- Email: [email protected]
P.1.e.020 Caudate grey matter volume in obsessivecompulsive disorder is influenced by adverse childhood experiences and ongoing drug treatment
S314
P.1.e. Basic and clinical neuroscience − Brain imaging
feedback conditions, adolescents share the same neural mechanism. EF compared to MF, the activated area were mainly distributed in the cortical midline structures which was correlated with the self-referential processing. MF compared to EF, the activated area were widely distributed in the temporo-parietooccipital network. In the future, more research are needed to investigate the meaning of different brain activation on various feedback condition. References [1] Xiaohong Pana, Yang Hua, Lei Li, Jianqi Li, 2009 Elsevier Ireland Lt. Evaluative-feedback stimuli selectively activate the self-related brain area: An fMRI study, 90−91.
P.1.e.019 Glutamate-related abnormalities in psychotic and non-psychotic depression: a magnetic resonance spectroscopy imaging study
toward a lower ratio in PD compared with NPD (p = 0.067). No significant differences was found in the Glx/Cr [F(2,55) = 1.52; p = 0.228]. An independent analysis considering the use of medication showed that the duration of use of antidepressants did not affect the values of Glu/Cr [F(4,26) = 0.06; p = 0.993] and Glx/Cr [F(4,26) = 0.71; p = 0.592]. However, a significant difference in the Glu/Cr [F(1,26) = 4.87; p = 0.036] was found due to the use of antipsychotics. Conclusions: Our preliminary results are in agreement with previous studies showing glutamate-related abnormalities in the brain of depressive patients [1]. However, caution is needed in interpreting the data, due to the possible effects of antipsychotics in reducing the ratio of Glu/Cr when patients with psychotic symptoms are analyzed. References ¨ ur, D., 2010. Magnetic resonance spectroscopy studies [1] Y¨uksel, C., Ong¨ of glutamate-related abnormalities in mood disorders. Biol Psychiatry. 68, 785−94.
H.P. S´a1 , C.M. Del-Ben1 ° , A.G. Balestra1 , P.R. Diniz2 , A.C. Santos2 , C.E.G. Salmon3 , M.S. Schaulferberger1 . 1 School of Medicine of Ribeir˜ ao Preto University of S˜ao Paulo, Department of Neuroscience and Behavior, Ribeir˜ao Preto, Brazil; 2 School of Medicine of Ribeir˜ao Preto University of S˜ao Paulo, Department of Internal Medicine, Ribeir˜ao Preto, Brazil; 3 Faculty of Philosophy and Sciences of Ribeir˜ ao Preto University of S˜ao Paulo, Department of Physics and Mathematics, Ribeir˜ao Preto, Brazil
S. Poletti1 ° , D. Radaelli1 , E. Pozzi1 , E. Smeraldi1 , F. Benedetti1 . 1 San Raffaele Scientific Institute, Deptartment of Clinical Neurosciences, Milan, Italy
Background and aims: Although there is evidence pointing to glutamate-related abnormalities in major depression [1], little is known about possible differences related to the subtypes of unipolar depression. The current study used proton magnetic resonance spectroscopy imaging (1 H-MRSI) to examine the levels of glutamate (Glu) and glutamate + glutamine (Glx) in the anterior cingulate cortex (ACC) of patients with psychotic (PD) or nonpsychotic (NPD) unipolar depression. Methods: The sample comprised 58 participants (40 females; 69.0%), aged between 18 and 64 years (mean = 38.9; SD = 12.1), being 16 diagnosed according to DSM-IV as PD, 19 as NPD, and 23 healthy controls (HC). Most of the patients were in their first (60.6%) or second (18.2%) depressive episode. The length of the current episode varied from 0 to 180 months (mean = 19.10; SD = 33.46) and the severity of the depressive symptoms (Hamilton scale) was similar between PD (mean = 37.7; SD = 13.0) and NPD (mean = 37.5; SD = 8.12). Most of the patients were off medication (20.0%), or in the beginning of the treatment (25.7% less than one week of use of antidepressant; 20.0%, 1 to 4 weeks), but 28.6% were in a long-term use of antidepressants. Each subject underwent MRS conducted on a 3T Phillips scanner, using a SV-PRESS sequence (TR/TE = 1500/31 ms). The voxel (3 cm×2 cm×1 cm) was placed in the ACC. Spectroscopy analysis was performed with LCModel software. The output was given as .txt files and the values were analyzed as ratios between peaks. Glu/Cr and Glx/Cr were compared by multivariate general linear model (GLM), with groups (PD, DNP HC) and sex as independent factors. Post-hoc analyses were done by Dunnett test. A level of P < 0.05 was considered to be significant. Results: No significant differences were found regarding age (p = 0.249), sex (p = 0.220) and duration of current depressive episode (p = 0.248]. There were significant differences among groups in the Glu/Cr [F(2,55) = 3.28, P = 0.045], due to a lower ratio in the ACC of PD compared with HC (p = 0.038) and a trend
Background: Current views on the pathogenesis of psychiatric disorders focus on the interplay between genetic and environmental factors, with individual variation in vulnerability and resilience to hazards being part of the multifactorial development of illness [1]. Between environmental factors exposure to adverse childhood experiences (ACE) is known to increases the risk of adult physical and mental health disorders, including obsessivecompulsive disorder (OCD). Moreover recent brain imaging studies in patients and healthy controls confirmed the influence of ACE on adult cortical neural responses and grey matter (GM) volumes. A sparse but consistent literature associated childhood emotional and physical abuse and neglect with the diagnosis of obsessivecompulsive disorder (OCD) in psychiatric patients [1], with the dimensions of OCD psychopathology in patients with OCD [2], and also with obsessive-compulsive symptoms in the general population. Robust neuroimaging findings associated OCD with cortico-striatal disfunction and with abnormal morphology and metabolism of cortical areas and basal ganglia. So far no study explored the brain correlates of ACE in patients with OCD. Following the above line of reasoning, we studied the effects of ACE on the brain grey matter morphometry of adult OCD patients. Methods: We explored the GM correlates of ACE in 40 patients with OCD (15 drug-na¨ıve and 25 drug-treated) with MRI voxelbased morphometry at 3.0 T. Severity of ACE was rated on the Risky Families Questionnaire (RFQ); Severity of symptoms was rated on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). To assess the statistical significance of group differences data were analyzed within the context of the General Linear Model (GLM). Regional GM volumes were the dependent variable, drug treatment (na¨ıve vs treated) and breadth of exposure to ACE (high vs low) were the factors of interest, and sex, duration of illness, and handedness were considered as nuisance covariates. Whole brain statistical threshold was p < 0.05 family-wise error corrected for multiple comparisons.
P.1.e.020 Caudate grey matter volume in obsessivecompulsive disorder is influenced by adverse childhood experiences and ongoing drug treatment
P.1.e. Basic and clinical neuroscience − Brain imaging Results: At the VBM analysis the effects of ACE and current drug treatment survived the statistical threshold in a single cluster of 55 mm3 in the head of the left caudate nucleus. Here, patients with higher ACE had bigger GM volumes than patients with lower ACE and patients taking drugs had significantly lower volumes than drug-na¨ıve. Moreover worse ACE were associated with earlier age at onset of OCD, medication treatment and mixed handedness. Conclusions: This is the first study that reports an effect of adverse childhood experiences and drug treatment on adult grey matter volumes in patients with OCD. Exposure to ACE increased, and ongoing drug treatment decreased, caudate GM in OCD. Increased caudate size and metabolism have been consistently associated with OCD. The caudate nucleus plays a crucial role in reward detection and goal representation, thus giving a fundamental contribution to successful goal-directed action. Our findings suggest a detrimental effect of ACE on the brain underpinnings of OCD, with an opposite effect of medications. References [1] Wermter AK, Laucht M, Schimmelmann BG, Banaschweski T, SonugaBarke EJ, Rietschel M, et al. 2010: From nature versus nurture, via nature and nurture, to gene × environment interaction in mental disorders. Eur Child Adolesc Psychiatry. 19:199–210. [2] Stein MB, Walker JR, Anderson G, Hazen AL, Ross CA, Eldridge G, et al. 1996: Childhood physical and sexual abuse in patients with anxiety disorders and in a community sample. Am J Psychiatry. 153:275–277.
P.1.e.021 [11 C]NS14492 as a novel alpha-7 nicotinic acetylcholine receptor PET radioligand: in vivo evaluation and drug occupancy measurements A. Ettrup1 ° , J.D. Mikkelsen1 , S. Lehel2 , J. Madsen2 , E.O. Nielsen3 , D.B. Timmermann3 , D. Peters3 , G.M. Knudsen1 . 1 Copenhagen University Hospital Rigshospitalet, Neurobiology Research Unit, Copenhagen, Denmark; 2 Copenhagen University Hospital Rigshospitalet, PET and Cyclotron Unit, Copenhagen, Denmark; 3 NeuroSearch A/S, Ballerup, Denmark Purpose: Small molecule a7 nicotinic acetylcholine receptor (a7 nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer’s disease. A suitable radiolabelled a7 nAChR positron emission tomography (PET) tracer would be important for in vivo quantification of a7 nAChR binding in human population or patient groups. Furthermore, PET studies would be of particular importance as a tool to measure a7 nAChR occupancy in drug development. However, only few a7 nAChR PET ligands are currently available, and none of them have shown significant blocking in vivo by selective ligands [1,2]. Here, we present the radiosynthesis and in vivo evaluation of [11 C]NS14492 as a new selective a7 nAChR PET radiotracer. Methods: a7 nAChR affinity and selectivity of NS14492 was characterized using in vitro binding assays, and NS14492 was radiolabelled by methylation of its desmethyl precursor with [11 C]methyl triflate. Five female Danish Landrace pigs were studied at baseline and after i.v. administration of blocking doses of either the a7 nAChR partial agonist SSR180711 (10 mg/kg, n = 2 and 1 mg/kg, n = 1) or unlabelled NS14492 (10 mg/kg, n = 2). [11 C]NS14492 was given as an intravenous bolus injection, and the pigs were scanned for 90 min both at baseline and in the blocked conditions with a high resolution research tomography
S315
(HRRT) PET camera. Arterial whole blood and plasma radioactivity were measured during the scanning sessions, along with HPLC measurements of plasma parent compound and radiolabelled metabolites. PET data was quantified with a graphical analysis with arterial input; [11 C]NS14492 regional distribution volumes (VT ) were calculated, and a7 nAChR occupancy was determined from occupancy plots with VT in the blocked and unblocked conditions, across ten regions. Results: The in vitro affinity of NS14492 for a7 nAChR was high (Ki value: 2.2±0.8 nM), while its affinity for a4b2 nAChRs was ~1000 fold lower (Ki value: 2.8±1.1 mM). Also against 5-HT3 and a broad range of different receptors, transporters, and ion channels, NS14492 was characterized as a highly a7 nAChRselective agonist. [11 C]NS14492 had a high uptake in the pig brain, with the highest binding found in the cerebral cortex and the thalamus in accordance with a7 nAChR distribution. Pretreatment with NS14492 and SSR180711 consistently decreased [11 C]NS14492 VT in all examined regions supporting that the radioligand binds selectively to a7 nAChR in vivo. Also, no lipophilic radiolabelled metabolites were observed in pig plasma following [11 C]NS14492 injection. The occupancy of a7 nAChR was 81% and 69% with 10 mg/kg SSR180711 given 30 minutes prior to the second scan, whereas 1 mg/kg SSR180711 lead to 61% occupancy. Similarly, 10 mg/kg NS14492, given 30 minutes prior to a second scan lead to 75% occupancy of a7 nAChR, and increasing the inter-scan interval to 4 hours lead to 60% occupancy, corresponding to lower plasma concentration of cold NS14492. Conclusions: We report here that [11 C]NS14492 is the first PET radioligand for a7 nAChR showing a dose-dependent decline in cerebral binding after receptor blockade. This compound is considered a promising PET tracer for in vivo measurements of a7 nAChR binding and drug occupancy in the human brain. References [1] Hashimoto K, Nishiyama S, Ohba H et al. 2008 [11C]CHIBA-1001 as a novel PET ligand for alpha7 nicotinic receptors in the brain: a PET study in conscious monkeys. PLoS One 3, e3231. [2] Deuther-Conrad W, Fischer S, Hiller A et al. 2009 Molecular imaging of alpha7 nicotinic acetylcholine receptors: design and evaluation of the potent radioligand [18F]NS10743. Eur J Nucl Med Mol Imaging 36, 791–800.
