Jens Benninghoff

University of Duisburg-Essen, Essen, North Rhine-Westphalia, Germany

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Publications (23)93.83 Total impact

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    ABSTRACT: Large-scale longitudinal neuroimaging studies with diffusion imaging techniques are necessary to test and validate models of white matter neurophysiological processes that change in time, both in healthy and diseased brains. The predictive power of such longitudinal models will always be limited by the reproducibility of repeated measures acquired during different sessions. At present, there is limited quantitative knowledge about the across-session reproducibility of standard diffusion metrics in 3T multi-centric studies on subjects in stable conditions, in particular when using tract based spatial statistics and with elderly people. In this study we implemented a multi-site brain diffusion protocol in 10 clinical 3T MRI sites distributed across 4 countries in Europe (Italy, Germany, France and Greece) using vendor provided sequences from Siemens (Allegra, Trio Tim, Verio, Skyra, Biograph mMR), Philips (Achieva) and GE (HDxt) scanners. We acquired DTI data (2x2x2 mm(3), b=700s/mm(2), 5 b0 and 30 diffusion weighted volumes) of a group of healthy stable elderly subjects (5 subjects per site) in two separate sessions at least a week apart. For each subject and session four scalar diffusion metrics were considered: fractional anisotropy (FA), mean diffusivity (MD), radial (RD) and axial (AD) diffusivity. The diffusion metrics from multiple subjects and sessions at each site were aligned to their common white matter skeleton using tract-based spatial statistics. The reproducibility at each MRI site was examined by looking at group averages of absolute changes relative to the mean (%) on various parameters: i) reproducibility of the signal-to-noise ratio (SNR) of the b0 images in centrum semiovale, ii) full brain test-retest differences of the diffusion metric maps on the white matter skeleton, iii) reproducibility of the diffusion metrics on atlas-based white matter ROIs on the white matter skeleton. Despite the differences of MRI scanner configurations across sites (vendors, models, RF coils and acquisition sequences) we found good and consistent test-retest reproducibility. White matter b0 SNR reproducibility was on average 7±1 % with no significant MRI site effects. Whole brain analysis resulted in no significant test-retest differences at any of the sites with any of the DTI metrics. The atlas-based ROI analysis showed that the mean reproducibility errors largely remained in the range 2-4% for FA and AD and 2-6% for MD and RD, averaged across ROIs. Our results show reproducibility values comparable to those reported in studies using a smaller number of MRI scanners, slightly different DTI protocols and mostly younger populations. We therefore show that the acquisition and analysis protocol used are appropriate for multi-site experimental scenarios.
    NeuroImage 07/2014; · 6.25 Impact Factor
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    ABSTRACT: A role of the HTR3A-E genes in obsessive-compulsive disorder (OCD) can be expected based on promising effects of 5-HT3 receptor antagonists as adjunctive treatment of OCD. We therefore genotyped six common coding or promoter variants within the HTR3A-E genes in a case-control-sample consisting of N=236 OCD patients and N=310 control subjects and in N=58 parent-child-trios. Given the heterogeneous OCD phenotype, we also investigated OCD symptom dimensions and cognitive endophenotypes in subsamples. OCD patients scoring high for the washing subtype were significantly more likely to carry the c.256G-allele of the HTR3E variant rs7627615 (p=0.0001) as compared to OCD patients low for this symptom dimension. Visual organization was impaired in OCD patients and unaffected relatives as compared to healthy control subjects and carriers of the HTR3E