Нейровизуализационные маркеры воспринимаемой стигматизации и ее структурных феноменов у лиц с психическими расстройствами и без них: систематический обзор предметного поля

Резюме. Наряду с традиционными исследованиями психиатрической стигмы в последнее время возрастает интерес к нейробиологическим факторам, ассоциированным со стигматизацией.

Цель исследования: изучить по данным научной литературы наиболее распространенные методы исследований нейробиологических коррелятов феномена стигматизации и ее компонентов, а также систематизировать результаты проведённых исследований с учетом их методологических ограничений.

Материал и методы: Обзор был проведен в соответствии с расширением PRISMA-ScR. Поиск исследований проводился в MEDLINE, EMBASE, PsycINFO с использованием платформы Ovid. В результате оценки 2358 статей в соответствии с критериями включения, невключения, исключения в окончательный анализ были включены 20 статей.

Результаты: Большая доля исследований проводилась на выборках здоровых респондентов и не имели группу контроля (14 статей). Средний возраст респондентов варьировал от 18,8 [1,0] до 42,7 [14,7] лет. Непосредственно психиатрическая стигма изучалась в 2 исследованиях, в остальных работах — различные составляющие стигмы, среди которых наиболее часто исследовалась чувствительность к социальному отвержению (13 статей). Наиболее популярной фМРТ-парадигмой была симуляция с применением Cyberball social exclusion task (10 статей). Изменения нейронной активности, коррелирующие с выраженностью стигмы и ее составляющих конструктов, были описаны передней поясной, префронтальной коре, островковой доле, таламусе, гипоталамусе, гиппокампе, парагиппокампальной извилине, вентральной области стриатума, скорлупе, амигдале.

Заключение: Функциональные магнитно-резонансные исследования могут быть эффективным инструментом верификации и оценки динамики психологического состояния лиц, переживающих явление стигматизации.

1. Бойкина Е.Э. Остракизм и родственные феномены: обзор зарубежных исследований. Психология и право. 2019;3(9):127–140. https://doi.org/10.17759/psylaw.2019090310

2. Лутова Н.Б., Макаревич О.В., Сорокин М.Ю., Новикова К.Е., Абрамчик С.С., Вид В.Д. Психиатрическая стигма: клинико-демографические или культуральные факторы. Социальная и клиническая психиатрия. 2019;29(4):50-56.https://doi.org/10.1111/J.1600-0447.2012.0812.X

3. Лутова Н.Б., Макаревич О.В., Новикова К.Е. Взаимосвязь психологических характеристик и самостигматизации больных с эндогенными психическими расстройствами (результаты оригинального исследования). Обозрение психиатрии и медицинской психологии имени В.М. Бехтерева. 2019;(2):46-54. https://doi.org/10.31363/2313-7053-2019-2-46-54

4. Маркин К.В. Функциональная магнитно-резонансная томография покоя при биполярном аффективном расстройстве Систематизированный зонтичный обзор. Обозрение психиатрии и медицинской психологии имени В.М. Бехтерева. 2023;57(3):15-29 https://doi.org/10.31363/2313-7053-2023-800

5. Achterberg M, van Duijvenvoorde ACK, BakermansKranenburg MJ, Crone EA. Control your anger! The neural basis of aggression regulation in response to negative social feedback. Soc Cogn Affect Neurosci. 2016;11(5):712-720. https://doi.org/10.1093/scan/nsv154

6. Barbour T, Holmes AJ, Farabaugh AH, et al. Elevated Amygdala Activity in Young Adults With Familial Risk for Depression: A Potential Marker of Low Resilience. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020;5(2):194-202. https://doi.org/10.1016/j.bpsc.2019.10.010

7. Barch DM, Burgess GC, Harms, MP, et al. Function in the human connectome: Task-fMRI and individual differences in behavior. NeuroImage. 2013;(80):169–189. https://doi.org/10.1016/j.neuroimage.2013.05.033

8. Benear SL, Ngo CT, Olson IR. Dissecting the Fornix in Basic Memory Processes and Neuropsychiatric Disease: A Review. Brain Connect. 2020;10(7):331354. https://doi.org/10.1089/brain.2020.0749

9. Berretz G, Packheiser J, Kumsta R, Wolf OT, Ocklenburg S. The brain under stress-A systematic review and activation likelihood estimation metaanalysis of changes in BOLD signal associated with acute stress exposure. Neurosci Biobehav Rev. 2021;124:89-99. https://doi.org/10.1016/J.NEUBIOREV.2021.01.001

10. Bolling DZ, Pitskel NB, Deen B, et al. Dissociable brain mechanisms for processing social exclusion and rule violation. Neuroimage. 2011;54(3):24622471. https://doi.org/10.1016/j.neuroimage.2010.10.049

11. (Bud) Craig AD. How do you feel — now? The anterior insula and human awareness. Nat Rev Neurosci. 2009;10(1):59-70. https://doi.org/10.1038/nrn2555

12. Burklund LJ, Eisenberger NI, Lieberman MD. The face of rejection: Rejection sensitivity moderates dorsal anterior cingulate activity to disapproving facial expressions. Soc Neurosci. 2007;2(3-4):238253. https://doi.org/10.1080/17470910701391711

13. Cáceda R, James GA, Stowe ZN, Delgado PL, Kordsmeier N, Kilts CD. The neural correlates of low social integration as a risk factor for suicide. Eur Arch Psychiatry Clin Neurosci. 2020;270(5):619-631. https://doi.org/10.1007/s00406-019-00990-6

14. Chapman AL. Borderline personality disorder and emotion dysregulation. Dev Psychopathol. 2019;31(3):1143-1156. https://doi.org/10.1017/S0954579419000658

15. Chester DS, DeWall CN. Prefrontal recruitment during social rejection predicts greater subsequent self-regulatory imbalance and impairment: neural and longitudinal evidence. Neuroimage. 2014;101:485-493. https://doi.org/10.1016/j.neuroimage.2014.07.054

16. Chester DS, DeWall CN. The pleasure of revenge: retaliatory aggression arises from a neural imbalance toward reward. Soc Cogn Affect Neurosci. 2016;11(7):1173-1182. https://doi.org/10.1093/SCAN/NSV082

17. Dedovic K, Rexroth M, Wolff E, et al. Neural correlates of processing stressful information: An event-related fMRI study. Brain Res. 2009;1293:4960. https://doi.org/10.1016/j.brainres.2009.06.044

18. DeWall CN, Masten CL, Powell C, Combs D, Schurtz DR, Eisenberger NI. Do neural responses to rejection depend on attachment style? An fMRI study. Soc Cogn Affect Neurosci. 2012;7(2):184-192. https://doi.org/10.1093/scan/nsq107

19. DeYoung CG, Beaty RE, Genç E, et al. Personality neuroscience: An emerging field with bright prospects. Personality Science. 2022;3. https://doi.org/10.5964/ps.7269

20. Downey G, Feldman SI. Implications of rejection sensitivity for intimate relationships. J Pers Soc Psychol. 1996;70(6):1327-1343. doi:10.1037//0022-3514.70.6.1327

21. Dubreucq J, Franck N. Neural and cognitive correlates of stigma and social rejection in individuals with Serious Mental Illness (SMI): A systematic review of the literature. Psychiatry Res. 2019;274:146-158. https://doi.org/10.1016/j.psychres.2019.02.023

22. Dubreucq J, Plasse J, Franck N. Self-stigma in Serious Mental Illness: A Systematic Review of Frequency, Correlates, and Consequences. Schizophr Bull. 2021;47(5):1261-1287. https://doi.org/10.1093/SCHBUL/SBAA181

23. Firmin RL, Lysaker PH, Luther L, et al. Internalized stigma in adults with early phase versus prolonged psychosis. Early Interv Psychiatry. 2019;13(4):745751. https://doi.org/10.1111/eip.12553

