Predictive Biomarkers of Conversion to Tourette Syndrome in Children With New-Onset Tics

Up to 30% of all children will have a tic at some point. However, tics that last a whole year (or more) occur in only 3% of the population. Thus tic persistence may be more unusual than tic onset, yet almost no data exist on which people with recent-onset tics go on to be diagnosable with Tourette syndrome or chronic tic disorder, versus those whose tics are only transient.

The overall goal of this research is to identify, prospectively, what imaging, clinical or neuropsychological features of children who just recently started ticcing will go on to develop a chronic tic disorder (including Tourette syndrome). Hypotheses are derived primarily from studies of patients with established tic disorders.

Aim 1. Study pathophysiology of recent-onset tics. Aim 1a. Identify clinical, neuropsychological, and brain imaging features that differentiate children with recent tic onset ("New Tics" group) from tic-free controls. We will test a priori hypotheses including tic suppression, inattentiveness, caudate nucleus volume, tic severity, and premonitory urges (see "Summary of hypotheses" on the 3rd page of Research Strategy). Secondary analyses will apply support vector machine (SVM) learning to a rich set of data to discover novel, multivariate differences in the New Tics group [3,45]. These data will also include tic phenomenology, psychiatric diagnosis, habit learning, motor dexterity, structural MRI, perfusion MRI, and resting state functional connectivity fMRI (rs-fcMRI).

Aim 1b. Compare New Tics subjects to a group of children who are matched for age but have already had tics for ≥1 year ("Existing TS/CTD"). Since both groups have tics, this comparison will highlight abnormalities that cannot be explained by the mere current presence of tics, including markers of chronicity or adaptation.

Aim 2. Prospective study of tic remission. We will re-evaluate New Tics subjects at the 1-year anniversary of tic onset (the accepted duration criterion for diagnosis of TS/CTD). Our pilot data show good variability in the change in tic symptom severity (i.e., change in YGTSS total tic score from baseline to followup: ΔTTS), so ΔTTS will be the primary dependent variable. We focus on outcome as a continuous variable because no reliable estimate exists for how many New Tics subjects will remit versus go on to diagnosis with TS/CTD. Remission rate also depends on definition and on the thoroughness of the follow-up evaluation [4].