Peter Schönknecht

University of Leipzig, Leipzig, Saxony, Germany

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Publications (170)600 Total impact

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    ABSTRACT: Recently, there has been an increased interest in the use of automatically segmented subfields of the human hippocampal formation derived from magnetic resonance imaging (MRI). However, little is known about the test-retest reproducibility of such measures, particularly in the context of multisite studies. Here, we report the reproducibility of automated Freesurfer hippocampal subfields segmentations in 65 healthy elderly enrolled in a consortium of 13 3T MRI sites (five subjects per site). Participants were scanned in two sessions (test and retest) at least one week apart. Each session included two anatomical 3D T1 MRI acquisitions harmonized in the consortium. We evaluated the test-retest reproducibility of subfields segmentation (i) to assess the effects of averaging two within-session T1 images and (ii) to compare subfields with whole hippocampus volume and spatial reliability. We found that within-session averaging of two T1 images significantly improved the reproducibility of all hippocampal subfields but not that of the whole hippocampus. Volumetric and spatial reproducibility across MRI sites were very good for the whole hippocampus, CA2-3, CA4-dentate gyrus (DG), subiculum (reproducibility error∼2% and DICE > 0.90), good for CA1 and presubiculum (reproducibility error ∼ 5% and DICE ∼ 0.90), and poorer for fimbria and hippocampal fissure (reproducibility error ∼ 15% and DICE < 0.80). Spearman's correlations confirmed that test-retest reproducibility improved with volume size. Despite considerable differences of MRI scanner configurations, we found consistent hippocampal subfields volumes estimation. CA2-3, CA4-DG, and sub-CA1 (subiculum, presubiculum, and CA1 pooled together) gave test-retest reproducibility similar to the whole hippocampus. Our findings suggest that the larger hippocampal subfields volume may be reliable longitudinal markers in multisite studies. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 06/2015; DOI:10.1002/hbm.22859 · 6.92 Impact Factor
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    ABSTRACT: α4β2* nicotinic receptors (α4β2* nAChRs) could provide a biomarker in neuropsychiatric disorders (e.g. Alzheimer´s and Parkinson’s disease, depressive disorders, and nicotine addiction). However, there is a lack of α4β2* nAChR specific PET radioligands with kinetics fast enough to enable quantification of nAChR within a reasonable time frame. Following on from promising preclinical results, the aim of the present study was to evaluate for the first time in humans the novel PET radioligand (-)-[18 F]Flubatine, formerly known as (-)-[18 F]NCFHEB, as a tool for α4β2* nAChR imaging and in vivo quantification.
    NeuroImage 05/2015; 118. DOI:10.1016/j.neuroimage.2015.05.065 · 6.13 Impact Factor
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    ABSTRACT: In preclinical studies, the hypothalamic polypeptide melanin-concentrating hormone (MCH) has been shown to be involved in depression-like behavior and modulations of MCH and MCH-receptors were proposed as potential new antidepressant drug targets. For the first time, MCH serum levels were explored in 30 patients with major depressive disorder (MDD) prior to (T1) and after 2 (T2) and 4 weeks (T3) of antidepressant treatment and in 30 age- and sex-matched healthy controls by applying a fluorescence immunoassay. Levels of MCH did not differ significantly between un-medicated patients (444.11±174.63pg/mL SD) and controls (450.68±210.03pg/mL SD). In MDD patients, MCH levels significantly decreased from T1 to T3 (F=4.663; p=0.013). Post-hoc analyses showed that these changes were limited to patients treated with mirtazapine but not escitalopram and female but not male patients. MCH-levels showed high correlations from T1 to T3 (r≥0.964, p<0.001) and were found to correlate significantly with parameters of sleep within the controls. Small sample size. No follow-up measures were performed within the control group. Our findings suggest peripheral MCH-levels not to be altered in depression but possibly reflecting depression-related state properties that can be modulated by sleep, medication and sex. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 04/2015; 180:207-213. DOI:10.1016/j.jad.2015.03.039 · 3.71 Impact Factor
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    ABSTRACT: The "Onset of Depression Inventory" (ODI) represents a patient interview which aims to register the speed of onset of depression systematically. The purpose of this study was to evaluate the patient-relative agreement regarding the speed of onset of depression in the patients. The ODI was investigated in 31 patients with a depressive episode. Moreover, 31 patients' relatives participated in an interview for which a modified version of the ODI (for relatives of depressed patients; ODI-A) was applied. There was a significant association between patients' estimation of the speed of onset of the depressive episode and relatives' estimation of this parameter in the case of patients and relatives living in a common household (rho = 0.68; p = 0.006). There was an agreement between patients and their relatives regarding the speed of onset of the current depressive episodes, however only if they lived in a common household.