c.256G/c.256G-genotype performed significantly worse (p=0.007). The case-control analyses revealed a nominal significant association of the HTR3D variant rs1000592 (p.H52R) with OCD (p=0.029) which was also evident after combination of the case-control and the trio-results (p=0.024). In male subjects, the variant rs6766410 (p.N163K) located in the HTR3C was significantly associated with OCD (p=0.007). The association findings of the HTR3C and the HTR3E remained significant after correction for the number of variants investigated. These findings indicate a role of common variants of the HTR3A-E genes in OCD and OCD-related phenotypes and further support the use of 5-HT3 receptor antagonists as novel treatment options. The HTR3E gene is a novel candidate gene impacting on the individual expression of OC symptoms and OCD-related cognitive dysfunction.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 08/2013; · 3.68 Impact Factor
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    ABSTRACT: Background: Parkinsonism with dopa-sensitivity and a correlating DaTSCAN turned out to be due to a D202N mutation which is associated with the Gerstmann-Sträussler-Scheinker (GSS) disease. Methods/Results: We report a 51-year old female who presented with left-dominant parkinsonism and a positive DaTSCAN. She was diagnosed with idiopathic Parkinson's syndrome. Dopaminergic medication reduced her symptoms. In addition, punding-like behavior, deficits in organizing daily life and abnormal sleep behavior were reported. Neuropsychological testing, EEG, polysomnography as well as PET imaging with fluorodexyglucose (FDG), [F-18]-desmethoxyfallypride (DMFP), and [C-11]-6-OH-BTA-1 (PIB) were not diagnostic. Cerebral spinal fluid analysis revealed no 14-3-3 protein, but elevated neuron-specific enolase (NSE) and S100-beta and a very low phospho-tau/total-tau ratio. Analysis of the prion gene disclosed the rare D202N mutation. Conclusions: The D202N prion mutation has been associated with GSS pathology and up to now was only reported post mortem. Our patient is the very first case diagnosed in vivo. © 2013 Movement Disorder Society.
    Movement Disorders 02/2013; 28(2):241-5. · 5.63 Impact Factor
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    ABSTRACT: The psychotomimetic effects of N-methyl-D-aspartate (NMDA) receptor antagonists in healthy humans and their tendency to aggravate psychotic symptoms in schizophrenic patients have promoted the notion of altered glutamatergic neurotransmission in the pathogenesis of schizophrenia. The NMDA-receptor antagonist MK-801 was chronically administered to rats (0.02 mg/kg intraperitoneally for 14 days). In one subgroup the antipsychotic haloperidol (1 mg/kg) was employed as a rescue therapy. Glutamate distribution and 3-NT (3-nitrotyrosine) as a marker of oxidative stress were assessed by immunohistochemistry in tissue sections. In parallel, the effects of MK-801 and haloperidol were investigated in primary embryonal hippocampal cell cultures from rats. Chronic NMDA-R antagonism led to a marked increase of intracellular glutamate in the hippocampus (126.1 +/- 10.4% S.E.M of control; p = 0.037), while 3-NT staining intensity remained unaltered. No differences were observed in extrahippocampal brain regions. Essentially these findings could be reproduced in vitro. The combined in vivo and in vitro strategy allowed us to assess the implications of disturbed glutamate metabolism for the occurrence of oxidative stress and to investigate the effects of antipsychotics. Our data suggest that oxidative stress plays a minor role in this model than previously suggested. The same applies to apoptosis. Moreover, the effect of haloperidol seems to be mediated through yet unidentified mechanisms, unrelated to D2-antagonism. These convergent lines of evidence indicate that further research should be focused on the glutamatergic system and that our animal model may provide a tool to explore the biology of schizophrenia.
