Genetic Variation, Pubertal Maturation, and Ventral Striatal Development in Adolescence: An Integrative Framework

Adolescence represents a critical period marked by profound changes in social contexts, biological maturation, neural reorganization, social-cognitive functioning, and the onset of psychopathology. During this sensitive window, developmental outcomes become increasingly heterogeneous. Intertwined processes, including genetic influences, pubertal maturation, and neurodevelopment, likely contribute to this variation. However, research on adolescent development in the past decades has often examined genetic variation, puberty, and neurodevelopment in isolation, with limited integration of how genetic and pubertal processes may interact to shape the developing brain. This is particularly important for understanding the ventral striatum (VS), which is sensitive to genetic and pubertal modulation and underlies a broad range of behaviors, including salient motivation, risk-taking, substance use, peer influence susceptibility, and psychopathology. In this review, we synthesized evidence from developmental neuroscience, neuroendocrinology, and behavioral genetics to propose a Gene-Puberty-Brain Cascade framework focused on VS development. We reviewed evidence that VS structure, activation, and network undergo significant reorganization during adolescence and are associated with both pubertal and genetic variation. Building on evidence that genetic variation is closely related to pubertal development (e.g., onset, timing, tempo, hormonal sensitivity, and stage), we argue that genetic and pubertal processes may dynamically interact to shape VS development, which underlies heterogeneity in adolescent development. Finally, we highlight how researchers can leverage large-scale longitudinal cohorts (e.g., ABCD), advanced longitudinal and statistical models, and multimodal computational neuroimaging frameworks to understand this process. This integrative framework offers a developmentally grounded understanding of how gene-puberty interplay may contribute to heterogeneity in adolescent development.