John Rothman

By John Rothman

A growing body of evidence supports a role for catecholaminergic dysfunction in the core symptoms of autism spectrum disorder (ASD). This paper reviews the direct and indirect role of catecholamines on the central and peripheral nervous systems in ASD. Catecholamines innervate every tissue in the body and almost all tracts of the brain, providing a common neurologic regulatory mechanism for all ASD symptoms. Because the morphology of the catecholaminergic synapse is regulated by growth factors that are released contemporaneously with neurotransmitters, an event that results in abnormally large catecholamine release, will also release high levels of growth factors, which can result in the budding and arborization of nerve terminals. Here, we hypothesize that a hypertrophic synaptic morphology can occur in catecholaminergic systems and increase catecholaminergic tone throughout the body, resulting in an imbalance between catecholaminergic neurologic mechanisms and those that oppose them, and consequently pathology. By exerting a presynaptic effect to inhibit tyrosine hydroxylase and thus the synthesis, storage and release of all catecholamines, L1–79 (a tyrosine hydroxylase inhibitor) may diminish neurotransmitter release and its associated growth factors exerting a therapeutic effect on ASD by reducing the hypertrophic morphology of the synapse and bringing catecholamines back into a homeostatic balance with oppositional neurologic and metabolic influences.

Part of the book: Autism Spectrum Disorder