    PLoS ONE 01/2013; 8(7):e59395. · 3.53 Impact Factor
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    ABSTRACT: Large-scale longitudinal multi-site MRI brain morphometry studies are becoming increasingly crucial to characterize both normal and clinical population groups using fully automated segmentation tools. The test–retest reproducibility of morphometry data acquired across multiple scanning sessions, and for different MR vendors, is an important reliability indicator since it defines the sensitivity of a protocol to detect longitudinal effects in a consortium. There is very limited knowledge about how across-session reliability of morphometry estimates might be affected by different 3 T MRI systems. Moreover, there is a need for optimal acquisition and analysis protocols in order to reduce sample sizes. A recent study has shown that the longitudinal FreeSurfer segmentation offers improved within session test–retest reproducibility relative to the cross-sectional segmentation at one 3 T site using a nonstandard multi-echo MPRAGE sequence. In this study we implement a multi-site 3 T MRI morphometry protocol based on vendor provided T1 structural sequences from different vendors (3D MPRAGE on Siemens and Philips, 3D IR-SPGR on GE) implemented in 8 sites located in 4 European countries. The protocols used mild acceleration factors (1.5–2) when possible. We acquired across-session test–retest structural data of a group of healthy elderly subjects (5 subjects per site) and compared the across-session reproducibility of two full-brain automated segmentation methods based on either longitudinal or cross-sectional FreeSurfer processing. The segmentations include cortical thickness, intracranial, ventricle and subcortical volumes. Reproducibility is evaluated as absolute changes relative to the mean (%), Dice coefficient for volume overlap and intraclass correlation coefficients across two sessions. We found that this acquisition and analysis protocol gives comparable reproducibility results to previous studies that used longer acquisitions without acceleration. We also show that the longitudinal processingis systematically more reliable across sites regardless of MRI system differences. The reproducibility errors of the longitudinal segmentations are on average approximately half of those obtained with the cross sectional analysis for all volume segmentations and for entorhinal cortical thickness. No significant differences in reliability are found between the segmentation methods for the other cortical thickness estimates. The average of two MPRAGE volumes acquired within each test–retest session did not systematically improve the across-session reproducibility of morphometry estimates. Our results extend those from previous studies that showed improved reliability of the longitudinal analysis at single sites and/or with non-standard acquisition methods. The multi-site acquisition and analysis protocol presented here is promising for clinical applications since it allows for smaller sample sizes per MRI site or shorter trials in studies evaluating the role of potential biomarkers to predict disease progression or treatment effects.
    NeuroImage 01/2013; 83:472-484. · 6.25 Impact Factor
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    ABSTRACT: In light of the dramatically increasing prevalence of Alzheimer's disease (AD) to be expected in the future, the development of novel therapeutics, improved differential and early diagnostics, and means for the identification of individuals at risk are urgently needed. At present, instruments for a reliable differential diagnosis in clinical dementia, mild cognitive impairment, or prodromal stages have direct practical implications for differentiating secondary dementias from neurodegenerative conditions and for treatment decisions. It may also be reasonable to enforce the incorporation of biomarkers into clinical studies as surrogate outcome parameters and as an attempt to optimize recruitment criteria. Recently, revised research criteria increasingly rely on the interpretation of biomarker patterns, including neuroimaging and CSF-based neurochemical dementia diagnosis (NDD) in supporting the clinical diagnosis. Here, we review the performance of current core CSF biomarkers (Aβ(42) peptide, total tau protein and phosphorylated tau species) and try to define objectives for prospective markers, also considering blood-based tests, which would increase the acceptance and wide application of NDD. Moreover, we evaluate the role and the limitations of genotyping in the predictive diagnosis of AD.
