Nitschke Jack B, Sarinopoulos Issidoros, Oathes Desmond J, Johnstone Tom, Whalen Paul J, Davidson Richard J, Kalin Ned H
Departments of Psychiatry and Psychology, University of Wisconsin, Madison, 53705-2280, USA.
Am J Psychiatry. 2009 Mar;166(3):302-10. doi: 10.1176/appi.ajp.2008.07101682. Epub 2009 Jan 2.
The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response.
Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine.
Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms.
These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.
对不良后果的预期，即担忧，是广泛性焦虑症的主要症状。先前对健康受试者的研究表明，预期厌恶事件会激活包括杏仁核和前扣带回皮质在内的一系列脑区。本研究旨在测试广泛性焦虑症患者在预期时杏仁核功能是否存在改变，以及前扣带回皮质的预期活动是否能预测治疗反应。
对14名广泛性焦虑症患者和12名年龄、性别及受教育程度相匹配的健康对照者进行功能磁共振成像（fMRI）检查。事件相关fMRI范式由一个在厌恶图片之前出现的警告提示和另一个在中性图片之前出现的提示组成。fMRI检查后，患者接受8周的缓释文拉法辛治疗。
在出现厌恶图片和中性图片之前，广泛性焦虑症患者双侧背侧杏仁核的预期活动均高于健康对照者。基于先前关于前扣带回皮质预处理活动可预测治疗反应的报道，该区域的预期活动与文拉法辛治疗8周后的临床结果相关。在预期厌恶图片和中性图片时，较高水平的前扣带回皮质预处理活动与焦虑和担忧症状的更大减轻相关。
这些关于广泛性焦虑症患者杏仁核对预期信号反应增强且无差别以及前扣带回皮质与治疗反应相关的发现，为预期过程在广泛性焦虑症病理生理学中的作用提供了神经生物学支持。
