Department of Psychiatry, University of California, San Diego, USA.
CNS Spectr. 2009 Oct;14(10):556-71. doi: 10.1017/s1092852900024044.
Exposure-based therapy for anxiety disorders is believed to operate on the basis of fear extinction. Studies have shown acute administration of D-cycloserine (DCS) enhances fear extinction in animals and facilitates exposure therapy in humans, but the neural mechanisms are not completely understood. To date, no study has examined neural effects of acute DCS in anxiety-disordered populations.
Two hours prior to functional magnetic resonance imaging scanning, 23 spider-phobic and 23 non-phobic participants were randomized to receive DCS 100 mg or placebo. During scanning, participants viewed spider, butterfly, and Gaussian-blurred baseline images in a block-design paradigm. Diagnostic and treatment groups were compared regarding differential activations to spider versus butterfly stimuli.
In the phobic group, DCS enhanced prefrontal (PFC), dorsal anterior cingulate (ACC), and insula activations. For controls, DCS enhanced ventral ACC and caudate activations. There was a positive correlation between lateral PFC and amygdala activation for the placebo-phobic group. Reported distress during symptom provocation was correlated with amygdala activation in the placebo-phobic group and orbitofrontal cortex activation in the DCS-phobic group.
Results suggest that during initial phobic symptom provocation DCS enhances activation in regions involved in cognitive control and interoceptive integration, including the PFC, ACC, and insular cortices for phobic participants.
焦虑障碍的暴露疗法被认为是基于恐惧消除的。研究表明，D-环丝氨酸（DCS）的急性给药可增强动物的恐惧消除，并促进人类的暴露治疗，但神经机制尚不完全清楚。迄今为止，尚无研究检查过焦虑障碍人群中急性 DCS 的神经效应。
在功能磁共振成像扫描前 2 小时，23 名蜘蛛恐惧症和 23 名非恐惧症参与者被随机分配接受 DCS 100mg 或安慰剂。在扫描过程中，参与者以块设计范式观看蜘蛛、蝴蝶和高斯模糊基线图像。比较诊断和治疗组对蜘蛛与蝴蝶刺激的差异激活。
在恐惧症组中，DCS 增强了前额叶（PFC）、背侧前扣带（ACC）和岛叶的激活。对于对照组，DCS 增强了腹侧 ACC 和尾状核的激活。对于安慰剂-恐惧症组，外侧 PFC 和杏仁核的激活呈正相关。在安慰剂-恐惧症组中，报告的症状诱发时的痛苦与杏仁核激活相关，在 DCS-恐惧症组中与眶额皮质激活相关。
结果表明，在最初的恐惧症症状诱发期间，DCS 增强了与认知控制和内脏整合相关的区域的激活，包括 PFC、ACC 和岛叶皮质，对于恐惧症参与者。
