Multimodal Voxel-Based Meta-Analysis of White Matter Abnormalities in Obsessive–Compulsive Disorder

Abstract

White matter (WM) abnormalities have long been suspected in obsessive-compulsive disorder (OCD) but the available evidence has been inconsistent. We conducted the first multimodal meta-analysis of WM volume (WMV) and fractional anisotropy (FA) studies in OCD. All voxel-wise studies comparing WMV or FA between patients with OCD and healthy controls in the PubMed, ScienceDirect, Google Scholar, Web of Knowledge and Scopus databases were retrieved. Manual searches were also conducted and authors were contacted soliciting additional data. Thirty-four data sets were identified, of which 22 met inclusion criteria (five of them unpublished; comprising 537 adult and pediatric patients with OCD and 575 matched healthy controls). Whenever possible, raw statistical parametric maps were also obtained from the authors. Peak and raw WMV and FA data were combined using novel multimodal meta-analytic methods implemented in effect-size signed differential mapping. Patients with OCD showed widespread WM abnormalities, but findings were particularly robust in the anterior midline tracts (crossing between anterior parts of cingulum bundle and body of corpus callosum), which showed both increased WMV and decreased FA, possibly suggesting an increase of fiber crossing in these regions. This finding was also observed when the analysis was limited to adult participants, and especially pronounced in samples with a higher proportion of medicated patients. Therefore, patients with OCD may have widespread WM abnormalities, particularly evident in anterior midline tracts, although these changes might be, at least in part, attributable to the effects of therapeutic drugs.

Mild White Matter Changes in Un-Medicated Obsessive-Compulsive Disorder Patients and Their Unaffected Siblings

“…The main finding of the present study is lower FA in the left cingulum bundle in un-medicated OCD patients compared with HC, which partially replicates the findings from the meta-analysis conducted by Radua et al (2014). We also found, in line with Radua et al, although at uncorrected significance level, lower FA in the other ROIs (except for the corpus callosum), i.e., the right cingulum bundle, the bilateral ILF/FOF, and the bilateral SLF.…”

“…Lower FA in the cingulum bundle has been reported by most studies that investigated adult OCD patients (Koch et al, 2014;Radua et al, 2014). Increasing evidence from structural and functional neuroimaging research in recent years has emphasized the impact of deficits in temporo-parietal-occipital regions in the pathophysiology of OCD besides the frontal-striatal and fronto-limbic neurocircuitries (Menzies et al, 2008a;Piras et al, 2013).…”

“…We compared the skeletonized diffusion parameters between OCD patients, the unaffected siblings and healthy controls using a ROI approach, including the 7 ROI's (i.e., the corpus callosum, the bilateral cingulum bundle, the bilateral ILF/FOF, and the bilateral SLF) based on the results from the meta-analysis of Radua et al (2014). The Johns Hopkins University (JHU) ICBM-DTI-81 white-matter labels atlas provided by FSL was chosen to define the ROIs.…”

“…We suggest several possible reasons for the reported discrepancies: (1) in OCD, white matter alterations might be subtle thus difficult to detect; (2) medication effects seem to confound the findings (Yoo et al, 2007;Fan et al, 2012;Benedetti et al, 2013;Radua et al, 2014); (3) results are highly variable across pediatric, adolescent and adult patients due to changes in white matter architecture throughout brain development (Peters et al, 2012); (4) debate has risen recently on whether FA alone is sufficient and sufficiently representative to indicate changes in white matter microstructure (Hasan, 2006;Fan et al, 2012;Szczepankiewicz et al, 2014); and (5) small samples and inconsistent methodologies have been used (Radua et al, 2014).…”

“…We used a region-of-interest (ROI) approach by selecting 7 ROIs, based on the results from the meta-analysis of Radua et al (2014), corpus callosum, the bilateral cingulum bundle, the bilateral ILF/FOF and the bilateral SLF. We hypothesized that OCD patients compared with HC would show lower FA with changes in diffusivity values in the ROIs.…”