    International Journal of Psychiatry in Clinical Practice 03/2015; DOI:10.3109/13651501.2015.1028413 · 1.31 Impact Factor
  • European Psychiatry 03/2015; 30:204. DOI:10.1016/S0924-9338(15)30164-4 · 3.21 Impact Factor
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    ABSTRACT: Objectives. Alterations in neuronal and glial integrity are considered to be of pathogenic impact on major depressive disorder (MDD). For MDD, data on cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) are lacking and scarce for glial protein S100B. Methods. We measured CSF levels of NSE and S100B in 31 patients with MDD and 32 mentally healthy controls using electrochemiluminescence immunoassays (ECLIA). Results. Adjusted means of NSE were significantly elevated in the MDD patients (11.73 ng/ml (9.95-13.52 95% CI) compared to the controls (6.17 ng/ml (4.55-7.78), F = 9.037, P = 0.004. Effect size for adjusted mean group difference of 5.57 ng/ml was found invariably high (Cohen's d = 1.23). Differentiating MDD from controls, a NSE cut-off of 7.94 ng/ml showed sensitivity of 81% (95% CI 63.7-90.8) and specificity of 75% (95% CI 57.9-86.7). Adjusted levels of S100B did not differ significantly between the two groups (1.12 ng/ml (0.77-1.48) in MDD, 0.97 ng/ml (0.64-1.30) in controls). Conclusions. Our results of elevated CSF-NSE levels support neuronal pathology in MDD and the potential use of CSF-NSE as marker in clinical diagnostics. Missing group differences in S100B do not promote a specific glial pathology in depressive disorders.
    The World Journal of Biological Psychiatry 02/2015; 16(2):106-113. DOI:10.3109/15622975.2014.952776 · 4.23 Impact Factor
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    ABSTRACT: Peripheral brain-derived neurotrophic factor (BDNF) is decreased in acute major depressive disorder (MDD) and bipolar disorder (BD) and recovered after treatment. Here we validated on a meta-analytical level whether BDNF restores differentially according to treatment response and whose measurements could be used as a biomarker, plasma or serum. Using strict inclusion criteria, we compared BDNF in healthy controls and patients with MDD (38 studies, n=6619), and BD (17 studies, n=1447). Pre- and post-treatment BDNF levels were meta-analyzed according to treatment response in patients from 21 MDD studies (n=735) and 7 BD studies (n=88). Serum and plasma subgroups were analyzed, publication bias was assessed and heterogeneity was investigated. Serum and plasma BDNF were decreased in acute MDD and BD, and did not differ in euthymia in comparison with control subjects. Antidepressive treatment increased serum BDNF levels in MDD in responders (Cohen׳s d (d)=1.27, p=4.4E-07) and remitters (d=0.89, p=0.01), significantly more than in non-responders (d=0.11, p=0.69). For plasma BDNF in MDD and for BD, the evidence was insufficient for a meta-analysis. Although no significant difference was found between serum and plasma ES, variance of plasma ES was higher. Between-study heterogeneity was explained only partially; signs of publication bias in serum studies. Serum BDNF might be regarded as a biomarker for the successful treatment of MDD. Serum measurements seem more reliable than plasma ones. Further research should focus on defining optimal time points for BDNF measurements and increase evidence for the usage of BDNF as a predictive biomarker in BD. Copyright © 2014 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 11/2014; 174C:432-440. DOI:10.1016/j.jad.2014.11.044 · 3.71 Impact Factor
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    ABSTRACT: Background: Depressive episodes show large interindividual differences concerning their speed of onset and speed of recovery, which might suggest differences in underlying pathophysiological processes. The aim of the present study was to assess whether there is a relationship between the speed of onset and the speed of recovery from depressive episodes. Methods: The speed of onset and the speed of recovery from depression were assessed using a structured patient interview, the Onset of Depression Inventory (ODI). In total, 28 patients with bipolar depression and 91 patients with unipolar depression were included. Results: The mean speed of onset of depression was significantly faster than the mean speed of recovery from depression (35.25, range 0-360 days vs. 59.60, range 0.13-720 days; Z = -3.40; p = 0.001). The correlation between these variables was positive, but numerically low (ρ = 0.22; p = 0.016). The speed of onset of the previous episode and that of the present episode were significantly correlated (ρ = 0.45; p < 0.001). Limitations: Data are based on retrospective patient reports within a naturalistic study. Conclusions: While the speed of onset of depressive episodes has been found to show large interindividual variability and some intraindividual stability, the data of this study do not indicate that the neurobiological processes involved in the onset of and in the recovery from depressive episodes are closely linked. © 2014 S. Karger AG, Basel.
