Neurobiological factors of self-harm behavior in patients with mental disorders

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Non-suicidal self-harm behavior in mental disorders is a complex clinical phenomenon with a high prevalence among various groups of patients. Such behavioral patterns often precede suicidal intentions. However, despite the growing number of studies, currently many questions about the role of biological factors in the self-harm remain debatable. In this regard, the purpose of this review was to systematize data on the role of neurobiological factors in the non-suicidal self-harm. According to the materials studied, one of the promising theories may be the violation of the endogenous opioid system, as well as the role of neuroendocrine factors (in particular, the hypothalamic-pituitary-adrenocortical system) and neuroinflammatory mechanisms, the activation of which would explain the motivation for mutilation and the mechanism provoking this phenomenon. Research in this area can provide a better understanding of the motivation of this behavior, suggest new pharmacological methods of therapeutic effects on these clinical manifestations, identify possible tactics for determining risk and preventing non-suicidal self-harm, as well as shed light on the treatment of mood disorders, including to overcome therapeutic resistance and prevent suicidal behavior. Non-suicidal self-harm in mood disorders is a complex and controversial clinical phenomenon. Despite a large number of studies, currently many questions regarding the role of biological factors in the formation of non-suicidal self-injury remain unresolved. One promising theory is the violation of the endogenous opioid system and neuroinflammatory mechanisms, the activation of which would explain the self-harm motivation and mechanism of these acts. Research in this area can offer new pharmacological methods of therapeutic impact on these clinical phenomena, as well as shedding light on the treatment of mood disorders, such as overcoming therapeutic resistance and decrease suicide risks.

About the authors

A. P. Protasov

FSBI “Bekhterev National Medical Research Center for Psychiatry and Neurology” of Russia Ministry of Health

Author for correspondence.
Email: alxprotasov@gmail.com
Russian Federation, Saint-Petersburg, 192019

G. V. Rukavishnikov

FSBI “Bekhterev National Medical Research Center for Psychiatry and Neurology” of Russia Ministry of Health

Email: grigory_v_r@mail.ru
Russian Federation, Saint-Petersburg, 192019

G. E. Mazo

FSBI “Bekhterev National Medical Research Center for Psychiatry and Neurology” of Russia Ministry of Health

