FMRI STUDIES IN PATHOLOGICAL GAMBLING AND TREATMENT-RESISTANT OCD

病理性赌博和难治性强迫症的 FMRI 研究

• 批准号: 7718160
• 负责人: Jennifer Adrienne Bartz
• 金额: $ 0.17万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718160
• 关键词: Anterior; Behavior; Behavior Disorders; Biochemical; Characteristics; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Diagnosis; Disease; Dopamine; Dorsal; Exhibits; Funding; Gambling; Genetic; Genetic Research; Grant; Impulsive Behavior; Individual; Institution; Insula of Reil; Lateral; Measures; Medial; Mental disorders; Midbrain structure; Nature; Neurobiology; Nucleus Accumbens; Numbers; Obsessive compulsive behavior; Outcome; Pathological Gambling; Pathway interactions; Phase; Phenotype; Pilot Projects; Prefrontal Cortex; Process; Punishment; Research; Research Personnel; Resistance; Resources; Rewards; Source; Structure; Testing; Thalamic structure; Thinking; United States National Institutes of Health; Ventral Striatum; cingulate cortex; disease classification; endophenotype; neurophysiology; neuropsychological; progesterone 11-hemisuccinate-(2-iodohistamine); response; reward processing

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although OCD is primarily marked by compulsive behaviors and pathological gambling is primarily marked by impulsive behaviors, these disorders have been conceptualized as obsessive-compulsive (OC) spectrum disorders because they share a number of phenomenological features (e.g., obsessionality and compulsivity) (Bartz & Hollander, in press; Stein & Hollander, 1993). More research, however, is needed to investigate the similarities and differences between these disorders as well as their neurobiological underpinnings. The objective of this pilot study research is to identify cognitive and neurobiological endophenotypes associated with these two OC spectrum disorders. Endophenotypes, which can be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological in nature, have become an important focus in the study of psychiatric disorders because they are thought to be indicators of the genetic underpinnings of disorders and, therefore, can be used to guide and inform genetic research, and aid in disease classification, diagnosis and treatment (Gottesman & Gould, 2003). Inherent in the notion of an OC spectrum of disorders is that although these disorders have different phenotypes, they likely share some common endophenotypes. Response inhibition deficits are a core feature of OCD and may also be characteristic of pathological gambling. Moreover, altered processing of rewards and/or punishments may be implicated in these two disorders. Preliminary findings (Bartz et al., 2005) suggest that deficient anticipation of rewards may underlie the pathological gambler's need to engage in risky gambling behavior. Along similar lines, increased sensitivity to punishments may be a factor in the OCD individual's difficulty resisting compulsions. The primary objective of this pilot study is to investigate the underlying neurocircuitry associated with response inhibition and reward processing in individuals diagnosed with treatment resistant OCD and in those diagnosed with pathological gambling in an effort to identify endophenotypic markers of these two disorders. First, we will attempt to show that pathological gamblers exhibit hypoactivation of the caudate, dorsolateral prefrontal and lateral orbitofrontal cortex as well as the anterior cingulate cortex during the go-nogo test, whereas those with treatment-resistant OCD will exhibit hyperactivation of these regions on the same task. Second, we will attempt to show that pathological gamblers exhibit hypoactivation of the ventral striatum during the anticipatory phase of reward processing, whereas those with treatment-resistant OCD exhibit hyperactivation of the ventral striatum during the anticipatory phase of reward processing. Finally, we will attempt to show that pathological gamblers are more sensitive to potential rewards, whereas those with treatment-resistant OCD are more sensitive to potential punishments/loses. In addition to the theoretical contribution this pilot research will make to understanding important processes underlying OCD and pathological gambling, by identifying cognitive and neurophysiological endophenotypic markers of these two disorders, the findings from this pilot studyresearch can be used to direct the focus of genetic research and to identify individuals who will respond to specific treatments. In addition to the theoretical contribution this pilot research will make to understanding important processes underlying OCD and pathological gambling, by