    Psychopathology 10/2014; 48(1). DOI:10.1159/000367601 · 1.56 Impact Factor
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    ABSTRACT: (-)-(18)F-flubatine is a promising tracer for neuroimaging of nicotinic acetylcholine receptors (nAChRs), subtype α4β2, using PET. Radiation doses after intravenous administration of the tracer in mice and piglets were assessed to determine the organ doses (ODs) and the effective dose (ED) to humans. The results were compared with subsequent clinical investigations in human volunteers.
    Journal of Nuclear Medicine 10/2014; 55(11). DOI:10.2967/jnumed.114.137059 · 5.56 Impact Factor
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    ABSTRACT: Background The relationship between leptin and affective disorders is still unknown. Methods We measured free and bound leptin in 13 drug naïve subjects. Results Leptin did not significantly differ between patients and controls. Conclusions As part of future studies, it also appears useful to distinguish between free and bound leptin.
    Psychiatry Research 10/2014; 219(2). DOI:10.1016/j.psychres.2014.05.030 · 2.68 Impact Factor
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    ABSTRACT: Introduction (-)-[18 F]Flubatine is a PET tracer with high affinity and selectivity for the nicotinic acetylcholine α4β2 receptor subtype. A clinical trial assessing the availability of this subtype of nAChRs was performed. From a total participant number of 21 Alzheimer’s disease (AD) patients and 20 healthy controls (HCs), the following parameters were determined: plasma protein binding, metabolism and activity distribution between plasma and whole blood. Methods Plasma protein binding and fraction of unchanged parent compound were assessed by ultracentrifugation and HPLC, respectively. The distribution of radioactivity (parent compound + metabolites) between plasma and whole blood was determined ex vivo at different time-points after injection by gamma counting after separation of whole blood by centrifugation into the cellular and non-cellular components. In additional experiments in vitro, tracer distribution between these blood components was assessed for up to 90 min. Results A fraction of 15 ± 2 % of (-)-[18 F]Flubatine was found to be bound to plasma proteins. Metabolic degradation of (-)-[18 F]Flubatine was very low, resulting in almost 90 % unchanged parent compound at 90 min p.i. with no significant difference between AD and HC. The radioactivity distribution between plasma and whole blood changed in vivo only slightly over time from 0.82 ± 0.03 at 3 min p.i. to 0.87 ± 0.03 at 270 min p.i. indicating the contribution of only a small amount of metabolites. In vitro studies revealed that (-)-[18 F]Flubatine was instantaneously distributed between cellular and non-cellular blood parts. Discussion (-)-[18 F]Flubatine exhibits very favourable characteristics for a PET radiotracer such as slow metabolic degradation and moderate plasma protein binding. Equilibrium of radioactivity distribution between plasma and whole blood is reached instantaneously and remains almost constant over time allowing both convenient sample handling and facilitated fractional blood volume contribution assessment.
    Nuclear Medicine and Biology 07/2014; 41(6). DOI:10.1016/j.nucmedbio.2014.03.018 · 2.41 Impact Factor
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    ABSTRACT: Early-onset (EOD) and late-onset depression (LOD) are associated with different neuropsychological syndromes and structural brain changes. In this article, neuroimaging studies examining structural brain changes in elderly depressed patients are reviewed. The presented findings support current assumptions that depression in the elderly generally is associated with volume reductions in brain structures, notably in the hippocampus and the orbitofrontal cortex (OFC). Concerning structural cerebral differences between EOD and LOD, the review yielded conflicting results—only for OFC, but not for amygdala or hippocampus, pronounced effects in LOD than in EOD can be assumed. © 2014 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 24, 149–160, 2014
    International Journal of Imaging Systems and Technology 06/2014; 24(2). DOI:10.1002/ima.22089 · 0.77 Impact Factor
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    Journal of Psychiatric Research 06/2014; 53. DOI:10.1016/j.jpsychires.2014.02.021 · 4.09 Impact Factor
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    ABSTRACT: Neuron-specific enolase (NSE) is a neuronal glycolytic enzyme of which cerebrospinal fluid (CSF) levels are found altered following acute or prolonged neuronal damage. Investigations concerning the role of NSE in Alzheimer's disease (AD) are conflicting with both elevated and reduced levels. We measured CSF-levels of NSE in 32 patients with AD and 32 healthy subjects (HS) using an electrochemiluminescence immunoassay (ECLIA). Mean levels of adjusted NSE were significantly elevated in AD (18.12ng/mL (95% CI 15.63-20.60), HS 8.46ng/mL (95% CI 5.98-10.94), p=0.00002) and effect size for mean group differences high (1.84). NSE alone (cut-off score 15.80ng/mL, 94% sensitivity, 97% specificity) and in combination with T-tau and P-Tau had high diagnostic accuracy to differentiate AD from HS. NSE correlated significantly with T-tau (r≥0.87, p<0.000001) and P-tau (r≥0.88, p<0.000001) in both AD and HS. Our results indicate elevated CSF-NSE levels to reflect altered neuronal metabolism in AD that may be used in supporting AD diagnostics.
