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

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 [I-123] 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 [I-123]-2 beta-carbomethoxy-3 beta-(4-iodophenyl) tropane. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [I-123] beta-CIT brain binding was used (BPND (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.