identifying cognitive and neurophysiological endophenotypic markers of these two disorders, the findings from this pilot studyresearch can be used to direct the focus of genetic research and to identify individuals who will respond to specific treatments. Hypotheses: 1. To explore abnormalities in activation of the frontostriatal circuit involved in response inhibition in pathological gamblers and those with treatment-resistant OCD a) Pathological gamblers vs. normal controls will exhibit decreased activity in the caudate, dorsolateral prefrontal and lateral orbitofrontal cortex as well as the anterior cingulate cortex during the go-nogo test (a measure of response inhibition); in addition, pathological gamblers may exhibit decreased activity in the ventromedial prefrontal cortex compared to normal controls. b) Individuals diagnosed with treatment resistant OCD vs. normal controls will exhibit increased activity in the caudate, dorsolateral prefrontal and lateral orbitofrontal cortex as well as anterior cingulate cortex during the go-nogo test. 2. To explore abnormalities in the neurocircuitry involved in the anticipation and outcome phases of reward processing in pathological gamblers and treatment-resistant OCD a) In response to monetary rewards (versus no reward), pathological gamblers vs. normal controls will exhibit decreased activity in the ventral striatum, nucleus accumbens, and anterior and medial caudate during the anticipatory phase of the MID task; in addition, the insula and structures associated with the dopamine pathway such as the dorsal thalamus and dorsal midbrain may similarly be hypoactivated during the anticipation of monetary rewards; b) Individuals diagnosed with treatment resistant OCD vs. normal controls will exhibit increased activation of the ventral striatum, nucleus accumbens, and anterior and medial caudate during the anticipatory phase of the MID task; in addition, the right insula and structures associated with the dopamine pathway such as the dorsal thalamus and dorsal midbrain may also be hyperactivated during reward anticipation; c) Pathological gamblers and those with OCD vs. normal controls will not exhibit differential activation during the outcome phase of the MID task; 3. To explore differences in the neurocircuitry in individuals diagnosed with treatment resistant OCD and PG with respect to response inhibition and reward processing a) While both the PG and OCD subjects will exhibit altered neurocircuitry in response to the go-nogo task, individuals diagnosed with PG will exhibit hypoactivation whereas those diagnosed with OCD will exhibit hyperactivation of the frontostriatal circuits during the go-nogo task. b) Pathological gamblers will primarily respond to potential rewards in the MID task, whereas those with OCD will primarily respond to potential losses.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 尽管强迫症主要由强迫性行为和病理赌博标记，主要由冲动行为标记，但这些疾病已被概念化为强迫症（OC）谱系障碍，因为它们具有许多现象学特征（例如，迷恋和强迫性）（Bartz＆Hollander，in Press in perss; Stepern＆Steen＆Steen＆steen＆hollander＆steen＆hollander＆sethin＆hollander＆hollander＆hollander＆hollander＆hollander＆hollander＆hollander＆hollander＆hollander，但是，需要进行更多的研究来研究这些疾病及其神经生物学基础之间的相似性和差异。 这项试验研究的目的是确定与这两种OC谱系障碍相关的认知和神经生物学内表型。可以是神经生理学，生物学，内分泌学，神经解剖学，认知或神经心理学的内部表型已成为研究精神疾病的研究中的重要重点古尔德，2003年）。 OC疾病谱系概念固有的是，尽管这些疾病具有不同的表型，但它们可能具有一些常见的内型型。反应抑制缺陷是强迫症的核心特征，也可能是病理赌博的特征。此外，这两种疾病可能涉及奖励和/或惩罚的改变处理。初步发现（Bartz等，2005）表明，对奖励的不足可能是病理性赌徒从事风险赌博行为的需求。沿着类似的线条，对惩罚的敏感性提高可能是强迫症个体难以抵抗强迫症的一个因素。这项试验研究的主要目的是研究与抑制治疗性强迫症的抑制作用和奖励处理相关的潜在神经通律，以及被诊断为病理赌博的患者，以识别这两种疾病的内型标记。首先，我们将试图表明病理赌徒表现出尾状，背外侧前额叶和侧眶额皮质以及在GO-NOGO测试期间的前扣带回皮质的过度激活，而具有治疗性OCD的患者将表现出相同任务的耐药性OCD的过度活化。其次，我们将试图表明，病理赌徒在奖励处理的预期阶段表现出腹侧纹状体的过度激活，而在奖励处理的预期阶段，患有耐药性强迫症的患者表现出腹侧纹状体的过度激活。最后，我们将试图表明病理赌徒对潜在的奖励更敏感，而具有耐药性强迫症的赌徒对潜在的惩罚/损失更敏感。 除了理论贡献外，这项试验研究还将通过确定这两个疾病的认知和神经生理的内表型标记来理解强迫症和病理赌博的重要过程，可以使用这项试验研究研究的发现来指导遗传研究的焦点并确定对特定治疗的响应的个人。 除了理论贡献外，这项试验研究还将通过确定这两个疾病的认知和神经生理的内表型标记来理解强迫症和病理赌博的重要过程，可以使用这项试验研究研究的发现来指导遗传研究的焦点并确定对特定治疗的响应的个人。 假设： 1。探索在病理赌徒和具有耐药性强迫症的额叶抑制作用涉及的额叶电路激活中的异常 a）病理赌徒与正常对照组将在尾状，背外侧前额叶和侧眶额皮层以及GO-NOGO测试期间的前扣带回皮质（量度抑制）中表现出降低的活性；此外，与正常对照相比，病理赌徒在腹侧前额叶皮层的活性降低。 b）在GO-NOGO测试期间，被诊断为抗治疗性强迫症与正常对照组的人与正常对照组将表现出增加的活性。 2。探索在病理赌徒和耐药性强迫症中奖励加工的预期和结果阶段所涉及的神经记录异常 a）响应货币奖励（与无奖励），在中期任务的预期阶段，病理赌徒与正常对照组将表现出腹侧纹状体，伏隔核以及前后尾状尾巴的活性下降；此外，在预期货币奖励期间，与多巴胺途径（例如背丘脑和背部中脑）相关的绝缘和结构可能会被降低。 b）在中期任务的预期阶段，被诊断为抗治疗性强迫症与正常对照的个体将表现出增加的腹纹状体，伏隔核以及前和内侧尾状的患者；另外，合适的绝缘和结构相关 随着多巴胺途径，例如背丘脑和背部脑的途径，在奖励预期期间也可能会过度激活； c）在中期任务的结果阶段，病理赌徒和具有强迫症与正常对照的患者与正常对照组不会表现出差异激活； 3。探索诊断为耐药性强迫症和PG的个体的神经记录差异，以抑制和奖励处理 a）虽然PG和强迫症受试者均表现出对GO-NOGO任务的神经通律变化，但被诊断为PG的人会表现出低均激活，而被诊断为OCD的人会在GO-NOGO任务期间表现出额叶纹状体电路的过度激活。 b）病理赌徒将主要对中期任务中的潜在奖励做出反应，而患有强迫症的赌徒则主要对潜在的损失做出反应。