Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2024; 70(6): 98-109


PHYSIOLOGICAL MECHANISMS OF STRESS AND POST-TRAUMATIC STRESS DISORDER

V.A. Gorbachenko, V.V. Olianin, O.O. Lukyanets

    Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz70.06.098


Abstract

Post-Traumatic Stress Disorder (PTSD) is a complex mental disorder that develops following exposure to severe traumatic events and is characterized by symptoms such as re-experiencing the trauma, heightened anxiety, and hyperarousal. Recent studies indicate that the pathophysiology of PTSD is largely influenced by dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis and disruptions in neurotransmitter regulation, which affect key brain structures, including the amygdala, hippocampus, and prefrontal cortex. The amygdala plays a central role in the formation and retention of fear, amplifying emotional responses to traumatic stimuli. Stress hormones, such as cortisol, adrenaline, and noradrenaline, in combination with neurotransmitters (serotonin, dopamine, glutamate), modulate amygdala activity, influencing the development of PTSD. This review highlights the importance of investigating biomarkers for early PTSD diagnosis and explores promising therapeutic strategies focused on correcting HPA axis dysfunction and restoring neurotransmitter balance to alleviate PTSD symptoms.

Keywords: post-traumatic stress disorder; traumatic events; neurobiology; amygdala; prefrontal cortex; hippocampus; endocrine system; cortisol; stress hormones; fear; memory; biomarkers; neural connections.

