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

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 patients with OCD and their unaffected first-degree relatives (UFDRs).

METHODS

Diffusion tensor imaging data were acquired from 32 patients with OCD (21 male), 32 UFDRs (16 male), and 32 healthy control subjects (16 male). White matter tracts in the goal-directed and habitual networks were reconstructed with seed-based probabilistic tractography. Partial least squares path modeling was used to measure the covariation between white matter connectivity, psychiatric symptoms, and cognitive flexibility.

RESULTS

Patients with OCD showed reduced connectivity in the fiber tracts within the goal-directed but not within the habitual network compared with healthy control subjects. Using partial least squares path modeling, patients' symptoms were negatively associated with connectivity within the goal-directed but not within the habitual network. Cognitive flexibility was correlated negatively with caudate-dorsolateral prefrontal cortex tracts in patients with OCD. UFDRs 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 patients with OCD. Similar alterations in the goal-directed network are present in UFDRs. The impaired goal-directed system may be an endophenotype of OCD.