P.1.e.022 Effect of electroconvulsive therapy on serotonin-1A receptor binding in major depressive disorder P. Baldinger1 ° , R. Lanzenberger1 , A. Hahn1 , M. Mitterhauser2 , W. Wadsak2 , Z. Micskei3 , J. Ungersb¨ock2 , D. Winkler1 , 1 Medical University of Vienna, S. Kasper1 , R. Frey1 . Department of Psychiatry and Psychotherapy, Vienna, Austria; 2 Medical University of Vienna, Department of Nuclear Medicine − PET Center, Vienna, Austria; 3 Medical University of Vienna, Department of Special Anaesthesia and Pain Management, Vienna, Austria Aim of the study: Electroconvulsive therapy (ECT) is used for the therapy of treatment-resistant depression due to its effectiveness in reducing depressive symptoms and the ameliorated practicability. The underlying neurobiological mechanisms are still unclear and the findings concerning this topic are inconsistent. However, several preclinical studies emphasize the significant involvement of the serotonergic system, particularly the main inhibitory 5-HT1A
P.1.e. Basic and clinical neuroscience − Brain imaging
feedback conditions, adolescents share the same neural mechanism. EF compared to MF, the activated area were mainly distributed in the cortical midline structures which was correlated with the self-referential processing. MF compared to EF, the activated area were widely distributed in the temporo-parietooccipital network. In the future, more research are needed to investigate the meaning of different brain activation on various feedback condition. References [1] Xiaohong Pana, Yang Hua, Lei Li, Jianqi Li, 2009 Elsevier Ireland Lt. Evaluative-feedback stimuli selectively activate the self-related brain area: An fMRI study, 90−91.
P.1.e.019 Glutamate-related abnormalities in psychotic and non-psychotic depression: a magnetic resonance spectroscopy imaging study
toward a lower ratio in PD compared with NPD (p = 0.067). No significant differences was found in the Glx/Cr [F(2,55) = 1.52; p = 0.228]. An independent analysis considering the use of medication showed that the duration of use of antidepressants did not affect the values of Glu/Cr [F(4,26) = 0.06; p = 0.993] and Glx/Cr [F(4,26) = 0.71; p = 0.592]. However, a significant difference in the Glu/Cr [F(1,26) = 4.87; p = 0.036] was found due to the use of antipsychotics. Conclusions: Our preliminary results are in agreement with previous studies showing glutamate-related abnormalities in the brain of depressive patients [1]. However, caution is needed in interpreting the data, due to the possible effects of antipsychotics in reducing the ratio of Glu/Cr when patients with psychotic symptoms are analyzed. References ¨ ur, D., 2010. Magnetic resonance spectroscopy studies [1] Y¨uksel, C., Ong¨ of glutamate-related abnormalities in mood disorders. Biol Psychiatry. 68, 785−94.
