Gold Mark S, Blum Kenneth, Febo Marcelo, Baron David, Modestino Edward Justin, Elman Igor, Badgaiyan Rajendra D
Department of Psychiatry, Washington University School of Medicine, St. Louis, Mo, USA.
Department of Psychiatry, McKnight Brain Institute, University of Florida, College of Medicine, Gainesville, FL, USA,
Front Biosci (Schol Ed). 2018 Mar 1;10(2):309-325. doi: 10.2741/s518.
Anhedonia is a condition that leads to the loss of feelings pleasure in response to natural reinforcers like food, sex, exercise, and social activities. This disorder occurs in addiction, and an array of related neuropsychiatric syndromes, including schizophrenia, depression, and Post Traumatic Stress Disorder (PTSD). Anhedonia may by due to derangements in mesolimbic dopaminergic pathways and their terminal fields (e.g., striatum, amygdala, and prefrontal cortex) that persist long after the traces of the causative drugs are eliminated (pharmacokinetically). Here we postulate that anhedonia is not a distinct entity but is rather an epiphenomenon of hypodopaminergic states and traits arising from the interaction of genetic traits and epigenetic neurobiological alterations in response to environmental influences. Moreover, dopaminergic activity is rather complex, and so it may give rise to differential pathophysiological processes such as incentive sensitization, aberrant learning and stress-like "anti-reward" phenomena. These processes may have additive, synergistic or antagonistic interactions with the concurrent reward deficiency states leading in some instances to more severe and long-lasting symptoms. Operant understanding of the neurogenetic antecedents to reward deficiency syndrome (RDS) and the elucidation of reward gene polymorphisms may provide a map for accessing an individual's genetic risk for developing Anhedonia. Prevention techniques that can restore homeostatic balance via physiological activation of dopaminergic receptors (D2/D3) may be instrumental for targeting not only anhedonia per se but also drug craving and relapse.
快感缺失是一种状况，会导致个体在面对食物、性、运动和社交活动等自然强化物时丧失愉悦感。这种障碍出现在成瘾以及一系列相关的神经精神综合征中，包括精神分裂症、抑郁症和创伤后应激障碍（PTSD）。快感缺失可能是由于中脑边缘多巴胺能通路及其终末区域（如纹状体、杏仁核和前额叶皮质）的紊乱所致，这些紊乱在致病药物的痕迹被消除（从药代动力学角度）后仍会长期持续。在此我们假定，快感缺失并非一个独特的实体，而是由遗传特征与表观遗传神经生物学改变相互作用以应对环境影响而产生的低多巴胺能状态和特质的一种附带现象。此外，多巴胺能活动相当复杂，因此可能引发不同的病理生理过程，如动机敏感化、异常学习和类似应激的“抗奖赏”现象。这些过程可能与同时存在的奖赏缺乏状态具有相加、协同或拮抗作用，在某些情况下导致更严重和持久的症状。对奖赏缺乏综合征（RDS）的神经遗传学前因进行操作性理解以及阐明奖赏基因多态性，可能为了解个体患快感缺失的遗传风险提供一个指引。通过多巴胺能受体（D2/D3）的生理激活来恢复内稳态平衡的预防技术，可能不仅对治疗快感缺失本身有帮助，而且对治疗药物渴望和复发也有作用。
