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Neurodevelopmental Trajectories: A PNEI and Developmental Pathway Linking Genetics, Epigenetics and Integrated Clinical Care

DOI
https://doi.org/10.3280/pnei2026oa23998
Submitted
ottobre 13, 2026
Published
2026-10-16

Abstract

This article examines the child’s neurodevelopmental trajectory from conception to the early years of life, focusing on the critical stages of typical and atypical neurodevelopment. Through the lens of Psychoneuroendocrinoimmunology (PNEI), the article analyzes the shift from genetic determinism to a dynamic and probabilistic model in which epigenetics plays a cen-tral role. The theoretical frameworks of the exposome and DOHaD (Developmental Origins of Health and Disease) are explored, highlighting the impact of environmental factors, maternal-fetal stress and maternal immune activation (MIA) on brain connectomics and on the genesis of neurodevelopmental disorders (NDDs), with particular reference to autism spectrum disorder (ASD). The article examines the molecular mechanisms of neuronal migration, microglia-mediated synaptic pruning and alterations of the gut-brain axis. Finally, it discusses the func-tional meaning of atypical sensory profiles and stereotypies, proposing a therapeutic paradigm shift based on brain plasticity, environmental modification and early clinical intervention aimed at relational and sensory enrichment.

References

  1. American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed.). Arlington, VA: American Psychiatric Publishing.
  2. Ayres A.J. (2005). Sensory integration and the child: Understanding hidden sensory challenges (25th anniver-sary ed., rev. and updated by Pediatric Therapy Network, with assistance from J. Robbins). Los An-geles, CA: Western Psychological Services.
  3. Barker D.J.P. (1995). The Wellcome Foundation Lecture, 1994. The fetal origins of adult disease. Proceed-ings of the Royal Society of London. Series B: Biological Sciences, 262(1363), 37–43. Doi: 10.1098/rspb.1995.0173
  4. Belmonte M.K., Allen G., Beckel-Mitchener A., Boulanger L.M., Carper R.A., & Webb S.J. (2004). Au-tism and abnormal development of brain connectivity. Journal of Neuroscience, 24(42), 9228–9231. Doi: 10.1523/JNEUROSCI.3340-04.2004
  5. Burgio E. (2015). Environment and fetal programming: the origins of some current «pandemics». Journal of Pediatric and Neonatal Individualized Medicine, 4(2), e040237. Doi: 10.7363/040237
  6. Caruso A., Gila L., Fulceri F., Salvitti T., Micai M., Baccinelli W., Bulgheroni M., & Scattoni M.L., on behalf of the NIDA Network Group (2020). Early motor development predicts clinical outcomes of siblings at high-risk for autism: Insight from an innovative motion-tracking technology. Brain Sciences, 10(6), 379. Doi: 10.3390/brainsci10060379
  7. Dinan T.G., & Cryan J.F. (2017). The microbiome-gut-brain axis in health and disease. Gastroenterology Clinics of North America, 46(1), 77–89. Doi: 10.1016/j.gtc.2016.09.007
  8. Ermer J., & Dunn W. (1998). The Sensory Profile: A discriminant analysis of children with and without disa-bilities. American Journal of Occupational Therapy, 52(4), 283–290. Doi: 10.5014/ajot.52.4.283
  9. Estes M.L., & McAllister A.K. (2016). Maternal immune activation: Implications for neuropsychiatric disorders. Science, 353(6301), 772–777. Doi: 10.1126/science.aag3194
  10. Fabbri-Destro M., Maugeri F., Ianni C., Corsini S., Di Stefano E., Scatigna S., Crifaci G., Bruzzi G., Berloffa S., Fantozzi P., Prato A., Muccio R., Valente E., Pelagatti S., Pecchini E., Zulli F., Rizzo R., Milone A., Viglione V.,
  11. Barone R., Masi G., & Narzisi A. (2022). Early sensory profile in autism spectrum disorders predicts emotional and behavioral issues. Journal of Personalized Medicine, 12(10), 1593. Doi: 10.3390/jpm12101593
  12. Holiga Š., Hipp J.F., Chatham C.H., Garces P., Spooren W., Liogier D’Ardhuy X., Bertolino A., Bou-quet C., Buitelaar J.K., Bours C., Rausch A., Oldehinkel M., Bouvard M., Amestoy A., Caralp M., Gueguen S., Ly-Le Moal M., Houenou J.,
  13. Beckmann C.F., Loth E., Murphy D., Charman T., Till-mann J., Laidi C., Delorme R., Beggiato A., Gaman A., Scheid I., Leboyer M., d’Albis M.A., Sevigny J., Czech C., Bolognani F., Honey G.D., & Dukart J. (2019). Patients with autism spectrum disorders display reproducible functional connectivity alterations. Science Translational Medicine, 11(481), eaat9223. Doi: 10.1126/scitranslmed.aat9223
  14. Hughes H.K., Mills Ko E., Rose D., & Ashwood P. (2018). Immune dysfunction and autoimmunity as pathological mechanisms in autism spectrum disorders. Frontiers in Cellular Neuroscience, 12, 405. Doi: 10.3389/fncel.2018.00405
  15. McElhanon B.O., McCracken C., Karpen S., & Sharp W.G. (2014). Gastrointestinal symptoms in au-tism spectrum disorder: A meta-analysis. Pediatrics, 133(5), 872–883. Doi: 10.1542/peds.2013-3995
  16. Nugent B.M., & Bale T.L. (2015). The omniscient placenta: Metabolic and epigenetic regulation of fetal programming. Frontiers in Neuroendocrinology, 39, 28–37. Doi: 10.1016/j.yfrne.2015.09.001
  17. Rogers S.J., & Dawson G. (2010). Early Start Denver Model for young children with autism: Promoting lan-guage, learning, and engagement. New York, NY: Guilford Press.
  18. Sporns O., Tononi G., & Kötter R. (2005). The human connectome: A structural description of the hu-man brain. PLoS Computational Biology, 1(4), e42. Doi: 10.1371/journal.pcbi.0010042
  19. Strohman R.C. (2003). Genetic determinism as a failing paradigm in biology and medicine: Implications for health and wellness. Journal of Social Work Education, 39(2), 169–191. Doi: 10.1080/10437797.2003.10779130
  20. Vargas D.L., Nascimbene C., Krishnan C., Zimmerman A.W., & Pardo C.A. (2005). Neuroglial activa-tion and neuroinflammation in the brain of patients with autism. Annals of Neurology, 57(1), 67–81. Doi: 10.1002/ana.20315
  21. Wild C.P. (2005). Complementing the genome with an «exposome»: the outstanding challenge of envi-ronmental exposure measurement in molecular epidemiology. Cancer Epidemiology, Biomarkers & Prevention, 14(8), 1847–1850. Doi: 10.1158/1055-9965.EPI-05-0456
  22. Woo V., & Alenghat T. (2022). Epigenetic regulation by gut microbiota. Gut Microbes, 14(1), 2022407. Doi: 10.1080/19490976.2021.2022407
  23. Zheng M., Wei X., Chen R., Wang C., & Xin L. (2026). The gut microbiota and autism spectrum disor-der: Current research and therapeutic insights. Behavioral Sciences, 16(4), 559. Doi: 10.3390/bs16040559