Rupert Lanzenberger

Medical University of Vienna, Wien, Vienna, Austria

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Publications (248)989.81 Total impact

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    ABSTRACT: The norepinephrine transporter (NET) has been demonstrated to be relevant to a multitude of neurological, psychiatric and cardiovascular pathologies. Due to the wide range of possible applications for PET imaging of the NET together with the limitations of currently available radioligands, novel PET tracers for imaging of the cerebral NET with improved pharmacological and pharmacodynamic properties are needed. The present study addresses the radiosynthesis and first preclinical evaluation of the novel NET PET tracer [(11)C]Me@HAPTHI by describing its affinity, selectivity, metabolic stability, plasma free fraction, blood-brain barrier (BBB) penetration and binding behaviour in in vitro autoradiography. [(11)C]Me@HAPTHI was prepared and displayed outstanding affinity and selectivity as well as excellent in vitro metabolic stability, and it is likely to penetrate the BBB. Moreover, selective NET binding in in vitro autoradiography was observed in human brain and rat heart tissue samples. All preclinical results and radiosynthetic key-parameters indicate that the novel benzothiadiazole dioxide-based PET tracer [(11)C]Me@HAPTHI is a feasible and improved NET radioligand and might prospectively facilitate clinical NET imaging.
    EJNMMI Research 12/2015; 5(1):113. DOI:10.1186/s13550-015-0113-3
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  • A. Komorowski · G. Gryglewski · G. James · M. Hienert · S. Kasper · R. Lanzenberger
  • Marie Spies · Gitte M Knudsen · Rupert Lanzenberger · Siegfried Kasper
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    ABSTRACT: Over the past 20 years, psychotropics affecting the serotonergic system have been used extensively in the treatment of psychiatric disorders. Molecular imaging, in particular PET, has allowed for elucidation of the essential contribution of the serotonin transporter to the pathophysiology of various psychiatric disorders and their treatment. We review studies that use PET to measure cerebral serotonin transporter activity in psychiatric disorders, focusing on major depressive disorder and antidepressant treatment. We also discuss opportunities and limitations in the application of this neuroimaging method in clinical practice. Although results from individual studies diverge, meta-analysis indicates a trend towards reduced serotonin transporter availability in patients with major depressive disorder. Inconsistencies in results might suggest symptom heterogeneity in major depressive disorder and might therefore be relevant for stratification of patients into clinical subsets. PET has enabled the elucidation of mechanisms of response to selective serotonin reuptake inhibitors (SSRIs) and hence provides a basis for rational pharmacological treatment of major depressive disorder. Such imaging studies have also suggested that the pattern of serotonin transporter binding before treatment might predict response to antidepressant treatment, which could potentially be clinically useful in the future. Additionally, this Review discusses PET studies investigating the serotonin transporter in anxiety, obsessive-compulsive disorder, and eating disorders. Few studies have shown changes in serotonin transporter activity in schizophrenia and attention deficit hyperactivity disorder. By showing the scarcity of data in these psychiatric disorders, we highlight the potential for further investigation in this field. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Psychiatry 08/2015; 2(8):743-55. DOI:10.1016/S2215-0366(15)00232-1
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    ABSTRACT: Functional connectivity analysis of brain networks has become an important tool for investigation of human brain function. Although functional connectivity computations are usually based on resting-state data, the application to task-specific fMRI has received growing attention. Three major methods for extraction of resting-state data from task-related signal have been proposed (1) usage of unmanipulated task data for functional connectivity; (2) regression against task effects, subsequently using the residuals; and (3) concatenation of baseline blocks located in-between task blocks. Despite widespread application in current research, consensus on which method best resembles resting-state seems to be missing. We, therefore, evaluated these techniques in a sample of 26 healthy controls measured at 7 Tesla. In addition to continuous resting-state, two different task paradigms were assessed (emotion discrimination and right finger-tapping) and five well-described networks were analyzed (default mode, thalamus, cuneus, sensorimotor, and auditory). Investigating the similarity to continuous resting-state (Dice, Intraclass correlation coefficient (ICC), R2) showed that regression against task effects yields functional connectivity networks most alike to resting-state. However, all methods exhibited significant differences when compared to continuous resting-state and similarity metrics were lower than test-retest of two resting-state scans. Omitting global signal regression did not change these findings. Visually, the networks are highly similar, but through further investigation marked differences can be found. Therefore, our data does not support referring to resting-state when extracting signals from task designs, although functional connectivity computed from task-specific data may indeed yield interesting information. Hum Brain Mapp, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
