A systemic and dialectical paradigm for Psychoneuroendocrineimmunology and integrated care science

Titolo Rivista PNEI REVIEW
Autori/Curatori Francesco Bottaccioli, Anna Giulia Bottaccioli
Pubblicazione Online First 14/01/2026 Fascicolo 2026/Online First
Lingua Inglese Numero pagine 35 P. 1-35 Dimensione file 0 KB
DOI 10.3280/pnei2025oa21668
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The integrated care needs of a philosophical paradigm. Psychoneuroendocrineimmunology can be it, provided that a consensus is created on its profound meaning. What is Psychoneuroendocrineimmunology (PNEI)? It is not Neuroendocrinoimmunology. PNEI (also called PNI, Psychoneuroimmunology) describes the relationships of mutual influence between the psyche and biological systems and between the whole organism and the physical and social environment, showing the scientific inconsistency of the reductionist dogma that makes the psyche a mere epiphenomenon of brain activity. We are in a phase of research that allows the definitive overcoming of the dualistic conception of the human being without falling into the trap of the mind-brain identity, in the reduction of the psychic dimension to the biological one, from which it undoubtedly originates but on which it influences. To this end, it is essential to critique the philosophical foundations of contemporary reductionism, while, at the same time, highlighting the theoretical-conceptual paradigm that underlies PNEI research and the practice of treatments that integrate medicine and psychology, which descend from this paradigm.

  1. Thakur S., Dhapola R., Sarma P. et al. (2023). Neuroin?ammation in Alzheimer’s Disease: Current Progress in Molecular Signaling and Therapeutics. In?ammation, 46(1): 1-17.
  2. Waddington C.H. (1942). The Epigenotype. Int J Epidemiol., 18-20.
  3. Watson J.B. (1920). Is Thinking merely the action of language mechanisms? British Journal of Psychology 11: 87-104. DOI: 10.1348/000712608X336095
  4. Weaver I.C., Cervoni N., Champagne F.A., D’Alessio A.C., Sharma S., Seckl J.R., Dymov S., Szyf M., Meaney M.J. (2004). Epigenetic programming by maternal behavior. Nat. Neurosci., 7: 847-854.
  5. Wittgenstein L. (1968). Philosophical Investigations. Oxford: Basil Blackwell; 3rd edition.
  6. Yang J., Liang J., Hu N., He N., Liu B., Liu G., Qin Y. (2024). The Gut Microbiota Modulates Neuroin?ammation in Alzheimer’s Disease: Elucidating Crucial Factors and Mechanistic Underpin-nings. CNS Neurosci Ther., 30(10), e70091.
  7. Ader R. (ed.) (2007). Psychoneuroimmunology, 4th ed., Rochester: Academic Press.
  8. Adorno, T.W. (1958). An introduction to dialectics. Cambridge: Polity, 2017.
  9. Alexander F. (1950). Psychosomatic Medicine. Its Principles and Applications. New York: Norton (re-print 1987).
  10. Amit M., Anastasaki C., Dantzer R., Demir I. E., Deneen B., Dixon K. O., Egeblad M., Gibson E.M., Hervey-Jumper S.L., Hondermarck H., Magnon C., Monje M., Na’ara S., Pan Y., Repasky E.A., Scheff N.N., Sloan E.K., Talbot S., Tracey K.J., Trotman L.C., … Borniger J.C. (2024). Next Directions in the Neuroscience of Cancers Arising outside the CNS. Cancer discovery, 14(4): 669-673. DOI: 10.1158/2159-8290.CD-23-1495
  11. Ballesio A., Zagaria A., Vacca M., Pariante C.M., Lombardo C. (2023). Comparative efficacy of psychological interventions on immune biomarkers: A systematic review and network meta-analysis (NMA). Brain Behav. Immun., 111: 424-435.
  12. Bauman Z. (1993). Modernity and ambivalence. Cambridge: Polity.
  13. Bellinger D.L., Nance D.M., Lorton D. (2013). Innervation of the Immune System. In: A.W. Kusnekov, H. Anisman (eds.), The Wiley-Blackwell Handbook of Psychoneuroimmunology, Chichester: Wiley-Blackwell, chap. 2.
