催产素调节恐惧情绪识别的双向作用及其机制 &#x0002A;

冯柔; 顾思梦; 王福顺

doi:10.16719/j.cnki.1671-6981.20230527

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心理科学 ›› 2023, Vol. 46 ›› Issue (5) : 1246-1253. DOI: 10.16719/j.cnki.1671-6981.20230527

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催产素调节恐惧情绪识别的双向作用及其机制 ^*

冯柔¹, 顾思梦², 王福顺^**1

作者信息 +

The Bidirectional Modulation Effects of Oxytocin on Fear Recognition and Its Mechanism

Feng Rou¹, Gu Simeng², Wang Fushun¹

Author information +

文章历史 +

摘要

恐惧情绪识别对人类社会生存与适应具有重要意义,催产素（oxytocin）已被证实既可以提高表情识别,也能抑制其加工。催产素是一种爱和依恋的激素,通过与中央杏仁核催产素受体结合抑制恐惧反应。但是,在应激状态下催产素也可以与HPA轴发生相互作用,从而增强恐惧情绪加工。此外,研究发现,催产素剂量、时间、内源水平差异都会影响其双向作用。未来需要跟踪实验前后体内催产素水平的变化,对实验给药与内源系统之间的相互作用进一步研究,为产后抑郁症等情绪疾病治疗提供理论依据。

Abstract

Fear recognition plays an important role in human survival and social adaptation. But the recognition accuracy of fear is often the lowest among the six basic emotions, especially in some patients with mood disorders. Oxytocin, a "love" and "attachment" hormone, has been widely used in recent years as a social-emotional cognitive therapy for autism patients. Oxytocin was found to bind to oxytocin receptors in the central amygdala to inhibit fear responses. However, oxytocin can also interact with the HPA axis (Hypothalamus - Pituitary - Adrenal axis), and enhance fear processing under stress. Consistently, intranasal oxytocin application reduced the accuracy and speed of fear recognition by inhibiting amygdala activation. However, some other studies with fear-recognition found that, intranasal oxytocin application enhanced amygdala responses and improved the accuracy of recognition, thereby promoted emotional understanding. These two-way effects were found in both healthy subjects and patients. The mechanism behind them may be related to the interaction between the oxytocin system with the HPA axis, both regulating fear-related behaviors in complex ways. Normally, oxytocin inhibits the medial output of the central amygdala, weakens the activity of the HPA axis, and reduces the secretion of stress hormones (cortisol, etc.) and fear recognition. However, under strong stress, the release of high concentration of oxytocin led to down-regulation of the receptors and the enhancement of HPA axis, and thus to improvement of the recognition of fear emotions. In human studies, the dose and time of oxytocin administration also affect this bidirectional mechanism. In addition, individual differences in the endogenous oxytocin system, such as experiences of early life stress, personality traits, and gender, may also influence the effects of the effects of oxytocin. In all, we can make these conclusions. First, different doses of exogenous oxytocin have different effects. High dose can improve the ability of fear recognition, whereas low dose can reduce the speed and accuracy of fear recognition. Second, the effects of oxytocin follow an "inverted U-shaped" curve after intranasal administration, peaking at about 45 minutes. Third, baseline levels of endogenous oxytocin vary significantly between individuals, and the efficacy of intranasal oxytocin application can be more easily observed by increasing oxytocin doses in attention-deficit individuals with lower baseline levels. In conclusion, there are complex combined mechanisms between exogenous and endogenous oxytocin systems. In the future, we need to pay more attention to the following aspects. First, it is better to combine eye movement with event-related potential technology, and to put more attention on regulation of oxytocin on fear recognition with different emotional cues. Second, facial perception involves multiple brain regions, but the exact mechanism by which oxytocin induces changes in amygdala functional connectivity is unclear and needs further exploration. Third, The HPA axis plays a complex role in the regulation and treatment of mood, social and behavior, but its interaction with oxytocin has been poorly studied. Finally, the individual differences of the subjects should be considered in the experiment, the changes of oxytocin levels before and after the experiment should be tracked, and the interaction between endogenous system and exogenous oxytocin drug therapy should be further studied by using biogenetic techniques.

