Risbrough Victoria B, Glynn Laura M, Davis Elysia P, Sandman Curt A, Obenaus Andre, Stern Hal S, Keator David B, Yassa Michael A, Baram Tallie Z, Baker Dewleen G
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
Center of Excellence for Stress and Mental Health, San Diego Veterans Administration, La Jolla, CA, USA.
Curr Top Behav Neurosci. 2018;38:249-265. doi: 10.1007/7854_2018_51.
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.
快感缺失，即体验愉悦的能力下降，是一种与多种神经精神疾病相关的维度性实体，在这些疾病中，它与治疗反应减弱、整体功能降低以及自杀倾向增加有关。有人提出，快感缺失以及与之相关的奖赏处理中断可能是日后出现精神症状的关键先兆。在此，我们研究跨物种证据，以支持早期生活经历调节奖赏处理发展这一假说，若奖赏处理受到干扰，就会导致快感缺失。重要的是，我们发现快感缺失可能会增加日后患神经精神疾病的风险，尤其是创伤后应激障碍（PTSD）。虽然长期以来，童年创伤一直与快感缺失增加以及成年后患创伤相关疾病的风险增加有关，但在此我们关注的是啮齿动物和人类快感缺失的另一个新出现的直接因素：发育关键期碎片化、混乱的环境信号（“FRAG”）。在啮齿动物中，最近的数据表明，青少年快感缺失可能源于愉悦/奖赏回路的异常成熟。在人类中，最近的纵向研究支持FRAG与青少年快感缺失增加有关。人类和啮齿动物暴露于FRAG也会导致海马体功能异常。正在进行前瞻性研究，以检验快感缺失是否也是PTSD风险的一个标志。这些初步的跨物种研究为未来研究成人创伤相关症状的病因以及预防性和治疗性干预措施的开发提供了一个关键框架。此外，对有和没有FRAG情况下奖赏回路发育的纵向研究对于检验早期生活FRAG改变奖赏回路这一机制假说至关重要，该假说认为这会对青少年出现的快感缺失产生后续影响，并导致成年后对创伤和压力的易感性及恢复力。
