Background: The hypothesis of a central sertonin (5HT) dysfunction in Obsessive Compulsive Disorder (OCD) stems largely from pharmacological treatment studies, where enhancement of 5HT neurotransmission is thought to be critical for treatment efficacy. Direct measures of central 5HT metabolism has recently been possible through Positron Emission Tomography (PET) coupled with the -[11C]-methyl-L-tryptophan (11C- Mtrp) tracer, believed to provide an index of the brain regional rates of 5-HT synthesis, through the measure of 11C-Mtrp brain trapping constant K*.
Method: In this study the 11C- Mtrp method was applied to compare medication-free patients with current OCD (n _ 21) to normal controls (n _ 21) matched for age and gender. The functional PET data were analyzed with Statistical parametric mapping (SPM99). Pairwise t-statistical maps were obtained comparing OCD patients to controls; the regions considered statistically significant had an extended threshold of 100 voxels with a peak threshold of p _ 0.005.
Results: 21 OCD patients and 21 controls participated in the study. There was no significant group effect in the whole sample, or in either sex analysed separately for global K* values (p _ 0.66). In the sample as a whole, - [11C]MTrp trapping was significantly higher for subjects with OCD in the right hippocampus and the Left Temporal Gyrus (BA 20). A region of interest (ROI) based analysis confirmed the SPM findings. In addition the ROI analysis conducted in males (n _ 15) revealed a main group effect in the caudate nucleus, with significantly higher regional trapping (p _ 0.05) in OCD subjects. No volumetric differences were found for any of the ROI between OCD subjects and healthy controls. In the sample as a whole YBOCS total score correlated positively with -[11C]MTrp trapping in the right middle and superior Temporal Gyrus (BAs 21, 38) and in the left inferior and middle Temporal Gyrus (BAs 20, 21).
Conclusion: These findings add to the cumulative evidence supporting serotonergic dysfunction in OCD, and more specifically a possible increase in brain regional 5HT in the hippocampus, the Temporal Gyrus and the Caudate nucleus.