Email: galina-mazo@yandex.ru
Russian Federation, Saint-Petersburg, 192019

References

  1. Горбунова А.П., Рукавишников Г.В., Касьянов Е.Д., Мазо Г.Э. Роль клеточного иммунитета и коэффициентов системного воспаления в механизмах формирования психических расстройств // Неврология, нейропсихиатрия, психосоматика. 2023. Т. 15. № 5. С. 72–78. doi: doi.org/10.32878/suiciderus.24-15-01(54)-31-52
  2. Гордеев С.А. Боль: классификация, структурно-функциональная организация ноцицептивной и антиноцицептивной систем, электронейромиографические методы исследования // Успехи физиол. наук. 2019. Т. 50. № 4. С. 87–104. doi: 10.1134/S0301179819040039
  3. Левицкая Н.Г., Каменский А.А. Меланокортиновая система // Успехи физиол. наук. 2009. Т. 40. № 1. С. 44–65.
  4. Овсянников В.Г., Бойченко А.Е., Алексеев В.В. и др. Антиноцицептивная система // Медицинский вестник Юга России. 2014. № 3. С. 46–54.
  5. Овсянников В.Г., Бойченко А.Е., Алексеев В.В. и др. Антиноцицептивная система. Эндогенные механизмы обезболивания // Патологическая физиология и экспериментальная терапия. 2019. Т. 63. № 4. С. 130–136. doi: 10 .25557/0031-2991.2019.04 . 130-136
  6. Bershad A.K., Ruiz N.A., de Wit H. Effects of buprenorphine on responses to emotional stimuli in individuals with a range of mood symptomatology // International Journal of Neuropsychopharmacology. 2018. V. 21. № 2. P. 120–127. doi: 10.1093/ijnp/pyx077
  7. Bodkin J.A., Zornberg G.L., Lukas S.E., Cole J.O. Buprenorphine treatment of refractory depression // Journal of clinical psychopharmacology. 1995. Т. 15. № 1. С. 49–57. doi: 10.1097/00004714-199502000-00008
  8. Bresin K., Gordon K.H. Endogenous opioids and nonsuicidal self-injury: A mechanism of affect regulation // Neuroscience & Biobehavioral Reviews. 2013. V. 37. № 3. P. 374–383. doi: 10.1016/j.neubiorev.2013.01.020
  9. Brown R.C., Plener P.L. Non-suicidal self-injury in adolescence // Current psychiatry reports. 2017. V. 19. P. 1–8. doi: 10.1007/s11920-017-0767-9
  10. Callaway E. Buprenorphine for depression: the un-adoptable orphan // Biological psychiatry. 1996. V. 39. № 12. P. 989–990. doi: 10.1016/0006-3223(96)00158-8
  11. Carlezon W.A. Jr, Béguin C., Knoll A.T., Cohen B.M. Kappa-opioid ligands in the study and treatment of mood disorders // Pharmacology & therapeutics. 2009. V. 123. № 3. P. 334–343. doi: 10.1016/j.pharmthera.2009.05.008
  12. Emrich H.M., Vogt P., Herz A. Possible antidepressive effects of opioids: action of buprenorphine // Annals of the New York Academy of Sciences. 1982. V. 398. № 1. P. 108–112. doi: 10.1111/j.1749-6632.1982.tb39483.x
  13. Fava M., Memisoglu A., Thase M.E. et al. Opioid modulation with buprenorphine/samidorphan as adjunctive treatment for inadequate response to antidepressants: a randomized double-blind placebo-controlled trial // American Journal of Psychiatry. 2016. V. 173. № 5. P. 499–508. doi: 10.1176/appi.ajp.2015.15070921
  14. Gibbons R.D., Hur K., Quinn P.D. Concomitant opioid and benzodiazepine use and risk of suicide attempt and intentional self-harm: pharmacoepidemiologic study // Drug and alcohol dependence. 2021. V. 228. P. 109046. doi: 10.1016/j.drugalcdep.2021.109046
  15. Gul Helvaci Celik F., Hocaoglu C. Implications of childhood trauma on suicidal behavior and deliberate self-harm in patients with major depressive disorder // Psychiatria Danubina. 2022. V. 34. № 1. P. 57–63. doi: 10.24869/psyd.2022.57
  16. Halicka J., Kiejna A. Non-suicidal self-injury (NSSI) and suicidal: Criteria differentiation // Adv Clin Exp Med. 2018. V. 27. № 2. P. 257–261. doi: 10.17219/acem/66353
  17. Hauger R.L., Risbrough V., Brauns O., Dautzenberg F.M. Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: new molecular targets // CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders). 2006. V. 5. № 4. P. 453–479. doi: 10.2174/187152706777950684
  18. Hsu D.T., Sanford B.J., Meyers K.K. et al. Response of the μ-opioid system to social rejection and acceptance // Molecular psychiatry. 2013. V. 18. № 11. P. 1211–1217. doi: 10.1038/mp.2013.96
  19. Hsu D.T., Sanford B.J., Meyers K.K. et al. It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder // Molecular psychiatry. 2015. V. 20. № 2. P. 193–200. doi: 10.1038/mp.2014.185
  20. Kang L., Li R., Liu H. et al. Nonsuicidal self-injury in undergraduate students with major depressive disorder: the role of psychosocial factors // Journal of affective disorders. 2021. V. 290. P. 102–108. doi: 10.1016/j.jad.2021.04.083
