Tic disorders: when habit forming neural systems form habits of their own?

Tourette syndrome (TS), obsessive-compulsive disorder (OCD) and related conditions are prevalent disorders affecting as many as 0.3-3% of the population. They are frequently chronic and can be associated with marked impairment and disability. Although clinical care has improved over the past decade, a significant number of patients fail to respond adequately or experience intolerable side effects. The etiology of these disorders is unknown. Compelling evidence suggests that the vulnerability to develop TS and OCD is mediated by both genetic and environmental factors, and that neural systems located in the basal ganglia and functionally related brain structures are involved in their pathogenesis. Based on explicit models of pathogenesis for TS and OCD and building on work accomplished over the past two decades, an array of clinical, neuropsychological, genetic, neuroimaging, epidemiological neurobiological, and treatment studies have been completed or are underway at the Child Study Center at Yale University. A multidisciplinary team of investigators has joined forces to test specific hypotheses through the integration and translation of basic and clinical neuroscience research. All subjects have been studied using identical clinical, neuropsychological, genetic, neurobiological, and pharmacological techniques. Current conceptualizations of TS have been shaped by advances in clinical phenomenology, genetics, systems neuroscience and the emerging understanding of the role of the basal ganglia in implicit learning and habit formation, neuroimmunology and psychopharmacology. An appreciation of the premonitory urges that precede tics and temporal dynamics of tics have provided useful viewpoints from which to regard the natural history of TS. While the long-term outcome of TS can be relatively benign, the presence of comorbid conditions such as attention deficit/hyperactivity disorder (ADHD), OCD or a major affective disorder can have lasting untoward consequences. The identification of susceptibility genes in TS will doubtless point in new therapeutic directions for treatment, as will the characterization of the putative autoimmune mechanisms active in subgroup of patients. Continued success in functional in vivo neuroimaging studies will lead to the targeting of specific brain circuits for more intensive study. Although ideal anti-tic therapies are not available, recently completed clinical trials with alpha-adrenergic agents and atypical neuroleptics are encouraging. Given these developments, TS can be considered a model disorder to study the dynamic interplay of genetic vulnerabilities, epigenetic events, and neurobiological systems active during early brain development. It is likely that the research paradigms utilized in these studies and many of the empirical findings resulting from them, will be relevant to other disorders of childhood onset and to our understanding of normal development.