Alexander Sartorius

Central Institute of Mental Health, Mannheim, Baden-Württemberg, Germany

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Publications (102)291.97 Total impact

  • The journal of ECT 11/2014; · 1.19 Impact Factor
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    ABSTRACT: Learned helplessness has excellent validity as an animal model for depression, but problems in reproducibility limit its use and the high degree of stress involved in the paradigm raises ethical concerns. We therefore aimed to identify which and how many trials of the learned helplessness paradigm are necessary to distinguish between helpless and non-helpless rats.
    Behavioral and Brain Functions 11/2014; 10(1):41. · 2.00 Impact Factor
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    ABSTRACT: Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment in severest or drug-resistant affective disorders. The potential relation between any peripheral biological marker and the seizure quality as a surrogate for treatment efficacy has not been investigated so far. We prospectively examined serum brain-derived neurotrophic factor (BDNF) levels in 20 patients with major depression before and after electroconvulsive therapy. A seizure quality sum score for every ECT session was build up on the basis of the seizure duration, seizure amplitude, central inhibition, interhemispheric coherence and sympathetic activation. Serum BDNF levels were significantly higher after ECT (P = 0.036). In the linear regression analysis, a significant correlation of the serum BDNF levels and the time between the last ECT and the blood withdrawal (P = 0.01) was observed. The ANOVA revealed a significant influence of the interval between the last ECT and the blood withdrawal (P = 0.0017) as well as the seizure quality (P = 0.038) on the variance of BDNF serum levels. Our data corroborate the neurotrophin hypothesis suggesting an ECT-induced central BDNF rise leading to a delayed (>6 days) and increased equilibrium of the peripheral BDNF. The association of seizure adequacy with a BDNF rise might underline the importance of monitoring seizure quality markers in daily practice.
    European Archives of Psychiatry and Clinical Neuroscience 09/2014; · 3.36 Impact Factor
  • The journal of ECT 07/2014; · 1.19 Impact Factor
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    ABSTRACT: The utilization of magnetic resonance imaging (MRI) methods in rodent models of psychiatric disorders provides considerable benefits for the identification of disease-associated brain circuits and metabolic changes. In this review, we discuss advantages and challenges of animal MRI and provide an overview of the major structural (voxel-based morphometry and diffusion tensor imaging) and functional approaches [resting-state functional MRI (rs-fMRI), MR spectroscopy (MRS), regional cerebral blood volume measurement and arterial spin labelling] that are applied in animal MRI research. The review mainly focuses on rs-fMRI and MRS. Finally, we take a look at some recent developments and refinements in the field. © 2014 S. Karger AG, Basel.
    Neuropsychobiology 05/2014; 69(4):187-201. · 2.30 Impact Factor
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    ABSTRACT: The mechanism of the reversible cognitive deficits that might occur within an electroconvulsive therapy (ECT) treatment has not been clarified in a substantial way yet. Although the data available so far do not point towards a cause due to any structural or diffuse damage, further clarification, especially of the role of S-100 seems to be necessary before robust conclusions can be drawn. Serum levels of protein S-100 and neuron-specific enolase (NSE) were analysed in 19 patients with depression, who received ECT. The sampling was adjusted for the short half-life of protein S-100. Several outcome parameters such as Hamilton Depression Rating Scale and Mini-mental state examination before and after the ECT, response and remission to the treatment were recorded. S-100 and NSE levels at baseline, 30 and 60 min after the third session and after the end of the ECT remained stable. S-100 and NSE levels were neither associated with antidepressant response or remission nor with alterations in the cognitive performance. Although aiming for detecting potential rise in these established brain damage markers, an increase due to ECT was not observed, which is in line with the previous studies concerning the safety of ECT on a cellular basis.