24. Glover GH. Overview of Functional Magnetic Resonance Imaging. Neurosurg Clin N Am. 2011;22(2):133-139. https://doi.org/10.1016/j.nec.2010.11.001

25. Grecucci A, Sulpizio S, Tommasello E, Vespignani F, Job R. Seeing emotions, reading emotions: Behavioral and ERPs evidence of the regulation of pictures and words. PLoS One. 2019;14(5):e0209461. https://doi.org/10.1371/journal.pone.0209461

26. Hadland KA, Rushworth MFS, Gaffan D, Passingham RE. The effect of cingulate lesions on social behaviour and emotion. Neuropsychologia. 2003;41(8):919-931. https://doi.org/10.1016/S0028-3932(02)00325-1

27. Kross E, Berman MG, Mischel W, Smith EE, Wager TD. Social rejection shares somatosensory representations with physical pain. Proceedings of the National Academy of Sciences. 2011;108(15):62706275. https://doi.org/10.1073/pnas.1102693108

28. Landa A, Fallon BA, Wang Z, et al. When it hurts even more: The neural dynamics of pain and interpersonal emotions. J Psychosom Res. 2020;128:109881. https://doi.org/10.1016/j.jpsychores.2019.109881

29. Lindner C, Dannlowski U, Walhöfer K, et al. Social Alienation in Schizophrenia Patients: Association with Insula Responsiveness to Facial Expressions of Disgust. PLoS One. 2014;9(1):e85014. https://doi.org/10.1371/journal.pone.0085014

30. Mao L, Wang K, Zhang Q, et al. Felt Stigma and Its Underlying Contributors in Epilepsy Patients. Front Public Health. 2022;10. https://doi.org/10.3389/fpubh.2022.879895

31. Martelli AM, Chester DS, Brown KW, Eisenberger NI, DeWall CN. When less is more: mindfulness predicts adaptive affective responding to rejection via reduced prefrontal recruitment. Soc Cogn Affect Neurosci. 2018;13(6):648-655. https://doi.org/10.1093/SCAN/NSY037

32. Masten CL, Morelli SA, Eisenberger NI. An fMRI investigation of empathy for “social pain” and subsequent prosocial behavior. Neuroimage. 2011;55(1):381-388. . https://doi.org/10.1016/J.NEUROIM-AGE.2010.11.060

33. Masten CL, Telzer EH, Eisenberger NI. An fMRI Investigation of Attributing Negative Social Treatment to Racial Discrimination. J Cogn Neurosci. 2011;23(5):1042-1051. https://doi.org/10.1162/jocn.2010.21520

34. Messina I, Grecucci A, Viviani R. Neurobiological models of emotion regulation: a meta-analysis of neuroimaging studies of acceptance as an emotion regulation strategy. Soc Cogn Affect Neurosci. 2021;16(3):257-267. https://doi.org/10.1093/scan/nsab007

35. Miller R. Neuroeducation: Integrating Brain-Based Psychoeducation into Clinical Practice. J Ment Health Couns. 2016;38(2):103-115. https://doi.org/10.17744/MEHC.38.2.02

36. Muscatell KA, Moieni M, Inagaki TK, et al. Exposure to an inflammatory challenge enhances neural sensitivity to negative and positive social feedback. Brain Behav Immun. 2016;57:21-29. https://doi.org/10.1016/J.BBI.2016.03.022

37. Muscatell KA, Merritt CC, Cohen JR, Chang L, Lindquist KA. The Stressed Brain: Neural Underpinnings of Social Stress Processing in Humans. Curr Top Behav Neurosci. 2022;54:373392. https://doi.org/10.1007/7854_2021_281/TABLES/1

38. Nakamura Y, Okada N, Ando S, et al. The Association Between Amygdala Subfield-Related Functional Connectivity and Stigma Reduction 12 Months After Social Contacts: A Functional Neuroimaging Study in a Subgroup of a Randomized Controlled Trial. Front Hum Neurosci. 2020;14. https://doi.org/10.3389/fnhum.2020.00356

