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Abstract: The serotonin transporter (5-HTT) and other markers of the serotonergic system have been of interest in the pathophysiology of obsessive-compulsive disorder (OCD). Previous studies using single photon emission computed tomography (SPECT) with [123I]β-CIT or positron emission tomography (PET) with [11C]McN5652 have not shown consistent findings about 5-HTT in OCD patients. The aim of the present study was to investigate 5-HTT binding using [11C]DASB, which has higher selectivity or specific binding-to-nonspecific binding ratios for 5-HTT compared to the aforementioned radioligands. Four drug-naive and 6 drug-free patients with OCD who were free of comorbid depression and 18 gender and age-matched healthy subjects underwent PET scans with [11C]DASB. The severity of OCD was assessed by Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) (mean±SD: 22±7.6, range: 7–32). The binding potential (BP ND ) of [11C]DASB was calculated using a two-parameter multilinear reference tissue model (MRTM2). The parametric images of BP ND were analyzed using a statistical parametric mapping system. Significant reductions of BP ND were observed in the right posterior and left anterior insular cortices in patients with OCD compared to controls. Region-of-interest analysis has also confirmed significant reduction of BP ND in the insular cortex. Although significantly reduced BP ND in the orbitofrontal cortex was also observed in patients with OCD compared to controls, this finding should be considered with caution because of the very low 5-HTT binding in the region. On the other hand, no significant correlation was observed between the Y-BOCS score and BP ND . The change in [11C]DASB binding in the insular cortex suggests that dysfunction of the serotonergic system in the limbic area might be involved in the pathophysiology of OCD. [Copyright &y& Elsevier]