- Email: [email protected]
First PET study on the influence of serotonin transporter (SERT) availability on clinical autoimmune disease
Abstracts / NeuroImage 41 (2008) T58–T200
T153
Poster Presentation No.: P093
First PET study on the influence of serotonin transporter (SERT) availability on clinical autoimmune disease Swen Hesse,a F. Then Bergh,b R. Regenthal,c M. Patt,a G.A. Becker,a E. Hess,b F. Moeller,b J. Kratzsch,d D. Fuehrer,e H. Knuepfer,c K. Kendziorra,a and O. Sabria a
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany b Department of Neurology, University of Leipzig, Leipzig, Germany c Institute for Clinical Pharmacology, University of Leipzig, Leipzig, Germany d Institute for Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University of Leipzig, Leipzig, Germany e Department of Internal Medicine, University of Leipzig, Leipzig, Germany Introduction: Serotonin is supposed to be the mediator of bidirectional interactions between the nervous system and the immune system. Thus, SERT knock-out influences the susceptibility to inflammatory infiltrate in mice [1]. To date, no in vivo imaging study has addressed these interactions. The aim of our study was therefore to investigate SERT availability with PET and [11C]DASB in multiple sclerosis (MS). We also considered SERT gene promoter polymorphism (SERT-LPR, short/long allele) since it might be linked with SERT in vivo expression, and both with stress reactivity. The latter was estimated by measuring hypothalamic–pituitary–adrenal axis (HPA) activity, which is increased in MS [2] and likewise in depression or anxiety. Methods: Seventeen patients with MS (10 females, 40 ± 11 yrs) underwent dynamic PET for 90 min after IV 90-sec injection of 517 ± 130 MBq [11C]DASB. Distribution volume ratios (DVR) were generated using the multilinear reference tissue model (MRTM2) [3] and VOI analysis was conducted after co-registration of the DVR maps with 3D MRI data set (MultiModality, HERMES Medical Solutions). HPA activity was investigated by dexamethasone/CRH test. All investigations were performed after withdrawal of immune modulatory therapy. Fatigue and depression were rated by Wü rzburger Erschö pfungsinventar bei MS (WEIMuS) and Beck Depression Inventory (BDI), respectively. Ten healthy volunteers served as controls (6 females, age 37 ± 10 yrs). Results: DVR were lower (age-adjusted) in MS patients in distinct brain areas including both insular regions (e.g. right 1.46 ± 0.10 vs 1.58 ± 0.14; p = 0.018), the left hippocampus (e.g. right 1.64 ± 0.14 vs 1.79 ± 0.15; p = 0.036), the thalamus (e.g. right 2.11 ± 0.22 vs 2.38 ± 0.32; p = 0.041), and hypothalamus (2.22 ± 0.38 vs 2.59 ± 0.39; p = 0.039). MS patients had a slight HPA hyperactivity, higher WEIMuS (22.6 ± 16.9 vs 3.2 ± 4.3; p = 0.08), and BDI (5.4 ± 4.9 vs 1.1 ± 1.7; p = 0.04). Only in MS patients, DVR correlated with BDI in the medial frontal cortex bilaterally (r = 0.52, p = 0.02 and r = 0.55, p = 0.012), with WEIMuS in the right caudate (r = 0.48, p = 0.03), with rise/mean curve location during dex/CRH challenge in the hypothalamus, midbrain/raphe, in hippocampus/amygdale and basal ganglia bilaterally. Cortisol secretion did not correspond with DVR, and we found no significant differences of DVR depending on SERT-LPR in either patients or controls. Conclusion: These preliminary data suppose a serotonergic involvement in MS affecting the insulae, thalamic cores, the hypothalamus and the hippocampus/amygdale. Fatigue/depression measures as well as HPA activity parameters seem to be differentially linked with the SERT availability in these patients. To what extent stress as an environmental factor contribute to interaction of serotonin, SERT-LPR, and neuroinflammation needs to be further investigated. [1] Hofstetter, H.H., Messner, R., Lesch, K.P., et al. Clin Exp Immunol: 142(1), pp. 39–44, 2005. [2] Then Bergh, F., Kümpfel, T., Trenkwalder, C., et al. Neurology: 53(4), pp. 772–777, 1999. [3] Ichise, M., Liow, J.-S., Lu, J.-Q., et al. J Cereb Blood Flow Metab: 23, pp. 1096–1112, 2003. doi:10.1016/j.neuroimage.2008.04.121
