Alexander Sartorius

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

Are you Alexander Sartorius?

Claim your profile

Publications (109)359.97 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aberrant prefrontal-hippocampal (PFC-HC) connectivity is disrupted in several psychiatric and at-risk conditions. Advances in rodent functional imaging have opened the possibility that this phenotype could serve as a translational imaging marker for psychiatric research. Recent evidence from functional magnetic resonance imaging (fMRI) studies has indicated an increase in PFC-HC coupling during working-memory tasks in both schizophrenic patients and at-risk populations, in contrast to a decrease in resting-state PFC-HC connectivity. Acute ketamine challenge is widely used in both humans and rats as a pharmacological model to study the mechanisms of N-methyl-D-aspartate (NMDA) receptor hypofunction in the context of psychiatric disorders. We aimed to establish whether acute ketamine challenge has consistent effects in rats and humans by investigating resting-state fMRI PFC-HC connectivity and thus to corroborate its potential utility as a translational probe. Twenty-four healthy human subjects (12 females, mean age 25 years) received intravenous doses of either saline (placebo) or ketamine (0.5 mg/kg body weight). Eighteen Sprague-Dawley male rats received either saline or ketamine (25 mg/kg). Resting-state fMRI measurements took place after injections, and the data were analyzed for PFC-HC functional connectivity. In both species, ketamine induced a robust increase in PFC-HC coupling, in contrast to findings in chronic schizophrenia. This translational comparison demonstrates a cross-species consistency in pharmacological effect and elucidates ketamine-induced alterations in PFC-HC coupling, a phenotype often disrupted in pathological conditions, which may give clue to understanding of psychiatric disorders and their onset, and help in the development of new treatments.
    Psychopharmacology 07/2015; DOI:10.1007/s00213-015-4022-y · 3.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment for severe psychiatric disorders. Ketamine is known as a core medication in anesthesiology and has recently gained interest in ECT practice as there are three potential advantages: (1) ketamine has no anticonvulsive actions, (2) according to recent studies ketamine could possess a unique intrinsic antidepressive potential and (3) ketamine may exhibit neuroprotective properties, which again might reduce the risk of cognitive side effects associated with ECT. The use of ketamine in psychiatric patients has been controversially discussed due to its dose-dependent psychotropic and psychotomimetic effects. This study was carried out to test if the occurrence of side effects is comparable and if seizure quality is better with ketamine when compared to thiopental. This retrospective study analyzed a total of 199 patients who received ketamine anesthesia for a total of 2178 ECT sessions. This cohort was compared to patients who were treated with thiopental for 1004 ECT sessions. A repeated measurement multiple logistic regression analysis revealed significant advantages in the ketamine group for seizure concordance and postictal suppression (both are surrogates for central inhibition). S-ketamin also necessitated the use of a higher dose of urapidil and a higher maximum postictal heart frequency. Clinically relevant psychiatric side effects were rare in both groups. No psychiatric side effects occurred in the subgroup of patients with schizophrenia (ketamine: n = 30). The mean dose of S-ketamine used increased in the first years but stabilized at 63 mg per patient in 2014. From these experiences it can be concluded that S-ketamine can be recommended at least as a safe alternative to barbiturates.
    Der Anaesthesist 05/2015; DOI:10.1007/s00101-015-0027-5 · 0.74 Impact Factor
  • Psych Pflege Heute 03/2015; 21(02):73-78. DOI:10.1055/s-0035-1548590
  • Sina Kohl, Lena Ebbert, Alexander Sartorius, Jens Kuhn
    [Show abstract] [Hide abstract]
    ABSTRACT: Obsessive-compulsive disorder represents one of the most disabling psychiatric disorders. The underlying pathophysiology is not fully understood. In a recent Science article, Ahmari and colleagues enlighten fundamental aspects of obsessive-compulsive disorder by means of optogenetic stimulation, thereby also elucidating the usefulness of SSRI in the treatment for OCD.
