Deficits in Conditioned Fear Extinction in Obsessive-Compulsive Disorder and Neurobiological Changes in the Fear Circuit
Deficits in Conditioned Fear Extinction in Obsessive-Compulsive Disorder and Neurobiological Changes in the Fear Circuit
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DOI：
10.1001/jamapsychiatry.2013.914
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发表时间：
2013-06-01
期刊：
影响因子：
25.8
通讯作者：
Wilhelm, Sabine
中科院分区：
文献类型：
--
作者：
Milad, Mohammed R.;Furtak, Sharon C.;Wilhelm, Sabine
重要性：强迫症 (OCD) 的特点可能是自我调节和行为抑制受损。恐惧和焦虑加剧是这种疾病的共同特征。恐惧调节和安全记忆巩固的神经生物学尚未在该患者群体中进行检查。目的：检查强迫症患者条件性恐惧消退的心理生理学和神经生物学相关性。设计：横断面、病例对照、功能性磁共振成像研究。地点：学术医疗中心。参与者：21 名强迫症患者和 21 名健康参与者。主要结果和措施：皮肤电导反应和血氧水平依赖性结果：我们的心理生理学测量（皮肤电导反应）中注意到的组间差异是在消退回忆期间：强迫症患者相对于对照受试者表现出消退回忆受损。关于功能磁共振成像数据，强迫症患者在整个训练阶段表现出腹内侧前额叶皮层的激活显着减少。此外，在恐惧调节过程中，强迫症患者的尾状核和海马体以及消退回忆过程中的小脑、后扣带皮层和壳核的激活减少。与我们的预测相反，强迫症症状的严重程度与消退记忆回忆的程度呈正相关。同样与我们的预测相反的是，腹内侧前额叶皮层的功能反应与症状严重程度呈正相关，背侧前扣带皮层的功能反应与症状严重程度呈负相关。 结论和相关性：正如预期的那样，我们的研究表明强迫症患者的恐惧消退及其神经基质受到损害。然而，这项研究还得出了一些令人惊讶和意想不到的结果，涉及消退能力及其神经基质与这种疾病中表达的症状严重程度之间的相关性。因此，我们的数据报告了强迫症患者恐惧消退不足的神经相关性。强迫症中恐惧消退缺陷与耶鲁-布朗强迫量表症状之间的负相关表明，除了恐惧消退缺陷之外，可能还有其他因素导致强迫症的精神病理学。
Importance: Obsessive-compulsive disorder (OCD) may be characterized by impaired self-regulation and behavioral inhibition. Elevated fear and anxiety are common characteristics of this disorder. The neurobiology of fear regulation and consolidation of safety memories have not been examined in this patient population.Objective: To examine the psychophysiological and neurobiological correlates of conditioned fear extinction in patients with OCD.Design: Cross-sectional, case-control, functional magnetic resonance imaging study.Setting: Academic medical center.Participants: Twenty-one patients with OCD and 21 healthy participants.Main Outcomes and Measures: Skin conductance responses and blood oxygenation level-dependent responses.Results: The between-group difference noted in our psychophysiological measure (skin conductance responses) was during extinction recall: patients with OCD showed impaired extinction recall relative to control subjects. Regarding the functional magnetic resonance imaging data, patients with OCD showed significantly reduced activation in the ventromedial prefrontal cortex across training phases. Moreover, reduced activation in the patients with OCD was noted in the caudate and hippocampus during fear conditioning, as well as in the cerebellum, posterior cingulate cortex, and putamen during extinction recall. Contrary to our prediction, OCD symptom severity was positively correlated with the magnitude of extinction memory recall. Also contrary to our prediction, functional responses of the ventromedial prefrontal cortex were positively correlated with symptom severity, and functional responses of the dorsal anterior cingulate cortex were inversely correlated with symptom severity.Conclusions and Relevance: As expected, our study showed that fear extinction and its neural substrates are impaired in patients with OCD. However, this study also yielded some surprising and unexpected results regarding the correlates between extinction capacity and its neural substrates and the severity of symptoms expressed in this disorder. Thus, our data report neural correlates of deficient fear extinction in patients with OCD. The negative correlations between fear extinction deficits and Yale-Brown Obsessive-Compulsive Scale symptoms in OCD suggest that there may be other factors, in addition to fear extinction deficiency, that contribute to the psychopathology of OCD.