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

Abstract

ObjectiveWe aimed to examine white matter microstructure and connectivity in individuals with obsessive–compulsive disorder (OCD) and their unaffected siblings, relative to healthy controls.MethodsDiffusion‐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).ResultsCompared 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.ConclusionTherefore, 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.

Association between gray/white matter contrast and white matter microstructural alterations in medication-naïve obsessive–compulsive disorder

“…Compared with HCs, this study showed decreased FA in several WM tracts involving the corpus callosum, cingulum, and inferior fronto-occipital fasciculus, among others, in patients with OCD. Our results are consistent with previous reports( Dikmeer et al, 2021 , Gan et al, 2017 , Piras et al, 2021 ) and provide evidence for the notion that the pathophysiology of OCD is not limited to the CSTC circuits but also involves abnormalities in more extended brain regions( Anticevic et al, 2014 ). The decreases in WM FA could be the microstructural basis for the disrupted structural and functional connectivity in distributed brain networks in OCD.…”

“…Indeed, previous imaging genetic studies have reported myelin-related white matter (WM) abnormalities in OCD( Atmaca et al, 2010 , Stewart et al, 2007 , Zai et al, 2021 ). Diffusion tensor imaging (DTI) studies have also found significant WM microstructural changes in OCD, suggesting disrupted WM myelin integrity in this disorder( Dikmeer et al, 2021 , Gan et al, 2017 , Piras et al, 2021 , Saito et al, 2008 ).…”

Aberrant rich club organization in patients with obsessive-compulsive disorder and their unaffected first-degree relatives

“…Previous researches found that the (functional) hypoconnectivity in frontal-striatal areas in both patients and their clinically asymptomatic relatives may serve as a biomarker for OCD ( Vaghi et al, 2017 , Chamberlain et al, 2008 ). Moreover, previous neuroimaging studies have revealed network abnormalities, such as atypical small-world properties ( Peng et al, 2013 ) and altered white matter ( Menzies et al, 2008 , Dikmeer et al, 2021 ), in both OCD patients and their FDR. However, whether the basis for information dissemination in those brain networks, namely the rich club, can be treated as a putative vulnerability biomarker, remains unknown.…”

Abnormal white‐matter rich‐club organization in obsessive–compulsive disorder

“…The present study preliminarily investigated rich‐club organization in a small group of unaffected siblings. Generally, neuroimaging markers of anomaly present in both patients and unaffected first‐degree relatives, but not in healthy controls, are good candidates, and potential endophenotypes have been identified in measures of white‐matter microstructure (Dikmeer et al, 2021; Fan et al, 2016; Menzies et al, 2008), network properties (Peng et al, 2014) and functional patterns of dysconnectivity (Chamberlain et al, 2008; Peng et al, 2014; Vaghi et al, 2017). Research on whether rich‐club organization could be considered as such is limited, with only one study reporting intermediate levels of rich‐club connectivity in unaffected siblings (Peng et al, 2021).…”

“…Given (Dikmeer et al, 2021;Menzies et al, 2008), network properties and functional patterns of dysconnectivity (Chamberlain et al, 2008;Vaghi et al, 2017). Research on whether rich-club organization could be considered as such is limited, with only one study reporting intermediate levels of rich-club connectivity in unaffected siblings (Peng et al, 2021).…”