T153
Poster Presentation No.: P093
First PET study on the influence of serotonin transporter (SERT) availability on clinical autoimmune disease Swen Hesse,a F. Then Bergh,b R. Regenthal,c M. Patt,a G.A. Becker,a E. Hess,b F. Moeller,b J. Kratzsch,d D. Fuehrer,e H. Knuepfer,c K. Kendziorra,a and O. Sabria a
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany b Department of Neurology, University of Leipzig, Leipzig, Germany c Institute for Clinical Pharmacology, University of Leipzig, Leipzig, Germany d Institute for Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University of Leipzig, Leipzig, Germany e Department of Internal Medicine, University of Leipzig, Leipzig, Germany Introduction: Serotonin is supposed to be the mediator of bidirectional interactions between the nervous system and the immune system. Thus, SERT knock-out influences the susceptibility to inflammatory infiltrate in mice [1]. To date, no in vivo imaging study has addressed these interactions. The aim of our study was therefore to investigate SERT availability with PET and [11C]DASB in multiple sclerosis (MS). We also considered SERT gene promoter polymorphism (SERT-LPR, short/long allele) since it might be linked with SERT in vivo expression, and both with stress reactivity. The latter was estimated by measuring hypothalamic–pituitary–adrenal axis (HPA) activity, which is increased in MS [2] and likewise in depression or anxiety. Methods: Seventeen patients with MS (10 females, 40 ± 11 yrs) underwent dynamic PET for 90 min after IV 90-sec injection of 517 ± 130 MBq [11C]DASB. Distribution volume ratios (DVR) were generated using the multilinear reference tissue model (MRTM2) [3] and VOI analysis was conducted after co-registration of the DVR maps with 3D MRI data set (MultiModality, HERMES Medical Solutions). HPA activity was investigated by dexamethasone/CRH test. All investigations were performed after withdrawal of immune modulatory therapy. Fatigue and depression were rated by Wü rzburger Erschö pfungsinventar bei MS (WEIMuS) and Beck Depression Inventory (BDI), respectively. Ten healthy volunteers served as controls (6 females, age 37 ± 10 yrs). Results: DVR were lower (age-adjusted) in MS patients in distinct brain areas including both insular regions (e.g. right 1.46 ± 0.10 vs 1.58 ± 0.14; p = 0.018), the left hippocampus (e.g. right 1.64 ± 0.14 vs 1.79 ± 0.15; p = 0.036), the thalamus (e.g. right 2.11 ± 0.22 vs 2.38 ± 0.32; p = 0.041), and hypothalamus (2.22 ± 0.38 vs 2.59 ± 0.39; p = 0.039). MS patients had a slight HPA hyperactivity, higher WEIMuS (22.6 ± 16.9 vs 3.2 ± 4.3; p = 0.08), and BDI (5.4 ± 4.9 vs 1.1 ± 1.7; p = 0.04). Only in MS patients, DVR correlated with BDI in the medial frontal cortex bilaterally (r = 0.52, p = 0.02 and r = 0.55, p = 0.012), with WEIMuS in the right caudate (r = 0.48, p = 0.03), with rise/mean curve location during dex/CRH challenge in the hypothalamus, midbrain/raphe, in hippocampus/amygdale and basal ganglia bilaterally. Cortisol secretion did not correspond with DVR, and we found no significant differences of DVR depending on SERT-LPR in either patients or controls. Conclusion: These preliminary data suppose a serotonergic involvement in MS affecting the insulae, thalamic cores, the hypothalamus and the hippocampus/amygdale. Fatigue/depression measures as well as HPA activity parameters seem to be differentially linked with the SERT availability in these patients. To what extent stress as an environmental factor contribute to interaction of serotonin, SERT-LPR, and neuroinflammation needs to be further investigated. [1] Hofstetter, H.H., Messner, R., Lesch, K.P., et al. Clin Exp Immunol: 142(1), pp. 39–44, 2005. [2] Then Bergh, F., Kümpfel, T., Trenkwalder, C., et al. Neurology: 53(4), pp. 772–777, 1999. [3] Ichise, M., Liow, J.-S., Lu, J.-Q., et al. J Cereb Blood Flow Metab: 23, pp. 1096–1112, 2003. doi:10.1016/j.neuroimage.2008.04.121