导出引用

冯柔, 顾思梦, 王福顺. 催产素调节恐惧情绪识别的双向作用及其机制 ^*[J]. 心理科学. 2023, 46(5): 1246-1253 https://doi.org/10.16719/j.cnki.1671-6981.20230527

Feng Rou, Gu Simeng, Wang Fushun. The Bidirectional Modulation Effects of Oxytocin on Fear Recognition and Its Mechanism[J]. Journal of Psychological Science. 2023, 46(5): 1246-1253 https://doi.org/10.16719/j.cnki.1671-6981.20230527

参考文献

[1] 靳宇倡, 吴静. (2016). 催产素对情绪识别的影响及其机制. 心理科学进展, 24(6), 934-945.
[2] 梁飞, 李红, 王福顺. (2021). 基本情绪的电生理活动: 来自ERP的证据. 应用心理学, 27(1), 42-56.
[3] 王天宇, 陈旭. (2020). 催产素对不安全依恋者人际适应性的影响. 心理科学进展, 28(3), 465-475.
[4] 吴璐瑶, 陈嘉卉, 赖保君, 胡静初. (2019). 催产素对恐惧情绪的作用: 双向调节还是方法学问题?生理学报, 71(6), 905-916.
[5] 张颖颖. (2019). 催产素及其受体基因对情绪加工的调节作用 (硕士学位论文). 电子科技大学, 成都.
[6] Alaerts K., Bernaerts S., Prinsen J., Dillen C., Steyaert J., & Wenderoth N. (2020). Oxytocin induces long-lasting adaptations within amygdala circuitry in autism: A treatment-mechanism study with randomized placebo-controlled design. Neuropsychopharmacology, 45(7), 1141-1149.
[7] Bakker-Huvenaars M. J., Greven C. U., Herpers P., Wiegers E., Jansen A., van der Steen R., & Buitelaar J. K. (2020). Saliva oxytocin, cortisol, and testosterone levels in adolescent boys with autism spectrum disorder, oppositional defiant disorder/conduct disorder and typically developing individuals. European Neuropsychopharmacology, 30, 87-101.
[8] Bernaerts S., Boets B., Bosmans G., Steyaert J., & Alaerts K. (2020). Behavioral effects of multiple-dose oxytocin treatment in autism: A randomized, placebo-controlled trial with long-term follow-up. Molecular Autism, 11(1), Article 6.
[9] Bertsch K., Gamer M., Schmidt B., Schmidinger I., Walther S., Kästel T., & Herpertz S. C. (2013). Oxytocin and reduction of social threat hypersensitivity in women with borderline personality disorder. American Journal of Psychiatry, 170(10), 1169-1177.
[10] Calcagnoli F., Kreutzmann J. C., de Boer S. F., Althaus M., & Koolhaas J. M. (2015). Acute and repeated intranasal oxytocin administration exerts anti-aggressive and pro-affiliative effects in male rats. Psychoneuroendocrinology, 51, 112-121.
[11] Chen T. J., Wang Y., Feng C. Z., & Feng W. F. (2020). Early integration of affectively contextual information when processing low-intensity fearful faces: Behavioral and electrophysiological evidence. International Journal of Psychophysiology, 156, 1-9.
[12] Clark-Elford R., Nathan P. J., Auyeung B., Mogg K., Bradley B. P., Sule A., & Baron-Cohen S. (2014). Effects of oxytocin on attention to emotional faces in healthy volunteers and highly socially anxious males. The International Journal of Neuropsychopharmacology, 18(2), Article pyu012.
[13] Dayi A., Kiray M., Sisman A., Ozbal S., Baykara B., Aksu I., & Uysal N. (2019). Dose dependent effects of oxytocin on cognitive defects and anxiety disorders in adult rats following acute infantile maternal deprivation stress. Biotechnic and Histochemistry, 94(7), 469-480.
[14] Di Simplicio M., Massey-Chase R., Cowen P. J., & Harmer C. J. (2009). Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers. Journal of Psychopharmacology, 23(3), 241-248.
[15] Domes G., Lischke A., Berger C., Grossmann A., Hauenstein K., Heinrichs M., & Herpertz S. C. (2010). Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology, 35(1), 83-93.
[16] Domes G., Heinrichs M., Kumbier E., Grossmann A., Hauenstein K., & Herpertz S. C. (2013). Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder. Biological Psychiatry, 74(3), 164-171.
[17] Ellenbogen, M. A. (2018). Oxytocin and facial emotion recognition. Current Topics in Behavioral Neurosciences, 35, 349-374.
[18] Feeser M., Fan Y., Weigand A., Hahn A., Gärtner M., Aust S., & Grimm S. (2014). The beneficial effect of oxytocin on avoidance-related facial emotion recognition depends on early life stress experience. Psychopharmacology, 231(24), 4735-4744.