    Journal of Neural Transmission 05/2014; · 2.87 Impact Factor
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    ABSTRACT: Phosphomono- and diesters, the major components of the choline peak in (1) H magnetic resonance spectroscopy, are associated with membrane anabolic and catabolic mechanisms. With the refocused insensitive nuclei-enhanced polarization transfer technique, these phospholipids are edited and enhanced in the (31) P MR spectrum. In depressed patients, alterations of the choline peak and cerebral volume have been found, indicating a possible relation. Thus, combining MR phosphorous spectroscopy and volumetry in depressed patients seems to be a promising approach to detect underlying pathomechanisms. Depressed in-patients were either treated with antidepressive medication or with electroconvulsive therapy and compared to matched healthy controls. (31) P magnetic resonance spectroscopy imaging was conducted before and after the treatment phases. A 3D MRI dataset for volumetry was acquired in a dedicated (1) H head coil. Phosphocholine and phosphoethanolamine were increased in depressed patients. Though patients responded to the treatments, phospholipids were not significantly altered. An increased age-related gray matter loss in fronto-limbic regions along with an altered relation of phosphomonoesters/phosphodiesters with age were found in depressed patients. The findings of increased phosphomonoesthers and an age*group interaction for gray matter volumes need further research to define the role of phospholipids in major depression and possible associations to gray matter loss. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 05/2014; · 3.40 Impact Factor
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    ABSTRACT: MRI and MRS in small rodents demand very high sensitivity. Cryogenic transmit/receive radiofrequency probes (CryoProbes) designed for (1) H MRI of mouse brain provide an attractive option for increasing the performance of small-animal MR systems. As the Larmor frequency of (13) C nuclei is four times lower than that for (1) H nuclei, an even larger sensitivity improvement is expected for (13) C applications. The aim of this work was to evaluate the performance of a prototype (13) C CryoProbe™ for mouse brain MRS. To investigate the possible gain of the (13) C CryoProbe™, we acquired localized single-voxel (13) C spectra and chemical shift images of a dimethyl sulfoxide phantom with the CryoProbe™, as well as with two room temperature resonators. The cryogenically cooled resonator achieved approximately four-fold higher signal-to-noise ratio in phantom tests when compared with the best-performing room temperature coil. In addition, we present localized (13) C spectra of mouse brain obtained with the CryoProbe™, as well as with one of the room temperature coils, demonstrating the performance in vivo. In summary, the cryogenic cooling technique significantly enhances the (13) C signal sensitivity at 9.4 T and enables the investigation of metabolism within mouse brain. Copyright © 2014 John Wiley & Sons, Ltd.
    NMR in Biomedicine 04/2014; · 3.56 Impact Factor
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    ABSTRACT: Preoxygenation and hyperventilation (with oxygen) in electroconvulsive therapy (ECT) may improve not only safety but also seizure quality. We retrospectively examined transcutaneous tissue partial pressure of oxygen (tcpO2) and carbon dioxide (tcpCO2) in 441 ECT sessions of 37 consecutive patients. All patients received standard face mask airway management. In parallel, seizure quality markers such as seizure duration, seizure amplitude, central inhibition, interhemispheric coherence, and sympathetic activation were documented and used to build up a seizure quality sum score. Mean (SD) tcpO2 was 289 (123) mm Hg and for tcpCO2 41 (11) mm Hg. A multivariate repeated measurement regression analysis revealed that the ratio of tcpO2/tcpCO2 had a significant influence on the seizure quality sum score (P = 0.033). Furthermore, a corresponding regression analysis with charge ("stimulation energy") as a dependent variable showed a significant influence of tcpO2 (P = 0.019) and of tcpO2/tcpCO2 (P = 0.03), too. We observed, in our typical clinical ECT sample of 37 patients, a significant and synergistic influence of tcpO2/tcpCO2 on seizure quality. Partial pressure of oxygen covaried with lower stimulation energy. The ratio tcpO2/tcpCO2 was associated with lower stimulation energy and still better seizure quality.
    The journal of ECT 03/2014; · 1.19 Impact Factor
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    Journal of clinical psychopharmacology 02/2014; · 5.09 Impact Factor
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    ABSTRACT: Dementia-related behavioral disturbances are mostly treated with antipsychotics; however, the observed beneficial effects are modest and the risk of serious adverse effects high. We report the case of a 57-year-old woman with severe early-onset Alzheimer's disease and severe agitation, whom we treated with electroconvulsive therapy (ECT). A significant clinical improvement was achieved over eight ECT sessions, which were tolerated well without cognitive worsening, and lasted approximately 3 months. Our case demonstrates the safe and effective use of ECT in pharmacotherapy-resistant severe agitation in Alzheimer's disease. The risk-benefit profile of ECT for dementia-related agitation should be further investigated in clinical trials.
