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Objectives

Pharmacological evidence suggests abnormalities in the brain serotonin (5-HT) system in OCD involving cortical 5-HT_2A receptors. As these are located on pyramidal cells and interneurons and may modulate glutamate (Glu) and GABA transmission, we measured 5-HT_2A receptor availability with PET, and Glx (Glu plus glutamine) and GABA levels with MRS in OCD patients and matched controls.

Methods

Nineteen unmedicated patients (ages 31 ± 10 years, 9 F, 10 M) and 19 matched healthy controls completed PET and MRS studies. [¹¹C]MDL100907 PET scans were acquired on an HR+ camera with arterial input function and analyzed with two-tissue kinetic modeling to generate BP_P in multiple ROIs. MRS data were acquired using a 3T GE system and an 8-channel phased-array head coil with the J edited spin echo difference technique from an anterior cingulate (ACC) and a dorsolateral prefrontal cortex (DLPFC) voxel to generate GABA and Glx ratios to water.

Results

PET and MRS outcome measures showed no regional differences between OCD and controls. Glx/W was 3.2 ± .99 in OCD and 3.3 ± .58 in controls in DLPFC (p = 0.8); GABA/W was 2.2 ± .62 in OCD and 2.4 ± .54 in controls in ACC (p = 0.2, all values times 10^-3). However, there were significant correlations between ACC GABA/W and [¹¹C]MDL100907 BP_P in multiple cortical regions in OCD but not controls. In orbital frontal cortex, where BP_P values were 37.4 ± 8.4 mL^.cm^-3 in OCD and 38.0 ± 14.4 mL^.cm^-3 in controls (p = 0.9), Pearson R values were -0.19 (p = 0.4) in controls and 0.67 (p = 0.002) in OCD.

Conclusions

We found no abnormalities in Glx or GABA levels or 5-HT_2A receptors in OCD. However, the strong correlations between PET and MRS data suggest heightened coupling in OCD between these systems. Further studies are needed to fully characterize the nature of this relationship.

Research Support

NIM

	Year	Citations

References