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: 9269262
• 负责人: Erika E Forbes
• 金额: $ 48.32万
• 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/9269262
• 关键词: Acute; 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; Heterogeneity; Impairment; Individual; Intervention; Link; Measures; Mediating; Mental disorders; Modeling; Morbidity - disease rate; Neurobiology; Neurocognitive; Neuropsychological Tests; Neuropsychology; Participant; 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; aged; behavior measurement; cingulate cortex; disorder subtype; effective therapy; enema administration; illness length; indexing; innovation; laxative; mental set; migration; mortality; neural correlate; neuromechanism; novel; operation; personalized medicine; public health relevance; 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)：成人神经性厌食症(AN)是一种严重且往往难以治愈的精神疾病，但对可能作为新干预措施开发目标的潜在机制知之甚少。推进AN病理生理学研究的一个挑战与该病的显著组内异质性有关。例如，《精神障碍诊断和统计手册》包括两个亚型：限食(An-R)和暴食/排泄(An-BP)，它们在暴食或排泄(即，自感呕吐或排泄)的存在方面有所不同 滥用泻药、利尿剂或灌肠)。尽管有一些证据表明An-R和An-BP是不同的，但区分这两个群体的机制仍然难以捉摸。此外，An-BP和神经性暴食症(BN)之间的相似和区别强调了识别An-R、An-BP和BN共有和独特的过程的必要性。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谱上症状呈现的异质性与认知不灵活性的两个方面-注意定势转移(即在两个抽象的注意之间转移注意力的能力)的显著差异联系起来 刺激维度)和反转学习(即，改变行为以应对强化偶发事件的变化的能力)。重要的是，注意定势转移和反转学习在神经生物学上是不同的，分别与腹外侧额叶皮质/前扣带回皮质和眼眶额叶皮质/腹侧纹状体相关。认知 作为AN的一个假定的生物标志物，僵硬已经受到了很多关注，但以前的研究主要依赖于多维临床神经心理测量，这些测量没有很好地映射到潜在的神经机制，结果喜忧参半。这项研究的指导假设是，可以通过识别额扣带回调节注意定势转移的额扣带回回路和介导反转学习的额纹状体回路功能变化的不同方面来阐明AN的异质性。因此，本研究将使用扫描仪外的行为任务(即来自剑桥神经心理测试自动化电池的传统的内侧/外侧移位任务和概率反转学习任务)和带有概念相关的神经认知探针的功能磁共振成像来评估和分离跨AN-BN频谱的注意定势转移和反转学习的行为和神经方面。研究对象包括4组，年龄18-55岁：1)无暴饮暴食或泻下病史的AN-R组(n=30)；2)AN-BP组(n=30)；3)无AN病史的BN(n=30)；以及4)精神健康对照组(n=30)。本研究具有创新性和重要意义，是首次尝试考察注意的不同贡献 集合转换和反转学习到AN-BN谱的表型异质性。这一发现将对进食障碍的神经生物学模型和针对亚组特定病理生理过程的新干预措施的开发具有重要意义。