    European Archives of Psychiatry and Clinical Neuroscience 09/2012; · 3.36 Impact Factor
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    ABSTRACT: Serotonergic transmission is considered relevant in the pathophysiology and the treatment of schizophrenia. Tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. While the TPH1 gene has been found to be associated with schizophrenia, studies focusing on TPH2 variants did not yield conclusive results for schizophrenia or the response to antipsychotic medication. We analyzed eleven TPH2 SNPs in two case-control samples consisting of 4453 individuals in total. Six SNPs were selected because of their potential functional relevance (rs4570625, rs11178997, rs11178998, rs7954758, rs7305115, and, rs4290270) and were supported by another 5 tagging SNPs selected based on HapMap LD information. In the discovery sample (1476 individuals), we observed a significant association with schizophrenia for rs10784941 (p = 0.009, OR minor G-allele 0.82 [0.71-0.95]) and rs4565946 (p = 0.011, OR minor T-allele 0.83 [0.71-0.96]). Association was also observed with a common rs4570625-rs4565946 haplotype (OR G-C haplotype 1.20 [1.02-1.40]; p = 0.0046). Single-marker associations could not be replicated in the replication sample consisting of 2977 individuals, but there was a strong trend regarding the rs4570625-rs4565946 G-C haplotype (OR 1.10 [0.98-1.24]; p(one-sided test) = 0.054). In smaller sub-samples, the rare rs4570625-rs4565946 T-T haplotype was associated with reduced processing speed (n = 193, p = 0.004) and sensorimotor gating (n = 68, p = 0.006) of schizophrenia patients. TPH2 variants and the rs4570625-rs4565946 G-C haplotype did not influence the beneficial response to antipsychotic drugs (n = 210) after four weeks of treatment administering the Positive and Negative Syndrome Scale of Schizophrenia (PANSS). We also investigated the association of the SNPs to treatment response, but did not get significant results. In sum, our results argue for only a minor role of TPH2 in schizophrenia.
    Journal of Psychiatric Research 05/2012; 46(8):1073-80. · 4.09 Impact Factor
  • U Fiedler, J Wiltfang, N Peters, J Benninghoff
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    ABSTRACT: Due to the demographic developments, diagnosis and treatment, dementia constitutes an increasing medical challenge and is likely to have an increasing socioeconomic impact. Dementia does not reflect a single disease but encompasses a variety of underlying conditions, heterogeneous clinical courses and therapeutic approaches, among which Alzheimer's disease represents the most common cause. Therefore, a thorough differential diagnosis of dementia is of major importance. To date the current diagnosis of dementia according to ICD-10/DMS-IV is based on clinical criteria. In addition, the concept of mild cognitive impairment comprises early cognitive dysfunction without clinically apparent dementia. Alzheimer's disease is more and more conceptualized as a disease continuum with mild cognitive impairment as an early and manifest dementia as the later stage of the disease. This review gives an overview on the current diagnostic approaches and the proposed revisions of diagnostic and research criteria for Alzheimer's disease.
    Der Nervenarzt 05/2012; 83(5):661-73. · 0.80 Impact Factor
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    ABSTRACT: Growing evidence implicates that abnormal stem cell proliferation and neurodegenerative mechanisms may be involved in the pathogenesis of neuropsychiatric disorders including schizophrenia. Here, we studied the underlying pathomechanisms of psychosis. We are employing a translational approach combining in vivo data with supplementary data from an adult neuronal stem cell-derived cell culture model by generating a large number of analytes in our specimens following a multiplexing strategy. In the animal model the NMDA receptor was chronically antagonized by MK-801 at ultralow doses. As a result of this, we were able to demonstrate a roughly twofold increased density of PCNA positive cells in the germinal zone of the dentate gyrus indicating enhanced neuroproliferative activity. In vitro stem cell experiments additionally pointed to this direction showing an increase both in proliferation and neuronal differentiation after MK-801 treatment. These alterations were partially prevented by coapplication of the dopamine receptor antagonist haloperidol. In addition, apoptotic activity assessed by immunohistochemical demonstration of cleaved caspase-3 stainings was unaffected by MK-801 treatment. These observations were largely supported by microarray gene expression analysis, which permits high-throughput multiplexed assessment of expression data from a comprehensive set of genes and showed parallels with data from human post mortem studies. In conclusion, our data support the notion, that abnormal proliferation due to anti-apoptotic mechanisms may represent a factor in the pathogenesis of psychosis. Thus, research on the exact interplay between glutamatergic neurotransmission and neuronal proliferation deserves more attention. This dual in vivo and in vitro strategy described here may prove as a suitable model for addressing complex neuropsychiatric diseases especially when taking advantage of the potential of multiplex technologies not only in diagnostics but also in basic research.
