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: 10.23). 11/2008; 132(Pt 4):853-68. DOI: 10.1093/brain/awn267
Source: PubMed

ABSTRACT 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.

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Available from: Harry Uylings, Aug 04, 2015
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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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    • "A resting-state functional magnetic resonance imaging study revealed significantly greater positive functional connectivity between the basal ganglia (striatum) and DLPFC in OCD patients, which is consistent with our meta-analysis results model (Sakai et al., 2010). Many imaging studies have reported abnormalities in the parietal lobe, especially in the angular gyri and IPL in patients with OCD (Kim et al., 2001; Menzies et al., 2008b; Szeszko et al., 2005; Valente et al., 2005; van den Heuvel et al., 2009). Furthermore, evidence from cognitive studies in OCD suggests that the parietal cortex plays a significant role in accounting for the cognitive deficits seen in OCD patients. "
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    ABSTRACT: Specific cortico-striato-thalamic circuits are hypothesised to underlie the aetiology of obsessive-compulsive disorder (OCD). However, findings from neuroimaging studies have been inconsistent. In the current study, we attempted to provide a complete overview of structural alterations in OCD by conducting signed differential mapping (SDM) meta-analysis on grey matter and white matter studies of patients with OCD based on voxel-based morphometry (VBM) studies and diffusion tensor imaging (DTI) studies. Fifteen VBM and seven DTI case-control studies were included in this meta-analysis. SDM meta-analyses were performed to assess grey matter volume and white matter integrity changes in OCD patients and healthy controls. We found that OCD patients had smaller grey matter volume than health controls in the frontal eye fields, medial frontal gyrus and anterior cingulate cortex. However, we showed that there was an increase in the grey matter volume in the lenticular nucleus, caudate nucleus and a small region in the right superior parietal lobule. OCD patients also had a lower fractional anisotropy (FA) in the cingulum bundles, inferior fronto-occipital fasciculus, and superior longitudinal fasciculus, while increased FA in the left uncinate fasciculus. The current findings confirm the structural abnormalities of cortico-striato-thalamic circuits in OCD.
    12/2012; 5(4):290-6. DOI:10.1016/j.ajp.2012.07.004
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    • "Only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation (Bloch et al., 2006). These differences suggest that OCD is a highly heterogeneous condition, and it is possible that there are biological differences among subgroups of OCD as defined by pharmacological response or symptom clusters (Gilbert et al., 2008; van den Heuvel et al., 2009; Sumitani et al., 2007; Buchsbaum et al., 2006). Two recent brain-imaging studies have suggested the presence of psychopharmacological subtypes within OCD. "
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    ABSTRACT: The objective of the present study was to compare brain activation of the patients with obsessive compulsive disorder (OCD) who received pharmacotherapy (selective serotonin reuptake inhibitor (SSRI) or a SSRI-risperidone combination) related to healthy controls using (99m)Tc-hexamethyl propyleneamine oxime (HMPAO) brain single photon emission tomography (SPECT). Twelve OCD patients achieving clinical response (seven SSRI responders, five patients responded to SSRI plus risperidone) underwent post-treatment SPECT scan. The baseline regional cerebral blood flows (rCBFs) were significantly reduced in a large part of cerebral cortex and left cingulate gyrus in OCD patients compared to controls. After 50% reduction of the OCD symptoms, bilaterally increased thalamus rCBF had significant time effect in both of the patient groups. In remitted status, although cingulate gyrus blood flow did not differ in SSRI responders from that of the control group, patients responding to SSRI+risperidone combination regimen showed significant hypoperfusion in the left anterior cingulate gyrus. In remission, SSRI responder had normalized rCBF in the frontal region relative to the control group. Consequently, depending on our results, we think that the thalamic rCBF alteration occurs to be related to SSRI treatment. Our results also suggested that brain perfusion changes associated with clinical remission may differ across patient subgroups.
    11/2012; 213(2). DOI:10.1016/j.pscychresns.2012.07.005
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