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] b-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]-2b-carbomethoxy-3b-(4-iodophenyl)tropane. For quantification of brain serotonin transporter availability, a ratio of specific to nondisplaceable [ 123 I] b-CIT brain binding was used (BP ND ¼ (thalamus and hypothalamusÀcerebellum)/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, po0.001). Correlations between brain SERT availability and OC symptomatology (Y-BOCS scores) revealed significantly negative associations both at baseline and after treatment (r ¼ À0.46; po0.05 and r ¼ À0.53; po0.01 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 ¼ 14.145 ± 4.514; t ¼ 3.133; p ¼ 0.005). These results provide further support for an important role of alterations in serotonergic neurons in the pathophysiology of OCD.

Evidence Why Paroxetine Dose Escalation is Not Effective in Major Depressive Disorder: A Randomized Controlled Trial With Assessment of Serotonin Transporter Occupancy

“…However, validation of this ex vivo method (in cultured cells) with concomitant in vivo SPECT or PET SERT occupancy (the gold standard) is not yet available. In addition, Zitterl et al (2008) found a significant relation between SERT occupancy and clinical response in obsessivecompulsive disorder treated with clomipramine (150 mg per day), but did not study the effects of dose escalation in their study. Therefore, our study optimally quantifies the neurobiological effects of dose escalation of antidepressants in patients.…”

Altered Brain Activation in Ventral Frontal-Striatal Regions Following a 16-week Pharmacotherapy in Unmedicated Obsessive-Compulsive Disorder

“…In contrast, Zitterl et al (28) reported a negative association between OCD symptom severity and thalamic/hypothalamic serotonin transporter availability in both the baseline and post-treatment conditions. Given the hyperactive pattern in the limbic and paralimbic regions, the inverse relationship between changes of thalamic activity and OC symptom severity may be a compensatory mechanism for unfulfilled improvement of OC symptoms or a overloaded result in the frontal-striatal circuit (7).…”

Of mice and marbles: Novel perspectives on burying behavior as a screening test for psychiatric illness

“…Furthermore, high stereotypy in deer mice correlates to reduced striatal serotonin transporter (SERT) density (Wolmarans et al, 2013), a recognized pathological feature of OCD (Zitterl et al, 2008), whereas SERT is also the preferential target for SSRIs (El Mansari & Blier, 2006). In this study, we challenged H animals with MB in order to screen for anxiety (neophobia) and compulsivity and to determine the response of said behavior to chronic escitalopram treatment, a known anxiety and OCD treatment modality.…”