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Abstract：
Drugs targeting N-methyl-d-aspartate (NMDA) receptors and the ability to learn new associations have been proposed as adjunct treatments to boost the success of exposure therapy for anxiety disorders. However, the effects of the NMDA partial agonist d-cycloserine on psychological treatment have been mixed. We investigated potential neurocognitive mechanisms underlying the clinical effects of d-cycloserine-augmented exposure, to inform the optimal combination of this and similar agents with psychological treatment. Panic disorder patients were randomised to single-dose d-cycloserine (250 mg; N = 17) or matching placebo (N = 16) 2hrs before one session of exposure therapy. Neurocognitive markers were assessed one day after treatment, including reaction-time based threat bias for fearful faces (primary outcome) and amygdala response to threat (secondary outcome). Clinical symptom severity was measured the day before and after treatment, and at 1- and 6-months follow-up (secondary outcome). d-cycloserine was associated with greater clinical recovery at 1-month follow-up than placebo (d-cyloserine 71% vs placebo 25%), with the placebo group matching the clinical gains of the d-cycloserine group during 6-months follow-up (d-cycloserine 71% vs placebo 44%). One day after treatment, threat bias for fearful faces and amygdala threat response was lower in the drug compared to placebo group. Lower amygdala magnitude predicted greater clinical improvement during follow-up across groups. While this experimental study is of a preliminary nature due to the limited sample size, these findings highlight a neurocognitive potential mechanism by which d-cycloserine may exert its augmentative effects on psychological treatment and bring forward a marker that may help understand and facilitate development of combination treatments for anxiety. (d-cycloserine Augmented CBT for Panic Disorder; clinicaltrials.gov; NCT01680107).
摘要：
针对N-甲基-d-天冬氨酸（NMDA）受体的药物以及学习新关联的能力已被提议作为辅助治疗，以提高焦虑症暴露治疗的成功率。然而,NMDA部分激动剂d-环丝氨酸对心理治疗的影响是混合的。我们调查了潜在的神经认知机制，潜在的临床效果的d-环丝氨酸增强暴露，告知这种药物和类似药物与心理治疗的最佳组合。在一次暴露治疗前2小时，将恐慌症患者随机分配给单剂量d-环丝氨酸（250mg;N=17）或匹配的安慰剂（N=16）。治疗后一天评估神经认知标志物，包括恐惧面孔的基于反应时间的威胁偏差（主要结果）和杏仁核对威胁的反应（次要结果）。在治疗前一天和治疗后一天测量临床症状严重程度，以及1个月和6个月的随访（次要结果）。与安慰剂相比，在1个月随访时，d-环丝氨酸与更大的临床恢复相关（d-环丝氨酸71％vs安慰剂25％），安慰剂组在6个月随访期间与d-环丝氨酸组的临床增益相匹配(d-环丝氨酸71%vs安慰剂44%).治疗后一天,与安慰剂组相比,该药物对恐惧面孔的威胁偏倚和杏仁核威胁反应较低.较低的杏仁核大小预测两组随访期间更大的临床改善。虽然由于样本量有限，这项实验研究具有初步性质，这些发现强调了一种神经认知的潜在机制,通过这种机制,d-环丝氨酸可能在心理治疗中发挥其增强作用,并提出了一个可能有助于理解和促进焦虑症联合治疗的标志物.（d-环丝氨酸增强CBT治疗惊恐障碍；clinicaltrials.gov；NCT01680107）。
