Proceedings of the National Academy of Sciences (LXI). 2026Monoamine transporters are critical regulators of neurotransmission during early brain development. The dopamine transporter (DAT), encoded by SLC6A3, and the serotonin transporter (SERT), encoded by SLC6A4, modulate extracellular monoamine levels via sodium-and chloride-dependent reuptake. This study integrates developmental neuroscience literature with secondary functional neuroimaging analysis of the OpenNeuro dataset (ds001420) to investigate how monoaminergic systems contribute to neural maturation. Functional MRI data were analyzed across ventral striatum, prefrontal cortex (PFC), amygdala, and hippocampus. Linear regression revealed a significant age-dependent increase in ventral striatal activation (β = 0.045, SE = 0.008, p < 0.001, R² = 0.52). ANOVA demonstrated significant developmental differences in PFC activation (F(2,87) = 11.4, p < 0.0001). Functional connectivity analyses showed strengthening frontostriatal coupling (r = 0.62, p < 0.001). These findings support a model of delayed dopaminergic maturation alongside earlier serotonergic stabilization. Importantly, loss-of-function mutations in SLC6A3 are linked to dopamine transporter deficiency syndrome (DTDS), highlighting the clinical relevance of transporter dysfunction. Overall, monoamine transporters play a central role in shaping neurodevelopmental trajectories.