From Genetic Determinism to Epigenetic Regulation: Paradigm Shifts in the Understanding of Neurodevelopmental Disorders

TL;DR

This paper explores how epigenetics is changing our understanding of neurodevelopmental disorders by linking genes, environment, and health outcomes.

Contribution

The paper synthesizes current evidence on shared mechanisms in neurodevelopmental disorders and highlights the role of epigenetics and environment.

Findings

Epigenetic mechanisms mediate the interaction between genetic and environmental factors in neurodevelopmental disorders.

Neurodevelopmental disorders show increasing prevalence and comorbidities, requiring integrated etiological models.

The epigenome acts as a molecular interface between the genome and environmental influences across generations.

Abstract

Over the past two decades, advances in the understanding of epigenetic mechanisms—driven by the rapid expansion of omics technologies—have catalyzed a major paradigm shift in biology: from the genetic determinism and linear causality of the Central Dogma toward the dynamic, networked complexity of systems biology and multilevel regulation. This reconceptualization extends to inheritance itself, highlighting the crucial role of the epigenome as a molecular interface between the genome and the exposome—the cumulative set of internal and external environmental influences experienced across the lifespan. Within this evolving framework, neurodevelopmental disorders exemplify the deep entanglement between genetic predisposition, environmental exposure, and epigenetic modulation. Their increasing global prevalence and frequent comorbidities underscore the need for an integrated etiological understanding that transcends reductionist models. This review tries to synthesize current evidence on the shared molecular and systemic mechanisms underlying neurodevelopmental spectrum disorders and examines how environmental and epigenetic factors jointly shape neurodevelopmental trajectories across generations. Finally, it discusses the broader implications of this paradigm shift for early diagnosis, prevention, and public health policies aimed at fostering healthy brain development in future generations.

Figures