Genetic and Environmental Influences on Fear Learning and Generalization.

Abstract

Understanding how excessive fear responses develop and persist is critical. Research using laboratory models of fear learning offers valuable insights on etiology. In this study, the influence of genetic and environmental etiology of baseline startle response and fear learning was examined, focusing on fear acquisition and generalization processes using the fear conditioning paradigm measuring fear-potentiated startle (FPS) in a sample of adolescents and young adult twins (15-20 years old). Participants (N = 794) completed fear acquisition and generalization training that consisted of quasi-randomly presented rings of gradually increasing size. The extreme sizes served as conditioned danger cues (CS+) paired with electric shock as the unconditioned stimulus and conditioned safety cues (CS-), with rings of intermediary size serving as generalization stimuli. As an index of fear learning, FPS was measured using the magnitude of eyeblink startle reflex to a sound probe. Twin model estimates indicated that both pre-acquisition startle (startle probe responses to stimuli prior to conditioning) and FPS (startle probe responses after conditioning during acquisition and generalization) exhibited modest to moderate heritability (26%-43%), aligning with previous studies on FPS. We also observed that the genetic influences on FPS were highly correlated with pre-acquisition startle, indicating minimal genetic innovation on FPS. This finding implies that fear responses might be regulated, from a genetic perspective, by general startle response as opposed to specific fear-learning-related factors. We discuss the resulting implications for measurement of biomarkers for fear and anxiety disorders.