我校生命科学与技术学院国际化科研团队“神经疗法·社会认知与情感神经科学（neuSCAN）实验室”（负责人Keith Kendrick教授、Benjamin Becker教授）在精神病学领域顶级期刊Biological Psychiatry（影响因子11.5）发表最新学术成果，揭示了利用药理学干预手段促进恐惧消退学习的神经机制。团队博士生周峰为第一作者，Benjamin Becker教授为通讯作者，电子科技大学为第一作者和通讯作者唯一单位。此研究是该外籍教授负责团队自2011年成立以来第17篇影响因子大于10或PNAS论文，也是电子科技大学首次以第一单位在该期刊发表科研成果。

恐惧（fear）是人类在面临环境威胁时的适应性反应，因此恐惧的习得在人类生存和进化中发挥着重要作用。然而，当先前与威胁相联系的线索不再与威胁相关时，如何快速适应这样的转变从而消除恐惧（即恐惧消退）同样至关重要。长期处于恐惧状态会导致各种与焦虑相关的精神疾病，如焦虑症（anxiety disorder）和创伤后应激障碍（post-traumatic stress disorder）等。针对此类患者，以恐惧消退为核心机制的暴露疗法是目前最有效的治疗方法之一。但是与其他干预方法一样，暴露疗法仅对一部分患者有效。前人研究表明，加强/加速恐惧消退是潜在的提高暴露疗法效率或者减少治疗时间的方法之一。因此，该研究采用随机双盲安慰剂对照实验，结合功能性磁共振成像技术（fMRI）和生理指标-皮肤电（skin conductance response，SCR），探索了科素亚对恐惧消退学习过程的影响。

70名健康受试者首先完成了恐惧习得任务，在该任务中某一种条件刺激（CS+，比如红色色块）消失后有43%的概率立即出现一次电击，而另一种条件刺激（CS-，比如蓝色色块）消失后则不会出现电击。随后，受试者被随机分成两组，一组服用科素亚（50mg），另一组服用安慰剂（糖片），二者均被装在胶囊中，受试者并不知道自己服用的是什么。90分钟后，所有受试者都参与了恐惧消退的任务，该任务与恐惧习得任务类似，只是从始至终都不会出现电击（图A）。

结果显示，科素亚加速了消退学习过程中对条件化的威胁刺激（CS+）恐惧反应（皮肤电）的降低（图B）。同时，科素亚增强了在消退学习初期面对威胁刺激时腹内侧前额叶脑区（ventralmedial prefrontal cortex, vmPFC）的激活（图C）以及它对基底外侧杏仁核（basolateral amygdala, BLA）的调节（图D）。为了进一步研究科素亚加速恐惧消退学习的脑机制，研究人员使用了基于体素水平的中介分析（voxel-level mediation analysis）和多变量模式分析（multivariate pattern analysis），结果表明，在消退学习初期（1）科素亚通过增强腹内侧前额叶对威胁刺激的激活从而减少生理上的恐惧反应（图E），（2）科素亚减少了全脑（特别是腹内侧前额叶）在对威胁刺激的反应模式上的表征。

该研究系统探索了科素亚对恐惧消退学习的调节作用及其相关脑机制，进一步指出科素亚结合暴露疗法或许可成为治疗焦虑障碍患者的新型治疗方法，这对于焦虑相关障碍患者的临床治疗具有开创性的启示意义。

NeuSCAN Team published new findings in Biological Psychiatry showing losartan enhances fear extinction in humans

Professor Benjamin Becker, together with his team in the “Neurotherapy, social cognition and affective neuroscience (neuSCAN) lab” recently published a new study in Biological Psychiatry (impact factor 11.5) demonstrating that the drug losartan has significant effects in improving fear extinction learning in humans via augmenting activity in the ventromedial prefrontal cortex of the brain and its functional connectivity with the amygdala, which plays a key role in fear processing and threat discrimination. This landmark paper entitled “Human extinction learning is accelerated by an angiotensin antagonist via ventromedial prefrontal cortex and its connections with basolateral amygdala” is the 17th paper published by neuSCAN with an impact factor greater than 10 or in PNAS since the lab was established in 2011.  

Anxiety-related disorders are one of the most common disorders in both children and adults and which can severely affect people’s social, emotional, work and family functioning. While exposure-based interventions are routinely applied in clinical practice to reduce excessive fear in patients with anxiety-related disorders, a significant number do not adequately respond to the therapy. Based on this background, the neuSCAN team conducted a randomized placebo-controlled pharmacological functional MRI experiment to determine the clinical potential of losartan, an angiotensin II type 1 receptor antagonist, in enhancing the effects of extinction learning.

In detail, 70 healthy male subjects underwent Pavlovian threat conditioning and received single-dose losartan (50mg) or placebo administration before extinction learning. Psychophysiological threat reactivity and neural activity during extinction served as primary outcomes. Psychophysiological interaction, voxel-based mediation and novel multivariate pattern classification analyses were employed to determine the underlying neural mechanism. Results show that losartan significantly accelerated the decline of the psychophysiological threat response during the extinction learning and enhanced ventromedial prefrontal cortex activation and its functional connectivity with the basolateral amygdala. The findings, as the first author Zhou Feng speculates, document a pivotal role of angiotensin regulation of extinction learning in humans and suggest that adjunct losartan administration has the potential to facilitate the efficacy of exposure-based interventions in anxiety disorders. 