39. Nejati V, Majdi R, Salehinejad MA, Nitsche MA. The role of dorsolateral and ventromedial prefrontal cortex in the processing of emotional dimensions. Sci Rep. 2021;11(1):1971. https://doi.org/10.1038/s41598-021-81454-7

40. Nezlek JB, Kowalski RM, Leary MR, Blevins T, Holgate S. Personality moderators of reactions to interpersonal rejection: Depression and trait selfesteem. Pers Soc Psychol Bull. 1997;23(12):12351244. https://doi.org/10.1177/01461672972312001

41. O’Donnell LJ, Westin CF. An Introduction to Diffusion Tensor Image Analysis. Neurosurg Clin N Am. 2011;22(2):185-196. https://doi.org/10.1016/j.nec.2010.12.004

42. Pelliccio LJ, Walker S. What is an interpersonal ostracism message?: bringing the construct of ostracism into communication studies. Atl J Commun. 2020;30(2):172-187. https://doi.org/10.1080/15456870.2020.1859509

43. Powers KE, Somerville LH, Kelley WM, Heatherton TF. Rejection Sensitivity Polarizes Striatal–Medial Prefrontal Activity When Anticipating Social Feedback. J Cogn Neurosci. 2013;25(11):1887-1895. https://doi.org/10.1162/jocn_a_00446

44. Premkumar P, Kumari V. Rejection sensitivity and its relationship to schizotypy and aggression: current status and future directions. Curr Opin Behav Sci. 2022;44:101110. https://doi.org/10.1016/j.cobeha.2022.101110

45. Raij TT, Korkeila J, Joutsenniemi K, Saarni SI, Riekki TJJ. Association of stigma resistance with emotion regulation — Functional magnetic resonance imaging and neuropsychological findings. Compr Psychiatry. 2014;55(3):727-735. https://doi.org/10.1016/j.comppsych.2013.10.010

46. Ramirez-Mahaluf JP, Perramon J, Otal B, Villoslada P, Compte A. Subgenual anterior cingulate cortex controls sadness-induced modulations of cognitive and emotional network hubs. Sci Rep. 2018;8(1):8566. https://doi.org/10.1038/s41598-018-26317-4

47. Ren D, Wesselmann ED, Williams KD. Hurt people hurt people: ostracism and aggression. Curr Opin Psychol. 2018;19:34-38. https://doi.org/10.1016/J.COPSYC.2017.03.026

48. Sankar A, Yttredahl AA, Fourcade EW, et al. Dissociable Neural Responses to Monetary and Social Gain and Loss in Women With Major Depressive Disorder. Front Behav Neurosci. 2019;13. https://doi.org/10.3389/fnbeh.2019.00149

49. Schaafsma J, Williams KD. Exclusion, intergroup hostility, and religious fundamentalism. J Exp Soc Psychol. 2012;48(4):829-837. https://doi.org/10.1016/J.JESP.2012.02.015

50. Schomerus G, Stolzenburg S, Freitag S, et al. Stigma as a barrier to recognizing personal mental illness and seeking help: a prospective study among untreated persons with mental illness. Eur Arch Psychiatry Clin Neurosci. 2019;269(4):469-479. https://doi.org/10.1007/s00406-018-0896-0.

51. Sen PN, Basser PJ. A Model for Diffusion in White Matter in the Brain. Biophys J. 2005;89(5):29272938. https://doi.org/10.1529/biophysj.105.063016

52. Sicorello M, Schmahl C. Emotion dysregulation in borderline personality disorder: A fronto–limbic imbalance? Curr Opin Psychol. 2021;37:114-120. https://doi.org/10.1016/j.copsyc.2020.12.002

53. Šimić G, Tkalčić M, Vukić V, et al. Understanding Emotions: Origins and Roles of the Amygdala. Biomolecules. 2021;11(6):823. https://doi.org/10.3390/biom11060823

