From Early Adversity to Lifespan Mental Health: The Interplay of Metabolism, Genetics, and Brain Plasticity.

Abstract

Early life adverse experience, whether prenatal or postnatal, is a prevalent risk factor for altered trajectories of biological development, often culminating in comorbid metabolic and psychiatric disorders in adulthood, which represent a substantial public health burden. In this article, we review evidence that adversity-induced metabolic reconfiguration, specifically involving insulin sensitivity and glucose homeostasis, disrupts developmental processes in neural circuits governing stress regulation, reward learning, and executive control. We discuss how this "metabolic embedding" contributes to specific psychiatric phenotypes, with an emphasis on immuno-metabolic depression. Furthermore, we examine how genomic information can be leveraged to enhance individual-level prediction of at-risk subjects, moving beyond static polygenic risk scores toward biologically informed metrics such as expression-based polygenic scores. We propose a lifespan framework that integrates metabolic, neurobiological, and genomics to advance precision prevention.