312 Increased Regional Cerebral Type 1 Cannabinoid Receptor Availability in Functional Dyspepsia: A [18F]MK9470 PET Study

Abstract

INTRODUCTION: Functional dyspepsia (FD) is defined as the presence of chronic epigastric symptoms in the absence of underlying structural or biochemical abnormalities likely to explain them. These dyspeptic symptoms are often meal-related and disturbances in appetite regulation and food intake might lead to unexplained weight loss. FD patients are also characterized by abnormal regional cerebral activity in key areas of the ‘pain neuromatrix'. However, it is unknown which neurotransmitter mechanisms underlie these abnormalities. Endocannabinoids are involved in pain processing, regulation of gastrointestinal function and reward/food intake AIM: To compare the regional cerebral availability of the type 1 cannabinoid (CB1) receptor between FD patients and healthy controls. METHODS: 12 FD patients (mean age 29.4 ± 10.6, 11 women) with significant weight loss (mean 13.2 kg) and 12 age-, genderand BMI-matched healthy controls participated in the study; psychiatric co-morbidity and intake of centrally acting medication or (recreational) drugs were exclusion criteria. Each subject underwent a 30 minute dynamic positron emission tomography scan consisting of 6 frames at 90 min postinjection of the CB1 receptor-selective radioligand [18F]MK9470. Parametric maps of CB1 receptor availability were constructed using modified standard uptake value (mSUV) values as estimate of receptor availability. These maps were spatially normalized to Montreal Neurological Institute space to allow whole-brain voxelbased analysis. A significance level of pheight < 0.001 (uncorrected) was used to compare CB1 receptor availability between both groups. RESULTS: Significantly higher CB1 receptor availability was found in FD patients with local maxima in the following brain regions: anterior cingulate cortex (ACC, perigenual), caudate head, insular cortex (INS, anterior/mid, bilateral), orbitofrontal cortex (bilateral) and putamen (Table 1). The large cluster also included the amygdala, globus pallidus, hypothalamus, PAG and ventral striatum (nucleus accumbens) (Figure 1). CONCLUSION: We report the first study demonstrating a significantly higher CB1 receptor availability in regions involved in the regulation of visceral sensation (ant/mid INS, ACC and amygdala), and reward/food intake (hypothalamus and (ventral) striatum) in FD patients compared to controls. Whether this elevated receptor availability predisposes to or is a consequence of FD symptoms remains to be elucidated. However, within the patients group weight loss was not associated with receptor binding in any of the brain regions. These results may indicate that the abnormal brain activity in several of these regions previously demonstrated in FD may be due to abnormal functioning of the endocannabinoid system, identifying it as a potential novel target for treatment. Table1