  14. Bierhaus A., Wolf J., Andrassy M. et al. (2003). A mechanism converting psychosocial stress into mononuclear cell activation. Proceedings of the National Academy of Sciences of the United States of America, 100(4): 1920-5.
  15. Blalock J.E. (1989). A molecular basis for bidirectional communication between the immune and neuroendocrine systems. Physiological reviews, 69: 1-32.
  16. Bohr N. (1960). The unity of human knowledge. In: Bohr N., Essays 1958-1962 on Atomic Physics and Human Knowledge, NY: Wiley.
  17. Bottaccioli A.G., Bottaccioli F., Minelli A. (2019). Stress and the psyche-brain immune network in psychiatric diseases based on psychoneuroendocrineimmunology: a concise review. Annals of the New York Academy of Sciences, 1437(1): 31-42.
  18. Bottaccioli A.G., Bologna M., Bottaccioli F. (2022). Psychic Life-Biological Molecule Bidirectional Relationship: Pathways, Mechanisms, and Consequences for Medical and Psychological Sciences-A Narrative Review. Int J Mol Sci., 23(7), 3932.
  19. Bottaccioli A. G., Bologna M., & Bottaccioli F. (2025). Rethinking Depression — Beyond Neurotransmitters: An Integrated Psychoneuroendocrineimmunology Framework for Depression’s Pathophysiology and Tailored Treatment. Int J Mol Sci., 26(6), 2759.
  20. Bottaccioli F. (2005). Psiconeuroendocrinoimmunologia. II ed. Milano: RED.
  21. Bottaccioli F. (2020). Filoso?a per la medicina. Medicina per la ?loso?a. Oriente e Occidente a confronto, 2nd ed. Milano: Tecniche Nuove.
  22. Bottaccioli F., Bottaccioli A.G. (2023). Epigenetica e Psiconeuroendocrinoimmunologia. II ed. Milano: Edra. Spanish.
  23. Bottaccioli F., Bottaccioli A.G. (2024a). The suggestions of ancient Chinese philosophy and medicine for contemporary scienti?c research, and integrative care. Brain Behavior Immunity Integrative, 5, 100024.
  24. Bottaccioli F., Bottaccioli A.G. (2024b). The Philosophical and Scienti?c Basis for the Integration of Medicine and Psychology. In: Rezaei N., Yazdanpanah N. (eds.). Psychoneuroimmunology Volume 1: Integration of Psychology, Neurology, and Immunology. Cham, Switzerland: Springer.
  25. Bottaccioli F., Bottaccioli A.G. (2024c). Franz Alexander, uno scienziato contemporaneo: un nuovo paradigma per la psicologia e la medicina. Psicoterapia e Scienze Umane, 58(2): 251-280. DOI: 10.3280/PU2024-002003
  26. Palma-Gudiel H., Córdova-Palomera A., Eixarch E., Deuschle M., Fañanás L. (2015). Maternal psychosocial stress during pregnancy alters the epigenetic signature of the glucocorticoid receptor gene promoter in their offspring: A meta-analysis. Epigenetics, 10, 893-902. DOI: 10.1080/15592294.2015.1088630
  27. Park H., Lee C.H. (2024). The contribution of the nervous system in the cancer progression. BMB reports, 57(4): 167-175.
  28. Pariante C.M. (2017). Why are depressed patients in?amed? A re?ection on 20 years of research on depression, glucocorticoid resistance and in?ammation. European neuropsychopharmacology, 27(6), 554-559.
  29. Ramanan V.K., Armstrong M.J., Choudhury P., Coerver K.A., Hamilton R.H., Klein B.C., Wolk D.A., Wessels S.R., Jones L.K., Jr, AAN Quality Committee (2023). Antiamyloid Monoclonal Antibody Therapy for Alzheimer Disease: Emerging Issues in Neurology. Neurology, 101(19): 842-852. DOI: 10.1212/WNL.0000000000207757
  30. Rezaei N., Yazdanpanah N (eds.) (2024). PsychoNeuroImmunology, Integrated Science. Vol. 1, 2. Berlin: Springer.
  31. Rosenberg S.A. (2024). Lymphocytes as a living drug for cancer. Science, 385(6704): 25-26.
  32. Russel B. (1918). The Philosophy of Logical Atomism. Open Court; New edition, 1998.
  33. Russel B. (1921). The analysis of mind. George Allen & Unwin, London. CreateSpace Independent Publishing Platform, 2018.
