School of Psychology, The University of New South Wales, Sydney, 2052, Australia.
Psychopharmacology (Berl). 2019 Jan;236(1):227-238. doi: 10.1007/s00213-018-5032-3. Epub 2018 Sep 13.
One approach to improving exposure therapy for anxiety disorders has focused on developing pharmacological adjuncts to enhance extinction, but these efforts have produced modest success in clinical trials. Understanding the factors that predict the efficacy of adjuncts will help to develop personalized treatments for anxiety.
We assessed whether individual differences in within-session extinction (fear reduction during extinction training) predict the extent to which the neurotrophin fibroblast growth factor-2 (FGF2) enhances extinction recall in rats.
We re-analyzed data from five experiments that involved administering FGF2 immediately after extinction training; extinction recall was assessed the following day.
Regression analyses revealed that fear responses at the end, but not the start, of extinction training predicted extinction recall in FGF2- but not vehicle-treated rats. Comparisons between FGF2- and vehicle-treated rats that exhibited better or worse extinction recall (determined by a median split in freezing during extinction recall) confirmed that FGF2-treated rats exhibiting better extinction recall had significantly lower freezing at the end of extinction training relative to FGF2-treated rats exhibiting poorer extinction recall. In contrast, vehicle-treated rats did not differ in within-session extinction based on their performance at extinction recall. Finally, even when classified as having poorer extinction recall, FGF2-treated rats had stronger extinction recall than vehicle-treated rats.
These results suggest that FGF2 may be most effective amongst rats that exhibit the lowest fear responses at the end of extinction training. Furthermore, FGF2 does not appear to exacerbate fear in rats that exhibit minimal fear reduction during extinction training.
一种提高焦虑障碍暴露疗法的方法侧重于开发药理学辅助手段来增强消退，但这些努力在临床试验中仅取得了适度的成功。了解预测辅助治疗效果的因素将有助于为焦虑症开发个性化治疗方法。
我们评估了个体在单次消退期间的差异（在消退训练期间的恐惧减少）是否可以预测神经营养因子成纤维细胞生长因子 2（FGF2）在多大程度上增强大鼠的消退记忆。
我们重新分析了五个实验的数据，这些实验涉及在消退训练后立即给予 FGF2；在第二天评估消退记忆。
回归分析显示，在 FGF2-而非载体处理的大鼠中，消退训练结束时的恐惧反应，但不是开始时的恐惧反应，预测了消退记忆。对 FGF2-和载体处理的大鼠进行比较，这些大鼠表现出更好或更差的消退记忆（通过在消退记忆期间的冻结进行中位数分割来确定），证实了 FGF2-处理的大鼠在消退训练结束时的冻结显著低于 FGF2-处理的大鼠表现出较差的消退记忆。相比之下，根据消退记忆中的表现，载体处理的大鼠在单次消退期间没有差异。最后，即使被归类为消退记忆较差，FGF2 处理的大鼠的消退记忆也比载体处理的大鼠更强。
这些结果表明，FGF2 可能对在消退训练结束时表现出最低恐惧反应的大鼠最有效。此外，FGF2 似乎不会加剧在消退训练中表现出最小恐惧减少的大鼠的恐惧。