    Methods 04/2012; 56(4):519-27. · 3.64 Impact Factor
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    ABSTRACT: Studies on the serotonin transporter (SERT) with regard to neurogenesis and neuroplastic effects on the adult brain are scarce. This is intriguing since neurogenesis is believed to play a decisive role in modulating the effect of selective serotonin reuptake inhibitors (SSRI), which are targeting SERT. Therefore, we reviewed the current scientific literature about the influence of serotonin on neurogenesis with particular emphasis on SERT in various settings, both in vivo and in vitro. Experiments using SERT KO (knock-out) animal models showed that SERT does not directly or indirectly influence neurogenesis in vitro, whereas compensatory mechanism seem to participate in vivo. At least with regard to adult neural stem cells, the impact of serotonin (5-HT) on neuroplasticity and neurogenesis is not due to SERT-mediated effcts. Instead, serotonergic fine-tuning may be exerted by a number of other different mechanisms including endogenous production of 5-HT in adult neural stem cells, uptake of 5-HT into adult neural stem cells by other monoamine transporters, and actions of the 5-HT1A receptors present on these cells.
    The World Journal of Biological Psychiatry 03/2012; 13(4):240-7. · 3.57 Impact Factor
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    ABSTRACT: Functional magnetic resonance imaging (fMRI) of default mode network (DMN) brain activity during resting is recently gaining attention as a potential noninvasive biomarker to diagnose incipient Alzheimer's disease. The aim of this study was to determine which method of data processing provides highest diagnostic power and to define metrics to further optimize the diagnostic value. fMRI was acquired in 21 healthy subjects, 17 subjects with mild cognitive impairment and 15 patients with Alzheimer's disease (AD) and data evaluated both with volumes of interest (VOI)-based signal time course evaluations and independent component analyses (ICA). The first approach determines the amount of DMN region interconnectivity (as expressed with correlation coefficients); the second method determines the magnitude of DMN coactivation. Apolipoprotein E (ApoE) genotyping was available in 41 of the subjects examined. Diagnostic power (expressed as accuracy) of data of a single DMN region in independent component analyses was 64%, that of a single correlation of time courses between 2 DMN regions was 71%, respectively. With multivariate analyses combining both methods of analysis and data from various regions, accuracy could be increased to 97% (sensitivity 100%, specificity 95%). In nondemented subjects, no significant differences in activity within DMN could be detected comparing ApoE ε4 allele carriers and ApoE ε4 allele noncarriers. However, there were some indications that fMRI might yield useful information given a larger sample. Time course correlation analyses seem to outperform independent component analyses in the identification of patients with Alzheimer's disease. However, multivariate analyses combining both methods of analysis by considering the activity of various parts of the DMN as well as the interconnectivity between these regions are required to achieve optimal and clinically acceptable diagnostic power.
    Neurobiology of aging 03/2012; 33(3):466-78. · 5.94 Impact Factor
  • Dan Rujescu, Just Genius, Jens Benninghoff, Ina Giegling
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    ABSTRACT: Schizophrenia is a devastating brain disease. The mode of inheritance is complex and non-Mendelian with a high heritability of ca. 65-80%. Given this complexity, until most recently it was notoriously difficult to identify disease genes. Due to new technologies the last few years have brought an explosion of interest in human genetics of complex diseases. The knowledge resulting from the availability of the complete sequence of the human genome, the systematic identification of single nucleotide polymorphisms (SNPs) throughout the genome, and the development of parallel genotyping technology (microarrays) established the conditions that brought about the current revolution in our ability to probe the genome for identifying disease genes. All these studies have opened a window into the biology of common complex diseases and have provided proof of principle and yielded a multitude of genes showing strong association with complex diseases. New findings in schizophrenia will be summarized in this review and discussed in the light of a possible translation into the development of better treatment.