    Human Brain Mapping 07/2015; DOI:10.1002/hbm.22897 · 5.97 Impact Factor
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    Dataset: PPP3CC gene
  • Markus Dold · Gernot Fugger · Martin Aigner · Rupert Lanzenberger · Siegfried Kasper
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    ABSTRACT: Non-response to an initial antipsychotic trial emerges frequently in the pharmacological management of schizophrenia. Increasing the dose (high-dose treatment, dose escalation) is an often applied strategy in this regard, but there are currently no meta-analytic data available to ascertain the evidence of this treatment option. We systematically searched for all randomized controlled trials (RCTs) that compared a dose increase directly to the continuation of standard-dose medication in patients with initial non-response to a prospective standard-dose pharmacotherapy with the same antipsychotic compound. Primary outcome was mean change in the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) total score. Secondary outcomes were positive and negative symptoms, response rates, and attrition rates. Hedges's g and risks ratios were calculated as effect sizes and the influence of the amount of the dose increase was examined by meta-regressions. Altogether, five trials with 348 patients investigating dose escalation with quetiapine, ziprasidone, haloperidol, and fluphenazine could be included. We did not find any significant difference for the mean PANSS/BPRS score change between the dose-increase and control group, neither for the pooled antipsychotic group nor for the individual antipsychotic drugs. Moreover, there were no between-group differences in positive and negative symptoms, response rates, and drop-out rates. The meta-regressions indicate no significant influence of the different amounts of dose increments on effect sizes. This meta-analysis suggests no evidence for a dose-escalation of the investigated antipsychotic drugs fluphenazine, haloperidol, quetiapine, and ziprasidone in case of initial non-response to standard-dose pharmacotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 05/2015; 166(1-3). DOI:10.1016/j.schres.2015.04.024 · 3.92 Impact Factor
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    ABSTRACT: Schizophrenia has been associated with disturbances of thalamic functioning. In the light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia, we assessed whether the modulation of the glutamatergic system via blockage of the NMDA-receptor might lead to changes of thalamic functional connectivity. Based on the "ketamine-model" of psychosis we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55 minutes resting-state scan. 30 healthy volunteers were measured with pharmacological functional magnetic resonance imaging (fMRI) using a double-blind, randomized, placebo-controlled, crossover design. Functional connectivity analysis revealed significant ketamine-specific changes within the "thalamus hub network", more precisely an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex. Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage. This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behaviour during the application of NMDA-receptor antagonists. © The Author 2014. Published by Oxford University Press on behalf of CINP.
    The International Journal of Neuropsychopharmacology 04/2015; DOI:10.1093/ijnp/pyv040 · 4.01 Impact Factor
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    ABSTRACT: Recent technological progress enables MRI recordings at ultra-high fields of 7 Tesla and above leading to brain images of higher resolution and increased signal-to-noise ratio. Despite these benefits, imaging at 7T exhibits distinct challenges due to B1 field inhomogeneities, causing decreased image quality and problems in data analysis. Although several strategies have been proposed, a systematic investigation of bias-corrected 7T data for voxel-based morphometry (VBM) is still missing and it is an ongoing matter of debate if VBM at 7T can be carried out properly. Here, an optimized VBM study was conducted, evaluating the impact of field strength (3T vs 7T) and pulse sequence (MPRAGE vs MP2RAGE) on gray matter volume (GMV) estimates. More specifically, twenty-two participants were measured under the conditions 3T MPRAGE, 7T MPRAGE and 7T MP2RAGE. Due to the fact that 7T MPRAGE data exhibited strong intensity inhomogeneities, an alternative preprocessing pipeline was proposed and applied for that data. VBM analysis revealed higher GMV estimates for 7T predominantly in superior cortical areas, caudate nucleus, cingulate cortex and the hippocampus. On the other hand, 3T yielded higher estimates especially in inferior cortical areas of the brain, cerebellum, thalamus and putamen compared to 7T. Besides minor exceptions, these results were observed for 7T MPRAGE as well for the 7T MP2RAGE measurements. Results gained in the inferior parts of the brain should be taken with caution, as native GM segmentations displayed misclassifications in these regions for both 7T sequences. This was supported by the test-retest measurements showing highest variability in these inferior regions of the brain for 7T also for the advanced MP2RAGE sequence. Hence, our data support the use of 7T MRI for VBM analysis in cortical areas, but direct comparison between field strengths and sequences requires careful assessment. Similarly, analysis of inferior cortical regions, cerebellum and subcortical regions still remains challenging at 7T even if the advanced MP2RAGE sequence is used. Copyright © 2015 Elsevier Inc. All rights reserved.
