Sheerin Christina M, Moore Ashlee A, Sawyers Chelsea, Kirkpatrick Robert, Hettema John M, Roberson-Nay Roxann
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.
Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA.
Psychophysiology. 2025 Apr;62(4):e70052. doi: 10.1111/psyp.70052.
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.
了解过度恐惧反应如何产生并持续存在至关重要。利用恐惧学习实验室模型进行的研究为病因学提供了宝贵的见解。在本研究中,我们考察了基线惊吓反应和恐惧学习的遗传和环境病因学影响,重点关注使用恐惧条件反射范式测量青少年和年轻成人双胞胎样本(15 - 20岁)中恐惧增强惊吓(FPS)的恐惧习得和泛化过程。参与者(N = 794)完成了恐惧习得和泛化训练,训练包括准随机呈现逐渐增大尺寸的环形。极端尺寸的环形作为条件危险线索(CS +),与电击作为无条件刺激配对,条件安全线索(CS -)则是中等尺寸的环形,中等尺寸的环形用作泛化刺激。作为恐惧学习的指标,使用对声音探针的眨眼惊吓反射幅度来测量FPS。双胞胎模型估计表明,习得前惊吓(对条件作用前刺激的惊吓探针反应)和FPS(习得和泛化过程中条件作用后对惊吓探针的反应)均表现出中等到中等偏高的遗传度(26% - 43%),这与之前关于FPS的研究结果一致。我们还观察到,对FPS的遗传影响与习得前惊吓高度相关,表明FPS上的遗传创新极小。这一发现意味着,从遗传角度来看,恐惧反应可能由一般惊吓反应而非特定的恐惧学习相关因素来调节。我们讨论了这一结果对恐惧和焦虑症生物标志物测量的影响。