    Current pharmaceutical biotechnology 01/2012; 13(8):1614-21. · 3.40 Impact Factor
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    ABSTRACT: Abstract Objectives. Increasing evidence indicates that canonical neurotransmitters act as regulatory signals during neuroplasticity. Here, we report that muscarinic cholinergic neurotransmission stimulates differentiation of adult neural stem cells in vitro. Methods. Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in culture with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Results. Carbachol (CCh), an analog of acetylcholine (ACh) significantly enhanced de novo differentiation into neurons on bFGF- and EGF-deprived stem cells as shown by the percentage of TUJ1 positive cells. By contrast, pirenzepine (PIR), a muscarinic M1 receptor antagonist, reduced the generation of neurons. Conclusion. Activation of cholinergic signaling drives the de novo differentiation of uncommitted stem cells into neurons. These effects appear to be predominantly mediated via the muscarinic M1 receptor subtype.
    The World Journal of Biological Psychiatry 10/2011; · 3.57 Impact Factor
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    ABSTRACT: Mutations of the transcription factor 4 (TCF4) gene cause mental retardation with or without associated facial dysmorphisms and intermittent hyperventilation. Subsequently, a polymorphism of TCF4 was shown in a genome-wide association study to slightly increase the risk of schizophrenia. We have further analysed the impact of this TCF4 variant rs9960767 on early information processing and cognitive functions in schizophrenia patients. We have shown in a sample of 401 schizophrenia patients that TCF4 influences verbal memory in the Rey Auditory Verbal Learning Test. Contrary to expectations, carriers of the schizophrenia-associated allele showed better recognition, thus indicating that while TCF4 influences verbal memory, the TCF4-mediated schizophrenia risk is not determined by the influence of TCF4 on verbal memory. TCF4 does not impact on various other cognitive functions belonging to the domains of attention and executive functions. Moreover, in a pharmacogenetic approach, TCF4 does not modulate the improvement of positive or negative schizophrenia symptoms during treatment with antipsychotics. Finally, we have assessed a key electrophysiological endophenotype of schizophrenia, sensorimotor gating. As measured by prepulse inhibition, the schizophrenia risk allele C of TCF4 rs9960767 reduces sensorimotor gating. This indicates that TCF4 influences key mechanisms of information processing, which may contribute to the pathogenesis of schizophrenia.
    European Archives of Psychiatry and Clinical Neuroscience 09/2011; 261 Suppl 2:S161-5. · 3.36 Impact Factor
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    Ina Giegling, Just Genius, Jens Benninghoff, Dan Rujescu
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    ABSTRACT: There is a relatively high genetic heritability of schizophrenia as shown by family, twin and adoption studies. A large number of hypotheses on the causes of schizophrenia occurred over time. In this review we focus on genetic findings related to potential alterations of intracellular Ca-homeostasis in association with schizophrenia. First, we provide evidence for the NMDA/glutamatergic theory of schizophrenia including calcium processes. We mainly focus on genes including: DAO (D-amino acid oxidase), DAOA (D-amino acid oxidase activator), DTNBP1 (Dysbindin 1, dystrobrevin-binding protein 1), NRG1 (Neuregulin 1), ERBB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4, avian), NOS1 (nitric oxide synthase 1, neuronal) and NRGN (Neurogranin). Furthermore, a gene coding for a calcium channel subunit (CACNA1C: calcium channel, voltage-dependent, L type, alpha 1C subunit) is discussed in the light of schizophrenia whereas genetic findings related to alterations in the intracellular Ca-homeostasis associated specifically with dopaminergic and serotonergic neurotransmission in schizophrenia are not herein closer reviewed. Taken together there is converging evidence for the contribution of genes potentially related to alterations in intracellular Ca-homeostasis to the risk of schizophrenia. Replications and functional studies will hopefully provide further insight into these genetic variants and the underlying processes.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2010; 34(8):1375-80. · 3.55 Impact Factor
