Changes in Thalamus–Hypothalamus Serotonin Transporter Availability during Clomipramine Administration in Patients with Obsessive–Compulsive Disorder

Abstract

To the authors' knowledge there is as of yet no study demonstrating in vivo alterations in human serotonin transporters (SERT) during clomipramine treatment in patients with obsessive-compulsive disorder. The only study in which SERT binding has been investigated in obsessive-compulsive disorder (OCD) patients before and after treatment is a small pilot study by Stengler-Wenzke et al (2006), who treated five OCD patients with citalopram. In the study at hand, we measured transporter availability in the thalamus-hypothalamus with [(123)I] beta-CIT single photon emission computed tomography (SPECT) in 24 patients with DSM-IV OCD. All patients displayed prominent behavioral checking compulsions (OC-checkers). At baseline and upon medication after 12 weeks of treatment with clomipramine (150 mg daily) 24 non-depressed OC-checkers underwent a SPECT measurement of brain SERT availability using [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [(123)I] beta-CIT brain binding was used (BP(ND)=(thalamus and hypothalamus-cerebellum)/cerebellum). The SERT availability was compared between baseline and after treatment and correlated with severity of OC symptomatology and treatment response as assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). After treatment with clomipramine patients showed a 48% reduced brain serotonin transporter availability in the thalamus-hypothalamus, as compared with values at baseline (0.72+/-0.12 vs 1.39+/-0.18, p<0.001). Correlations between brain SERT availability and OC symptomatology (Y-BOCS scores) revealed significantly negative associations both at baseline and after treatment (r=-0.46; p<0.05 and r=-0.53; p<0.01 respectively). These data suggest that the SERT availability values could be considered a biological indicator of disease severity. Moreover, in search of predictors we found that higher pretreatment SERT availability significantly predicted better treatment response 12 weeks later (B=14.145+/-4.514; t=3.133; p=0.005). These results provide further support for an important role of alterations in serotonergic neurons in the pathophysiology of OCD.