  21. Karp J.F., Butters M.A., Begley A.E. et al. Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults // The Journal of clinical psychiatry. 2014. V. 75. № 8. P. 18861. doi: 10.4088/JCP.13m08725
  22. Kerr P.L., Muehlenkamp J.J., Turner J.M. Nonsuicidal self-injury: a review of current research for family medicine and primary care physicians // The Journal of the American Board of Family Medicine. 2010. V. 23. № 2. P. 240–259. doi: 10.3122/jabfm.2010.02.090110
  23. Klonsky E.D. The functions of self-injury in young adults who cut themselves: Clarifying the evidence for affect-regulation // Psychiatry research. 2009. V. 166. № 2–3. P. 260–268. doi: 10.1016/j.psychres.2008.02.008
  24. Kross E., Berman M.G., Mischel W., Smith E.E., Wager T.D. Social rejection shares somatosensory representations with physical pain // Proceedings of the National Academy of Sciences. 2011. V. 108. № 15. P. 6270–6275. doi: 10.1073/pnas.1102693108
  25. Madge N., Hewitt A., Hawton K. et al. Deliberate self‐harm within an international community sample of young people: comparative findings from the Child & Adolescent Self‐harm in Europe (CASE) Study // Journal of child Psychology and Psychiatry. 2008. V. 49. № 6. P. 667–677. doi: 10.1111/j.1469-7610.2008.01879.x
  26. Millington G.W.M. Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors // Clinical and experimental dermatology. 2006. V. 31. № 3. P. 407–412. doi: 10.1111/j.1365-2230.2006.02128.x
  27. Miola A., Dal Porto V., Tadmor T. et al. Increased C-reactive protein concentration and suicidal behavior in people with psychiatric disorders: A systematic review and meta-analysis // Acta Psychiatr Scand. 2021. V. 144. № 6. P. 537–552. doi: 10.1111/acps.13351
  28. Moran P., Coffey C., Romaniuk H. et al. The natural history of self-harm from adolescence to young adulthood: a population-based cohort study // The Lancet. 2012. V. 379. № 9812. P. 236–243. doi: 10.1016/S0140-6736(11)61141-0
  29. Nagy L.M., Shanahan M.L., Seaford S.P. Nonsuicidal self‐injury and rumination: A meta‐analysis // Journal of Clinical Psychology. 2023. V. 79. № 1. P. 7–27. doi: 10.1002/jclp.23394
  30. Nater U.M., Bohus M., Abbruzzese E. et al. Increased psychological and attenuated cortisol and alpha-amylase responses to acute psychosocial stress in female patients with borderline personality disorder // Psychoneuroendocrinology. 2010. V. 35. № 10. P. 1565–1572. doi: 10.1016/j.psyneuen.2010.06.002
  31. Nock M.K., Prinstein M.J. A functional approach to the assessment of self-mutilative behavior // Journal of consulting and clinical psychology. 2004. V. 72. № 5. P. 885–890. doi: 10.1037/0022-006X.72.5.885.
  32. Nock M.K., Prinstein M.J. Contextual features and behavioral functions of self-mutilation among adolescents // Journal of abnormal psychology. 2005. V. 114. № 1. P. 140–146. doi: 10.1037/0021-843X.114.1.140
  33. Nock M.K., Prinstein M.J., Sterba S.K. Revealing the form and function of self-injurious thoughts and behaviors: A real-time ecological assessment study among adolescents and young adults // Journal of abnormal psychology. 2009. V. 118. № 4. P. 816–827. doi: 10.1037/a0016948
  34. Nyhuis P.W., Gastpar M., Scherbaum N. Opiate treatment in depression refractory to antidepressants and electroconvulsive therapy // Journal of clinical psychopharmacology. 2008. V. 28. № 5. P. 593–595. doi: 10.1097/JCP.0b013e31818638a4
  35. Ogden J., Bennett A. Self-harm as a means to manage the public and private selves: A qualitative study of help seeking by adults // Health Psychology Open. 2015. V. 2. № 2. P. 2055102915605987. doi: 10.1177/2055102915605987
  36. Padmanathan P., Forbes H., Redaniel M.T. et al. Self-harm and suicide during and after opioid agonist treatment among primary care patients in England: a cohort study // The Lancet Psychiatry. 2022. V. 9. № 2. P. 151–159. doi: 10.1016/S2215-0366(21)00392-8
  37. Peciña M., Karp J.F., Mathew S. et al. Endogenous opioid system dysregulation in depression: implications for new therapeutic approaches // Molecular psychiatry. 2019. V. 24. № 4. P. 576–587. doi: 10.1038/s41380-018-0117-2
  38. Prossin A.R., Love T.M., Koeppe R.A., Zubieta J.K., Silk K.R. Dysregulation of regional endogenous opioid function in borderline personality disorder // American Journal of Psychiatry. 2010. V. 167. № 8. P. 925–933. doi: 10.1176/appi.ajp.2010.09091348
