Threat Learning Processes as Mechanisms Linking Childhood Trauma and Psychopathology: Translating Between Environmental Experience, Neurobiology, and Behavior

Abstract

Exposure to childhood trauma is one of our most robust known risk indicators for the development of psychopathology, yet the mechanisms linking childhood trauma with transdiagnostic psychopathology remain incompletely understood. Childhood trauma, defined as exposure to serious forms of interpersonal violence like physical abuse, sexual abuse, and domestic violence, is characterized by an unexpected introduction of danger or threat into the environment. These experiences may fundamentally alter the way individuals learn to detect, interpret, and respond to environmental threat in ways that contribute to trajectories towards psychopathology. Across a series of three studies, this dissertation investigates the ways in which neurobiological, psychophysiological, and behavioral bases of three threat learning processes may serve as mechanisms linking childhood trauma with transdiagnostic psychopathology in developmental populations. In Study 1 (N = 147, ages 8-16), we examined the temporal dynamics of neural activation and patterns of functional connectivity during threat conditioning in youth with (n = 77) and without (n = 70) exposure to childhood trauma and evaluated whether these patterns mediated the association of childhood trauma and psychopathology in a longitudinal design. Youth with childhood trauma exposure exhibited neural patterns broadly consistent with difficulty discriminating between threat and safety cues and reduced coupling between regions involved in threat learning and contextual processing. These alterations mediated the link between childhood trauma and transdiagnostic psychopathology two years later, suggesting altered threat conditioning is one pathway from childhood trauma to mental health difficulties. Study 2 (N = 100, ages 9-19) builds upon Study 1 by examining whether neural alterations in threat reversal learning served as a mechanism linking childhood trauma and psychopathology, targeting the ability to flexibly update conditioned threat and safety associations based on changing contextual significance. In this paradigm, where heightened unpredictability is highlighted due to the contingency reversal, youth with childhood trauma demonstrated heightened discrimination between cues in a key threat-learning region and reduced discrimination in safety-learning regions that mediated the link between childhood trauma and lower transdiagnostic anxiety symptoms within the trauma group only. This pattern of results suggests a potential environmental experience-dependent pathway to resilience. Study 3 (N = 75, ages 13-18) extends a similar line of inquiry to the physiological and behavioral underpinnings of threat generalization in a developmental sample with a wide range of exposure to childhood trauma, measured dimensionally. Using a novel methodological approach to the operationalization of threat generalization employing advanced machine learning techniques and nonlinear modeling, we demonstrate the ability to identify distinctly shaped gradients of generalization across measurement modalities. While we did not find associations of threat generalization with childhood trauma and observed weak evidence for potential associations of threat generalization with psychopathology, this occurred in the context of important limitations related to the sample and power. This study serves as a preliminary proof-of-concept and suggests that the question of whether altered threat generalization mediates the link between childhood trauma and psychopathology merits further investigation. Taken together, this series of studies highlights the myriad of ways that learning about threat may be altered following exposure to childhood trauma in ways that are relevant to mental health. Elucidating the underpinnings of these mechanisms aims to provide valuable insight towards the etiology of psychopathology, ultimately aiming to inform the optimization and innovation of clinical interventions.