Orbitofrontal dysfunction in patients with obsessive–compulsive disorder and their unaffected relatives

Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Box 189, Cambridge CB2 0QQ, UK.
Science (Impact Factor: 31.48). 07/2008; 321(5887):421-2. DOI: 10.1126/science.1154433
Source: PubMed

ABSTRACT Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviors associated with underlying dysregulation of frontostriatal circuitry. Central to neurobiological models of OCD is the orbitofrontal cortex, a neural region that facilitates behavioral flexibility after negative feedback (reversal learning). We identified abnormally reduced activation of several cortical regions, including the lateral orbitofrontal cortex, during reversal learning in OCD patients and their clinically unaffected close relatives, supporting the existence of an underlying previously undiscovered endophenotype for this disorder.

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    • "Therefore, it is striking that the region that emerged from our whole-brain analysis as most relevant for predicting improvements in contamination anxiety was in our target area of the OFC/BA 10. Taken together with a large body of data highlighting the importance of the OFC and anterior prefrontal cortex in obsessive-compulsive symptoms (Swedo et al., 1992; Chamberlain et al., 2008; Menzies et al., 2008; Harrison et al., 2009; Sakai et al., 2011; Anticevic et al., 2014; Beucke et al., 2013), this gives us confidence that we are targeting a biologically relevant brain area. Notably, OFC/BA 10 connectivity predicted the response to the intervention in both healthy subjects and OCD patients, suggesting a shared neurobiological mechanism for improved control over contamination anxiety across groups. "
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    ABSTRACT: Tailoring treatments to the specific needs and biology of individual patients-personalized medicine-requires delineation of reliable predictors of response. Unfortunately, these have been slow to emerge, especially in neuropsychiatric disorders. We have recently described a real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback protocol that can reduce contamination-related anxiety, a prominent symptom of many cases of obsessive-compulsive disorder (OCD). Individual response to this intervention is variable. Here we used patterns of brain functional connectivity, as measured by baseline resting-state fMRI (rs-fMRI), to predict improvements in contamination anxiety after neurofeedback training. Activity of a region of the orbitofrontal cortex (OFC) and anterior prefrontal cortex, Brodmann area (BA) 10, associated with contamination anxiety in each subject was measured in real time and presented as a neurofeedback signal, permitting subjects to learn to modulate this target brain region. We have previously reported both enhanced OFC/BA 10 control and improved anxiety in a group of subclinically anxious subjects after neurofeedback. Five individuals with contamination-related OCD who underwent the same protocol also showed improved clinical symptomatology. In both groups, these behavioral improvements were strongly correlated with baseline whole-brain connectivity in the OFC/BA 10, computed from rs-fMRI collected several days prior to neurofeedback training. These pilot data suggest that rs-fMRI can be used to identify individuals likely to benefit from rt-fMRI neurofeedback training to control contamination anxiety.
    Frontiers in Behavioral Neuroscience 09/2014; 8:338. DOI:10.3389/fnbeh.2014.00338 · 4.16 Impact Factor
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    • "motivational aspects of behavior. Alterations within these circuits may explain executive dysfunction, low cognitivebehavioral flexibility and impaired decision-making which are common in OCD [Chamberlain et al., 2008; Menzies et al., 2008a; Rotge et al., 2009a; Saxena et al., 2001]. More specifically, previous DTI studies of OCD have shown increased FA in prefrontal white matter [Li et al., 2011; Menzies et al., 2008b; Yoo et al., 2007; Zarei et al., 2011] that is correlated with symptom severity [Zarei et al., 2011] and is possibly related to increased myelination and neuronal remodeling [Beaulieu, 2002]. "
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    ABSTRACT: Diffusion tensor imaging (DTI) studies have revealed group differences in white matter between patients with obsessive-compulsive disorder (OCD) and healthy controls. However, the results of these studies were based on average differences between the two groups, and therefore had limited clinical applicability. The objective of this study was to investigate whether fractional anisotropy (FA) of white matter can be used to discriminate between patients with OCD and healthy controls at the level of the individual. DTI data were acquired from 28 OCD patients and 28 demographically matched healthy controls, scanned using a 3T MRI system. Differences in FA values of white matter between OCD and healthy controls were examined using a multivariate pattern classification technique known as support vector machine (SVM). SVM applied to FA images correctly identified OCD patients with a sensitivity of 86% and a specificity of 82% resulting in a statistically significant accuracy of 84% (P ≤ 0.001). This discrimination was based on a distributed network including bilateral prefrontal and temporal regions, inferior fronto-occipital fasciculus, superior fronto-parietal fasciculus, splenium of corpus callosum and left middle cingulum bundle. The present study demonstrates subtle and spatially distributed white matter abnormalities in individuals with OCD, and provides preliminary support for the suggestion that that these could be used to aid the identification of individuals with OCD in clinical practice. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 06/2014; 35(6). DOI:10.1002/hbm.22357 · 6.92 Impact Factor
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    • "Results from familial risk studies suggest that OCD is a familial disorder [30] [61]. Furthermore, results from imaging studies suggest that unaffected first-degree relatives of OCD patients share some frontostriatal functional abnormalities [16] [17], abnormal error-related brain activity [69], and white matter abnormalities [55]. Based on suggestions that smoking may exacerbate OCD pathology via nicotine effects on an putatively hyperactive frontal cortex [7], and evidence for shared neurobiological abnormalities in unaffected first-degree relatives of OCD patients, we hypothesized that unaffected parents of OCD probands would also show lower prevalence rates of smoking compared to the general population. "
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    ABSTRACT: Background Cigarette smoking is more prevalent among individuals with psychiatric disorders than the general population. Obsessive-compulsive disorder (OCD) may be an intriguing exception, although no recent study has investigated this hypothesis in OCD patients. Moreover, it is unknown whether reduced smoking rates are present in unaffected first-degree relatives of OCD patients. Methods We assessed smoking prevalence in adults with OCD and unaffected parents of youth with OCD (PYOCD). To this end, 113 adults with OCD completed online questionnaires assessing symptom severity and smoking status. Smoking status was obtained from an independent sample of 210 PYOCD assessed for psychiatric diagnoses. Results Smoking prevalence rates in adults with OCD (13.3%; n = 15) and PYOCD (9.5%; n = 20) samples were significantly lower than those found in representative samples of the general population (19–24%, all P < .001) and Axis I disorders (36–64%; all P < .001). There were no smokers in the adult OCD subset without clinically significant depressive symptoms (n = 54). Conclusion Low prevalence of smoking in OCD may be familial and unique among psychiatric disorders, and might represent a possible state-independent OCD marker. Hypotheses concerning the uncharacteristically low prevalence rates are discussed with relation to OCD phenomenology and pathophysiology.
    European Psychiatry 03/2014; 30(1). DOI:10.1016/j.eurpsy.2013.12.003 · 3.21 Impact Factor
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