Widespread changes of white matter microstructure in obsessive-compulsive disorder: effect of drug status

Diffusion tensor imaging (DTI) allows the study of white matter (WM) structure. Literature suggests that WM structure could be altered in obsessive-compulsive disorder (OCD) proportional to the severity of the disease. Heterogeneity of brain imaging methods, of the studied samples, and of drug treatments make localization, nature, and severity of the WM abnormalities unclear. We applied Tract-Based Spatial Statistics (TBSS) of DTI measures to compare fractional anisotropy (FA), mean, axial, and radial diffusivity of the WM skeleton in a group of 40 consecutively admitted inpatients affected by severe OCD (18 drug-naive, and 22 with an ongoing drug treatment) and 41 unrelated healthy volunteers from the general population. Data were analyzed accounting for the effects of multiple comparisons, and of age, sex, and education as nuisance covariates. Compared to controls, OCD patients showed a widespread reduction of FA with a concurrent increase of mean and radial diffusivity. In no brain areas patients had higher FA or lower diffusivity values than controls. These differences were observed in drug-treated patients compared to drug-naive patients and healthy controls, which in turn did not differ among themselves in any DTI measure. Reduced FA with increased mean and radial diffusivity suggests significant changes in myelination of WM tracts, without axonal loss. Drug treatments could modify the structure of cell membranes and myelin sheaths by influencing cellular lipogenesis, cholesterol homeostasis, autophagy, oligodendrocyte differentiation and remyelination. Changes of DTI measures in drug-treated OCD patients could reflect pathophysiological underpinnings of OCD, or a yet unexplored part of the mechanism of action of drugs.