Roeckner Alyssa R, Lin Esther R-H, Hinrichs Rebecca, Harnett Nathaniel G, Lebois Lauren A M, van Rooij Sanne J H, Ely Timothy D, Jovanovic Tanja, Murty Vishnu P, Bruce Steven E, House Stacey L, Beaudoin Francesca L, An Xinming, Neylan Thomas C, Clifford Gari D, Linnstaedt Sarah D, Germine Laura T, Rauch Scott L, Haran John P, Storrow Alan B, Lewandowski Christopher, Musey Paul I, Hendry Phyllis L, Sheikh Sophia, Jones Christopher W, Punches Brittany E, Swor Robert A, Hudak Lauren A, Pascual Jose L, Seamon Mark J, Datner Elizabeth M, Pearson Claire, Peak David A, Merchant Roland C, Domeier Robert M, Rathlev Niels K, O'Neil Brian J, Sergot Paulina, Sanchez Leon D, Joormann Jutta, Sheridan John F, Harte Steven E, Koenen Karestan C, Kessler Ronald C, McLean Samuel A, Ressler Kerry J, Stevens Jennifer S
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
Neuropsychopharmacology. 2025 May 3. doi: 10.1038/s41386-025-02115-1.
Amygdala hyperreactivity early-post trauma has been a demonstrable neurobiological correlate of future posttraumautic stress disorder (PTSD). The basolateral amygdala (BLA) particularly is vital for fear memory and threat processing, but BLA functional dynamics following a traumatic event are unexplored. BLA reactivity to threat may be a trait that can predict PTSD and persist over time. Alternatively, BLA responsivity to threat cues may change over time and be related to PTSD severity. As part of a larger, multisite study, AURORA, participants 18-75 years old were enrolled in an emergency department (ED) within 72 h of a traumatic event (N = 304, 199 female). At 2-weeks and 6-months post-trauma, PTSD symptoms, BLA responses to threat (fearful>neutral faces), and functional connectivity (FC) during fMRI were assessed. Generalizability of findings was assessed in an external replication sample of ED patients (n = 33). Two weeks post-trauma right BLA reactivity positively predicted later PTSD severity. However, left BLA reactivity to threat at 6 months post-trauma was negatively associated with PTSD severity at that timepoint (ΔPseudo-R = 0.04, IRR = 0.38, p < 0.001). In addition, a decrease in BLA reactivity from 2-weeks to 6-months predicted greater PTSD severity at 6 months (ΔPseudo-R = 0.03, IRR = 0.58, p < 0.001). This replicated in the external sample. A reduction in left BLA FC with the dorsal attention network predicted increased PTSD severity over time. These findings support a shift in BLA function within the first 6 months post-trauma that predicts PTSD pathology and stand in contrast to prior conceptualizations of amygdala hyperreactivity as a trait-like PTSD risk factor.
创伤后早期杏仁核反应过度一直是未来创伤后应激障碍（PTSD）可证实的神经生物学关联因素。基底外侧杏仁核（BLA）对于恐惧记忆和威胁处理尤为重要，但创伤事件后BLA的功能动态尚未得到探索。BLA对威胁的反应性可能是一种能够预测PTSD并随时间持续存在的特质。或者，BLA对威胁线索的反应性可能随时间变化，并与PTSD严重程度相关。作为一项更大规模的多中心研究“极光”（AURORA）的一部分，18至75岁的参与者在创伤事件发生后72小时内被纳入急诊科（N = 304，199名女性）。在创伤后2周和6个月时，评估PTSD症状、BLA对威胁的反应（恐惧面孔>中性面孔）以及功能磁共振成像（fMRI）期间的功能连接（FC）。在急诊科患者的外部重复样本（n = 33）中评估研究结果的可推广性。创伤后两周，右侧BLA反应性可正向预测后期PTSD严重程度。然而，创伤后6个月时左侧BLA对威胁的反应性与该时间点的PTSD严重程度呈负相关（Δ伪R = 0.04，IRR = 0.38，p < 0.001）。此外，从2周到6个月BLA反应性的降低预示着6个月时PTSD严重程度更高（Δ伪R = 0.03，IRR = 0.58，p < 0.001）。这在外部样本中得到了重复。左侧BLA与背侧注意网络的功能连接减少预示着随时间推移PTSD严重程度增加。这些发现支持了创伤后前6个月内BLA功能的转变，这种转变可预测PTSD病理，与之前将杏仁核反应过度视为特质样PTSD风险因素的概念形成对比。
