Adolescent dopamine development: connecting experience with vulnerability or resilience to psychiatric disease
2021
Abstract Adolescence is a period of dynamic physical, hormonal, and behavioral changes that coincide with the transition from a juvenile state to independence. In humans, this period has historically been framed as occurring between 12 and 20 years of age, although advances in research indicate that the boundaries are more fluid than previously considered. Adolescence is also a time when psychiatric conditions, including major depression, addiction, and schizophrenia, tend to emerge. These disorders involve the dysfunction of the prefrontal cortex—a brain region still maturing in adolescence—and are kindled by environmental insult. Adverse experiences at this age, such as exposure to abused drugs, appear to disrupt prefrontal cortex development and to precipitate the onset of symptoms. Understanding the adolescent neurodevelopmental program, and the cellular and molecular processes by which its subtle perturbation alters risk for psychopathology, is essential for developing and/or improving prevention and intervention strategies targeted to adolescent boys and girls. In this chapter we describe the maturational changes occurring in the adolescent prefrontal cortex and the organizational role that dopaminergic innervation plays in this process. We outline studies in animal models describing how adolescent experiences alter dopamine trajectories, shaping prefrontal cortex development. We discuss how guidance cue genes, which are the first-known molecular regulators of adolescent neurodevelopment, organize the targeting and growth of dopamine pathways, are regulated by experience in adolescence, and are altered in psychiatric disorders. Environmental regulation of development is a two-way street: experiences can be harmful or beneficial; guidance cues are therefore promising sites for targeted intervention to promote healthy brain development in adolescence.
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