    European Archives of Psychiatry and Clinical Neuroscience 02/2015; DOI:10.1007/s00406-015-0584-2 · 3.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dear Editor,We are grateful to answer the questions arising from the fruitful comments of Marc Molendijk and Maryna Polyakova [1]. We absolutely agree on their general criticism on statistical approaches in neuroscience, especially with regard to the literature they cited [2, 3].We are aware of the fact that a t test approach per se is statistically not absolutely correct, and we agree with Nieuwenhuis et al. that its use is not justifiable by the fact that it is commonly used in high-ranking journals. But as Nieuwenhuis et al. also stated, we think that this does not mean that results are meaningless or even not present in all cases.The idea of presenting data just from a subsample of patients with sufficient seizures [4] comes from our extensive clinical impression that such seizures are necessary to induce a significant antidepressive effect and that many circumstances may influence seizure quality [5-8].In our study, the t test of BDNF level increase (pre-post ECT) of patients in w ...
    European Archives of Psychiatry and Clinical Neuroscience 02/2015; 265(4). DOI:10.1007/s00406-015-0580-6 · 3.36 Impact Factor
  • The journal of ECT 11/2014; 31(1). DOI:10.1097/YCT.0000000000000200 · 1.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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 11/2014; 10:2147-2151. DOI:10.2147/NDT.S71008 · 2.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background 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. Findings A trial-by-trial reanalysis of tests from 163 rats with congenital learned helplessness or congenital non-learned helplessness and comparison of 82 rats exposed to inescapable shock with 38 shock-controls revealed that neither the first test trials, when rats showed unspecific hyperlocomotion, nor trials of the last third of the test, when almost all animals responded quickly to the stressor, contributed to sensitivity and specificity of the test. Considering only trials 3–10 improved the classification of helpless and non-helpless rats. Conclusions The refined analysis allows abbreviation of the test for learned helplessness from 15 trials to 10 trials thereby reducing pain and stress of the experimental animals without losing statistical power.
    Behavioral and Brain Functions 11/2014; 10(1):41. DOI:10.1186/1744-9081-10-41 · 2.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; 265(3). DOI:10.1007/s00406-014-0543-3 · 3.36 Impact Factor
  • The journal of ECT 07/2014; 30(4). DOI:10.1097/YCT.0000000000000159 · 1.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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 06/2014; 27(6). DOI:10.1002/nbm.3110 · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    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. DOI:10.1159/000360859 · 2.30 Impact Factor
  • [Show abstract] [Hide abstract]
    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; 121(11). DOI:10.1007/s00702-014-1228-9 · 2.87 Impact Factor
  • [Show abstract] [Hide abstract]
    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 04/2014; 73(4). DOI:10.1002/mrm.25278 · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    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; 30(4). DOI:10.1097/YCT.0000000000000109 · 1.39 Impact Factor
  • Source
    Journal of clinical psychopharmacology 02/2014; DOI:10.1097/JCP.0b013e3182aa019f · 3.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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 02/2014; 24(2). DOI:10.1002/hipo.22227 · 4.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; 24(3). DOI:10.1016/j.euroneuro.2013.12.004 · 5.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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 12/2013; 23(12). DOI:10.1002/hipo.22171 · 4.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; 39(4). DOI:10.1038/npp.2013.290 · 7.83 Impact Factor

Publication Stats

1k Citations
359.97 Total Impact Points

Institutions

  • 2008–2014
    • Universität Heidelberg
      • • Department of Psychiatry and Psychotherapy
      • • Faculty of Medicine Mannheim and Clinic Mannheim
      • • Central Institute of Mental Health
      Heidelburg, Baden-Württemberg, Germany
  • 1999–2014
    • Central Institute of Mental Health
      • Klinik für Abhängiges Verhalten und Suchtmedizin
      Mannheim, Baden-Württemberg, Germany