Modest Stimulant Benefit and Larger Gains from Structural Synaptic Restoration Among Untreated Childhood-Diagnosed ADHD: A Reinforcement-Learning Simulation

Many adults with ADHD, especially those diagnosed in childhood, do not achieve full symptom relief with first-line stimulant medication, even when treatment is adequate. This pattern suggests that differences in treatment response may reflect underlying biological variation rather than medication failure alone. Recent molecular findings indicate that ADHD may follow different developmental pathways depending on age at diagnosis, with childhood-diagnosed cases showing stronger signals related to microglial activity, immune pathways, and synaptic pruning.To examine how these differences might shape long-term treatment outcomes, we developed a reinforcement-learning model based on an early-diagnosed ADHD profile. The model was initialized with marked synaptic sparsity and persistent internal noise, then trained on a four-choice decision task across five developmental stages of increasing cognitive demand. Four treatment conditions were tested across 20 independent runs: no treatment, stimulant treatment beginning in childhood, stimulant treatment beginning in adulthood, and adult stimulant treatment combined with a synaptic regrowth mechanism.The untreated model reached 26.14% accuracy in adulthood. Childhood-onset stimulant treatment produced a modest improvement to 29.58%, while stimulants introduced only in adulthood resulted in little additional benefit at 26.58%. The largest improvement was observed when adult stimulants were combined with synaptic regrowth, increasing accuracy to 39.43%. This was also the only condition that reversed the model's extreme synaptic sparsity, whereas reductions in internal stress-related noise were similar across all stimulant-treated conditions.These results provide a computational explanation for why some adults with childhood-diagnosed ADHD may respond only partially to standard stimulants. If early developmental pruning leaves lasting structural underconnectivity, then dopaminergic treatment alone may reduce noise without restoring the underlying network. Age at diagnosis may therefore act as a practical marker of a biologically distinct subtype of ADHD, one that may benefit more from treatments aimed at synaptic restoration than from stimulant therapy alone.