  34. Ryle G. (1949). The concept of Mind. University of Chicago Press; 1st edition, 2000.
  35. Sender R., Fuchs S., Milo R. (2016). Revised estimates for the number of human and bacteria cells in the body. PLoS biology 14, 8, e1002533.
  36. Salvador, A.F.M., Kipnis, J. (2023). Introduction to Neuroimmunology. In: Paul’s Fundamental Immunology, 8th edition. Philadelpia: Wolters Kluwer.
  37. Salvador A.F.M., Abduljawad N., Kipnis J. (2024). Meningeal Lymphatics in Central Nervous System Diseases. Annual Review of Neuroscience 47: 323-44.
  38. Sheehan D.V., Harnett-Sheehan K., Spann M.E., Thompson H.F., Prakash A. (2011). Assessing remission in major depressive disorder and generalized anxiety disorder clinical trials with the discan metric of the Sheehan disability scale. Int. Clin. Psychopharmacol., 26: 75-83.
  39. Schiller M., Ben-Shaanan T.L., Roll, A. (2020). Neuronal regulation of immunity: Why, how, and where? Nature Reviews Immunology, 21: 20-36.
  40. Selye H. (1956). The Stress of Life. 1956. Revised Edition 1976; New York, NY, USA: McGraw-Hill Companies, Inc.
  41. Selye H. (1976). Forty years of stress research: Principal remaining problems and misconceptions. Can. Med. Assoc. J., 115: 53-56.
  42. Smith K.J., Gavey S., Riddell N.E., Kontari P., Victor C. (2020). The association between loneli-ness, social isolation and in?ammation: A systematic review and meta-analysis. Neurosci. Biobehav. Rev., 112: 519-541.
  43. Sterling P. Eyer, J. (1988). Allostasis: A new paradigm to explain arousal pathology. In: Fisher, S., Reason, J. (eds.). Handbook of Life Stress, Cognition and Health, Hoboken, NJ, USA: JohnWiley & Sons, pp. 629-649.
  44. Stiglitz J.E. (2024). The Road to Freedom: Economics and the Good Society. New York: W. W. Norton & Company.
  45. Sugama S., Kakinuma Y. (2021). Noradrenaline as a key neurotransmitter in modulating microglial activation in stress response. Neurochemistry international, 143: 104943.
  46. Szyf M. (2021). Perinatal stress and epigenetics. Handb. Clin. Neurol., 180: 125-148. DOI: 10.1016/B978-0-12-820107-7.00008-2
  47. Talbot S., Foster S.L., Woolf C.J. (2016). Neuroimmunity: Physiology and pathology. Annual review of immunology, 34: 421-447.
  48. Heneka M.T., Carson M.J., El Khoury J., Landreth G.E., Brosseron F., Feinstein D.L., Jacobs A.H., Wyss-Coray T., Vitorica J., Ransohoff R.M., Herrup K., Frautschy S.A., Finsen B., Brown G.C., Verkhratsky A., Yamanaka K., Koistinaho J., Latz E., Halle A., Petzold G.C., … Kummer M.P. (2015). Neuroin?ammation in Alzheimer’s disease. The Lancet. Neurology, 14(4): 388-405. DOI: 10.1016/S1474-4422(15)70016-5
  49. Hoffman S.A., Sakic B. (2009). Autoimmunity and brain dysfunction. In: Siegel A., Zalcman S. (eds.), The Neuroimmunological Basis of Behavior and Mental Disorders. Berlin: Springer Science.
  50. Hoffman S.A., Harbeck R.J., Shucard D.W. (1998). The immune system can affect learning: chron-ic immune complex disease in a rat model. J. Neuroimmunol., 86: 163-170.
  51. Huh J.R., Veiga-Fernandes H. (2019). Neuroimmune circuits in interorgan communication, Na-ture Reviews Immunology, 20: 217-228.
