White matter microstructure and connectivity in patients with obsessive-compulsive disorder and their unaffected siblings.

OBJECTIVE: We aimed to examine white matter microstructure and connectivity in individuals with obsessive-compulsive disorder (OCD) and their unaffected siblings, relative to healthy controls. METHODS: Diffusion-weighted magnetic resonance imaging (dMRI) scans were acquired in 30 patients with OCD, 21 unaffected siblings, and 31 controls. We examined white matter microstructure using measures of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Structural networks were examined using network-based statistic (NBS). RESULTS: Compared to controls, OCD patients showed significantly reduced FA and increased RD in clusters traversing the left forceps minor, inferior fronto-occipital fasciculus, anterior thalamic radiation, and cingulum. Furthermore, the OCD group displayed significantly weaker connectivity (quantified by the streamline count) compared to controls in the right hemisphere, most notably in edges connecting subcortical structures to temporo-occipital cortical regions. The sibling group showed intermediate streamline counts, FA and RD values between OCD and healthy control groups in connections found to be abnormal in patients with OCD. However, these reductions did not significantly differ compared to controls. CONCLUSION: Therefore, siblings of OCD patients display intermediate levels in dMRI measures of microstructure and connectivity, suggesting white matter abnormalities might be related to the familial predisposition for OCD.

Cortical thickness and surface area in patients with obsessive compulsive disorder and their unaffected siblings.

Little is known about the underlying neurobiological mechanisms in patients with obsessive-compulsive disorder (OCD). We aimed to examine cortical thickness and surface area in individuals with OCD and their unaffected siblings, comparing them to healthy controls. 30 patients with OCD, 21 unaffected siblings (SIB) and 30 controls underwent structural magnetic resonance imaging. Structural images were analyzed using the FreeSurfer software package (version 6.0). Compared to healthy controls, both OCD and SIB groups showed significantly lower cortical thickness in the right anterior insula. Surface areas of the superior frontal gyrus, paracentral gyrus and precuneus of the right hemisphere were also reduced in OCD patients compared to controls. There were no significant differences in cortical thickness and surface area between the OCD and SIB groups. We did not detect any significant differences in subcortical volumes between groups. Lower cortical thickness in the right anterior insula in both OCD patients and unaffected siblings may represent a potential structural endophenotype for OCD.

Fronto-striatal structures related with model-based control as an endophenotype for obsessive-compulsive disorder.

Recent theories suggest a shift from model-based goal-directed to model-free habitual decision-making in obsessive-compulsive disorder (OCD). However, it is yet unclear, whether this shift in the decision process is heritable. We investigated 32 patients with OCD, 27 unaffected siblings (SIBs) and 31 healthy controls (HCs) using the two-step task. We computed behavioral and reaction time analyses and fitted a computational model to assess the balance between model-based and model-free control. 80 subjects also underwent structural imaging. We observed a significant ordered effect for the shift towards model-free control in the direction OCD > SIB > HC in our computational parameter of interest. However less directed analyses revealed no shift towards model-free control in OCDs. Nonetheless, we found evidence for reduced model-based control in OCDs compared to HCs and SIBs via 2nd stage reaction time analyses. In this measure SIBs also showed higher levels of model-based control than HCs. Across all subjects these effects were associated with the surface area of the left medial/right dorsolateral prefrontal cortex. Moreover, correlations between bilateral putamen/right caudate volumes and these effects varied as a function of group: they were negative in SIBs and OCDs, but positive in HCs. Associations between fronto-striatal regions and model-based reaction time effects point to a potential endophenotype for OCD.