Cognitive Inflexibility and Phenotypic Heterogeneity in Anorexia Nervosa

神经性厌食症的认知僵化和表型异质性

• 批准号: 9102250
• 负责人: Erika E Forbes
• 金额: $ 47.13万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-18 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9102250
• 关键词: Adult; Age; Anorexia Nervosa; Anterior; Attention; Back; Behavior; Behavioral; Binge Eating; Biological Markers; Body Weight; Bulimia; Clinical; Cognitive; Comorbidity; Corpus striatum structure; Development; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders; Dimensions; Diuretics; Eating Disorders; Evidence based treatment; Exhibits; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Handedness; Health; Heterogeneity; Impairment; Individual; Intervention; Link; Maps; Measures; Mediating; Mental disorders; Modeling; Morbidity - disease rate; Neurobiology; Neurocognitive; Neuropsychological Tests; Participant; Pathology; Patients; Performance; Personality Traits; Phenotype; Prefrontal Cortex; Process; Psychological reinforcement; Psychopathology; Recording of previous events; Recruitment Activity; Recurrence; Refractory; Research; Reversal Learning; Sorting - Cell Movement; Stimulus; Subgroup; Symptoms; Testing; Variant; Ventral Striatum; Vomiting; Weight; Wisconsin; Work; abstracting; aged; behavior measurement; cingulate cortex; disorder subtype; effective therapy; enema administration; illness length; indexing; innovation; laxative; mental set; migration; mortality; neural correlate; neuromechanism; neuropsychological; novel; operation; personalized medicine; purge; relating to nervous system; response; sex; therapy design

DESCRIPTION (provided by applicant): Anorexia nervosa (AN) in adults is a serious and often refractory psychiatric illness, yet little is known about underlying mechanisms that might serve as targets for the development of novel interventions. One challenge in advancing research on the pathophysiology of AN relates to the substantial within-group heterogeneity that characterizes the illness. For example, the Diagnostic and Statistical Manual of Mental Disorders includes two subtypes of AN - restricting (AN-R) and binge-eating/purging (AN-BP) that differ with respect to the presence of binge eating or purging (i.e., self-induced vomiting or the misuse of laxative, diuretics or enemas) episodes. Although there is some evidence that AN-R and AN-BP are distinct, the mechanisms that separate these groups remain elusive. Moreover, similarities and distinctions between AN-BP and bulimia nervosa (BN) underscore the need to identify processes that are shared by and unique to AN-R, AN-BP and BN. Accordingly, the overall goal of this study is to test a conceptual model linking heterogeneity in symptom presentation across the AN-BN spectrum to variations in the salience of two facets of cognitive inflexibility - attentional set-shifting (i.e., the ability to shift attention between two abstract stimulus dimensions) and reversal learning (i.e., the ability to alter behavior in response to changes in reinforcement contingencies). Importantly, attentional set-shifting and reversal learning are neurobiologically distinct, with correlates in the ventrolateral prefrontal cortex/anterior cingulate cortex and orbitofrontal cortex/ventral striatum, respectively. Cognitive inflexibility has received much attention as a putative biomarker of AN, but previous studies have relied primarily on multidimensional clinical neuropsychological measures that do not map on well to underlying neural mechanisms, and findings have been mixed. This study is guided by the hypothesis that heterogeneity in AN can be elucidated by identifying distinct aspects of altered function in fronto-cingulate circuitry mediating attentional set-shifting and fronto-striatl circuitry mediating reversal learning. Thus, this study will use both behavioral tasks outside of the scanner (i.e., Intradimensional/Extradimensional shift task from the Cambridge Neuropsychological Test Automated Battery and a probabilistic reversal learning task) and functional magnetic resonance imaging with conceptually-relevant neurocognitive probes to assess and separate behavioral and neural facets of attentional set-shifting and reversal learning across the AN-BN spectrum. Four groups of participants aged 18-55 years will be recruited: 1) AN-R with no history of binge eating or purging (n = 30); 2) AN-BP (n = 30); 3) BN with no history of AN (n = 30); and 4) psychiatrically healthy controls (n = 30). This study is innovative and significant as the first effort to examine the separate contributions of attentional set-shifting and reversal learning to phenotypic heterogeneity across the AN-BN spectrum. Findings will have important implications for neurobiological models of eating disorders and the development of novel interventions designed to target subgroup-specific pathophysiological processes.

描述（由申请人提供）：成年人中的神经性厌食症（AN）是一种严重且经常难治性的精神病，但对于可能是发展新干预措施的目标的潜在机制知之甚少。在进行有关某种病理生理学的研究的挑战之一是与疾病所特有的实质内部异质性有关。例如，精神障碍的诊断和统计手册包括两种亚型 - 限制（AN-R）和暴饮暴食/清除/清除（AN-BP），这些亚型在暴饮暴食或清除（即自我诱发的呕吐或呕吐或清除）方面有所不同 滥用泻药，利尿剂或灌肠的滥用。尽管有证据表明AN-R和AN-BP是不同的，但分离这些群体的机制仍然难以捉摸。此外，AN-BP和神经性贪食症（BN）之间的相似性和区别强调了确定由AN-R，AN-BP和BN共享和独特的过程的需求。因此，这项研究的总体目标是测试一个概念模型，该模型将AN-BN频谱中症状表现的异质性连接到认知僵化性的两个方面的显着性变化 - 注意力集中转移（即，两个摘要之间的注意力（即，） 刺激维度）和逆转学习（即，对强化意外事件的变化改变行为的能力）。重要的是，注意力集中和逆转学习在神经生物学上是不同的，在腹侧前额叶皮层/前扣带回皮层和轨道额/腹侧纹状体中，相关性。认知的 作为AN的推定生物标志物，僵化性受到了很多关注，但先前的研究主要依赖于多维临床神经心理学指标，这些临床神经心理学指标无法很好地映射到潜在的神经机制上，并且发现结果混合在一起。这项研究的指导下是通过假设，即可以通过识别额额分隔电路的不同方面来阐明一个介导注意力固定转移和额纹式电路介导反向学习的不同方面。因此，这项研究将使用扫描仪之外的两项行为任务（即，从剑桥神经心理学测试自动化电池和概率逆转学习任务）以及功能上的磁共振成像以及概念上相关的神经认知探测器，以评估和分离神经置于概念上的神经镜头，并在概念上进行跨性别的镜头，并在概率上进行跨性别的镜头，并跨越概率的磁共振成像。将招募四组18-55岁的参与者：1）AN-R没有暴饮暴食的历史（n = 30）； 2）AN-BP（n = 30）; 3）BN没有历史记录（n = 30）; 4）精神健康的对照（n = 30）。这项研究是创新的，并且是研究注意力的单独贡献的第一个努力 在AN-BN频谱中，设置转移和逆转学习到表型异质性。发现将对饮食失调的神经生物学模型以及旨在针对亚组特异性病理生理过程的新干预措施的发展具有重要意义。