A recent α-[¹¹C]MTrp study of OCD patients identified a pattern of effects that was opposite to that seen in the previously tested patient groups. Berney et al. (2011) compared regional K* values of unmedicated OCD patients (n = 21) with those of age- and gender-matched healthy controls (n = 21). All patients were without current comorbid disorders and reported never having used the alleged SERT-inhibiting neurotoxic substances 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA). Patients with a past history of depression secondary to OCD were included in this study, but no significant correlations were found between K* values and Beck Depression Inventory (BDI) scores, suggesting that this was not a confounding variable. Regions of interest included cortical areas such as the OFC and ACG and subcortical areas such as the caudate, based on previous implications of these regions in OCD pathology. OCD patients showed significantly higher K* values in the right hippocampus and left inferior temporal gyrus and did not show significantly lower K* values in any of the regions of interest. The larger subgroup of male patients also showed significantly higher K* values in the caudate nucleus bilaterally. Furthermore, estimates of 5-HT synthesis in the temporal cortex and right caudate correlated positively with symptom severity (Table 17.1).

These findings suggest that OCD patients, as a group, relative to non-symptomatic healthy volunteers, may have abnormally elevated rates of 5-HT synthesis in brain regions such as the hippocampus, temporal cortex and caudate. Although this study alone could not establish whether elevated 5-HT synthesis in limbic and striatal regions reflects a primary or secondary compensatory event, these findings connote the failed attempt by the inhibitory system to regain control. This interpretation was deemed plausible and emphasized.

Extending the findings of Berney et al. (2011), a recent unpublished study by our group has investigated the change in brain regional 5-HT synthesis rates after behavioural and drug therapy for OCD. By also using PET in combination with the α-[¹¹C]MTrp tracer, brain 5-HT synthesis was estimated before and after CBT or sertraline treatment. Participating patients were randomly assigned to 12 weeks of either biweekly CBT sessions (n = 6) or daily doses of sertraline (n = 6). CBT included cognitive therapy for symptom-related difficulties such as dysfunctional beliefs and tolerance of distress, and exposure and response prevention with therapist assistance in naturalistic environments (e.g. home, work) as needed. Sertraline doses were gradually increased to a maximum of 200 mg, and the mean daily dose received was 133 mg/day (SD = 52 mg/day). Both SPM8 and volume of interest analyses were performed, and Yale-Brown Obsessive Compulsive Scale (Y-BOCS), BDI, and Go/NoGo task scores were assessed prior to and following treatment. Although a total of 16 patients were recruited, the preliminary PET analyses presented here are limited to a subset of 12 patients. As such, the following results are preliminary, and the proposed interpretations, based upon the intriguing patterns that have emerged thus far, are provocative and must be considered speculative. Significant improvement in symptom severity was observed in both treatment modalities (see Fig. 17.2), with four patients in the sertraline group and five in the CBT group showing a minimum 30 % decrease in Y-BOCS scores, classifying them as responders to treatment (Table 17.2).

Interestingly, in both treatment modalities, there was a significant positive correlation between symptom improvement and K* value change in the right striatum, right hippocampus, and cerebellum (p < .05). That is, both CBT and sertraline treatment appear to have increased α-[¹¹C]MTrp trapping in regions previously found to have abnormally high α-[¹¹C]MTrp trapping in unmedicated OCD patients (Berney et al. 2011). These findings suggest that a modulation of central serotonergic neurotransmission could contribute to further coping, thus providing the support needed to effectively control OC symptoms. The direction of change in K* values suggested that the response seen here was associated with a further enhancement of 5-HT synthesis, in essence allowing any inhibitory influence to achieve full potential and act effectively as a brake against obsessions and compulsions. Additionally, tracer trapping (K*) at baseline correlated positively with treatment response, independently of the nature of treatment. The higher the 5-HT synthesis in the pons before treatment, the more patients benefitted from either CBT or sertraline treatment (see Fig. 17.3). The ability of K* values at baseline to predict response to treatment is consistent with the proposed braking system hypothesis.

Furthermore, responders showed substantial increases in unidirectional α-[¹¹C]MTrp trapping, suggesting that these changes were not merely a regression towards the mean, as shown in Fig. 17.4. These increases in regional 5-HT synthesis appear to be restricted to the right side of the brain; whether such asymmetry is meaningful or relevant is not known, as this effect could reflect on sample size and “disappear” with a larger sample studied for a longer time. Those responders whose baseline K* values in the temporal cortex, frontal cortex, and cerebellum were below the average control K* values in these regions of healthy controls from a study by Berney et al. (2011) showed increases in K* values well above mean control K* values. Similarly, responders whose K* values in the striatum and hippocampus were already above mean control K* values at baseline also showed a substantial increase in regional 5-HT synthesis. The marked increases in α-[¹¹C]MTrp trapping were not observed in nonresponders, thus suggesting that dysfunction in the nonresponders may well be differentially mediated.