Valence processing alterations in SAPAP3 knockout mice and human OCD.
Valence processing alterations in SAPAP3 knockout mice and human OCD.
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SAPAP3 敲除小鼠和人类强迫症中的价处理变化。
DOI：
10.1016/j.jpsychires.2022.05.024
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发表时间：
2022
影响因子：
4.8
通讯作者：
Gunaydin,LisaA
中科院分区：
文献类型：
--
作者：
Kajs,BridgetL;vanRoessel,PeterJ;Davis,GwynneL;Williams,LeanneM;Rodriguez,CarolynI;Gunaydin,LisaA
效价处理的异常——对厌恶或食欲刺激的处理——可能是强迫症（OCD）的一个未被充分认识的组成部分。临床前啮齿动物模型在进一步了解强迫症的病理生理学方面至关重要，然而，关于啮齿动物强迫行为模型是否显示出与强迫症患者相一致的价系统改变的研究却很缺乏。在这项研究中，我们试图评估强迫行为的临床前啮齿动物模型，SAPAP3敲除（KO）小鼠模型的价加工，并将我们的临床前研究结果与强迫症患者的类似行为现象进行比较。在SAPAP3 KO小鼠中，我们使用听觉恐惧条件反射和消失来检测负价价加工的变化，使用基于奖励的操作性条件反射来检测正价价加工的变化。我们发现SAPAP3 KO小鼠通过增强的恐惧学习和受损的恐惧消退表现出负价加工的增强证据。SAPAP3 KO小鼠在奖励获取和目标导向行为方面也表现出缺陷，表明正价加工受损。在强迫症患者中，我们使用了有效的行为测试来评估与恐惧相关的面部表情（负效价）和社会奖励的快乐表情（正效价）的外显和内隐加工。我们在强迫症患者中发现了类似的趋势，即增强的阴性和受损的正价处理。总的来说，我们的研究结果揭示了临床前啮齿动物强迫行为模型中与强迫症患者相似的价加工异常，这意味着价加工改变将成为转化研究领域的新治疗靶点。
Abnormalities in valence processing – the processing of aversive or appetitive stimuli – may be an underrecognized component of obsessive-compulsive disorder (OCD). Preclinical rodent models have been critical in furthering pathophysiological understanding of OCD, yet there is a dearth of investigations examining whether rodent models of compulsive behavior show alterations in valence systems congruent with those seen in individuals with OCD. In this study, we sought to assess valence processing in a preclinical rodent model of compulsive behavior, the SAPAP3 knockout (KO) mouse model, and compare our preclinical findings to similar behavioral phenomena in OCD patients. In SAPAP3 KO mice, we used auditory fear conditioning and extinction to examine alterations in negative valence processing and reward-based operant conditioning to examine alterations in positive valence processing. We find that SAPAP3 KO mice show evidence of heightened negative valence processing through enhanced fear learning and impaired fear extinction. SAPAP3 KO mice also show deficits in reward acquisition and goal-directed behavior, suggesting impaired positive valence processing. In OCD patients, we used validated behavioral tests to assess explicit and implicit processing of fear-related facial expressions (negative valence) and socially-rewarding happy expressions (positive valence). We find similar trends towards enhanced negative and impaired positive valence processing in OCD patients. Overall, our results reveal valence processing abnormalities in a preclinical rodent model of compulsive behavior similar to those seen in OCD patients, with implications for valence processing alterations as novel therapeutic targets across a translational research spectrum.