H.P. S´a1 , C.M. Del-Ben1 ° , A.G. Balestra1 , P.R. Diniz2 , A.C. Santos2 , C.E.G. Salmon3 , M.S. Schaulferberger1 . 1 School of Medicine of Ribeir˜ ao Preto University of S˜ao Paulo, Department of Neuroscience and Behavior, Ribeir˜ao Preto, Brazil; 2 School of Medicine of Ribeir˜ao Preto University of S˜ao Paulo, Department of Internal Medicine, Ribeir˜ao Preto, Brazil; 3 Faculty of Philosophy and Sciences of Ribeir˜ ao Preto University of S˜ao Paulo, Department of Physics and Mathematics, Ribeir˜ao Preto, Brazil
S. Poletti1 ° , D. Radaelli1 , E. Pozzi1 , E. Smeraldi1 , F. Benedetti1 . 1 San Raffaele Scientific Institute, Deptartment of Clinical Neurosciences, Milan, Italy
Background and aims: Although there is evidence pointing to glutamate-related abnormalities in major depression [1], little is known about possible differences related to the subtypes of unipolar depression. The current study used proton magnetic resonance spectroscopy imaging (1 H-MRSI) to examine the levels of glutamate (Glu) and glutamate + glutamine (Glx) in the anterior cingulate cortex (ACC) of patients with psychotic (PD) or nonpsychotic (NPD) unipolar depression. Methods: The sample comprised 58 participants (40 females; 69.0%), aged between 18 and 64 years (mean = 38.9; SD = 12.1), being 16 diagnosed according to DSM-IV as PD, 19 as NPD, and 23 healthy controls (HC). Most of the patients were in their first (60.6%) or second (18.2%) depressive episode. The length of the current episode varied from 0 to 180 months (mean = 19.10; SD = 33.46) and the severity of the depressive symptoms (Hamilton scale) was similar between PD (mean = 37.7; SD = 13.0) and NPD (mean = 37.5; SD = 8.12). Most of the patients were off medication (20.0%), or in the beginning of the treatment (25.7% less than one week of use of antidepressant; 20.0%, 1 to 4 weeks), but 28.6% were in a long-term use of antidepressants. Each subject underwent MRS conducted on a 3T Phillips scanner, using a SV-PRESS sequence (TR/TE = 1500/31 ms). The voxel (3 cm×2 cm×1 cm) was placed in the ACC. Spectroscopy analysis was performed with LCModel software. The output was given as .txt files and the values were analyzed as ratios between peaks. Glu/Cr and Glx/Cr were compared by multivariate general linear model (GLM), with groups (PD, DNP HC) and sex as independent factors. Post-hoc analyses were done by Dunnett test. A level of P < 0.05 was considered to be significant. Results: No significant differences were found regarding age (p = 0.249), sex (p = 0.220) and duration of current depressive episode (p = 0.248]. There were significant differences among groups in the Glu/Cr [F(2,55) = 3.28, P = 0.045], due to a lower ratio in the ACC of PD compared with HC (p = 0.038) and a trend
Background: Current views on the pathogenesis of psychiatric disorders focus on the interplay between genetic and environmental factors, with individual variation in vulnerability and resilience to hazards being part of the multifactorial development of illness [1]. Between environmental factors exposure to adverse childhood experiences (ACE) is known to increases the risk of adult physical and mental health disorders, including obsessivecompulsive disorder (OCD). Moreover recent brain imaging studies in patients and healthy controls confirmed the influence of ACE on adult cortical neural responses and grey matter (GM) volumes. A sparse but consistent literature associated childhood emotional and physical abuse and neglect with the diagnosis of obsessivecompulsive disorder (OCD) in psychiatric patients [1], with the dimensions of OCD psychopathology in patients with OCD [2], and also with obsessive-compulsive symptoms in the general population. Robust neuroimaging findings associated OCD with cortico-striatal disfunction and with abnormal morphology and metabolism of cortical areas and basal ganglia. So far no study explored the brain correlates of ACE in patients with OCD. Following the above line of reasoning, we studied the effects of ACE on the brain grey matter morphometry of adult OCD patients. Methods: We explored the GM correlates of ACE in 40 patients with OCD (15 drug-na¨ıve and 25 drug-treated) with MRI voxelbased morphometry at 3.0 T. Severity of ACE was rated on the Risky Families Questionnaire (RFQ); Severity of symptoms was rated on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). To assess the statistical significance of group differences data were analyzed within the context of the General Linear Model (GLM). Regional GM volumes were the dependent variable, drug treatment (na¨ıve vs treated) and breadth of exposure to ACE (high vs low) were the factors of interest, and sex, duration of illness, and handedness were considered as nuisance covariates. Whole brain statistical threshold was p < 0.05 family-wise error corrected for multiple comparisons.
