Peer-reviewed article
The developmental dopamine trajectory hypothesis of ADHD across the lifespan
Raly James Perez Custodio, Stephan Getzmann, Edmund Wascher, Michael C. Pan, Florence Ingred Samante et al. ·
Summary
Written by AI, not yet AICS's view · claude-sonnet-5-5This paper puts forward a theoretical framework, called the Developmental Dopamine Trajectory Hypothesis, to explain why ADHD looks different in childhood, adolescence and adulthood. It proposes that a problem with dopamine regulation, linked to the dopamine transporter (DAT), affects brain circuits differently depending on how mature those circuits are. Childhood symptoms are linked to developing frontostriatal networks, adolescent symptoms to reward and emotion circuits, and adult symptoms to mature control and motivation systems. The authors say the framework draws on longitudinal clinical, imaging, electrophysiology, drug, genetic and animal-model evidence. It offers predictions to be tested in future research rather than testing an intervention.
Key points
- ADHD is increasingly seen as a lifespan neurodevelopmental disorder, but why its symptoms change over development is poorly understood.
- Childhood ADHD is typically marked by hyperactivity, impulsivity and inattention, while later symptoms shift toward reward dysregulation, executive dysfunction, motivational problems, internal restlessness and changing emotional dysregulation.
- The central proposal is that the effects of DAT-related dopamine dysregulation depend on the developmental state of the brain circuits it acts on.
- The framework predicts differences in symptom trajectories, developmental biomarkers and treatment responsiveness across ages.
- Adolescence is proposed as a critical neurodevelopmental transition period.
Limitations
This is a hypothesis paper, not an empirical study, so it does not test its claims or measure outcomes in children. The abstract does not name any country or population studied, and it gives no evidence on interventions or on child well-being in specific settings.
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized as a lifespan neurodevelopmental disorder, yet the mechanisms underlying its changing clinical presentation across development remain poorly understood. Although childhood ADHD is typically characterized by hyperactivity, impulsivity, and inattention, symptom expression frequently evolves during adolescence and adulthood toward greater reward dysregulation, executive dysfunction, motivational impairment, internal restlessness, and changing manifestations of emotional dysregulation. Existing neurobiological models have substantially advanced understanding of ADHD pathophysiology but provide limited explanation for how symptom continuity can coexist with developmental changes in clinical expression. Here, we propose the Developmental Dopamine Trajectory Hypothesis, which posits that DAT related dopaminergic dysregulation may interact with the sequential maturation of frontostriatal, mesolimbic, and mesocortical circuits to contribute to developmental changes in ADHD symptom expression across the lifespan. A central proposition of the framework is that the functional consequences of DAT related dopaminergic dysregulation depend on the developmental state of the neural circuits on which it acts. Within this framework, childhood manifestations may arise primarily from interactions between dopaminergic vulnerability and developing frontostriatal networks, adolescent manifestations from increasing involvement of reward and emotion related circuitry, and adult manifestations from interactions with mature executive control and motivational systems. By integrating evidence from longitudinal clinical studies, neuroimaging, electrophysiology, pharmacology, genetics, and translational DAT models, the proposed framework provides a mechanistic model for how developmental changes in neural circuit state may contribute to changing symptom expression despite continuity of underlying neurobiological vulnerability. The hypothesis generates testable predictions regarding longitudinal symptom trajectories, developmental biomarker changes, potential developmental differences in treatment responsiveness, and adolescence as a proposed critical neurodevelopmental transition period. Reconceptualizing ADHD through a developmental dopaminergic framework places developmental timing and neural circuit maturation at the center of the relationship between dopaminergic vulnerability and clinical phenotype, providing a basis for future longitudinal, mechanistic, and developmentally informed research across the lifespan.