The links between histaminergic neurotransmission and tics, suggested by our genetic findings, are further supported by previous studies of pharmacologic agents that target the presynaptic autoreceptor H3R. Highly selective antagonists and inverse agonists increase histaminergic neurotransmission and decrease both the locomotor effects of stimulants and the behavioral sensitization seen in rodents.18-20 Several such compounds have been developed and are under investigation in humans. The convergence of our findings with data from mouse models and the presence of therapeutic agents that would be expected to moderate deficits in histaminergic neurotransmission suggest an approach to treatment that may prove relevant not just to our rare kindred but also to others with Tourette's syndrome.