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    ABSTRACT: Serotonin (5-HT) and the serotonergic system have recently been indicated as modulators of adult hippocampal neurogenesis. In this study, we evaluated the role of 5-HT on the functional features in neurospheres derived from adult neural stem cells (ANSC). We cultured neurospheres derived from mouse hippocampus in serum-free medium containing epidermal (EGF) and type-2 fibroblast growth factor (FGF2). Under these conditions ANSC expressed both isoforms of tryptophane-hydroxylase (TPH) and produced 5-HT. Blocking TPH function by para-chlorophenylalanine (PCPA) reduced ANSC proliferation, which was rescued by exogenous 5-HT. 5-HT action on ANSC was mediated predominantly by the serotonin receptor subtype 5-HT1A and, to a lesser extent, through the 5-HT2C (receptor) subtype, as shown by selectively antagonizing these receptors. Finally, we documented a 5-HT-induced increase of ANSC migration activity. In summary, we demonstrated a powerful serotonergic impact on ANSC functional features, which was mainly mediated by 5-HT1A receptors.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 12/2009; 35(4):893-903. · 8.68 Impact Factor
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    ABSTRACT: Gilles de la Tourette syndrome (GTS) (MIM 137580) is a complex neuropsychiatric disorder probably originating from a disturbed interplay of several neurotransmitter systems in the prefrontal-limbic-basal ganglia loop. Polygenetic multifactorial inheritance has been postulated; nevertheless, no confirmed susceptible genes have been identified yet. As neuroimaging studies allude to dopaminergic and serotonergic dysfunction in GTS and serotonin as an important factor for dopamine release, genotyping of common polymorphisms in the serotonergic receptor (HTR1A: C-1019G; HTR2A: T102C, His452Tyr, A-1438G; HTR2C: C-759T, G-697C) and transporter genes (SLC6A4) was carried out in 87 patients with GTS, compared with 311 matched controls. We found a nominally significant association between both polymorphisms in the HTR2C and the GTS, which was more pronounced in male patients. Analysis of the further serotonergic polymorphisms did not reveal any significant result. A modified function of these promoter polymorphisms may contribute to the complex interplay of serotonin and dopamine and then to the manifestation of GTS.
    Psychiatric genetics 12/2009; 20(1):35-8. · 2.33 Impact Factor
  • Alzheimer's and Dementia 07/2009; 5(4). · 17.47 Impact Factor
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    ABSTRACT: In a thought experiment we want to test how the emergence of adult neural stem cells could constitute an example for a scientific revolution in the sense of Thomas Kuhn. In his major work, “The structure of scientific revolutions, 3rd edn, University of Chicago Press, Chicago” (Kuhn 1996), the philosopher of science, Thomas Kuhn, states that scientific progress is not a cumulative process, but new theories appear by a rather revolutionary sequence of events. Kuhn built his theory on landmark events taken from chemistry and physics, lacking examples from biology. Beginning with Ramon y Cajal’s famous quote, “no new neurons after birth”, from the early years of the twentieth century, and Reynolds and Weiss’s conflicting finding in 1992 of adult neural stem cells giving rise to new neurons, we will test how the finding of neural stem cells in the adult brain matches with Kuhn’s theory. The pivotal problem of defining a paradigm will be our main focus, since the emergence of adult neural stem cells has been acclaimed by the scientific community as the rebuttal of Ramon y Cajal’s paradigm. Ziel ist es, in einem Gedankenexperiment zu testen, wie die