References

  1. Kuznetsov O, Kokorev D, Sustretov O, Kozlov A, Lyamin A, Sheyfer M, et al. Genetic factors of PTSD: The role of single nucleotide variants, gene interactions, and haplotypes in developing preventive measures for PTSD. Psychiatr Danubina. 2023;35(Suppl 2):141-9.
  2. Yehuda R, LeDoux J. Response variation following trauma: a translational neuroscience approach to understanding PTSD. Neuron. 2007;56(1):19-32. CrossRef PubMed
  3. Pitman RK, Rasmusson AM, Koenen KC, Shin LM, Orr SP, Gilbertson MW, et al. Biological studies of post-traumatic stress disorder. Nature Rev Neurosci. 2012;13(11):769-87. CrossRef PubMed PubMedCentral
  4. Tyshchenko Yu N, Lukyanetz EA. The role of betaamyloid in norm and at Alzheimer's disease. Fiziol Zh. 2020;66(06):88-96. CrossRef
  5. Ganzha vv, lukyanetz ea. Role of mitochondrial disfunction in the development of Alzheimer's disease. Fiziol Zh. 2021;67(1):57-66. CrossRef
  6. Kang JE, Cirrito JR, Dong H, Csernansky JG, Holtzman DM. Acute stress increases interstitial fluid amyloid-beta via corticotropin-releasing factor and neuronal activity. Proc Natl Acad Sci USA. 2007;104(25):10673-8. CrossRef PubMed PubMedCentral
  7. Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010;35(1):169-91. CrossRef PubMed PubMedCentral
  8. Roozendaal B, McEwen BS, Chattarji S. Stress, memory and the amygdala. Nature Rev Neurosci. 2009;10(6):423- CrossRef PubMed
  9. McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol. 2008;583(2-3):174-85. CrossRef PubMed PubMedCentral
  10. Ulrich-Lai YM, Herman JP. Neural regulation of endocrine and autonomic stress responses. Nature Rev Neurosci. 2009;10(6):397-409. CrossRef PubMed PubMedCentral
  11. Brewin CR, Gregory JD, Lipton M, Burgess N. Intrusive images in psychological disorders: characteristics, neural mechanisms, and treatment implications. Psychol Rev. 2010;117(1):210-32. CrossRef PubMed PubMedCentral
  12. Gallagher M, Chiba AA. The amygdala and emotion. Current Opin Neurobiol. 1996;6(2):221-7. CrossRef PubMed
  13. Ball J, Darby I. Mental health and periodontal and periimplant diseases. Periodontology 2000. 2022;90(1):106-24. CrossRef PubMed PubMedCentral
  14. Krabbe S, Gründemann J, Lüthi A. Amygdala inhibitory circuits regulate associative fear conditioning. Biol Psychiatr. 2018;83(10):800-9. CrossRef PubMed
  15. Bath KG, Schilit A, Lee FS. Stress effects on BDNF expression: effects of age, sex, and form of stress. Neuroscience. 2013;239:149-56. CrossRef PubMed
  16. Young EA, Korszun A. The hypothalamic-pituitarygonadal axis in mood disorders. Endocrinol Metab Clin North America. 2002;31(1):63-78. CrossRef PubMed
  17. Herman JP, McKlveen JM, Ghosal S, Kopp B, Wulsin A, Makinson R, et al. Regulation of the hypothalamicpituitary-adrenocortical stress response. Comprehen Physiol. 2016;6(2):603-21. CrossRef PubMed PubMedCentral
  18. Nosenko ND, Tarasenko LV, Sinitsyn PV, Sachyns'ka OV, Hanzhy I, Reznikov OH. The dynamics of hormonal changes in female rats exposed to chronic stress and androgen excess during pubescence. Fiziol Zh. 2012;58(3):3-8. CrossRef
  19. Davis LL, Hamner MB. Post-traumatic stress disorder: the role of the amygdala and potential therapeutic interventions - a review. Front Psychiatr. 2024;15:1356563. CrossRef PubMed PubMedCentral
  20. Joseph L. The amygdala and emotion: a view through fear. Amygdala. 2000:289-310. CrossRef
  21. Harnett NG, Goodman AM, Knight DC. PTSD-related neuroimaging abnormalities in brain function, structure, and biochemistry. Exp Neurol. 2020;330:113331. CrossRef PubMed
  22. Sah P, Faber ES, Lopez De Armentia M, Power J. The amygdaloid complex: anatomy and physiology. Physiol Rev. 2003;83(3):803-34. CrossRef PubMed
  23. Mahan AL, Ressler KJ. Fear conditioning, synaptic plasticity and the amygdala: implications for posttraumatic stress disorder. Trends Neurosci. 2012;35(1):24-35. CrossRef PubMed PubMedCentral
  24. Toyoda H, Li XY, Wu LJ, Zhao MG, Descalzi G, Chen T, et al. Interplay of amygdala and cingulate plasticity in emotional fear. Neural Plastic. 2011;2011:813749. CrossRef PubMed PubMedCentral
  25. Izadi MS, Radahmadi M. Overview of the central amygdala role in feeding behaviour. Br J Nutrit. 2021;127(6):953-60. CrossRef PubMed
  26. Nutt DJ, Malizia AL. Structural and functional brain changes in posttraumatic stress disorder. J Clin Psychiatr. 2004;65 Suppl 1:11-7.