P.1.e.020 Caudate grey matter volume in obsessivecompulsive disorder is influenced by adverse childhood experiences and ongoing drug treatment
P.1.e. Basic and clinical neuroscience − Brain imaging Results: At the VBM analysis the effects of ACE and current drug treatment survived the statistical threshold in a single cluster of 55 mm3 in the head of the left caudate nucleus. Here, patients with higher ACE had bigger GM volumes than patients with lower ACE and patients taking drugs had significantly lower volumes than drug-na¨ıve. Moreover worse ACE were associated with earlier age at onset of OCD, medication treatment and mixed handedness. Conclusions: This is the first study that reports an effect of adverse childhood experiences and drug treatment on adult grey matter volumes in patients with OCD. Exposure to ACE increased, and ongoing drug treatment decreased, caudate GM in OCD. Increased caudate size and metabolism have been consistently associated with OCD. The caudate nucleus plays a crucial role in reward detection and goal representation, thus giving a fundamental contribution to successful goal-directed action. Our findings suggest a detrimental effect of ACE on the brain underpinnings of OCD, with an opposite effect of medications. References [1] Wermter AK, Laucht M, Schimmelmann BG, Banaschweski T, SonugaBarke EJ, Rietschel M, et al. 2010: From nature versus nurture, via nature and nurture, to gene × environment interaction in mental disorders. Eur Child Adolesc Psychiatry. 19:199–210. [2] Stein MB, Walker JR, Anderson G, Hazen AL, Ross CA, Eldridge G, et al. 1996: Childhood physical and sexual abuse in patients with anxiety disorders and in a community sample. Am J Psychiatry. 153:275–277.
P.1.e.021 [11 C]NS14492 as a novel alpha-7 nicotinic acetylcholine receptor PET radioligand: in vivo evaluation and drug occupancy measurements A. Ettrup1 ° , J.D. Mikkelsen1 , S. Lehel2 , J. Madsen2 , E.O. Nielsen3 , D.B. Timmermann3 , D. Peters3 , G.M. Knudsen1 . 1 Copenhagen University Hospital Rigshospitalet, Neurobiology Research Unit, Copenhagen, Denmark; 2 Copenhagen University Hospital Rigshospitalet, PET and Cyclotron Unit, Copenhagen, Denmark; 3 NeuroSearch A/S, Ballerup, Denmark Purpose: Small molecule a7 nicotinic acetylcholine receptor (a7 nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer’s disease. A suitable radiolabelled a7 nAChR positron emission tomography (PET) tracer would be important for in vivo quantification of a7 nAChR binding in human population or patient groups. Furthermore, PET studies would be of particular importance as a tool to measure a7 nAChR occupancy in drug development. However, only few a7 nAChR PET ligands are currently available, and none of them have shown significant blocking in vivo by selective ligands [1,2]. Here, we present the radiosynthesis and in vivo evaluation of [11 C]NS14492 as a new selective a7 nAChR PET radiotracer. Methods: a7 nAChR affinity and selectivity of NS14492 was characterized using in vitro binding assays, and NS14492 was radiolabelled by methylation of its desmethyl precursor with [11 C]methyl triflate. Five female Danish Landrace pigs were studied at baseline and after i.v. administration of blocking doses of either the a7 nAChR partial agonist SSR180711 (10 mg/kg, n = 2 and 1 mg/kg, n = 1) or unlabelled NS14492 (10 mg/kg, n = 2). [11 C]NS14492 was given as an intravenous bolus injection, and the pigs were scanned for 90 min both at baseline and in the blocked conditions with a high resolution research tomography
