Brain serotonin synthesis capacity in obsessive-compulsive disorder: effects of cognitive behavioral therapy and sertraline

Abstract

Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are both effective treatments for some patients with obsessive-compulsive disorder (OCD), yet little is known about the neurochemical changes related to these treatment modalities. Here, we used positron emission tomography and the α-[11C]methyl-L-tryptophan tracer to examine the changes in brain regional serotonin synthesis capacity in OCD patients following treatment with CBT or SSRI treatment. Sixteen medication-free OCD patients were randomly assigned to 12 weeks of either CBT or sertraline treatment. Pre-to-post treatment changes in the α-[11C]methyl-L-tryptophan brain trapping constant, K* (ml/g/min), were assessed as a function of symptom response, and correlations with symptom improvement were examined. Responders/partial responders to treatment did not show significant changes in relative regional tracer uptake; rather, in responders/partial responders, 12 weeks of treatment led to serotonin synthesis capacity increases that were brain-wide. Irrespective of treatment modality, baseline serotonin synthesis capacity in the raphe nuclei correlated positively with clinical improvement. These observations suggest that, for some patients, successful remediation of OCD symptoms might be associated with greater serotonergic tone.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1. OCD symptom improvement over time with CBT or sertraline treatment.

Change in mean Y-BOCS scores during 12 weeks of CBT or sertraline treatment, as measured approximately every 2 weeks. Y-BOCS Yale-Brown Obsessive Compulsive Scale, CBT cognitive behavioral therapy, SSRI selective serotonin re-uptake inhibitor

Fig. 2. Pre–post treatment increases in serotonin synthesis capacity in responders/partial responders and non-responders.

Maximum intensity projections of the t-values, showing brain regions where absolute K* values (K*Absolute) were higher post-treatment compared to pre-treatment in clinical response sub-groups. a Responders and partial responders to either CBT or SSRI treatment (n = 9) demonstrated widespread pre–post treatment increases in absolute regional K* values. b Non-responders (n = 6) did not show any significant pre–post changes in absolute regional K* values. For visualization purposes, the displayed t-map threshold was T8 = 3.4 for responders/partial responders and T5 = 4.0 for non-responders, with p = 0.005 and an extent threshold of 50 voxels

Fig. 3. Positive correlation between baseline K* values and OCD symptom improvement.

Statistical parametric maps (SPM12), with an anatomical MRI overlay, demonstrating brain regions where pre-treatment K* values correlated positively with ΔY-BOCS in the whole sample of OCD patients (n = 15). The t-map threshold was 3.85, with p = 0.001 and an extent threshold of 50 voxels. A significant cluster was found in the right rostral raphe nuclei (t13 = 6.66, k = 67 voxels, coordinates x, y, z = 6, −20, −22 mm)

Fig. 4. Changes in global K* values vs. changes in OCD symptom severity.

Pre–post treatment changes in global K* values (ΔK*global) correlated positively with % decrease in Y-BOCS scores (rs = 0.46, p = 0.08). Notably, there was a clear outlier in this correlation (with the outlier removed, rs = 0.67, p = 0.009); the outlier (red circle) was not included in the least-squares linear fit to the data shown here. Patients treated with sertraline are represented by triangles, and patients treated with CBT are represented by circles. The ΔY-BOCS score cut-off for responder/partial responder and non-responder subgroups is indicated with the dashed vertical line. Y-BOCS Yale-Brown Obsessive-Compulsive Scale, rs Spearman’s rank correlation coefficient