Background: Functional brain imaging studies have shown deviant amygdala responses to emotional stimuli in subjects suffering from anxiety and depressive disorder, but both hyperactivity and hypoactivity compared to healthy controls have been reported. To account for these discrepant findings, we hypothesize that genetic and environmental risk factors differently impact on amygdala functioning. Methods: To test this hypothesis, we assessed amygdala responses to an emotional faces paradigm during functional magnetic resonance imaging in monozygotic twin pairs discordant for the risk of anxiety and depression (n = 10 pairs) and in monozygotic twin pairs concordant for high (n = 7 pairs) or low (n = 15 pairs) risk for anxiety and depression. Results: Main effects (all faces vs. baseline) revealed robust bilateral amygdala activity across groups. In discordant twins, increased amygdala responses were found for negatively valenced stimuli (angry/anxious faces) in high-risk twins compared to their low-risk co-twins. In contrast, concordant high-risk pairs revealed blunted amygdala reactivity to both positive and negative faces compared with concordant low-risk pairs. Post-hoc analyses showed that these findings were independent of 5-HTTLPR genotype. Conclusions: Our findings indicate amygdala hyperactivity in subjects who are at high risk for anxiety and depression through environmental factors and amygdala hypoactivity in those at risk mainly through genetic factors. We suggest that this result reflects a difference in baseline amygdala activation in these groups. Future imaging studies on anxiety and depression should aim to avoid admixture of subjects who are at genetic risk with those at risk due to environmental factors.

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The High-Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomography (PET) scanner. Recently, a 3D filtered backprojection (3D-FBP) reconstruction method has been implemented to reduce bias in short duration frames, currently observed in 3D ordinary Poisson OSEM (3D-OP-OSEM) reconstructions. Further improvements might be expected using a new method of variance reduction on randoms (VRR) based on coincidence histograms instead of using the delayed window technique (DW) to estimate randoms. The goal of this study was to evaluate VRR in combination with 3D-OP-OSEM and 3D-FBP reconstruction techniques. To this end, several phantom studies and a human brain study were performed. For most phantom studies, 3D-OP-OSEM showed higher accuracy of observed activity concentrations with VRR than with DW. However, both positive and negative deviations in reconstructed activity concentrations and large biases of grey to white matter contrast ratio (up to 88%) were still observed as a function of scan statistics. Moreover 3D-OP-OSEM+VRR also showed bias up to 64% in clinical data, i.e. in some pharmacokinetic parameters as compared with those obtained with 3D-FBP+VRR. In the case of 3D-FBP, VRR showed similar results as DW for both phantom and clinical data, except that VRR showed a better standard deviation of 6-10%. Therefore, VRR should be used to correct for randoms in HRRT PET studies.

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Purpose: NK1 receptors have been implicated in various neuropsychiatric and other disorders. R116301 is a selective NK1 receptor antagonist. In this pilot study, [11 C]R116301 was evaluated as a potential positron emission tomography (PET) ligand for the NK1 receptor. Procedures:Two dynamic PET studies were performed in three normal volunteers before and after a blocking dose of aprepitant. Data were analyzed using striatum to cerebellum standardized uptake value (SUV) ratios.Results: Baseline SUV ratios at 60-90 min after injection ranged from 1.22 to 1.70. Following aprepitant administration, this specific signal was completely blocked. Aprepitant administration did not significantly affect uptake in cerebellum, confirming the absence of NK1 receptors in cerebellum. Conclusion:These preliminary results indicate that [ 11 C]R116301 has potential as a radioligand for in vivo assessment of NK1 receptors in the human brain.