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Many studies have identified changes in the brain associated with obsessive–compulsive disorder (OCD), but few have examined the relationship between genetic determinants of OCD and brain variation.
We present the first genome-wide investigation of overlapping genetic risk for OCD and genetic influences on subcortical brain structures.
Using single nucleotide polymorphism effect concordance analysis, we measured genetic overlap between the first genome-wide association study (GWAS) of OCD (1465 participants with OCD, 5557 controls) and recent GWASs of eight subcortical brain volumes (13 171 participants).
We found evidence of significant positive concordance between OCD risk variants and variants associated with greater nucleus accumbens and putamen volumes. When conditioning OCD risk variants on brain volume, variants influencing putamen, amygdala and thalamus volumes were associated with risk for OCD.
These results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.
Declaration of interest
The authors have declared that no competing interests exist.
There is accumulating evidence for the role of fronto-striatal and associated circuits in obsessive–compulsive disorder (OCD) but limited and conflicting data on alterations in cortical thickness.
To investigate alterations in cortical thickness and subcortical volume in OCD.
In total, 412 patients with OCD and 368 healthy adults underwent magnetic resonance imaging scans. Between-group analysis of covariance of cortical thickness and subcortical volumes was performed and regression analyses undertaken.
Significantly decreased cortical thickness was found in the OCD group compared with controls in the superior and inferior frontal, precentral, posterior cingulate, middle temporal, inferior parietal and precuneus gyri. There was also a group x age interaction in the parietal cortex, with increased thinning with age in the OCD group relative to controls.
Our findings are partially consistent with earlier work, suggesting that group differences in grey matter volume and cortical thickness could relate to the same underlying pathology of OCD. They partially support a frontostriatal model of OCD, but also suggest that limbic, temporal and parietal regions play a role in the pathophysiology of the disorder. The group x age interaction effects may be the result of altered neuroplasticity.
The need for symmetry and ordering objects related to a “just right”-feeling is a common symptom in Tourette's syndrome (TS) and resembles symmetry behavior in obsessive-compulsive disorder, but its pathophysiology is unknown. We used a symptom provocation paradigm to investigate the neural correlates of symmetry behavior in TS and hypothesized the involvement of frontal-striatal and limbic brain areas.
Pictures of asymmetrically and symmetrically arranged objects were presented in randomized blocks (4 blocks of each condition) to 14 patients with TS and 10 matched healthy controls (HC). A H215O positron emission tomography scan was acquired during each stimulus block, resulting in 8 scans per subject. After each scan, state anxiety and symmetry behavior (the urge to rearrange objects) were measured using a visual analogue scale.
During the asymmetry condition, TS patients showed increased regional cerebral blood flow (rCBF) in the anterior cingulate cortex, supplementary motor area, and inferior frontal cortex, whereas HC showed increased rCBF in the visual cortex, primary motor cortex, and dorsal prefrontal cortex. Symmetry ratings during provocation correlated positively with orbitofrontal activation in the TS group and sensorimotor activation in the HC group, and negatively with dorsal prefrontal activity in HC.
Results suggest that both motor and limbic circuits are involved in symmetry behavior in TS. Motor activity may relate to an urge to move or perform tics, and limbic activation may indicate that asymmetry stimuli are salient for TS patients. In contrast, symmetry provocation in HC resulted in activation of brain regions implicated in sensorimotor function and cognitive control.
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