White Matter Abnormalities In Patients With Obsessive-Compulsive Disorder And Their First-Degree Relatives: A Diffusion Tensor Imaging Study

Object：On the one hand, to investigate the microstructural integrity of whitematter in patients with obsessive-compulsive disorder(OCD) by diffusiontensor imaging(DTI)，and try to make further understanding of the mechanismof nosogenesis of OCD; On the other hand, to explore whether suchabnormalities occur in unaffected first-degree relatives of patients, indicatingthey may be endophenotypes representing increased genetic risk for OCD.Materials and Methods:We enrolled patients with OCD according to the diagnosis criteria ofDSM·IV-TR and CCMD-3Handbook. The patients also gave consent for afirst-degree relative to be contacted (preferably a similarly aged sibling,alternatively a child or parent: five relatives were siblings, seven were parents,and four were children). At the same time, healthy controls whose age,genderand educational level matched were enrolled．All subjects were assessed usingYale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton AnxietyRating Scale (HAMA), Hamilton Depression Rating Scale (HAMD). Y-BOCSscores≥16and HAMD scores＜21were needed in OCD. All the participantswere excluded if they had a history of serious head injury, substance abuse, orepilepsy or contraindications to MRI. Additionally, all participants were freefrom DSM-IV axis I disorders (including major depressive disorder andTourette’s syndrome).After a complete description of the study, writteninformed consent was obtained from all participants. Then, all subjects accepted the MRI-DTI scans． First of all, ROIs were placed by anexperienced neuroimaging investigator using a DTI-MRI atlas of human whitematter for determining fiber tract orientation using DTI Studio/ROI Editorsoftware for15OCD patients and15healthy controls, to find whether therewere white matter abnormal areas; Group comparisons including all ROIs forthe FA values were done using Student’s t-tests (P<0.05).In patients,correlation analyses were conducted using the parametric Pearson’scoefficient followed by confirmatory non-parametric Spearman’s coefficientto investigate relations between DTI-derived metrics (FA) and clinicalmetrics (Y-BOCS).Secondly, we used voxel-based analysis to compare FAvalue in whole brain white matter with the normal controls respectively：(1)the OCD group with the normal control group;(2) the first-degree relativegroup with the normal control group.The areas with continous30voxels andabove were considered be a significant different area(P<0.001, uncorrected,2tailed).At last, we used Xjview soft to show common areas of abnormality inwhole brain white matter both in OCD patients and their first-degree relatives.FA value represents the internal level of consistency degree of fiber structure,which was the most used in brain imaging reflecting the change of whitematter fiber microstructure.Results:Our results indicate that:(1) compared with the normal controls, OCDpatients showed lower FA values in the right anterior cingulate and therostrum of corpus callosum, and we also found higher FA values in the leftanterior cingulate and right orbital frontal cortex in OCD patients. Nosignificant correlations between FA value and severity of OCDsymptoms(Y-BOCS score) were found (P>0.05).(2) Both the16OCDpatients and their unaffected first-degree relatives exhibited significantdecrease in FA values in the left midfrontal gyrus, the right temporal gyrusand increase in FA values in the right midoccipital gyrus and bilateralcerebellum.Conclusions: 1. Our study found that patients with OCD exist abnormalities of FAvalues in the bilateral anterior cingulate, bilateral prefrontal lobe, the rostrumof corpus callosum, the right temporal lobe, the right occipital lobe andbilateral cerebellum, indicating that OCD is associated with white matterabnormalities supporting the hypothesis of abnormality in the loop oforbitfrontal-striatum. what‘s more, other regions such as the posterior brainregions may also have very important effects in the occurrence anddevelopment in OCD.2. There was no significant correlation between abnormal FA values andseverity of OCD symptoms.3. We identified whiter matter abnormalities also exist in the unaffectedfirst-degree relatives of OCD patients in the left prefrontal lobe, righttemporal lobe, right occipital lobe and bilateral cerebellum, suggesting thatthey are white matter endophenotypes representing markers of increasedgenetic risk for OCD.