Department of Psychiatry, University of Naples SUN, Naples, Italy.
Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jan 3;80(Pt B):132-142. doi: 10.1016/j.pnpbp.2017.02.020. Epub 2017 Mar 1.
Anorexia nervosa and bulimia nervosa are severe eating disorders whose etiopathogenesis is still unknown. Clinical features suggest that eating disorders may develop as reward-dependent syndromes, since eating less food is perceived as rewarding in anorexia nervosa while consumption of large amounts of food during binge episodes in bulimia nervosa aims at reducing the patient's negative emotional states. Therefore, brain reward mechanisms have been a major focus of research in the attempt to contribute to the comprehension of the pathophysiology of these disorders. Structural brain imaging data provided the evidence that brain reward circuits may be altered in patients with anorexia or bulimia nervosa. Similarly, functional brain imaging studies exploring the activation of brain reward circuits by food stimuli as well as by stimuli recognized to be potentially rewarding for eating disordered patients, such as body image cues or stimuli related to food deprivation and physical hyperactivity, showed several dysfunctions in ED patients. Moreover, very recently, it has been demonstrated that some of the biochemical homeostatic modulators of eating behavior are also implicated in the regulation of food-related and non-food-related reward, representing a possible link between the aberrant behaviors of ED subjects and their hypothesized deranged reward processes. In particular, changes in leptin and ghrelin occur in patients with anorexia or bulimia nervosa and have been suggested to represent not only homeostatic adaptations to an altered energy balance but to contribute also to the acquisition and/or maintenance of persistent starvation, binge eating and physical hyperactivity, which are potentially rewarding for ED patients. On the basis of such findings new pathogenetic models of EDs have been proposed, and these models may provide new theoretical basis for the development of innovative treatment strategies, either psychological and pharmacological, with the aim to improve the outcomes of so severe disabling disorders.
神经性厌食症和神经性贪食症是严重的进食障碍,其发病机制仍不清楚。临床特征表明,进食障碍可能发展为依赖于奖励的综合征,因为在神经性厌食症中,少吃食物被认为是一种奖励,而在神经性贪食症中,大量进食是为了减轻患者的负面情绪状态。因此,大脑奖励机制一直是研究的重点,试图为理解这些疾病的病理生理学做出贡献。结构性脑成像数据提供的证据表明,神经性厌食症或神经性贪食症患者的大脑奖励回路可能发生改变。同样,功能性脑成像研究探索了食物刺激以及被认为对进食障碍患者有潜在奖励作用的刺激(如身体形象线索或与食物剥夺和身体过度活动相关的刺激)对大脑奖励回路的激活,结果显示 ED 患者存在多种功能障碍。此外,最近还证明,一些进食行为的生化稳态调节剂也参与了与食物相关和非食物相关奖励的调节,这代表了 ED 患者异常行为与其假设的奖励过程紊乱之间的可能联系。特别是,瘦素和胃饥饿素在神经性厌食症或神经性贪食症患者中发生变化,据推测,这些变化不仅是对能量平衡改变的稳态适应,而且还有助于持续饥饿、暴食和身体过度活动的获得和/或维持,这些对 ED 患者具有潜在的奖励作用。基于这些发现,提出了新的 ED 发病机制模型,这些模型可能为开发创新的治疗策略(包括心理和药理学策略)提供新的理论基础,旨在改善这些严重致残疾病的治疗效果。