S315
(HRRT) PET camera. Arterial whole blood and plasma radioactivity were measured during the scanning sessions, along with HPLC measurements of plasma parent compound and radiolabelled metabolites. PET data was quantified with a graphical analysis with arterial input; [11 C]NS14492 regional distribution volumes (VT ) were calculated, and a7 nAChR occupancy was determined from occupancy plots with VT in the blocked and unblocked conditions, across ten regions. Results: The in vitro affinity of NS14492 for a7 nAChR was high (Ki value: 2.2±0.8 nM), while its affinity for a4b2 nAChRs was ~1000 fold lower (Ki value: 2.8±1.1 mM). Also against 5-HT3 and a broad range of different receptors, transporters, and ion channels, NS14492 was characterized as a highly a7 nAChRselective agonist. [11 C]NS14492 had a high uptake in the pig brain, with the highest binding found in the cerebral cortex and the thalamus in accordance with a7 nAChR distribution. Pretreatment with NS14492 and SSR180711 consistently decreased [11 C]NS14492 VT in all examined regions supporting that the radioligand binds selectively to a7 nAChR in vivo. Also, no lipophilic radiolabelled metabolites were observed in pig plasma following [11 C]NS14492 injection. The occupancy of a7 nAChR was 81% and 69% with 10 mg/kg SSR180711 given 30 minutes prior to the second scan, whereas 1 mg/kg SSR180711 lead to 61% occupancy. Similarly, 10 mg/kg NS14492, given 30 minutes prior to a second scan lead to 75% occupancy of a7 nAChR, and increasing the inter-scan interval to 4 hours lead to 60% occupancy, corresponding to lower plasma concentration of cold NS14492. Conclusions: We report here that [11 C]NS14492 is the first PET radioligand for a7 nAChR showing a dose-dependent decline in cerebral binding after receptor blockade. This compound is considered a promising PET tracer for in vivo measurements of a7 nAChR binding and drug occupancy in the human brain. References [1] Hashimoto K, Nishiyama S, Ohba H et al. 2008 [11C]CHIBA-1001 as a novel PET ligand for alpha7 nicotinic receptors in the brain: a PET study in conscious monkeys. PLoS One 3, e3231. [2] Deuther-Conrad W, Fischer S, Hiller A et al. 2009 Molecular imaging of alpha7 nicotinic acetylcholine receptors: design and evaluation of the potent radioligand [18F]NS10743. Eur J Nucl Med Mol Imaging 36, 791–800.
P.1.e.022 Effect of electroconvulsive therapy on serotonin-1A receptor binding in major depressive disorder P. Baldinger1 ° , R. Lanzenberger1 , A. Hahn1 , M. Mitterhauser2 , W. Wadsak2 , Z. Micskei3 , J. Ungersb¨ock2 , D. Winkler1 , 1 Medical University of Vienna, S. Kasper1 , R. Frey1 . Department of Psychiatry and Psychotherapy, Vienna, Austria; 2 Medical University of Vienna, Department of Nuclear Medicine − PET Center, Vienna, Austria; 3 Medical University of Vienna, Department of Special Anaesthesia and Pain Management, Vienna, Austria Aim of the study: Electroconvulsive therapy (ECT) is used for the therapy of treatment-resistant depression due to its effectiveness in reducing depressive symptoms and the ameliorated practicability. The underlying neurobiological mechanisms are still unclear and the findings concerning this topic are inconsistent. However, several preclinical studies emphasize the significant involvement of the serotonergic system, particularly the main inhibitory 5-HT1A