Entstehung adulter neuraler Stammzellen als Beispiel für eine wissenschaftliche Revolution im Sinne Thomas Kuhns dienen könnte. In seinem Hauptwerk, “The Structure of Scientific Revolutions” (Kuhn 1996), erklärt der Wissenschaftsphilosoph Thomas Kuhn, dass wissenschaftlicher Fortschritt kein kumulativer Prozess sei, sondern dass neue Theorien durch eine geradezu revolutionäre Abfolge von Ereignissen entstehen. Kuhns Theorie fußt auf bahnbrechendenden Entwicklungen aus der Chemie und Physik, Beispiele aus der Biologie fehlen. Wir beginnen mit Ramon y Cajals berühmtem Zitat “Keine neuen Neuronen nach der Geburt” aus dem frühen 20. Jahrhundert und der Erkenntnis von Reynolds und Weiss aus dem Jahr 1992, dass adulte neurale Stammzellen neue Neuronen entstehen lassen, die dem Zitat von Ramon y Cajal widerspricht. Von dieser Situation ausgehend, testen wir, wie die Erkenntnis über neurale Stammzellen im erwachsenen Gehirn mit Kuhns Theorie zusammenpasst. Dabei konzentrieren wir uns auf das zentrale Problem der Definition eines Paradigmas, da die Entstehung adulter neuraler Stammzellen von der Wissenschaftsgemeinschaft als Widerlegung des Paradigmas von Ramon y Cajal begrüßt wurde. Dans un processus de cheminement intellectuel, nous voulons vérifier si l’émergence des cellules souches neurales adultes constitue un exemple de révolution scientifique au sens où l’entend Thomas Kuhn. Dans son œuvre principale, “The Structure of Scientific Revolutions” (Kuhn 1996), le philosophe scientifique Thomas Kuhn énonce que le progrès scientifique n’est pas un processus cumulatif mais plutôt que les nouvelles théories apparaissent suite à une séquence d’évènements révolutionnaires. La biologie ne lui apportant que peu d’exemples, c’est en se basant sur la physique et la chimie que Kuhn a construit sa théorie sur ces évènements clés. À partir de la célèbre citation de Ramon y Cajal: “aucun nouveau neurone après la naissance”, datant du début du vingtième siècle, et de la découverte contradictoire de cellules souches neurales adultes, par Reynold et Weiss, donnant lieu à de nouveaux neurones, en 1992, nous analysons si la théorie de Kuhn se vérifie avec cette découverte. La question centrale de la définition d’un paradigme constitue notre principale préoccupation puisque la découverte de cellules souche adultes a été encesée par la communauté scientifique comme un réfus du paradigme de Ramon y Cajal.
    Poiesis & Praxis 02/2009; 6(1):3-11.
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    Jens Benninghoff
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    ABSTRACT: Exploring stem cells is a fascinating task, especially in a discipline where the use of stem cells seems far-fetched at first glance, as is the case in psychiatry. In this article we would like to provide a brief overview of the current situation in relation to the treatment of mental diseases. For reasons that we will explain, this review will focus on affective disorders. The following section will give a more detailed account of stem-cell biology including current basic science approaches presenting in-vivo and in-vitro techniques. The final part will then look into future perspectives of using these stem cells to cure mental illnesses, and discuss the related challenges and opportunities.
    Dialogues in clinical neuroscience 01/2009; 11(4):397-404.

Publication Stats

118 Citations
93.83 Total Impact Points

Institutions

  • 2011–2014
    • University of Duisburg-Essen
      • Klinik für Psychiatrie und Psychotherapie (LVR)
      Essen, North Rhine-Westphalia, Germany
  • 2011–2013
    • University of Bonn
      • Department of Neurobiology
      Bonn, North Rhine-Westphalia, Germany
  • 2009–2012
    • University of Technology Munich
      • Institute of Radiology
      München, Bavaria, Germany
    • Trinity College Dublin
      Dublin, Leinster, Ireland
  • 2010
    • Ludwig-Maximilian-University of Munich
      • Department of Psychiatry
      München, Bavaria, Germany
  • 2003
    • University of Wuerzburg
      • Department of Psychiatry, Psychosomatics, and Psychotherapy
      Würzburg, Bavaria, Germany