    NeuroImage 03/2015; 113. DOI:10.1016/j.neuroimage.2015.03.019 · 6.36 Impact Factor
  • M. Dold · M. Aigner · R. Lanzenberger · S. Kasper
    European Psychiatry 03/2015; 30:795. DOI:10.1016/S0924-9338(15)30619-2 · 3.44 Impact Factor
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    ABSTRACT: We investigated whether s-ketamine differentially affects strategic allocation of attention. In Experiment 1, (1) a less visible cue was weakly masked by the onsets of competing placeholders or (2) a better visible cue was not masked because it was presented in isolation. Both types of cue appeared more often opposite of the target (75%) than at target position (25%). With this setup, we tested for strategic attention shifts to the opposite side of the cues and for exogenous attentional capture toward the cue's side in a short cue-target interval, as well as for (reverse) cueing effects in a long cue-target interval after s-ketamine and after placebo treatment in a double-blind within-participant design. We found reduced strategic attention shifts after cues presented without placeholders for the s-ketamine compared to the placebo treatment in the short interval, indicating an early effect on the strategic allocation of attention. No differences between the two treatments were found for exogenous attentional capture by less visible cues, suggesting that s-ketamine does not affect exogenous attentional capture in the presence of competing distractors. Experiment 2 confirmed that the competing onsets of the placeholders prevented the strategic cueing effect. Taken together, the results indicate that s-ketamine affects strategic attentional capture, but not exogenous attentional capture. The findings point to a more prominent role of s-ketamine during top-down controlled forms of attention that require suppression of automatic capture than during automatic capture itself. Copyright © 2015. Published by Elsevier Inc.
    Consciousness and Cognition 02/2015; 35. DOI:10.1016/j.concog.2015.01.009 · 2.31 Impact Factor
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    ABSTRACT: For over a decade, the European Group for the Study of Resistant Depression (GSRD) has examined single nucleotide polymorphisms (SNP) and clinical parameters in regard to treatment outcome. However, an interaction based model combining these factors has not been established yet. Regarding the low effect of individual SNPs, a model investigating the interactive role of SNPs and clinical variables in treatment-resistant depression (TRD) seems auspicious. Thus 225 patients featured in previous work of the GSRD were enrolled in this investigation. According to data availability and previous positive results, 12 SNPs in HTR2A, COMT, ST8SIA2, PPP3CC and BDNF as well as 8 clinical variables featured in other GSRD studies were chosen for this investigation. Random forests algorithm were used for variable shrinkage and k-means clustering for surfacing variable characteristics determining treatment outcome. Using these machine learning and clustering algorithms, we detected a set of 3 SNPs and a clinical variable that was significantly associated with treatment response. About 62% of patients exhibiting the allelic combination of GG-GG-TT for rs6265, rs7430 and rs6313 of the BDNF, PPP3CC and HTR2A genes, respectively, and without melancholia showed a HAM-D decline under 17 compared to about 34% of the whole study sample. Our random forests prediction model for treatment outcome showed that combining clinical and genetic variables gradually increased the prediction performance recognizing correctly 25% of responders using all 4 factors. Thus, we could confirm our previous findings and furthermore show the strength of an interaction-based model combining statistical algorithms in identifying and operating treatment predictors. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
    European Neuropsychopharmacology 02/2015; 25(4). DOI:10.1016/j.euroneuro.2015.01.001 · 4.37 Impact Factor
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    ABSTRACT: Serotonergic neurotransmission is thought to underlie a dynamic interrelation between different key structures of the serotonin system. The serotonin transporter (SERT), which is responsible for the reuptake of serotonin from the synaptic cleft into the neuron, as well as the serotonin-1A (5-HT1A) and -1B (5-HT1B) receptors, inhibitory auto-receptors in the raphe region and projection areas, respectively, are likely to determine serotonin release. Thereby, they are involved in the regulation of extracellular serotonin concentrations and the extent of serotonergic effects in respective projection areas. Complex receptor interactions can be assessed in vivo with positron emission tomography (PET) and single-nucleotide-polymorphisms, which are thought to alter protein expression levels. Due to the complexity of the serotonergic system, gene x gene interactions are likely to regulate transporter and receptor expression and therefore subsequently serotonergic transmission. In this context, we measured 51 healthy subjects (mean age 45.5±12.9, 38 female) with PET using [carbonyl-(11)C]WAY-100635 to determine 5-HT1A receptor binding potential (5-HT1A BPND). Genotyping for rs6296 (HTR1B) and 5-HTTLPR (SERT gene promoter polymorphism) was performed using DNA isolated from whole blood. Voxel-wise whole-brain ANOVA revealed a positive interaction effect of genotype groups (5-HTTLPR: LL, LS+SS and HTR1B: rs6296: CC, GC+GG) on 5-HT1A BPND with peak t-values in the bilateral parahippocampal gyrus. More specifically, highest 5-HT1A BPND was identified for individuals homozygous for both the L-allele of 5-HTTLPR and the C-allele of rs6296. This finding suggests that the interaction between two major serotonergic structures involved in 5-HT release, specifically the SERT and 5-HT1B receptor, results in a modification of the inhibitory serotonergic tone mediated via 5-HT1A receptors. Copyright © 2015 Elsevier Inc. All rights reserved.
