Is Peripheral Nerve Hyperexcitability More Common in Adults with ADHD? A Hypothesis-Generating Perspective

Attention-deficit/hyperactivity disorder (ADHD) in adults involves heterogeneous alterations of catecholaminergic signalling and inhibitory motor control. Dopamine and gamma-aminobutyric acid (GABA) interact within cortical and subcortical networks, while transcranial magnetic stimulation studies suggest altered cortical inhibition in some ADHD populations. These observations raise a separate, unresolved question: could adults with ADHD have a higher prevalence of peripheral nerve hyperexcitability (PNH) than adults without ADHD? This perspective critically distinguishes central motor disinhibition from spontaneous peripheral motor-axonal activity and examines clinical phenotypes, electrophysiological findings, medication effects and rare genetic disorders. The literature identified provides indirect mechanistic support and isolated clinical observations but does not establish an increased prevalence of electrophysiologically confirmed peripheral nerve hyperexcitability in typical adult ADHD. Negative cortical findings, non-uniform GABA measurements and substantial confounding further constrain interpretation. Three alternative explanatory models are considered: independent coexistence, shared biological predisposition, and indirect influences mediated by treatment, sleep or stress. A testable research framework combines standardised clinical phenotyping with electromyography, peripheral nerve stimulation and, where feasible, complementary central and axonal excitability measurements. The epidemiological hypothesis must be tested before neurotransmitter mechanisms are inferred. Appropriately controlled studies, particularly involving medication-naïve adults, are required; the present hypothesis does not justify routine electrophysiological screening of all adults with ADHD.