A cross-species assay demonstrates that reward responsiveness is enduringly impacted by adverse, unpredictable early-life experiences.

Abstract

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.