Reduced serotonin transporter binding in the insular cortex in patients with obsessive–compulsive disorder: A [11C]DASB PET study
Introduction
Obsessive–compulsive disorder (OCD) is a common chronic psychiatric disorder characterized by recurrent obsessions and compulsions. OCD has a high lifetime prevalence rate of 2–3% in the general population and is considered to be among the twenty leading causes of disability in the United States and other countries (Michaud et al., 2006). Based on a number of pertinent findings, such as the effect of serotonin reuptake inhibitors (SSRIs), high comorbidity of depression, reduced densities of platelet serotonin transporter (5-HTT), and the association of 5-HTT gene polymorphism in OCD (Greist and Jefferson, 1998, Greist et al., 1995, Lin, 2007, March et al., 1997), the serotonergic system including 5-HTT has attracted considerable attention in relation to the pathophysiology of OCD.
5-HTT in living human brain can be measured by positron emission tomography (PET) and single photon emission computed tomography (SPECT) with several radioligands. Inconsistent findings in [123I]β-CIT binding in the thalamus and midbrain of patients with OCD were reported by SPECT studies (Hesse et al., 2005, Pogarell et al., 2003, Simpson et al., 2003, Stengler-Wenzke et al., 2004, Zitterl et al., 2007). Since [123I]β-CIT also has affinity to dopamine transporter, it is not an ideal radioligand for quantifying 5-HTT. In a prior PET study using [11C]McN5652, a selective radioligand for 5-HTT, no significant differences were observed in patients with OCD compared to normal subjects (Simpson et al., 2003). However, [11C]McN5652 shows relatively higher nonspecific binding and lower specific binding-to-nonspecific binding ratios compared to [11C]DASB (Huang et al., 2002), a radioligand with higher specific binding to 5-HTT (Wilson et al., 2002) that allows the quantification of binding of not only 5-HTT-rich regions but also relatively low density regions such as cerebral cortices (Ichise et al., 2003, Kim et al., 2006). The aim of the present study was to investigate 5-HTT in the brain of patients with OCD using [11C]DASB.
Section snippets
Subjects
Ten patients with OCD and 18 healthy control subjects participated in this study. All patients met DSM-IV criteria for OCD. Clinical diagnosis was completed by three trained psychiatrists. Based on conventional unstructured interviews and medical histories, we excluded patients with psychiatric disorders other than OCD, such as current major depressive disorder, schizophrenia, bipolar disorders, other anxiety disorders, and substance abuse. To rule out somatic disorders, all patients underwent
Results
SPM analysis of BPND parametric images revealed significant reductions in the right posterior and left anterior insular cortex in the patients with OCD compared to healthy controls (Fig. 1).
ROI analysis revealed that the BPND values of the OCD patients had a tendency to be lower compared to control subjects in all regions (Table 2). Among them, the BPND values showed significant reductions compared to healthy controls in the insular cortex (p = 0.0008 < 0.001) and orbitofrontal cortex (p = 0.0005 <
Discussion
In the present study, significantly lower BPND values in the insular cortex were observed by [11C]DASB PET study in OCD patients free of comorbid depression, compared to healthy controls. Especially, voxel-based analysis of parametric images over the whole brain contributed to the above new finding. Intriguingly, the [11C]DASB BPND values in the orbitofrontal cortex also showed a significant reduction in OCD patients compared to healthy controls. The orbitofrontal cortex is one of the regions
Acknowledgments
This study was supported by a Grant-in-Aid for the Molecular Imaging Program from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japanese Government. We are grateful to all members of the cyclotron team at the National Institute of Radiological Sciences for their technical support in radioisotope production and all the radiological technicians for their help with the PET experiment. We also thank Ms. Yoshiko Fukushima for her help as clinical research coordinator.
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