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<p>The neural mechanisms underlying fear learning are critical for survival. Childhood maltreatment increases the risk of psychopathology by disrupting these processes, yet it remains unclear whether such effects reflect the cumulative burden of maltreatment types or arise from timing-specific exposures during sensitive developmental periods. In this study, 213 young adults (18–28 years) completed the Maltreatment and Abuse Chronology of Exposure (MACE), which retrospectively assesses the severity and timing of ten maltreatment types across childhood. During fMRI, participants underwent a Pavlovian fear-conditioning paradigm, allowing us to measure BOLD activation in the centromedial amygdala, basolateral amygdala, and hippocampus, as well as their functional connectivity with the ventromedial prefrontal cortex (vmPFC). Using machine-learning feature selection combined with a targeted maximum likelihood estimation (TMLE) framework, we identified the most influential type-by-age exposures and evaluated their effects on neural responses under standard causal assumptions. Two distinct windows of vulnerability emerged. Early maltreatment was associated with heightened threat–safety discrimination, reflected by stronger CS+–CS− separation in regional activation and vmPFC coupling, whereas late maltreatment was associated with blunted discrimination and reduced coupling, accompanied by relatively elevated CS− responding. Although directionally opposite, both patterns may represent adaptive phenotypes that confer heightened long-term vulnerability to psychopathology. These findings highlight sensitive periods during which maltreatment disproportionately alters corticolimbic dynamics, providing a developmental framework for timing targeted interventions to reduce mental-health risk in vulnerable youth.</p>

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Opposing sensitive period effects of early and late childhood maltreatment on corticolimbic responses in fear conditioning

  • 期刊论文

  • 发表日期：

    2026年6月17日

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  • Jianjun Zhu,
  • Lejia Zhou,
  • Yuxin Zou,
  • Yanqing Zhang,
  • Yannan Liu,
  • Martin H. Teicher

摘要

The neural mechanisms underlying fear learning are critical for survival. Childhood maltreatment increases the risk of psychopathology by disrupting these processes, yet it remains unclear whether such effects reflect the cumulative burden of maltreatment types or arise from timing-specific exposures during sensitive developmental periods. In this study, 213 young adults (18–28 years) completed the Maltreatment and Abuse Chronology of Exposure (MACE), which retrospectively assesses the severity and timing of ten maltreatment types across childhood. During fMRI, participants underwent a Pavlovian fear-conditioning paradigm, allowing us to measure BOLD activation in the centromedial amygdala, basolateral amygdala, and hippocampus, as well as their functional connectivity with the ventromedial prefrontal cortex (vmPFC). Using machine-learning feature selection combined with a targeted maximum likelihood estimation (TMLE) framework, we identified the most influential type-by-age exposures and evaluated their effects on neural responses under standard causal assumptions. Two distinct windows of vulnerability emerged. Early maltreatment was associated with heightened threat–safety discrimination, reflected by stronger CS+–CS− separation in regional activation and vmPFC coupling, whereas late maltreatment was associated with blunted discrimination and reduced coupling, accompanied by relatively elevated CS− responding. Although directionally opposite, both patterns may represent adaptive phenotypes that confer heightened long-term vulnerability to psychopathology. These findings highlight sensitive periods during which maltreatment disproportionately alters corticolimbic dynamics, providing a developmental framework for timing targeted interventions to reduce mental-health risk in vulnerable youth.