[19] Fischer-Shofty M., Shamay-Tsoory S. G., Harari H., & Levkovitz Y. (2010). The effect of intranasal administration of oxytocin on fear recognition. Neuropsychologia, 48(1), 179-184.
[20] Flanagan J. C., Sippel L. M., Santa Maria, M. M. M., Hartwell K. J., Brady K. T., & Joseph J. E. (2019). Impact of Oxytocin on the neural correlates of fearful face processing in PTSD related to childhood Trauma. European Journal of Psychotraumatology, 10(1), Article 1606626.
[21] Frijling J. L., van Zuiden M., Koch S. B. J., Nawijn L., Veltman D. J., & Olff M. (2016). Intranasal oxytocin affects amygdala functional connectivity after trauma script-driven imagery in distressed recently trauma-exposed individuals. Neuropsychopharmacology, 41(5), 1286-1296.
[22] Gerbella M., Caruana F., & Rizzolatti G. (2019). Pathways for smiling, disgust and fear recognition in blindsight patients. Neuropsychologia, 128, 6-13.
[23] Gu S. M., Jing L. Y., Li Y., Huang J. H., & Wang F. S. (2018). Stress induced hormone and neuromodulator changes in menopausal depressive rats. Frontiers in Psychiatry, 9, Article 253.
[24] Gu S. M., Wang W., Wang F. S., & Huang J. H. (2016). Neuromodulator and emotion biomarker for stress induced mental disorders. Neural Plasticity, 2016, Article 2609128.
[25] Horta M., Ziaei M., Lin T., Porges E. C., Fischer H., Feifel D., & Ebner N. C. (2019). Oxytocin alters patterns of brain activity and amygdalar connectivity by age during dynamic facial emotion identification. Neurobiology of Aging, 78, 42-51.
[26] Huang H. P., Michetti C., Busnelli M., Managò F., Sannino S., Scheggia D., & Papaleo F. (2014). Chronic and acute intranasal oxytocin produce divergent social effects in mice. Neuropsychopharmacology, 39(5), 1102-1114.
[27] Jurek, B., & Neumann, I. D. (2018). The oxytocin receptor: From intracellular signaling to behavior. Physiological Reviews, 98(3), 1805-1908.
[28] Kim Y. R., Eom J. S., Yang J. W., Kang J., & Treasure J. (2015). The impact of oxytocin on food intake and emotion recognition in patients with eating disorders: A double blind single dose within-subject cross-over design. PLoS ONE, 10(9), Article e0137514.
[29] Kirkpatrick M. G., Lee R., Wardle M. C., Jacob S., & de Wit H. (2014). Effects of MDMA and intranasal oxytocin on social and emotional processing. Neuropsychopharmacology, 39(7), 1654-1663.
[30] Kirsch P., Esslinger C., Chen Q., Mier D., Lis S., Siddhanti S., & Meyer-Lindenberg A. (2005). Oxytocin modulates neural circuitry for social cognition and fear in humans. The Journal of Neuroscience, 25(49), 11489-11493.
[31] Knobloch H. S., Charlet A., Hoffmann L. C., Eliava M., Khrulev S., Cetin A. H., & Grinevich V. (2012). Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron, 73(3), 553-566.
[32] Koch K., Stegmaier S., Schwarz L., Erb M., Reinl M., Scheffler K., & Ethofer T. (2018). Neural correlates of processing emotional prosody in unipolar depression. Human Brain Mapping, 39(8), 3419-3427.
[33] Koch S. B. J., van Zuiden M., Nawijn L., Frijling J. L., Veltman D. J., & Olff M. (2016). Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients. Neuropsychopharmacology, 41(6), 1495-1504.
[34] Kou J., Le J., Fu M., Lan C., Chen Z., Li Q., & Kendrick K. M. (2019). Comparison of three different eye-tracking tasks for distinguishing autistic from typically developing children and autistic symptom severity. Autism Research, 12(10), 1529-1540.
[35] Labuschagne I., Phan K. L., Wood A., Angstadt M., Chua P., Heinrichs M., & Nathan P. J. (2010). Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology, 35(12), 2403-2413.
[36] Leppanen J., Ng K. W., Tchanturia K., & Treasure J. (2017). Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions. Neuroscience and Biobehavioral Reviews, 78, 125-144.
[37] Le J., Kou J., Zhao W. H., Fu M. N., Zhang Y. Y., Becker B., & Kendrick K. M. (2020). Oxytocin biases eye-gaze to dynamic and static social images and the eyes of fearful faces: Associations with trait autism. Translational Psychiatry, 10(1), Article 142.