    Neuropsychiatric Disease and Treatment 01/2014; 10:2147-2151. · 2.15 Impact Factor
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    ABSTRACT: Treatment-resistant depression (TRD) remains a pressing clinical problem. Optimizing treatment requires better definition of the function and specificity of the brain circuits involved. To investigate disease-related alterations of brain function we used a genetic animal model of TRD, congenital learned helplessness (cLH), and functional magnetic resonance imaging as a translational tool. High-resolution regional cerebral blood volume (rCBV) and resting-state functional connectivity measurements were acquired at 9.4T to determine regional dysfunction and interactions that could serve as vulnerability markers for TRD. Effects of cLH on rCBV were determined by statistical parametric mapping using 35 atlas-based regions of interest. Effects of cLH on functional connectivity were assessed by seed region analyses. Significant bilateral rCBV reductions were observed in the lateral habenula, dentate gyrus and subiculum of cLH rats. In contrast, focal bilateral increase in rCBV was observed in the bed nucleus of stria terminalis (BNST), a component of the habenular neurocircuitry. Functional connectivity was primarily enhanced in cLH rats, most notably with respect to serotonergic projections from the dorsal raphe nucleus to the forebrain, within the hippocampal-prefrontal network and between the BNST and lateral frontal regions. Dysregulation of neurocircuitry similar to that observed in depressed patients was detected in cLH rats, supporting the validity of the TRD model and suitability of high-field fMRI as a translational technology to detect and monitor vulnerability markers. Our findings also define neurocircuits that can be studied for TRD treatment in patients, and could be employed for translational research in rodent models.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 12/2013; · 3.68 Impact Factor
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    ABSTRACT: Recently a larger hippocampus was found in exercising mice and men. Here we studied the morphological underpinnings in wheel running mice by longitudinal magnetic resonance imaging. Voxel-based morphometry revealed that running increases hippocampal volume by inhibiting an early age-related gray matter loss. Disruption of neurogenesis-related neuroplasticity by focalized irradiation is sufficient to block positive effects of exercise on macroscopic brain morphology. © 2013 Wiley Periodicals, Inc.
    Hippocampus 11/2013; · 4.30 Impact Factor
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    ABSTRACT: Dysfunctional connectivity within the hippocampal-prefrontal (HC-PFC) circuit is associated with schizophrenia, major depression and neurodegenerative disorders, and both the hippocampus and prefrontal cortex have dense populations of N-methyl-D-aspartate (NMDA) receptors. Ketamine, a potent NMDA receptor antagonist, is of substantial current interest as a mechanistic model of glutamatergic dysfunction in animal and human studies, a psychotomimetic agent and a rapidly acting antidepressant. In the present study, we sought to understand the modulatory effect of acute ketamine administration on functional connectivity in the HC-PFC system of the rat brain using resting-state fMRI (rs-fMRI). Sprague-Dawley rats in 4 parallel groups (N=9/group) received either saline or one of three behaviorally-relevant, sub-anesthetic doses of S-ketamine (5, 10 and 25 mg/kg, s.c.), and connectivity changes 15 and 30 min post-injection were studied. The strongest effects were dose- and exposure-dependent increases in functional connectivity within the prefrontal cortex and in anterior-posterior connections between the posterior hippocampus and retrosplenial cortex, and prefrontal regions. The increased prefrontal connectivity is consistent with ketamine-induced increases in HC-PFC electroencephalographic gamma band power, possibly reflecting a psychotomimetic aspect of ketamine's effect, and is contrary to the data from chronic schizophrenic patients suggesting that ketamine effect does not necessarily parallel the disease pattern but might rather reflect a hyperglutamatergic state. These findings may help to clarify the brain systems underlying different dose-dependent behavioral profiles of ketamine in the rat.Neuropsychopharmacology accepted article preview online, 18 October 2013; doi:10.1038/npp.2013.290.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2013; · 8.68 Impact Factor
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    ABSTRACT: In humans, resting state BOLD signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low frequency BOLD fluctuations temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated following global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting state fMRI as a translational imaging method between rat models and humans.
    Brain connectivity. 08/2013;
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    Biological psychiatry 08/2013; · 8.93 Impact Factor
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    ABSTRACT: Deep brain stimulation (DBS) for intractable cases of depression has emerged as a valuable therapeutic option during the last decade. While several locations have been intensely investigated in recent years, the literature is lacking an all-encompassing perspective thereupon asking if and how these stimulation sites relate to each other and what this may imply for the underlying mechanisms of action of this treatment modality. We aim at proposing a model of DBS mechanism of action with particular focus on several puzzling aspects regarding an apparent temporo-spatial specificity of antidepressant action, i.e. the discrepancy between protracted response after initiation of stimulation and rapid relapse upon discontinuation, as well as differential effects on psychopathology. We suggest that the pre-treatment depressive state is determined by the interaction of individual traits with dysfunctional adaptive processes as responses to stress, resulting in a disease-associated, overtly dysfunctional, equilibrium. The antidepressant action of DBS is thought to modify and re-set this equilibrium in a temporospatially distinct manner by influencing the activity states of two different brain circuitries. The idea of sequential and temporospatially distinct mechanisms of action bears implications for the assessment of psychopathology and behavior in clinical and preclinical studies as well as investigations into brain circuit activity states.
    Medical Hypotheses 08/2013; · 1.15 Impact Factor
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    ABSTRACT: Electroconvulsive therapy (ECT) is a uniquely effective treatment for major depressive disorder. An increase in hippocampal neurogenesis is implicated in the recovery from depression. We used an inducible genetic mouse model in which only GFAP-expressing stem-like cells (type-1 cells) and their progeny are selectively labeled with reporter protein β-galactosidase to track the process of neurogenesis in the dentate gyrus over three months following electroconvulsive seizures (ECS), the mouse equivalent of ECT. All ECS protocols tested induced a transient increase in type-1 cell divisions. While this led to an expansion of the type-1 cell pool after high-frequency ECS sessions for five consecutive days (5-ECS), asymmetric divisions drove neurogenesis by giving rise to Doublecortin (DCX)-expressing neuroblasts that matured into NeuN+ neurons. Significantly, the increase in newly generated DCX+ and NeuN+ cells after 5-ECS could be traced back to proliferating type-1 cells. Low-frequency continuation ECS (c-ECS) consisting of five single ECS sessions administered every two weeks resulted in a similar increase in newborn neurons as the high-frequency 5-ECS protocol. Moreover, the combination of 5-ECS and c-ECS led to a further significant increase in newborn neurons, suggesting a cellular mechanism responsible for the propitious effects of high-frequency ECT followed by continuation ECT in severely depressed patients. The ability of high- and low-frequency ECS to induce normally quiescent type-1 cells to proliferate and generate new neurons sets it apart from other antidepressant treatments and may underlie the superior clinical efficacy of ECT. © 2013 Wiley Periodicals, Inc.
    Hippocampus 07/2013; · 4.30 Impact Factor
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    ABSTRACT: Electroconvulsive therapy (ECT) is an effective therapy for several psychiatric disorders, including severe major depression, mania and certain forms of schizophrenia. It had been proposed that ECT acts by modulating local plasticity via the stimulation of neurogenesis. In fact, among antidepressant therapies, ECT is the most robust enhancer of neurogenesis in the hippocampus of rodents and non-human primates. The existence of ECT-triggered neurogenesis in other brain areas, particularly in those adjacent to the other main locus of neurogenesis, the subventricular zone (SVZ), had so far remained unknown. Here we show that ECT also strongly enhances neurogenesis in frontal brain areas, especially in the rostro-medial striatum, generating specific, small-size calretinin-positive interneurons. We provide here the first evidence that ECT stimulates neurogenesis in areas outside the hippocampus. Our data may open research possibilities that focus on the plastic changes induced by ECT in frontal limbic circuitry.
    PLoS ONE 07/2013; 8(7):e69869. · 3.53 Impact Factor
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    ABSTRACT: In electroconvulsive therapy (ECT), the use of anesthetics without relevant anticonvulsant properties such as ketamine and etomidate may be favorable for seizure quality. Since there is a relative paucity of studies devoted to this issue, our aim was to compare different anesthetics for ECT regarding their impact on seizure quality and different seizure parameters. We retrospectively compared ketamine (n = 912 anesthesias), etomidate (n = 227 anesthesias), thiopental (n = 2,751 anesthesias), and propofol (n = 42 anesthesias) on their influence on general seizure quality and different seizure parameters by multivariate repeated measurement regression analyses. The use of ketamine and etomidate as anesthetics led to seizures that were overall higher in quality and also longer in motor seizure activity when compared to anesthesia with thiopental and propofol. Ketamine was most favorable concerning central inhibitory potential that was indirectly quantified by concordance and postictal suppression. The worst seizure quality was observed with propofol anesthesia; further, this substance had a negative impact on autonomic activation and seizure duration. Based on the data of this retrospective study, the use of ketamine or etomidate as anesthetic in ECT might be advantageous due to the induction of high-quality seizures.
    European Archives of Psychiatry and Clinical Neuroscience 07/2013; · 3.36 Impact Factor

Publication Stats

981 Citations
291.97 Total Impact Points


  • 1999–2014
    • Central Institute of Mental Health
      • Klinik für Abhängiges Verhalten und Suchtmedizin
      Mannheim, Baden-Württemberg, Germany
  • 2004–2013
    • Universität Heidelberg
      • • Faculty of Medicine Mannheim and Clinic Mannheim
      • • Central Institute of Mental Health
      Heidelburg, Baden-Württemberg, Germany
  • 2012
    • Indiana University East
      Indiana, United States
  • 2011
    • Technische Universität Dresden
      Dresden, Saxony, Germany
    • Johannes Gutenberg-Universität Mainz
      • Institute of Physical Chemistry
      Mainz, Rhineland-Palatinate, Germany
  • 2010
    • University of Milan
      • Department of Pharmacological Sciences
      Milano, Lombardy, Italy