White Matter Alterations of the Goal-Directed System in Obsessive-Compulsive Disorder Patients and Their Unaffected First-Degree Relatives

Abstract Background It has been postulated that the neurobiological mechanism responsible for the onset of symptoms of obsessive-compulsive disorder (OCD), especially compulsive behavior, is related to alterations of the goal-directed and habitual learning systems. However, little is known about whether changes in these learning systems co-occur with changes in the white matter structure of OCD patients and their unaffected first-degree relatives (UFDR). Methods Diffusion tensor imaging (DTI) data were acquired from 32 OCD patients (21 male), 32 UFDR (16 male), and 32 healthy controls (HC) (16 male). White matter tracts in the goal-directed and habitual networks were reconstructed with seed-based probabilistic tractography. Partial least squares path modelling (PLS-PM) was used to measure the covariation between the white-matter connectivity, psychiatric symptoms, and cognitive flexibility. Results OCD patients showed reduced connectivity on the fiber tracts within the goal-directed, but not within the habitual network compared to HC. Using the PLS-PM, patients’ symptoms were negatively associated with connectivity within the goal-directed but not within the habitual network. Cognitive flexibility was correlated negatively with caudate-dlPFC tracts in OCD. UFDR also exhibited reduced white matter connectivity in the goal-directed network. Conclusions These findings suggest that the balance of learning systems in OCD may be disrupted, mainly impairing white matter in the goal-directed network. Alterations of the goal-directed network could explain overt symptoms and impaired cognitive flexibility in OCD patients. Similar alterations in the goal-directed network are present in UFDR. The impaired goal-directed system may be an endophenotype of OCD.