[38] Müller L. E., Bertsch K., Bülau K., Herpertz S. C., & Buchheim A. (2019). Emotional neglect in childhood shapes social dysfunctioning in adults by influencing the oxytocin and the attachment system: Results from a population-based study. International Journal of Psychophysiology, 136, 73-80.
[39] Mielke E. L., Neukel C., Bertsch K., Reck C., Möhler E., & Herpertz S. C. (2018). Alterations of brain volumes in women with early life maltreatment and their associations with oxytocin. Hormones and Behavior, 97, 128-136.
[40] Modi M. E., Connor-Stroud F., Landgraf R., Young L. J., & Parr L. A. (2014). Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques. Psychoneuroendocrinology, 45, 49-57.
[41] Neumann I. D., Maloumby R., Beiderbeck D. I., Lukas M., & Landgraf R. (2013). Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice. Psychoneuroendocrinology, 38(10), 1985-1993.
[42] Neumann, I. D., & Slattery, D. A. (2016). Oxytocin in general anxiety and social fear: A translational approach. Biological Psychiatry, 79(3), 213-221.
[43] Parker K. J., Oztan O., Libove R. A., Sumiyoshi R. D., Jackson L. P., Karhson D. S., & Hardan A. Y. (2017). Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proceedings of the National Academy of Sciences of the United States of America, 114(30), 8119-8124.
[44] Peters S., Slattery D. A., Uschold-Schmidt N., Reber S. O., & Neumann I. D. (2014). Dose-dependent effects of chronic central infusion of oxytocin on anxiety, oxytocin receptor binding and stress-related parameters in mice. Psychoneuroendocrinology, 42, 225-236.
[45] Petrovic P., Kalisch R., Singer T., & Dolan R. J. (2008). Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. Journal of Neuroscience, 28(26), 6607-6615.
[46] Pincus D., Kose S., Arana A., Johnson K., Morgan P. S., Borckardt J., & Nahas Z. (2010). Inverse effects of oxytocin on attributing mental activity to others in depressed and healthy subjects: A double-blind placebo controlled fMRI study. Frontiers in Psychiatry, 1, Article 134.
[47] Quintana D. S., Westlye L. T., Alnæs D., Rustan Ø. G., Kaufmann T., Smerud K. T., & Andreassen O. A. (2016). Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial. Psychoneuroendocrinology, 69, 180-188.
[48] Schwaiger M., Heinrichs M., & Kumsta R. (2019). Oxytocin administration and emotion recognition abilities in adults with a history of childhood adversity. Psychoneuroendocrinology, 99, 66-71.
[49] Shahrestani S., Kemp A. H., & Guastella A. J. (2013). The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: A meta-analysis. Neuropsychopharmacology, 38(10), 1929-1936.
[50] Shin N. Y., Park H. Y., Jung W. H., & Kwon J. S. (2018). Effects of intranasal oxytocin on emotion recognition in Korean male: A dose-response study. Psychiatry Investigation, 15(7), 710-716.
[51] Shin N. Y., Park H. Y., Jung W. H., Park J. W., Yun J. Y., Jang J. H., & Kwon J. S. (2015). Effects of oxytocin on neural response to facial expressions in patients with schizophrenia. Neuropsychopharmacology, 40(9), 1919-1927.
[52] Spengler F. B., Schultz J., Scheele D., Essel M., Maier W., Heinrichs M., & Hurlemann R. (2017). Kinetics and dose dependency of intranasal oxytocin effects on amygdala reactivity. Biological Psychiatry, 82(12), 885-894.
[53] Striepens N., Kendrick K. M., Hanking V., Landgraf R., Wüllner U., Maier W., & Hurlemann R. (2013). Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans. Scientific Reports, 3, Article 3440.
[54] Wang F. S., Yang J. J., Pan F., Ho R. C., & Huang J. H. (2020). Editorial: Neurotransmitters and emotions. Frontiers in Psychology, 11, Article 21.
[55] Wynn J. K., Green M. F., Hellemann G., Reavis E. A., & Marder S. R. (2019). A dose-finding study of oxytocin using neurophysiological measures of social processing. Neuropsychopharmacology, 44(2), 289-294.