  39. Rasmussen S., Hawton K., Philpott-Morgan S., O’Connor R.C. Why Do Adolescents Self-Harm? // Crisis. 2016. V. 3. № 37. P. 176–183. doi: 10.1027/0227-5910/a000369
  40. Serafini G., Adavastro G., Canepa G. et al. The efficacy of buprenorphine in major depression, treatment-resistant depression and suicidal behavior: a systematic review // International journal of molecular sciences. 2018. V. 19. № 8. P. 2410. doi: 10.3390/ijms19082410
  41. Sher L., Stanley B.H. The role of endogenous opioids in the pathophysiology of self-injurious and suicidal behavior //Archives of Suicide Research. 2008. V. 12. № 4. P. 299–308. doi: 10.1080/13811110802324748
  42. Smith B.D. Self-mutilation and pharmacotherapy // Psychiatry (Edgmont). 2005. V. 2. № 10. P. 28.
  43. Stanley B., Sher L., Wilson S. et al. Non-suicidal self-injurious behavior, endogenous opioids and monoamine neurotransmitters // Journal of affective disorders. 2010. V. 124. № 1–2. P. 134–140. doi: 10.1016/j.jad.2009.10.028
  44. Symons F.J., Thompson A., Rodriguez M.C. Selfinjurious behavior and the efficacy of naltrexone treatment: A quantitative synthesis // Mental retardation and developmental disabilities research reviews. 2004. V. 10. № 3. P. 193–200. doi: 10.1002/mrdd.20031
  45. Taylor T., Dluhy R.G., Williams G.H. β-Endorphin suppresses adrenocorticotropin and cortisol levels in normal human subjects // The Journal of Clinical Endocrinology & Metabolism. 1983. V. 57. № 3. P. 592–596. doi: 10.1210/jcem-57-3-592
  46. Turncliff R., DiPetrillo L., Silverman B., Ehrich E. Single-and multiple-dose pharmacokinetics of samidorphan, a novel opioid antagonist, in healthy volunteers // Clinical Therapeutics. 2015. V. 37. № 2. P. 338–348. doi: 10.1016/j.clinthera.2014.10.001
  47. Turner B.J., Austin S.B., Chapman A.L. Treating nonsuicidal self-injury: a systematic review of psychological and pharmacological interventions // The Canadian Journal of Psychiatry. 2014. V. 59. № 11. P. 576–585. doi: 10.1177/070674371405901103
  48. Van der Venne P., Balint A., Drews E. et al. Pain sensitivity and plasma beta-endorphin in adolescent non-suicidal self-injury // Journal of affective disorders. 2021. V. 278. P. 199–208. doi: 10.1016/j.jad.2020.09.036
  49. Van der Venne P., Mürner-Lavanchy I., Höper S., Koenig J., Kaess M. Physiological response to pain in female adolescents with nonsuicidal self-injury as a function of severity //Journal of affective disorders. 2023. V. 339. P. 64–73. doi: 10.1016/j.jad.2023.06.041
  50. Walsh S.L., Preston K.L., Stitzer M.L., Cone E.J., Bigelow G.E. Clinical pharmacology of buprenorphine: ceiling effects at high doses // Clinical Pharmacology & Therapeutics. 1994. V. 55. № 5. P. 569–580. doi: 10.1038/clpt.1994.71
  51. Wisłowska-Stanek A., Kołosowska K., Maciejak P. Neurobiological Basis of Increased Risk for Suicidal Behaviour // Cells. 2021. V. 10. № 10. P. 2519. doi: 10.3390/cells10102519
  52. Yarushkina N.I., Filaretova L.P. The peripheral corticotropin-releasing factor (CRF)-induced analgesic effect on somatic pain sensitivity in conscious rats: involving CRF, opioid and glucocorticoid receptors // Inflammopharmacology. 2018. V. 26. № 2. P. 305–318. doi: 10.1007/s10787-018-0445-5
  53. Yovell Y., Bar G., Mashiah M. et al. Ultra-low-dose buprenorphine as a time-limited treatment for severe suicidal ideation: a randomized controlled trial // American journal of psychiatry. 2016. V. 173. № 5. P. 491–498. doi: 10.1176/appi.ajp.2015.15040535
  54. Zanarini M.C., Laudate C.S., Frankenburg F.R., Wedig M.M., Fitzmaurice G. Reasons for self-mutilation reported by borderline patients over 16 years of prospective follow-up // Journal of personality disorders. 2013. V. 27. № 6. P. 783–794. doi: 10.1521/pedi_2013_27_115
  55. Zheng Q., Liu J., Ji Y. et al. Elevated levels of monocyte-lymphocyte ratio and platelet-lymphocyte ratio in adolescents with non-suicidal self-injury // BMC psychiatry. 2022. Т. 22. № 1. P. 618. doi: 10.1186/s12888-022-04260-z
  56. Zubieta J.K., Ketter T.A., Bueller J.A. et al. Regulation of human affective responses by anterior cingulate and limbic µ-opioid neurotransmission // Archives of general psychiatry. 2003. V. 60. № 11. P. 1145–1153. doi: 10.1001/archpsyc.60.11.1145

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Russian Academy of Sciences