The major symptom dimensions of obsessive–compulsive disorder are mediated by partially distinct neural systems

Department of Psychiatry, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
Brain (Impact Factor: 9.2). 11/2008; 132(Pt 4):853-68. DOI: 10.1093/brain/awn267
Source: PubMed


Obsessive-compulsive disorder (OCD) is a clinically heterogeneous disorder characterized by multiple, temporally stable symptom dimensions. Preliminary functional neuroimaging studies suggest that these symptom dimensions may have distinct neural substrates. Whole-brain voxel-based morphometry was used to examine the common and distinct neuroanatomical (structural) substrates of the major symptom dimensions of OCD. First, we compared 55 medication-free patients with OCD and 50 age-matched healthy control subjects. Multiple regression analyses were then used to examine the relationship between global and regional grey matter (GM) and white matter (WM) volumes and symptom dimension scores within the patient group. OCD patients showed decreased GM volume in left lateral orbitofrontal (BA47), left inferior frontal (BA44/45), left dorsolateral prefrontal (BA9) and right medial prefrontal (BA10) cortices and decreased bilateral prefrontal WM volume. Scores on the 'symmetry/ordering' dimension were negatively correlated with 'global' GM and WM volumes. Scores on the 'contamination/washing' dimension were negatively correlated with 'regional' GM volume in bilateral caudate nucleus and WM volume in right parietal region. Scores on the 'harm/checking' dimension were negatively correlated with regional GM and WM volume in bilateral temporal lobes. Scores on the 'symmetry/ordering' dimension were negatively correlated with regional GM volume in right motor cortex, left insula and left parietal cortex and positively correlated with bilateral temporal GM and WM volume. The results remained significant after controlling for age, sex, educational level, overall illness severity, global WM and GM volumes and excluding patients with comorbid depression. The reported symptom dimension-specific GM and WM alterations support the hypothesis that OCD is an etiologically heterogeneous disorder, with both overlapping and distinct neural correlates across symptom dimensions. These results have clear implications for the current neuroanatomical model of OCD and call for a substantial revision of such model which takes into account the heterogeneity of the disorder.


Available from: Harry Uylings
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    • "An earlier study reported reduced volumes of the left and right inferior frontal gyri, observed even as far as the anterior insula in individuals with OCD (Yoo et al., 2008), but this was inconsistent with others that found greater volumes (e.g., Rotge, Langbour, et al., 2009) or within the normal range (Peng et al., 2012; Pujol et al., 2004) volume of the inferior frontal cortex/anterior insula. So, de wit and colleagues (2014) finding of smaller medial and inferior frontal WM volumes bilaterally in individuals with OCD is important given previous reports that have been conflicting (e.g., Pujol et al., 2004; Togao et al., 2010; van den Heuvel et al., 2009) and is consistent with previous studies that have found alterations in the frontal–striatal WM microstructure in individuals with OCD (Peng et al., 2012). Impairments in cognitive functions are frequently exhibited in patients with OCD, which include impaired emotional regulation and cognitive control. "
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    ABSTRACT: This article will explore recent studies that have identified alterations in brain regions in individuals with obsessive–compulsive disorder (OCD). Specifically, alterations have been found in the cortical surface anatomy, the white matter, the gray matter, the cerebellum, the olfactory-processing structures, the temporal lobe, the prefrontal cortex, and the amygdala. Although some emerging data implicate these brain regions in OCD, the cortico–striatal–thalamic–cortical circuitry remains the prime focus of research. This article will also give an overview of studies that have found different symptom dimensions in individuals with OCD to have distinct neural correlates.
    Brain Mapping An Encyclopedic Reference, Edited by Editor-in-Chief: Arthur W. Toga, 02/2015: chapter Volume 3: Social Cognitive Neuroscience, Cognitive Neuroscience, Clinical Brain Mapping: pages Pages 993–1000; Elsevier Inc.., ISBN: ISBN: 978-0-12-397316-0
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    • "Functional magnetic resonance imaging (fMRI) studies have revealed that the human OFC is involved in reward learning, decision making, control of emotion and motivation , cognitive flexibility, and social behavior [Kringelbach, 2005; Kringelbach and Rolls, 2004; Rolls and Grabenhorst, 2008]. Furthermore, several mental disorders are characterized by structural and functional deficits of the OFC [Crespo-Facorro et al., 2000; Lacerda et al., 2004; van den Heuvel et al., 2009]. These findings highlight the importance of investigation of the human OFC. "
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    ABSTRACT: The human orbitofrontal cortex (OFC) is an enigmatic brain region that cannot be parcellated reliably using diffusional and functional magnetic resonance imaging (fMRI) because there is signal dropout that results from an inherent defect in imaging techniques. We hypothesise that the OFC can be reliably parcellated into subregions based on gray matter volume (GMV) covariance patterns that are derived from artefact-free structural images. A total of 321 healthy young subjects were examined by high-resolution structural MRI. The OFC was parcellated into subregions-based GMV covariance patterns; and then sex and laterality differences in GMV covariance pattern of each OFC subregion were compared. The human OFC was parcellated into the anterior (OFCa), medial (OFCm), posterior (OFCp), intermediate (OFCi), and lateral (OFCl) subregions. This parcellation scheme was validated by the same analyses of the left OFC and the bilateral OFCs in male and female subjects. Both visual observation and quantitative comparisons indicated a unique GMV covariance pattern for each OFC subregion. These OFC subregions mainly covaried with the prefrontal and temporal cortices, cingulate cortex and amygdala. In addition, GMV correlations of most OFC subregions were similar across sex and laterality except for significant laterality difference in the OFCl. The right OFCl had stronger GMV correlation with the right inferior frontal cortex. Using high-resolution structural images, we established a reliable parcellation scheme for the human OFC, which may provide an in vivo guide for subregion-level studies of this region and improve our understanding of the human OFC at subregional levels. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2014; 36(2). DOI:10.1002/hbm.22645 · 5.97 Impact Factor
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    • "Thus, a loss in right parietal volume might arise from starvation, but may help to subsequently maintain the disorder. The reduced activation observed in the right parietal lobe in the AN group is consistent with findings from individuals with OCD, in whom structural abnormalities in the parietal lobe are associated with the severity of ordering symptoms; scores on the symmetry/ordering dimension have been reported as being negatively correlated with grey matter volume in the parietal lobe in OCD [54]. "
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    ABSTRACT: Anorexia nervosa (AN), obsessive-compulsive disorder (OCD), and obsessive-compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of 'ordering' symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN.
    PLoS ONE 05/2014; 9(5):e97998. DOI:10.1371/journal.pone.0097998 · 3.23 Impact Factor
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