    NeuroImage 01/2015; 111. DOI:10.1016/j.neuroimage.2015.01.049 · 6.36 Impact Factor
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    ABSTRACT: Purpose: The adenosine A3 receptor (A3R) is involved in cardiovascular, neurological and tumour-related pathologies and serves as an exceptional pharmaceutical target in the clinical setting. A3R antagonists are considered antiinflammatory, antiallergic and anticancer agents, and to have potential for the treatment of asthma, COPD, glaucoma and stroke. Hence, an appropriate A3R PET tracer would be highly beneficial for the diagnosis and therapy monitoring of these diseases. Therefore, in this preclinical in vivo study we evaluated the potential as a PET tracer of the A3R antagonist [(18)F]FE@SUPPY. Methods: Rats were injected with [(18)F]FE@SUPPY for baseline scans and blocking scans (A3R with MRS1523 or FE@SUPPY, P-gp with tariquidar; three animals each). Additionally, metabolism was studied in plasma and brain. In a preliminary experiment in a mouse xenograft model (mice injected with cells expressing the human A3R; three animals), the animals received [(18)F]FE@SUPPY and [(18)F]FDG. Dynamic PET imaging was performed (60 min in rats, 90 min in xenografted mice). In vitro stability of [(18)F]FE@SUPPY in human and rat plasma was also evaluated. Results: [(18)F]FE@SUPPY showed high uptake in fat-rich regions and low uptake in the brain. Pretreatment with MRS1523 led to a decrease in [(18)F]FE@SUPPY uptake (p = 0.03), and pretreatment with the P-gp inhibitor tariquidar led to a 1.24-fold increase in [(18)F]FE@SUPPY uptake (p = 0.09) in rat brain. There was no significant difference in metabolites in plasma and brain in the treatment groups. However, plasma concentrations of [(18)F]FE@SUPPY were reduced to levels similar to those in rat brain after blocking. In contrast to [(18)F]FDG uptake (p = 0.12), the xenograft model showed significantly increased uptake of [(18)F]FE@SUPPY in the tissue masses from CHO cells expressing the human A3R (p = 0.03). [(18)F]FE@SUPPY was stable in human plasma. Conclusion: Selective and significant tracer uptake of [(18)F]FE@SUPPY was found in xenografted mice injected with cells expressing human A3R. This finding supports the strategy of evaluating [(18)F]FE@SUPPY in "humanized animal models". In conclusion, preclinical evaluation points to the suitability of [(18)F]FE@SUPPY as an A3R PET tracer in humans.
    European journal of nuclear medicine and molecular imaging 01/2015; 42(5). DOI:10.1007/s00259-014-2976-3 · 5.38 Impact Factor

Publication Stats

3k Citations
989.81 Total Impact Points


  • 2000–2015
    • Medical University of Vienna
      • • Department of Psychiatry and Psychotherapy
      • • Department of Nuclear Medicine
      • • Department of Neurology
      • • Clinical Department of Virology
      Wien, Vienna, Austria
  • 2012
    • University of Queensland
      Brisbane, Queensland, Australia
  • 2001–2008
    • University of Vienna
      • • Department of Neurobiology
      • • Neurological Clinic
      Wien, Vienna, Austria
  • 2007
    • University College Cork
      • Department of Psychiatry
      Corcaigh, Munster, Ireland
  • 2000–2001
    • Vienna General Hospital
      Wien, Vienna, Austria