PDF(Pubmed)
Abstract：
Anhedonia, the reduced ability to experience pleasure, is a dimensional entity linked to multiple neuropsychiatric disorders, where it is associated with diminished treatment response, reduced global function, and increased suicidality. It has been suggested that anhedonia and the related disruption in reward processing may be critical precursors to development of psychiatric symptoms later in life. Here, we examine cross-species evidence supporting the hypothesis that early life experiences modulate development of reward processing, which if disrupted, result in anhedonia. Importantly, we find that anhedonia may confer risk for later neuropsychiatric disorders, especially posttraumatic stress disorder (PTSD). Whereas childhood trauma has long been associated with increased anhedonia and increased subsequent risk for trauma-related disorders in adulthood, here we focus on an additional novel, emerging direct contributor to anhedonia in rodents and humans: fragmented, chaotic environmental signals (\"FRAG\") during critical periods of development. In rodents, recent data suggest that adolescent anhedonia may derive from aberrant pleasure/reward circuit maturation. In humans, recent longitudinal studies support that FRAG is associated with increased anhedonia in adolescence. Both human and rodent FRAG exposure also leads to aberrant hippocampal function. Prospective studies are underway to examine if anhedonia is also a marker of PTSD risk. These preliminary cross-species studies provide a critical construct for future examination of the etiology of trauma-related symptoms in adults and for and development of prophylactic and therapeutic interventions. In addition, longitudinal studies of reward circuit development with and without FRAG will be critical to test the mechanistic hypothesis that early life FRAG modifies reward circuitry with subsequent consequences for adolescent-emergent anhedonia and contributes to risk and resilience to trauma and stress in adulthood.
摘要：
快感缺失,体验快乐的能力下降，是与多种神经精神疾病有关的维度实体，它与治疗反应减弱有关，减少全局函数，增加自杀倾向。有人认为，快感缺乏症和相关的奖励处理中断可能是以后生活中精神症状发展的关键前兆。这里,我们研究了跨物种的证据，支持早期生活经历调节奖励处理发展的假设，如果中断，导致快感缺失。重要的是,我们发现快感缺失可能会导致后来的神经精神疾病，尤其是创伤后应激障碍（PTSD）。尽管童年创伤长期以来与成年后快感缺失和创伤相关疾病的风险增加有关，在这里，我们专注于另一部小说，正在出现的啮齿动物和人类快感缺乏症的直接贡献者：支离破碎，发展关键时期的混沌环境信号(“FRAG”)。在啮齿动物中，最近的数据表明，青少年快感缺乏可能源于异常的愉悦/奖励回路成熟。在人类中,最近的纵向研究支持FRAG与青春期快感缺乏症相关。人类和啮齿动物FRAG暴露都会导致海马功能异常。正在进行前瞻性研究，以检查快感缺乏是否也是PTSD风险的标志。这些初步的跨物种研究为将来检查成人创伤相关症状的病因以及预防和治疗干预措施的发展提供了关键的构建。此外,有和没有FRAG的奖励回路发育的纵向研究对于检验以下机制假设至关重要,即生命早期FRAG会改变奖励回路,随后会对青少年出现的快感缺失产生影响,并有助于成年后对创伤和压力的风险和复原力.