54. Sorokin MY, Lutova NB, Bocharova MO, Khobeysh MA, Wied VD. Computational psychiatry approach to stigma subtyping in patients with mental disorders: explicit and implicit internalized stigma. Consortium Psychiatricum. 2023;4(3):13-21. https://doi.org/10.17816/CP6556

55. Streit F, Haddad L, Paul T, et al. A functional variant in the neuropeptide S receptor 1 gene moderates the influence of urban upbringing on stress processing in the amygdala. Stress. 2014;17(4):352-361. https://doi.org/10.3109/10253890.2014.921903

56. Sun J, Zhuang K, Li H, Wei D, Zhang Q, Qiu J. Perceiving rejection by others: Relationship between rejection sensitivity and the spontaneous neuronal activity of the brain. Soc Neurosci. 2018;13(4):429438. https://doi.org/10.1080/17470919.2017.1340335

57. Tricco AC, Lillie E, Zarin W, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018;169(7):467-473. https://doi.org/10.7326/M18-0850

58. Way BM, Taylor SE, Eisenberger NI. Variation in the μ-opioid receptor gene ( OPRM1 ) is associated with dispositional and neural sensitivity to social rejection. Proceedings of the National Academy of Sciences. 2009;106(35):15079-15084. https://doi.org/10.1073/pnas.0812612106

59. Wesselmann ED, Ren D, Williams KD. Motivations for responses to ostracism. Front Psychol. 2015;6(FEB). https://doi.org/10.3389/FPSYG.2015.00040

60. Wikman P, Moisala M, Ylinen A, et al. Brain Responses to Peer Feedback in Social Media Are Modulated by Valence in Late Adolescence. Front Behav Neurosci. 2022;16. https://doi.org/10.3389/FNBEH.2022.790478

61. Williams KD. Ostracism. Annu Rev Psychol. 2007;58:425-452. https://doi.org/10.1146/ANNUREV.PSYCH.58.110405.085641

62. Williams KD. Chapter 6 Ostracism. A Temporal Need-Threat Model. Adv Exp Soc Psychol. 2009;41:275-314. https://doi.org/10.1016/S0065-2601(08)00406-1

63. Williams KD, Cheung CKT, Choi W. Cyberostracism: effects of being ignored over the Internet. J Pers Soc Psychol. 2000;79(5):748-762. https://doi.org/10.1037//0022-3514.79.5.748

64. Williams KD, Forgas JP, Hippel W von. The social outcast ostracism, social exclusion, rejection, and bullying. 2005.

65. Williams KD, Nida SA. Ostracism: Consequences and coping. Curr Dir Psychol Sci. 2011;20(2):7175. https://doi.org/10.1177/0963721411402480

66. Wrege JS, Ruocco AC, Euler S, et al. Negative affect moderates the effect of social rejection on frontal and anterior cingulate cortex activation in borderline personality disorder. Cogn Affect Behav Neurosci. 2019;19(5):1273-1285. https://doi.org/10.3758/s13415-019-00716-0

67. Yılmaz E, Okanlı A. The Effect of Internalized Stigma on the Adherence to Treatment in Patients With Schizophrenia. Arch Psychiatr Nurs. 2015;29(5):297-301. https://doi.org/10.1016/j.apnu.2015.05.006

68. Zadro L, Williams KD, Richardson R. Riding the “O” train: Comparing the effects of Ostracism and verbal dispute on targets and sources. Group Processes and Intergroup Relations. 2005;8(2 SPEC. ISS.):125-143. https://doi.org/10.1177/1368430205051062

69. Zhang M, Peng Y. Anterior insula and dorsal anterior cingulate cortex as a hub of self-regulation: combining activation likelihood estimation metaanalysis and meta-analytic connectivity modeling analysis. Brain Struct Funct. 2023;228(5):13291345. https://doi.org/10.1007/s00429-023-02652-9

70. Zhang Y, Zhou W, Wang S, et al. The Roles of Subdivisions of Human Insula in Emotion Perception and Auditory Processing. Cerebral Cortex. 2019;29(2):517-528. https://doi.org/10.1093/cercor/bhx334