Differential white matter involvement in drug-naïve children with obsessive-compulsive disorder and Tourette syndrome

Background/Objective: Early-onset obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are frequently associated conditions. Evidence is accumulating in support of a common genetic liability of the two disorders [1-2], which has raised new interest for their comorbidity (TS+OCD), both in terms of clinical course and response to treatment. However, little is known on the relationship between OCD and TS in terms of early-stage white matter development and organisation. In this study we investigated white matter changes in drug-naïve children with OCD, TS and TS+OCD, to shed light on primary neural underpinnings and specifically characterise those of comorbid TS+OCD. Methods: Fifty-one drug-naïve participants (mean age 10.2 years, SD=0.5) underwent magnetic resonance imaging (MRI) examination. By means of diffusion tensor imaging (DTI) analysis, white matter microstructure from pure TS (N=16), TS+OCD (N=14), OCD (N=10) children and 11 age-matched controls was investigated in five tracts of interest, i.e., the cortico-spinal tract (CST), the anterior thalamic radiations (ATR), the inferior longitudinal fasciculus (ILF), the corpus callosum (CC), and the cingulum. Tract selection was based on previous studies showing consistent white matter alterations in TS or OCD [3-6]. DTI changes were correlated to symptom severity assessed through the Yale Global Tic Severity Scale (YGTSS) and Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Results: TS and TS+OCD exhibited a shared pattern of DTI changes compared to controls, i.e., an increased fractional anisotropy (FA) within CST, ATR, ILF and CC. FA values showed a negative correlation with tic severity in the TS/TS+OCD group, suggesting an inverse relationship between white-matter organization and disorder expression. Within the same white-matter bundles, OCD showed an inverse pattern of microstructural abnormalities, i.e., decreased FA in respect to controls. FA values were negatively correlated to obsessive-compulsive symptoms, indicating that more severe clinical phenotypes were underpinned by less organized white-matter in OCD children. Conclusions: Our study highlights differential white matter involvement in pediatric TS/TS+OCD as opposed to OCD. Our findings extend our prior observations on functional connectivity [7] and cerebellar involvement [8] in the two disorders. Compared to the normative population, the overall TS group showed a unique pattern of increased FA in callosal bundles and in tracts linking the frontal, occipital and temporal cortices with each other and with the thalamus. Conversely, children with OCD showed widespread reduced organization of callosal, temporo-occipital and fronto-thalamic bundles. Findings in TS may be regarded as neuroadaptive changes in response to tic pathophysiology, while in OCD they may derive from delay or damage to white matter development, but confirmation of these possibilities awaits longitudinal studies. The observation of shared DTI correlates of TS and TS+OCD gives preliminary support to the conceptualisation of TS+OCD as a peculiar subtype of TS. By characterising and differentiating early-stage neural underpinnings of OCD and TS, targeted interventions may be developed.