Morphometric Study Of Subcortical Structures In Medication-Free Patients With Obsessive-Compulsive Disorder

Objective:Subcortical nuclei are important components in the pathology model of obsessive-compulsive disorder(OCD),and subregions of these structures subserve different functions that may distinctively contribute to OCD symptoms.Exploration of the subregional-level profile of structural abnormalities of these nuclei is needed to develop a better understanding of the neural mechanism of OCD.Vertex-based shape analysis can reveal local deformation of the subcortical nuclei,together with state-ofart subfields/subregional segmentation algorithms,would benefit the understanding of pathology model of OCD from a subnuclei level.Moreover,gender effect could also contribute to clinical heterogenies of OCD but was rarely studied from psychoradiology point of view.Herein,the current study aims to provide a subnuclei level profile of neuroanatomic alteration of OCD,and taking gender effect into consideration.Materials and Methods:A total of 94 medication-free,non-comorbid OCD patients and 95 age-and sexmatched healthy controls were recruited,and high-resolution T1-weighted MR images were obtained for all participants.The Yale-Brown Obsessive Compulsive Scale(YBOCS)was used to evaluate severity of the OCD symptoms.Hamilton Anxiety Scale(HAMA,14 items)and Hamilton Depression Scale(HAMD,17 items)were used to assess the anxiety and depression levels,respectively.The overall volume and shape of the subcortical nuclei(including the nucleus accumbens,amygdala,caudate,pallidum,putamen and thalamus)were quantified and compared with an automated parcellation approach and vertex-wise shape analysis using FSL-FIRST software.Gender effects in these measurements were also explored with an exploratory subgroup analysis.The hippocampus and amygdala were further segmented into subfields/subnuclei using Free Surfer software.The volumes of subfields/subnuclei were extracted and compared between groups with analysis of covariates,corrected for age,sex and total brain volume.Partial correlation analyses were used to examine the correlation between volumes and clinical measurements.Results:Volumetric analysis showed no significant differences between patients and healthy control subjects.Relative to healthy control subjects,the OCD patients showed an expansion of the lateral amygdala(right hemisphere)and right pallidum.These deformities were associated with illness duration and symptom severity of OCD.Exploratory subgroup analysis by sex revealed amygdala deformity in male patients and caudate deformity in female patients.The volume of right hippocampus was significantly reduced in OCD patients.Follow-up analysis of right hemisphere subfields showed reduced volume in right subiculum,presubiculum,CA2/3,and hippocampal tail,while the volume of right fimbria was increased.Shape analysis revealed a bilateral outward bending in the hippocampal body related to a lateral displacement of hippocampus from the body to the tail.Symptom severity was correlated with volumes of presubiculum and fimbria,and with the lateral shift of middle and posterior hippocampus(with obsessions).Patients with OCD had reduced amygdala volume bilaterally compared with healthy controls.Volume reductions were greater in the CeA than in the BLA.Volume reductions in the CeA were associated with illness duration.Exploratory analysis revealed smaller medial and cortical nuclei in patients with OCD compared with healthy controls.Conclusion:The amygdala,hippocampus and the dorsal pallidum were associated with OCD.Neuroanatomic evidence of sexual dimorphism was also found in OCD.Our study not only provides deeper insight into how these structures contribute to OCD symptoms by revealing these subregional-level deformities but also suggests that gender effects may be important in OCD studies.