的目的是：（1）验证假设的基因/环境/自我调节风险表型，该表型赋予对自我调节失败的脆弱性，以及（2）测试一组新的认知/行为技术，我们预测这些技术将急剧逆转自我调节失败的基础功能障碍。拟议的研究将在两个样本中进行：青少年，他们容易引发一些健康风险行为和心理问题，以及大学生，其中一些人已经经常从事此类行为并表现出心理困难。我们预测，三个促成因素的组合--调节焦点的个体差异、COMT基因型和长期未能达到某种特定的个人目标--创造了一条自我调节的途径，导致行为紊乱，具有重大的公共卫生影响。 公共卫生关系：R 01申请的目的是：（1）进行一项转化研究计划，验证一种假设的基因/环境/自我调节风险表型，该表型赋予自我调节失败的脆弱性，以及（2）测试一组新的认知/行为技术，我们预测这些技术将急剧逆转自我调节失败的基础功能障碍。我们预测，我们将在青少年和大学生样本中观察到，三个促成因素的组合-调节焦点的个体差异，COMT基因型和长期未能实现特定类型的个人目标-创造了一条自我调节途径，导致广泛的紊乱行为和心理状态，具有重大的公共卫生影响，包括烟草使用，酗酒，情绪障碍肥胖饮食失调和冲动基于该模型，我们预计基于理论的短暂改变技术将被证明是有效的，并最终为未来研究中有效的更广泛的治疗和预防干预提供基础。

项目成果

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders.

• DOI: 10.1016/j.neuron.2015.05.034
• 发表时间: 2015-06-03
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Arloth J;Bogdan R;Weber P;Frishman G;Menke A;Wagner KV;Balsevich G;Schmidt MV;Karbalai N;Czamara D;Altmann A;Trümbach D;Wurst W;Mehta D;Uhr M;Klengel T;Erhardt A;Carey CE;Conley ED;Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (PGC);Ruepp A;Müller-Myhsok B;Hariri AR;Binder EB;Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium PGC
• 通讯作者: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium PGC

Neuroimaging for psychotherapy research: current trends.

• DOI: 10.1080/10503307.2014.883088
• 发表时间: 2015
• 期刊: Psychotherapy research : journal of the Society for Psychotherapy Research
• 作者: Weingarten CP;Strauman TJ
• 通讯作者: Strauman TJ