  52. Jerne N.K. (1974). Towards a network theory of the immune system. Annales d’immunologie, 125C (1-2): 373-389.
  53. Jording C., Hoffman S.A. (2024). Theoretico-conceptual frameworks for psychoneuroimmunology. Brain Behavior and Immunity Integrative, 7, 100066
  54. Jung J., Choi S., Han K.M. et al. (2020). Alterations in functional brain networks in depressed patients with a suicide attempt history. Neuropsychopharmacology, 45, 6: 964-974.
  55. Kemenade B.L.V.-V., Cohen N., Chadzinska M. (2017). Neuroendocrine-immune interaction: Evolutionarily conserved mechanisms that maintain allostasis in an everchanging environment. Developmental & Comparative Immunology, 66: 2-23.
  56. Koren T., Yifa R., Amer M. et al. (2021). Insular cortex neurons encode and retrieve speci?c immune responses. Cell, 184, 25: 6211.
  57. Khun T. (1996). The structure of scienti?c revolutions. Chicago: University of Chicago Press, 3rd Edn.
  58. Kwon D. (2022). Guardians of the brain: How a special immune system protects our grey matter. Nature, 606, 7912: 22-24.
  59. LeDoux J. (2002). Synaptic self: how our brains become who we are. New York: Viking, Penguin Group.
  60. Li Y.M., Kelley K.W. (2024). Traditional Chinese Medicine: What Does Modern Immunology Have to Do With It? Brain Behavior and Immunity Integrative.
  61. Louveau A., Smirnov I., Keyes T.J. et al. (2015). Structural and functional features of central nervous system lymphatic vessels. Nature 16, 523, 7560: 337-341.
  62. Ma Y., Kroemer G. (2024). The cancer-immune dialogue in the context of stress. Nat Rev Immunol., 24(4): 264-281.
  63. Mann E.R., Lam Y.K., Uhlig H.H. (2024). Short-chain fatty acids: linking diet, the microbiome and immunity. Nat Rev Immunol., 24(8): 577-595.
  64. Marx K. (1857). Introduction To the Critique of the Political Economy. In: Marx, A Contribution to the Critique of the Political Economy: Translated from the Second German Edition, By N. I. Stone with an Appendix, Lector House, 2020.
  65. Magnon C., Hondermarck H. (2023). The neural addiction of cancer. Nature reviews Cancer, 23(5): 317-334.
  66. McEwen B.S. (1998). Protective and damaging effects of stress mediators. N. Engl. J. Med., 338: 171-179. DOI: 10.1056/NEJM199801153380307
  67. McEwen B.S. (2004). Protection and damage from acute and chronic stress: allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Annals of the New York Academy of Sciences, 1032: 1-7.
  68. McEwen B.S. (2007). Physiology and neurobiology of stress and adaptation: central role of the brain. Physiological reviews, 87(3), 873-904.
  69. Bower J.E., Shiao S.L., Sullivan P., Lamkin D.M., Atienza R., Mercado F., Arevalo J., Asher A., Ganz P.A., Cole S.W. (2018). Prometastatic Molecular Pro?les in Breast Tumors from Socially Isolated Women. JNCI cancer spectrum, 2(3), pky029.
  70. Cai Y., Liu J., Wang B. et al. (2022). Microglia in the Neuroin?ammatory Pathogenesis of Alz-heimer’s Disease and Related Therapeutic Targets. Frontiers in immunology, 13, 856376.
  71. Carnap R. (1935). Philosophy and Logical Syntax. London: Kegan Paul.
  72. Castellani G., Croese T., Peralta Ramos J.M., Schwartz M. (2023). Transforming the understand-ing of brain immunity. Science, 380(6640), eabo7649.
  73. Chen W.G., Schloesser D., Arensdorf A.M. et al. (2021). The emerging science of interoception: Sensing, integrating, interpreting, and regulating signals within the self. Trends in neuroscience, 44, 1: 3-16.
  74. Chen Y., Yu D., Qian H., Shi Y., & Tao Z. (2024). CD8+ T cell-based cancer immunotherapy. Journal of translational medicine, 22(1): 394.
  75. Churchland P.S. (1986). Neurophilosophy: toward a uni?ed science of mind/brain: toward a uni?ed science of the mind-brain. Cambridge: MIT Press.
