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 [(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.
Zitterl
Werner
W
Department of Psychiatry, Medical University of Vienna, Vienna, Austria. werner.zitterl@meduniwien.ac.at
Aigner
Martin
M
Stompe
Thomas
T
Zitterl-Eglseer
Karin
K
Gutierrez-Lobos
Karin
K
Wenzel
Thomas
T
Zettinig
Georg
G
Hornik
Kurt
K
Pirker
Walter
W
Thau
Kenneth
K
D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D015283:Citalopram; D002997:Clomipramine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013788:Thalamus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D055815:Young Adult
D015283:Citalopram; D002997:Clomipramine; D007457:Iodine Radioisotopes; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors