The psychoneuroimmuneendocrine system, epigenetics, and the integration of morphogenetic fields: a systematic review of their role in unconscious ontogenesis

Background Unconscious/implicit processes are increasingly conceptualized as biologically instantiated, multisystem regulatory functions rather than purely psychological constructs. This review examines whether an integrative framework linking psychoneuroimmuneendocrine (PINE) regulation, epigenetic mechanisms, and principles of morphogenetic organization can help organize evidence relevant to “unconscious ontogenesis.” Objective To systematically review empirical evidence on PINE-related regulation and epigenetic modifications associated with unconscious/implicit processing, and to evaluate developmental morphogenetic principles as an organizing conceptual template (distinct from direct evidence of adult unconscious processing). Methods We searched PubMed/MEDLINE, Web of Science, and Scopus (1990–2024), plus gray literature sources, for experimental and observational studies, systematic reviews/meta-analyses, and a limited set of theoretical/historical works used only for conceptual context. Unconscious/implicit processing was operationalized as outcomes measured with implicit or non-conscious paradigms (behavioral tasks) and/or biological proxies of automatic regulation (e.g., autonomic, endocrine, immune, epigenetic, or neuroimaging markers) when the study design or authors’ framework explicitly linked these measures to implicit/unconscious processing. Risk of bias was assessed with RoB 2, ROBINS-I, Newcastle-Ottawa Scale, and GRADE as appropriate; theoretical works were excluded from quantitative synthesis and bias assessment. No language restrictions were applied at the search stage; non-English studies were screened via available abstracts and full texts were used when accessible. Results From 1,245 records identified, 58 studies met inclusion criteria; 30 contributed to the quantitative synthesis. Evidence most consistently supported associations between PINE-system dysregulation and stress-adaptive behavioral/physiological outcomes, as well as between environmental exposures and epigenetic modifications relevant to neurodevelopment and stress regulation. In contrast, morphogenetic fields and morphogen-gradient principles were supported as established developmental biology mechanisms but did not provide direct quantitative evidence for adult unconscious processes, and were therefore treated exclusively as a conceptual organizational layer. Conclusion Available evidence supports PINE regulation and epigenetic mechanisms as empirically grounded contributors to multisystem integration relevant to unconscious/implicit regulation. Morphogenetic principles are best interpreted as a developmental organizing template rather than as empirically supported mechanisms of unconscious processing, generating testable hypotheses for future prospective and mechanistic studies. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier [CRD42024594352].