  76. Churchland P.M. (1994). Folk psychology. In: Guttenplan S. (ed.). A companion to the philosophy of mind. Oxford: Blackwell.
  77. Cole S.W., Capitanio J.P., Chun K., Arevalo J.M., Ma J., Cacioppo J.T. (2015). Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation. Proc. Natl. Acad. Sci., 112: 15142-15147.
  78. Crick F. (1970). Central dogma of molecular biology. Nature, 227: 561-3.
  79. Dalile B., Van Oudenhove L., Vervliet B., Verbeke K. (2019). The role of short-chain fatty acids in microbiota-gut-brain communication. Nat. Rev. Gastroenterol. Hepatol., 16: 461-478.
  80. Dantzer R. (2018). Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa. Physiological reviews 98: 477-504.
  81. Del Rey A., Besedovsky H. (2013). The immune-neuroendocrine network in health and disease. In: A.W. Kusnekov, H. Anisman (eds.), The Wiley-Blackwell Handbook of Psychoneuroimmunology, Chichester: Wiley-Blackwell, pp. 99-119.
  82. Descartes R. (1641) Meditations on ?rst philosophy, 2nd. Cambridge University Press, 2017.
  83. Edelman G. (2006). Second nature: brain science and human knowledge. Yale: Yale University Press.
  84. Engel G.L. (1977). The need for a new medical model: A challenge for biomedicine. Science, 196, 4286: 129-136.
  85. Esposito R (2012). Living thought: the origins and actuality of Italian philosophy. Stanford: Stanford University Press.
  86. Fava G.A., McEwen B.S., Guidi J., Gostoli S., Offidani E., Sonino N. (2019). Clinical characterization of allostatic overload. Psychoneuroendocrinology, 108: 94-101.
  87. Felten D.L., Felten S.Y., Carlson S.L. et al. (1985). Noradrenergic and peptidergic innervation of lymphoid tissue. Journal of immunology, 135, 2 (Suppl): 755s-765s.
  88. Flajnik M.F., Singh N.J., Holland S.M. (2023) (eds). Paul’s Fundamental Immunology, 8th edition. Philadelphia: Wolters Kluwer.
  89. Globig A.M., Zhao S., Roginsky J. et al. (2023). The ß1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature, 622(7982): 383-392.
  90. Godinho-Silva C., Cardoso F., Veiga-Fernandes H. (2019). Neuro-immune cell units: A new paradigm in physiology. Annual Review of Immunology, 37: 19-46.
  91. Hegel G.W.F. (1807). The phenomenology of spirit. Cambridge: Cambridge University Press, 2019.
  92. McEwen B.S., Eiland L., Hunter R.G., Miller M.M. (2012). Stress and anxiety: structural plasticity and epigenetic regulation as a consequence of stress. Neuropharmacology, 62(1): 3-12.
  93. McEwen C.A., McEwen B.S. (2017). Social Structure, Adversity, Toxic Stress, and Intergenerational Poverty: An Early Childhood Model. Annu. Rev. Sociol., 43: 445-72,
  94. Nannini S. (2018). The mind-body problem in the philosophy of mind and cognitive neuroscience: a physicalist naturalist solution. Neurol Sci., 39(9): 1509-1517.
  95. Nannini S. (2021). L’anima e il corpo. Un’introduzione storica alla ?loso?a della mente, Nuova edizione. Bari-Roma: Laterza.
  96. Neurath O., Hahn H., Carnap R. (1929). Wissenschaftliche Weltauffassung: Der Wiener Kreis. Vienna: Artur Wolf. Trad. eng.: The Scientific Conception of the World: The Vienna Circle. In: Neurath M., Cohen R.S. (eds.), Empiricism and Sociology. Vienna Circle Collection, vol. 1. Dordrecht: Springer, 1973.
  97. Pais A. (1991). Niels Bohr’s Time. In Physics, Philosophy, Polity. Oxford: Oxford University Press.

Francesco Bottaccioli, Anna Giulia Bottaccioli, A systemic and dialectical paradigm for Psychoneuroendocrineimmunology and integrated care science in "PNEI REVIEW" Online First/2026, pp 1-35, DOI: 10.3280/pnei2025oa21668