  27. Zilcha-Mano S, Zhu X, Lazarov A, Suarez-Jimenez B, Helpman L, Kim Y, et al. Structural brain features signaling trauma, PTSD, or resilience? A systematic exploration. Depress Anxiety. 2022;39(10-11):695-705. CrossRef PubMed PubMedCentral
  28. Bremner JD, Southwick SM, Johnson DR, Yehuda R, Charney DS. Childhood physical abuse and combatrelated posttraumatic stress disorder in Vietnam veterans. Am J Psychiatr. 1993;150(2):235-9. CrossRef PubMed
  29. Davis LL, Hamner MB. Post-traumatic stress disorder: the role of the amygdala and potential therapeutic interventions - a review. Front Psychiatr. 2024;15. CrossRef PubMed PubMedCentral
  30. Holzel B, Carmody J, Evans K, Hoge EA, Dusek J, Morgan L, et al. Stress reduction correlates with structural changes in the amygdale. Soc Cogn Affect Neurosci. 2009;5:11-7. CrossRef PubMed PubMedCentral
  31. Yang L, Li H, Meng Y, Shi Y, Ge A, Zhang G, et al. Dynamic changes in brain structure in patients with posttraumatic stress disorder after motor vehicle accident: A voxel-based morphometry-based follow-up study. Front Psychol. 2022;13. CrossRef PubMed PubMedCentral
  32. Morey RA, Gold AL, LaBar KS, Beall SK, Brown VM, Haswell CC, et al. Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group. Arch Gen Psychiatr. 2012;69(11):1169- CrossRef PubMed PubMedCentral
  33. Bremner JD, Wittbrodt MT. Stress, the brain, and trauma spectrum disorders. Int Rev Neurobiol. 2020;152:1-22. CrossRef PubMed PubMedCentral
  34. Shin LM, Rauch SL, Pitman RK. Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. Ann New York Acad Scie. 2006;1071:67-79. CrossRef PubMed
  35. Goldway N, Jalon I, Keynan JN, Hellrung L, Horstmann A, Paret C, et al. Feasibility and utility of amygdala neurofeedback. Neurosci Biobehav Rev. 2022;138:104694. CrossRef PubMed
  36. Williams LM. Amygdala-guided neurofeedback for major depression. Am J Psychiatr. 2017;174(8):717-8. CrossRef PubMed
  37. Vaisvaser S, Lin T, Admon R, Podlipsky I, Greenman Y, Stern N, et al. Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity. Front Human Neurosci. 2013;7:313. CrossRef PubMed PubMedCentral
  38. Sherin JE, Nemeroff CB. Post-traumatic stress disorder: the neurobiological impact of psychological trauma. Dialog Clin Neurosci. 2011;13(3):263-78. CrossRef PubMed PubMedCentral
  39. Bremner JD. Traumatic stress: effects on the brain. Dialog Clin Neurosci. 2006;8(4):445-61. CrossRef PubMed PubMedCentral
  40. Bremner JD, Elzinga B, Schmahl C, Vermetten E. Structural and functional plasticity of the human brain in posttraumatic stress disorder. Progr Brain Res. 2008;167:171-86. CrossRef PubMed
  41. Bocchio M, Nabavi S, Capogna M. Synaptic plasticity, engrams, and network oscillations in amygdala circuits for storage and retrieval of emotional memories. Neuron. 2017;94(4):731-43. CrossRef PubMed
  42. Ben-Zion Z, Korem N, Fine NB, Katz S, Siddhanta M, Funaro MC, et al. Structural neuroimaging of hippocampus and amygdala subregions in posttraumatic stress disorder: A scoping review. Biol Psychiatr Global Open Sci. 2024;4(1):120-34. CrossRef PubMed PubMedCentral
  43. Morey RA, Gold AL, LaBar KS, Beall SK, Brown VM, Haswell CC, et al. Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group. Arch Gen Psychiatr. 2012;69(11):1169-78. CrossRef PubMed PubMedCentral
  44. Seo D, Patrick CJ, Kennealy PJ. Role of serotonin and dopamine system interactions in the neurobiology of impulsive aggression and its comorbidity with other clinical disorders. Aggress Violent Behav. 2008;13(5):383-95. CrossRef PubMed PubMedCentral
  45. Quah SKL, McIver L, Roberts AC, Santangelo AM. Trait anxiety mediated by amygdala serotonin transporter in the common marmoset. J Neurosci. 2020;40(24):4739-49. CrossRef PubMed PubMedCentral
  46. Brierley B, Shaw P, David AS. The human amygdala: a systematic review and meta-analysis of volumetric magnetic resonance imaging. Brain Res Brain Res Rev. 2002;39(1):84-105. CrossRef PubMed
  47. Šimić G, Tkalčić M, Vukić V, Mulc D, Španić E, Šagud M, et al. Understanding emotions: origins and roles of the amygdala. Biomolecules. 2021;11(6). CrossRef PubMed PubMedCentral
  48. Steimer T. The biology of fear- and anxiety-related behaviors. Dialog Clin Neurosci. 2002;4(3):231-49. CrossRef PubMed PubMedCentral
  49. Tyng CM, Amin HU, Saad MNM, Malik AS. The influences of emotion on learning and memory. Front Psychol. 2017;8. CrossRef PubMed PubMedCentral

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2025.