Correlations of gene expression with ratings of inattention and hyperactivity/impulsivity in tourette syndrome: a pilot study

BACKGROUND: Inattentiveness, impulsivity and hyperactivity are the primary behaviors associated with attention-deficit hyperactivity disorder (ADHD). Previous studies showed that peripheral blood gene expression signatures can mirror central nervous system disease. Tourette syndrome (TS) is associated with inattention (IA) and hyperactivity/impulsivity (HI) symptoms over 50% of the time. This study determined if gene expression in blood correlated significantly with IA and/or HI rating scale scores in participants with TS. METHODS: RNA was isolated from the blood of 21 participants with TS, and gene expression measured on Affymetrix human U133 Plus 2.0 arrays. To identify the genes that correlated with Conners’ Parents Ratings of IA and HI ratings of symptoms, an analysis of covariance (ANCOVA) was performed, controlling for age, gender and batch. RESULTS: There were 1201 gene probesets that correlated with IA scales, 1625 that correlated with HI scales, and 262 that correlated with both IA and HI scale scores (P<0.05, |Partial correlation (r(p))|>0.4). Immune, catecholamine and other neurotransmitter pathways were associated with IA and HI behaviors. A number of the identified genes (n=27) have previously been reported in ADHD genetic studies. Many more genes correlated with either IA or HI scales alone compared to those that correlated with both IA and HI scales. CONCLUSIONS: These findings support the concept that the pathophysiology of ADHD and/or its subtypes in TS may involve the interaction of multiple genes. These preliminary data also suggest gene expression may be useful for studying IA and HI symptoms that relate to ADHD in TS and perhaps non-TS participants. These results will need to be confirmed in future studies.