Neurobiological issues in Tourette's syndrome

Tourette's syndrome (TS) is characterized by the presence of chronic motor and vocal tics and is commonly associated with a variety of behavioral and emotional problems. In his manuscript published in 1885, Gilles de la Tourette (1) noted no anatomical or pathological cause in the syndrome that bears his name and referred scientists interested in pursuing pathophysiological mechanisms to the field of psychology. Although much information has been acquired pertaining to the underlying anatomy and physiology of tic disorders, many perplexing questions remain. The fact that tics resolve or diminish in many individuals suggests the possibility of a developmental alteration rather than a fixed or progressive disorder. There is convincing evidence that cortico-striatal-thalamo-cortical (aka frontal-subcortical) pathways are involved in the expression of TS and its accompanying neuropsychiatric problems, but the precise location(s) remains speculative. A twopathway model of circuits (direct and indirect) through the basal ganglia is often cited in discussions of hyperkinetic and hypokinetic movement disorders, but this concept represents an oversimplification of complex interactions and newer models have been proposed. Intrinsic neurotransmitters utilized within cortico-striatal-thalamo-cortical pathways are well established, but each has its own complex system of message transduction as well as MD: KURLAN, JOB: 03329, PAGE: interaction with other transmitter agents. Although TS is generally accepted as a genetic disorder, environmental factors, such as streptococci infection, have been proposed as contributing factors.