A cross-species assay demonstrates that reward responsiveness is enduringly impacted by adverse, unpredictable early-life experiences.
A cross-species assay demonstrates that reward responsiveness is enduringly impacted by adverse, unpredictable early-life experiences.
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DOI：
10.1038/s41386-021-01250-9
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Pizzagalli DA
中科院分区：
文献类型：
--
作者：
Kangas BD;Short AK;Luc OT;Stern HS;Baram TZ;Pizzagalli DA
暴露于早期生活逆境（ELA）与几种神经精神疾病有关，包括重度抑郁症，但因果关系很难在人类中建立。最近在啮齿类动物中的研究表明，ELA暴露后，类快感缺失行为中的奖赏回路信号传导受损。快感缺乏，即对先前的奖励刺激缺乏反应，是与ELA相关的精神疾病常见的一种转诊断结构。在这里，我们采用了一种跨物种验证的奖励反应性分析，即概率奖励任务（PRT）。在PRT中，健康的参与者可靠地对更丰富的奖励刺激产生反应偏差，而快感缺失的参与者表现出与当前和未来快感缺失相关的迟钝反应偏差。在一个建立良好的ELA模型中，该模型产生了一个紧张，混乱和不可预测的早期生活环境，ELA导致两个独立队列的PRT中的反应偏差变钝，重现了人类快感缺乏的发现。相同的ELA大鼠具有钝化的蔗糖偏好，进一步支持它们的快感缺失样表型。探索ELA的方面，可能会引起这些赤字，我们量化的不可预测性的母鼠/幼鼠的相互作用使用熵的措施，并发现，不可预测性的母亲护理显着较高的ELA组中，PRT和蔗糖偏好奖励赤字是目前在以后的生活。总之，这些数据将在临床患者人群中建立的PRT定位为评估ELA对跨物种奖励回路影响的有效工具。这些发现也暗示了在生命早期母体信号的不可预测性是奖励敏感性缺陷的重要驱动因素。
Exposure to early-life adversity (ELA) is associated with several neuropsychiatric conditions, including major depressive disorder, yet causality is difficult to establish in humans. Recent work in rodents has implicated impaired reward circuit signaling in anhedonic-like behavior after ELA exposure. Anhedonia, the lack of reactivity to previously rewarding stimuli, is a transdiagnostic construct common to mental illnesses associated with ELA. Here, we employed an assay of reward responsiveness validated across species, the Probabilistic Reward Task (PRT). In the PRT, healthy participants reliably develop a response bias toward the more richly rewarded stimulus, whereas participants with anhedonia exhibit a blunted response bias that correlates with current and future anhedonia. In a well-established model of ELA that generates a stressful, chaotic, and unpredictable early-life environment, ELA led to blunted response biases in the PRT in two separate cohorts, recapitulating findings in humans with anhedonia. The same ELA rats had blunted sucrose preference, further supporting their anhedonic-like phenotypes. Probing the aspects of ELA that might provoke these deficits, we quantified the unpredictability of dam/pup interactions using entropy measures and found that the unpredictability of maternal care was significantly higher in the ELA groups in which PRT and sucrose preference reward deficits were present later in life. Taken together, these data position the PRT, established in clinical patient populations, as a potent instrument to assess the impact of ELA on the reward circuit across species. These findings also implicate the unpredictability of maternal signals during early life as an important driver of reward sensitivity deficits.
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早期逆境对年轻人奖励加工的影响：EEG-FMRI是由25年以上的一项前瞻性研究引起的。
影响因子：
3.7
作者：
Boecker R;Holz NE;Buchmann AF;Blomeyer D;Plichta MM;Wolf I;Baumeister S;Meyer-Lindenberg A;Banaschewski T;Brandeis D;Laucht M
通讯作者：
Laucht M
影响因子：
3
作者：
Bolton, Jessica L.;Short, Annabel Katherine;Baram, Tallie Z.
通讯作者：
Baram, Tallie Z.
影响因子：
16.2
作者：
Authement, Michael E.;Kodangattil, Jayaraj N.;Nugent, Fereshteh S.
通讯作者：
Nugent, Fereshteh S.
影响因子：
7.6
作者：
Brodnik, Zachary D.;Black, Emily M.;Espana, Rodrigo A.
通讯作者：
Espana, Rodrigo A.
影响因子：
--
作者：
Green, Jennifer Greif;McLaughlin, Katie A.;Berglund, Patricia A.;Gruber, Michael J.;Sampson, Nancy A.;Zaslavsky, Alan M.;Kessler, Ronald C.
通讯作者：
Kessler, Ronald C.