Threat Learning in Individuals with Adverse Childhood Experiences

Abstract

Adverse childhood experiences (ACE) constitute a major risk factor for the development of various forms of psychopathology, yet the mechanisms linking early adversity to later mental health problems remain insufficiently understood. Through associative learning, individuals form predictive links between environmental cues and their outcomes, thereby shaping affective and behavioral responses towards those cues. ACEs are thought to alter the normative development of associative learning trajectories, leading to maladaptive response patterns that might ultimately manifest in psychopathology. This thesis investigates the role of ACEs in experimental threat learning across three complementary projects: a systematic literature review of the existing studies in the field of experimental threat and reward learning, including a critical methodological discussion with a focus on sample and paradigm specifications; as well as a comprehensive experimental fear conditioning study examining the association of threat and safety responding in individuals with ACEs across behavioral, physiological and neural outcome measures covering different phases of the classical fear conditioning paradigm – constituting the central project of this thesis. An additional project focuses on methodological aspects of ACE assessment and includes a detailed content analysis of commonly applied self-report questionnaires in experimental threat and reward learning. The results reveal that research on ACEs is complicated by substantial heterogeneity in ACE assessment approaches. Specifically, the plethora of existing ACE assessment instruments has shown to capture surprisingly distinct sets of adverse experiences and events, limiting the comparability of study results based on different instruments. These findings highlight the importance of working towards a more comprehensive and uniform ACE assessment approach to better capture overall adversity load and control for co-occurring experiences. Consistent with the literature review, in the empirical work, higher cumulative ACE load was associated with reduced discrimination between threat and safety cues, driven primarily by blunted responses to threat-predicting stimuli. These effects were most pronounced in subjective arousal ratings and neural activation in key regions involved in fear learning, including the striatum and ventromedial prefrontal cortex. Notably, extinction learning and explicit knowledge about cue-outcome contingencies were found to be intact. These findings suggest that ACEs primarily impair affective anticipatory appraisal rather than basic associative learning mechanisms and threat responding, providing a potential pathway linking ACEs to maladaptive decision-making and health-risk behaviors.