Serotonin and dopamine transporter availability in social anxiety disorder after combined treatment with escitalopram and cognitive-behavioral therapy

Abstract

Selective serotonin reuptake inhibitors (SSRIs) and internet-based cognitive behavioral therapy (ICBT) are recommended treatments of social anxiety disorder (SAD), and often combined, but their effects on monoaminergic signaling are not well understood. In this multi-tracer positron emission tomography (PET) study, 24 patients with SAD were randomized to treatment with escitalopram+ICBT or placebo+ICBT under double-blind conditions. Before and after 9 weeks of treatment, patients were examined with positron emission tomography and the radioligands [¹¹C]DASB and [¹¹C]PE2I, probing the serotonin (SERT) and dopamine (DAT) transporter proteins respectively. Both treatment combinations resulted in significant improvement as measured by the Liebowitz Social Anxiety Scale (LSAS). At baseline, SERT-DAT co-expression was high and, in the putamen and thalamus, co-expression showed positive associations with symptom severity. SERT-DAT co-expression was also predictive of treatment success, but predictor-outcome associations differed in direction between the treatments. After treatment, average SERT occupancy in the SSRI + ICBT group was >80%, with positive associations between symptom improvement and occupancy in the nucleus accumbens, putamen and anterior cingulate cortex. Following placebo+ICBT, SERT binding increased in the raphe nuclei. DAT binding increased in both groups in limbic and striatal areas, but relations with symptom improvement differed, being negative for SSRI + ICBT and positive for placebo + ICBT. Thus, serotonin-dopamine transporter co-expression exerts influence on symptom severity and remission rate in the treatment of social anxiety disorder. However, the monoamine transporters are modulated in dissimilar ways when cognitive-behavioral treatment is given concomitantly with either SSRI-medication or pill placebo.

Fig. 1. Whole sample pre-treatment SERT and DAT binding.

Left panel shows serotonin transporter non-displaceable binding potential pre treatment and the rightpanel shows non-displaceable binding potential for the dopamine transporter.

Fig. 2. PET results from the SSRI + ICBT group.

Regions where significant positive associations between SERT occupancy and symptom improvement were detected, i.e., the left anterior cingulate, right nucleus accumbens and left putamen.

Fig. 3. Scatterplots of significant group differences in associations between symptom improvement, as measured with the Liebowitz Social Anxiety Scale (LSAS), and the percentage change in DAT BPND in the left nucleus accumbens (L NAcc), right NAcc (R NAcc) and left thalamus.

Clusters of significant voxels (P_FWE < 0.05) shown overlaid on a standard anatomical brain template.