Department of Psychiatry, University of California at San Diego, San Diego.
Department of Psychiatry, University of Colorado, Anschutz Medical Campus, Aurora.
JAMA Psychiatry. 2021 Oct 1;78(10):1123-1133. doi: 10.1001/jamapsychiatry.2021.1580.
Eating disorders are severe psychiatric disorders; however, disease models that cross subtypes and integrate behavior and neurobiologic factors are lacking.
To assess brain response during unexpected receipt or omission of a salient sweet stimulus across a large sample of individuals with eating disorders and healthy controls and test for evidence of whether this brain response is associated with the ventral striatal-hypothalamic circuitry, which has been associated with food intake control, and whether salient stimulus response and eating disorder related behaviors are associated.
DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional functional brain imaging study, young adults across the eating disorder spectrum were matched with healthy controls at a university brain imaging facility and eating disorder treatment program. During a sucrose taste classic conditioning paradigm, violations of learned associations between conditioned visual and unconditioned taste stimuli evoked the dopamine-related prediction error. Dynamic effective connectivity during expected sweet taste receipt was studied to investigate hierarchical brain activation between food intake relevant brain regions. The study was conducted from June 2014 to November 2019. Data were analyzed from December 2019 to February 2020.
Prediction error brain reward response across insula and striatum; dynamic effective connectivity between hypothalamus and ventral striatum; and demographic and behavior variables and their correlations with prediction error brain response and connectivity edge coefficients.
Of 317 female participants (197 with eating disorders and 120 healthy controls), the mean (SD) age was 23.8 (5.6) years and mean (SD) body mass index was 20.8 (5.4). Prediction error response was elevated in participants with anorexia nervosa (Wilks λ, 0.843; P = .001) and in participants with eating disorders inversely correlated with body mass index (left nucleus accumbens: r = -0.291; 95% CI, -0.413 to -0.167; P < .001; right dorsal anterior insula: r = -0.228; 95% CI, -0.366 to -0.089; P = .001), eating disorder inventory-3 binge eating tendency (left nucleus accumbens: r = -0.207; 95% CI, -0.333 to -0.073; P = .004; right dorsal anterior insula: r = -0.220; 95% CI, -0.354 to -0.073; P = .002), and trait anxiety (left nucleus accumbens: r = -0.148; 95% CI, -0.288 to -0.003; P = .04; right dorsal anterior insula: r = -0.221; 95% CI, -0.357 to -0.076; P = .002). Ventral striatal to hypothalamus directed connectivity was positively correlated with ventral striatal prediction error in eating disorders (r = 0.189; 95% CI, 0.045-0.324; P = .01) and negatively correlated with feeling out of control after eating (right side: r = -0.328; 95% CI, -0.480 to -0.164; P < .001; left side: r = -0.297; 95% CI, -0.439 to -0.142; P = .001).
The results of this cross-sectional imaging study support that body mass index modulates prediction error and food intake control circuitry in the brain. Once altered, this circuitry may reinforce eating disorder behaviors when paired with behavioral traits associated with overeating or undereating.
饮食失调是严重的精神疾病；然而，缺乏跨亚型的疾病模型，无法将行为和神经生物学因素整合在一起。
在大量饮食失调患者和健康对照者中，评估在意外收到或遗漏显著甜味刺激时大脑的反应，并测试这种大脑反应是否与腹侧纹状体-下丘脑回路有关，该回路与食物摄入控制有关，以及显著的刺激反应和与饮食失调相关的行为是否相关。
设计、地点和参与者：在这项横断面功能脑成像研究中，在大学脑成像设施和饮食失调治疗计划中，将饮食失调谱系中的年轻成年人与健康对照者相匹配。在蔗糖味觉经典条件反射范式中，违反了条件视觉和非条件味觉刺激之间的习得关联，引发了多巴胺相关的预测误差。研究了预期甜味摄入期间的动态有效连接，以研究与食物摄入相关的脑区之间的分层脑激活。该研究于 2014 年 6 月至 2019 年 11 月进行。数据于 2019 年 12 月至 2020 年 2 月进行分析。
岛叶和纹状体的预测误差脑奖励反应；下丘脑和腹侧纹状体之间的动态有效连接；以及人口统计学和行为变量及其与预测误差脑反应和连接边系数的相关性。
在 317 名女性参与者（197 名饮食失调患者和 120 名健康对照组）中，平均（SD）年龄为 23.8（5.6）岁，平均（SD）体重指数为 20.8（5.4）。厌食症患者的预测误差反应升高（威尔克斯 λ，0.843；P = .001），饮食失调患者的预测误差反应与体重指数呈负相关（左侧伏隔核：r = -0.291；95%置信区间，-0.413 至-0.167；P < .001；右侧背侧前岛叶：r = -0.228；95%置信区间，-0.366 至-0.089；P = .001），与饮食失调问卷-3 暴食倾向（左侧伏隔核：r = -0.207；95%置信区间，-0.333 至-0.073；P = .004；右侧背侧前岛叶：r = -0.220；95%置信区间，-0.354 至-0.073；P = .002），以及特质焦虑（左侧伏隔核：r = -0.148；95%置信区间，-0.288 至-0.003；P = .04；右侧背侧前岛叶：r = -0.221；95%置信区间，-0.357 至-0.076；P = .002）。饮食失调患者中，腹侧纹状体到下丘脑的定向连接与腹侧纹状体的预测误差呈正相关（r = 0.189；95%置信区间，0.045-0.324；P = .01），与进食后失去控制的感觉呈负相关（右侧：r = -0.328；95%置信区间，-0.480 至-0.164；P < .001；左侧：r = -0.297；95%置信区间，-0.439 至-0.142；P = .001）。
这项横断面成像研究的结果支持体重指数调节大脑中的预测误差和食物摄入控制回路。一旦发生改变，当与暴饮暴食或节食等与饮食失调相关的行为特征结合时，这种回路可能会加强饮食失调行为。
