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David Mataix-Cols, PhD; Sarah Wooderson, MSc; Natalia Lawrence, PhD; Michael J. Brammer, PhD; Anne Speckens, MD; Mary L. Phillips, MD

Arch Gen Psychiatry. 2004;61:564-576.

Context  Obsessive-compulsive disorder (OCD) is clinically heterogeneous, yet most previous functional neuroimaging studies grouped together patients with mixed symptoms, thus potentially reducing the power and obscuring the findings of such studies.

Objective  To investigate the neural correlates of washing, checking, and hoarding symptom dimensions in OCD.

Design  Symptom provocation paradigm, functional magnetic resonance imaging, block design, and nonparametric brain mapping analyses.

Setting  University hospital.

Participants  Sixteen patients with OCD (11 inpatients, 5 outpatients) with mixed symptoms and 17 healthy volunteers of both sexes.

Intervention  All subjects participated in 4 functional magnetic resonance imaging experiments. They were scanned while viewing alternating blocks of emotional (washing-related, checking-related, hoarding-related, or aversive, symptom-unrelated) and neutral pictures, and imagining scenarios related to the content of each picture type.

Main Outcome Measure  Blood oxygenation level–dependent response.

Results  Both patients and control subjects experienced increased subjective anxiety during symptom provocation (patients significantly more so) and activated neural regions previously linked to OCD. Analyses of covariance, controlling for depression, showed a distinct pattern of activation associated with each symptom dimension. Patients demonstrated significantly greater activation than controls in bilateral ventromedial prefrontal regions and right caudate nucleus (washing); putamen/globus pallidus, thalamus, and dorsal cortical areas (checking); left precentral gyrus and right orbitofrontal cortex (hoarding); and left occipitotemporal regions (aversive, symptom-unrelated). These results were further supported by correlation analyses within patients, which showed highly specific positive associations between subjective anxiety, questionnaire scores, and neural response in each experiment. There were no consistently significant differences between patients with (n = 9) and without (n = 7) comorbid diagnoses.

Conclusions  The findings suggest that different obsessive-compulsive symptom dimensions are mediated by relatively distinct components of frontostriatothalamic circuits implicated in cognitive and emotion processing. Obsessive-compulsive disorder may be best conceptualized as a spectrum of multiple, potentially overlapping syndromes rather than a unitary nosologic entity.

From the Departments of Psychological Medicine (Drs Mataix-Cols, Lawrence, and Phillips and Ms Wooderson), Biostatistics (Dr Brammer), and Psychology (Drs Mataix-Cols and Speckens), Institute of Psychiatry, London, England.

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