SPECIAL REPORT: OCD AND RELATED DISORDERS
Despite considerable heterogeneity in the precise symptoms experienced across patient populations, there is growing realization that common neurobiological processes may contribute to OCD vulnerability and its persistence. OCD is regarded as the archetypal disorder of compulsivity (ie, a tendency toward repetitive habitual actions that the patient feels a need to perform, with untoward functional consequences such as detracting from overall life goals, or quality of life). Disorders of compulsivity include OCD and related disorders such as hoarding disorder, body dysmorphic disorder, trichotillomania, skin picking disorder, and Tourette syndrome. In this article, we focus on recent advances in understanding the neurobiology of OCD, and the clinical implications of this knowledge viewed in the context of prevailing disease models.
Brain circuitry in OCD
Claire, a 21-year-old student, reports a 5-year history of moderately severe OCD, mainly relating to taboo sexual thoughts and the repeated need to confess. Claire signs up for a research study exploring the neurobiology of OCD, in which she undertakes a clinical assessment, cognitive tests, and a structural brain scan. At the end of the session, Claire asks whether her brain scan can be used to help confirm that she has OCD. She says she has read on the Internet about research that can accurately diagnose OCD using brain scans. She asks if she can have a picture of her brain to see the changes that happen with OCD.
Structural and functional changes within the brain have long been implicated in the pathophysiology of OCD. Cortical and sub-cortical brain regions comprise a series of segregated circuits that may play different roles in thought and behavior. Neuroimaging work in OCD has identified structural and functional abnormalities, typically involving the orbitofrontal cortices and basal ganglia (caudate nucleus)—the orbitofrontal circuit. These findings support the classic model that consider OCD to be a disorder of maladaptive habit circuitry. This model has gained traction and evolved into conceptualizations focusing on habit and loss of top-down control by cortically mediated inhibitory mechanisms (ie, disinhibition).1,2
In recent years, it has become apparent that OCD involves changes across a broad range of fronto-striatal loop circuits, although abnormalities of the orbitofrontal cortices and basal ganglia have commonly been reported.3 OCD has been associated with grey matter volume increases in sub-cortical structures (such as the putamen and globus pallidus), and with grey matter reductions in the cortex (especially ventral and dorsal medial cortex, and inferior frontal cortex).4 In terms of measures of cortical thickness (a proxy for the number of neurons in a particular brain region), more widespread reductions have been typically observed, including not only in the frontal but also in the parietal and temporal parts of the brain. Reduced fractional anisotropy (a measure of fiber density, axonal diameter, and myelination in white matter) in anterior midline tracts (including parts of the corpus callosum and cingulate bundle) is also seen. Collectively, these data suggest that OCD is associated with changes across anatomically disparate brain structures, both in terms of grey matter and white matter tracts.
One approach used to explore brain structure in OCD has been to pool structural neuroimaging scans from diverse group studies—a mega-analysis. Findings from one such mega-analysis indicate that OCD may be associated with smaller hippocampal volumes and larger pallidum volumes; however, there were no significant differences in the caudate or putamen.5 OCD has also been associated with decreased cortical thickness in various frontal, parietal, and temporal cortical regions.6 These results highlight the existence of structural brain abnormalities outside of the classic orbitofrontal loop circuit.
We can also think of the neurobiological underpinnings of OCD in terms of function of distributed brain networks, whether in the resting state or during cognitive tasks. Indeed, a meta-analysis of resting state functional connectivity neuroimaging studies identified hypo-connectivity within and across some circuits; with dysconnectivity (no particular direction of connectivity changes) in other circuits.7
Cognitive neuroimaging studies in OCD have typically focused on domains previously found to be impaired, such as motor inhibitory control, cognitive flexibility, and executive planning. Imaging can be used to assess neurobiological underpinnings of cognitive task performance in two ways: by measuring activation in particular brain regions and by examining functional connectivity or “coupling” between these brain regions. In a meta-analysis of functional neuroimaging studies using inhibitory control tasks, patients with OCD exhibited underactivation in several brain areas (rostral and ventral anterior cingulate cortices, bilateral thalamus/caudate, right anterior insula/frontal operculum, supramarginal gyus, and orbitofrontal cortex).8
Recent findings from case-control studies of functional connectivity indicate that OCD patients and their clinically asymptomatic first-degree relatives had reduced functional connectivity between anterior and posterior cortical regions during a motor inhibition task (Figure).9 In another study functional connectivity between the ventrolateral prefrontal cortex and dorsal caudate nucleus was linked with worse cognitive flexibility in OCD.10 Elsewhere, dysconnectivity was identified between the cortex and basal ganglia (putamen) in both OCD patients and their clinically asymptomatic first-degree relatives.11 Because some of these brain changes extend to first-degree family members, they may represent vulnerability markers for OCD.
The imaging evidence suggests that OCD is associated with distributed, subtle, structural and functional brain changes involving not only the orbito-frontal loop but also other circuits. This information, including awareness of what the literature does and does not show, can be helpful when asked questions from patients, such as in the case of Claire in the Case Vignette above. In answer to Claire’s question about whether OCD would “show” OCD on her brain scan, we would explain that although brain changes have been reported when comparing groups of people with OCD to those without OCD, these are average differences and are very subtle. They cannot be seen on an individual’s brain scan.
To address Claire’s other question, about whether OCD can be diagnosed using a brain scan, the answer is, “No.” There is no appropriately validated algorithm that can be used to diagnose OCD based on a brain scan. There have been studies using multivariate pattern analysis to build predictive models that are capable of classifying scans (eg, into OCD or control groups); however, one cannot conclude from this that these algorithms would generalize to OCD at large, or to other research or clinical settings. For example, smaller studies can result in model over-fit—a statistical issue whereby a model can apparently give astoundingly high accuracy; but this just reflects statistical fallacy and results would not generalize.
Dr Grant is Professor, Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL; Dr Chamberlain is Wellcome Trust Fellow and Honorary Consultant Psychiatrist, Department of Psychiatry, University of Cambridge; and Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), UK. Dr Grant reports that he has received research grants from Promentis and Otsuka Pharmaceuticals; he receives yearly compensation from Springer Publishing for acting as Editor-in-Chief of the Journal of Gambling Studies; he has also receives royalties from Oxford University Press, American Psychiatric Publishing, Inc, Norton Press, and McGraw Hill. Dr Chamberlain consults for Promentis, and Ieso Digital Health; he receives a stipend for his role as Associate Editor at Neuroscience and Biobehavioral Reviews and Comprehensive Psychiatry.
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