参考文献 Link to the paper：

Zhou F, Geng Y, Xin F, Li J, Feng P, Liu C, Zhao W, Feng T, Guastella AJ, Ebstein RP, Kendrick KM, Becker B. (2019) Human extinction learning is accelerated by an angiotensin antagonist via ventromedial prefrontal cortex and its connections with basolateral amygdala. Biological Psychiatry (in press) (IF=11.5)

https://www.biologicalpsychiatryjournal.com/article/S0006-3223(19)31540-9/fulltext

Biological Psychiatry介绍（相关链接） About the journal：

https://www.biologicalpsychiatryjournal.com/content/bps-aims

团队历年影响因子大于10或PNAS论文清单

List of the papers in Journals with IF > 10 or in PNAS：

1. Striepens N, Kendrick KM#, Maier W and Hurlemann R# (2011) Prosocial effects of oxytocin and clinical evidence for its therapeutic potential. Frontiers in Neuroendocrinology, 32(4):426-450. (IF =11.43) #为共同通讯作者
2. Becker B, Mihov Y, Scheele D, Kendrick KM, Feinstein JS, Matusch A, Aydin M, Reich H, Urbach H, Oros-Peusquens AM, Shah NJ, Kunz WS, Schlaepfer TE, Zilles K, Maier W and Hurlemann R. (2012) Fear processing and social networking without a functional amygdala. Biological Psychiatry, 72(1):70-77.(IF =11.5) 
3. Scheele D*, Mihov Y*, Kendrick KM*, Maier W and Hurlemann R. (2012) Amygdala lesion profoundly alters altruistic punishment. Biological Psychiatry, 72(3):e5-7 (IF =11.5) *为共同第一作者
4. Tao H*, Guo S*, Ge T*, Kendrick KM*, Xue Z, Liu Z and Feng J. (2013) Depression uncouples brain hate circuit. Molecular Psychiatry, 18, 101-111. (IF=13.67) 
5. Mihov Y*, Kendrick KM*, Becker B, Zschernack J, Reich H, Maier W, Keysers C and Hurlemann R. (2013) Mirroring fear in the absence of a functional amygdala. Biological Psychiatry, 73(7):e9-11. (IF =11.5)  
6. Scheele D*, Wille A*, Kendrick KM*, Becker B, Güntürkün O, Maier W and Hurlemann R. (2013) Oxytocin enhances brain reward system responses in men viewing the face of their female partner. Proceedings National Academy of Sciences USA 10(50): 20308-20313. *Joint first authors. (IF=9.74) 
7. Eckstein M, Becker B, Scheele D, Scholz C, Preckel K, Schlaepfer TE, Grinevich V, Kendrick KM, Maier W and Hurlemann R (2015) Oxytocin facilitates the extinction of conditioned fear in humans. Biological Psychiatry, 78(3):194-202. (IF=11.5)
8. Becker B, Wagner D, Koester P, Tittgemeyer M, Mercer-Chalmers-Bender K, Hurlemann R, Zhang J, Gouzilis-Mayfrank E, Kendrick KM* and Dauman J.* (2015) Smaller amygdala and medial prefrontal cortex predict escalating stimulant use. Brain 138(7):2074-86. (IF=10.103).  
9. Zhang J, Cheng W, Liu Z, Zhang K, Lei X, Yao Y, Becker B, Liu Y, Kendrick KM, Lu G, Feng J (2016) Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders. Brain, 139(8):2307-21. (IF=10.103).  
10. Gao S, Becker B, Luo L, Geng Y, Zhao W, Yin Y, Hu J, Gao Z, Gong Q, Hurlemann R, Yao D and Kendrick KM (2016) Oxytocin, the peptide that bonds the sexes also divides them. Proceedings of the National Academy of Sciences U S A. 113(27):7650-4. doi: 10.1073/pnas.1602620113 (IF=9.423). 
11. Spengler F*, Becker B*#, Kendrick K, Conrad R, Hurlemann R, Schade G (2017) Emotional dysregulation in psychogenic voice loss. Psychotherapy and Psychosomatics, 86:121-123. (IF=13.1) 
12. Kendrick KM and Yao D (2017) Can computer-based cognitive therapy become a front-line option for prevention and treatment of mental disorders? The American Journal of Psychiatry, 174: 303-304. (IF=13.5) 
13. Zhao Z, Yao S, Li K, Sindermann C, Zhou F, Zhao W, Li L, Goebel R, Kendrick KM, Becker B. (2019) Real-time functional connectivity-based neurofeedback of amygdala-frontal pathways reduces anxiety. Psychotherapy and Psychosomatics, 88:5-15. (IF=13.1) 
14. Zhao W*, Becker B*, Yao S, Ma X, Kou J, Kendrick KM. (2019) Oxytocin enhancement of the placebo effect may be a novel therapy for working memory impairments. Psychotherapy and Psychosomatics, 88:125-126. (IF=13.1)
15. Li J, Xu L, Zheng X, Fu M, Zhou F, Xu X, Ma X, Li K, Kendrick KM, Becker B. (2019) Common and dissociable contributions of alexithymia and autism to domain-specific interceptive dysregulations – a dimensional neuroimaging approach. Psychotherapy and Psychosomatics, 88:187-189. (IF=13.1)
16. Zhou F, Geng Y, Xin F, Li J, Feng P, Liu C, Zhao W, Feng T, Guastella AJ, Ebstein RP, Kendrick KM, Becker B. (2019) Human extinction learning is accelerated by an angiotensin antagonist via ventromedial prefrontal cortex and its connections with basolateral amygdala. Biological Psychiatry (in press) (IF=11.5) 
17. Maier A, Gieling C, Heinen-Ludwig L, Schulz J, Stefan V, Gunturkun O, Becker B, Hurlemann R, Scheele D (2019) Childhood maltreatment hampers interpersonal distance and social touch in adulthood. American Journal of Psychiatry (in press) (IF=13.7)