Catecholamine-related gene expression in blood correlates with tic severity in tourette syndrome

Abstract

Tourette syndrome (TS) is a heritable disorder characterized by tics that are decreased in some patients by treatment with alpha adrenergic agonists and dopamine receptor blockers. Thus, this study examines the relationship between catecholamine gene expression in blood and tic severity. TS diagnosis was confirmed using Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and tic severity measured using the Yale Global Tic Severity Scale (YGTSS) for 26 un-medicated subjects with TS. Whole blood was collected and Ribonucleic acid (RNA) processed on Affymetrix Human Exon 1.0 ST arrays. An Analysis of Covariance (ANCOVA) identified 3627 genes correlated with tic severity (p<0.05). Searches of Medical Subject Headings, Gene Ontology, Allen Mouse Brain Atlas, and PubMed determined genes associated with catecholamines and located in the basal ganglia. Using GeneCards, PubMed, and manual curation, seven genes associated with TS were further examined: DRD2, HRH3, MAOB, BDNF, SNAP25, SLC6A4, and SLC22A3. These genes are highly associated with TS and have also been implicated in other movement disorders, Attention Deficit Hyperactivity Disorder (ADHD), and Obsessive–Compulsive Disorder (OCD). Correlation of gene expression in peripheral blood with tic severity may allow inferences about catecholamine pathway dysfunction in TS subjects. Findings built on previous work suggest that at least some genes expressed peripherally are relevant for central nervous system (CNS) pathology in the brain of individuals with TS.