Abstract
Objective Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder with moderate genetic influences and white matter (WM) abnormalities in frontal-striatal and limbic regions. Inconsistencies in reported WM results from diffusion tensor imaging (DTI) studies can be explained, at least partly, by medication use and between-group differences in disease profile and stage. We used a family design aiming to establish whether WM abnormalities, if present in un-medicated OCD patients, also exist in their unaffected siblings. Method Forty-four un-medicated OCD patients, 15 of their unaffected siblings and 37 healthy controls (HC) underwent DTI using a 3-Tesla MRI-scanner. Data analysis was done using tract-based spatial statistics (TBSS). Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) values were compared within seven skeletonised regions of interest (ROIs), i.e., corpus callosum (CC), bilateral cingulum bundle (CB), bilateral inferior longitudinal fasciculus/frontal-occipital fasciculus (ILF/FOF) and bilateral superior longitudinal fasciculus (SLF). Results Un-medicated OCD patients, compared with HC, had significantly lower FA in the left CB. FA was trend-significantly lower in all other ROIs, except for the CC. Significant three-group differences in FA (and in RD at trend-significant level) were observed in the left CB, with the unaffected siblings representing an intermediate group between OCD patients and HC. Conclusions OCD patients showed lower FA in the left CB, partly driven by trend-significantly higher values in RD. Since the unaffected siblings were found to be an intermediate group between OCD patients and HC, this WM alteration may be considered an endophenotype for OCD.
Highlights
Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder characterized by obsessions and/or compulsions
This study reported effects for environmental as opposed to genetic influences on regional white matter volume: the predominant fractional anisotropy (FA) decrease found in inferior frontal regions in the MZ concordant-high vs. concordant-low twins was suggested to reflect genetic effects, whereas the within MZ discordant twin comparison revealed increased dorsolateral prefrontal white matter changes in the high scoring twins, thought to reflect changes due to environmental effects
OCD patients scored higher compared with healthy controls (HC) and the unaffected siblings (p < 0.01); the sibling group did not significantly differ from the HC group on these measures
Summary
Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder characterized by obsessions (intrusive recurrent thoughts) and/or compulsions (repetitive behaviors). The genetic basis of OCD is complex, multi-factorial, and under strong environmental influence (Grisham et al, 2008) Both structural and functional neural correlates of OCD have been found in the unaffected first-degree relatives of OCD patients (Chamberlain et al, 2008; Menzies et al, 2008b; de Wit et al, 2012; de Vries et al, 2014), suggesting that at least in part, the alterations are state-independent and might be regarded as correlates of genetic vulnerability, called endophenotypes (Gottesman and Gould, 2003). A recent OCD Brain Imaging Consortium mega-analysis (de Wit et al, 2014), involving 412 OCD patients and 368 healthy controls (HC), reported decreased white matter volumes in frontal regions in the patient group, suggesting abnormalities of white matter connections between the prefrontal and subcortical regions within the frontal-striatal circuits. White matter volume alterations have been reported for the parietal and occipital lobes (Riffkin et al, 2005; Lázaro et al, 2009, 2011)
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