    Neuroscience Letters 04/2014; 570. DOI:10.1016/j.neulet.2014.04.007 · 2.06 Impact Factor
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    ABSTRACT: Structural and metabolic alterations in prefrontal brain areas, including the subgenual (SGPFC), medial (MPFC) and dorsolateral prefrontal cortex (DLPFC), have been shown in major depressive disorder (MDD). Still it remains largely unknown how brain connectivity within these regions is altered at the level of neuronal oscillations. Therefore, the goal was to analyze prefrontal electroencephalographic phase synchronization in MDD and its changes after antidepressant treatment. In 60 unmedicated patients and 60 healthy controls (HC), a 15-min resting electroencephalogram (EEG) was recorded in subjects at baseline and in a subgroup of patients after 2 weeks of antidepressant medication. EEG functional connectivity between the SGPFC and the MPFC/DLPFC was assessed with eLORETA (low resolution brain electromagnetic tomography) by means of lagged phase synchronization. At baseline, patients revealed increased prefrontal connectivity at the alpha frequency between the SGPFC and the left DLPFC/MPFC. After treatment, an increased connectivity between the SGPFC and the right DLPFC/MPFC at the beta frequency was found for MDD. A positive correlation was found for baseline beta connectivity and reduction in scores on the Hamilton Depression Rating Scale. MDD is characterized by increased EEG functional connectivity within frontal brain areas. These EEG markers of disturbed neuronal communication might have potential value as biomarkers.
    Psychiatry Research Neuroimaging 03/2014; DOI:10.1016/j.pscychresns.2014.02.010 · 2.83 Impact Factor
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    ABSTRACT: The functional organization of the brain in segregated neuronal networks has become a leading paradigm in the study of brain diseases. Diffusion tensor imaging (DTI) allows testing the validity and clinical utility of this paradigm on the structural connectivity level. DTI in Alzheimer's disease (AD) suggests a selective impairment of intracortical projecting fiber tracts underlying the functional disorganization of neuronal networks supporting memory and other cognitive functions. These findings have already been tested for their utility as clinical markers of AD in large multicenter studies. Affective disorders, including major depressive disorder (MDD) and bipolar disorder (BP), show a high comorbidity with AD in geriatric populations and may even have a pathogenetic overlap with AD. DTI studies in MDD and BP are still limited to small-scale monocenter studies, revealing subtle abnormalities in cortico-subcortial networks associated with affect regulation and reward/aversion control. The clinical utility of these findings remains to be further explored. The present paper presents the methodological background of diffusion imaging, including DTI and diffusion spectrum imaging, and discusses key findings in AD and affective disorders. The results of our review strongly point toward the necessity of large-scale multicenter multimodal transnosological networks to study the structural and functional basis of neuronal disconnection underlying different neuropsychiatric diseases.
    European Archives of Psychiatry and Clinical Neuroscience 03/2014; 264(6). DOI:10.1007/s00406-014-0496-6 · 3.36 Impact Factor
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    Clinical EEG and neuroscience; 12/2013
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    Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS) 12/2013; 44(4):E1-121. · 3.16 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 12/2013; 83:472-484. DOI:10.1016/j.neuroimage.2013.05.007 · 6.13 Impact Factor
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    ABSTRACT: Animal epidemiological and clinical studies suggest that cholesterol is a risk factor for Alzheimer's disease (AD). Nevertheless, the relation of cholesterol to mild cognitive impairment (MCI), influence of APOE genotype and its changes in lifespan is controversial. We investigated the potential impact of plasma total cholesterol (TC) on development of MCI and AD in the interdisciplinary longitudinal study on adult development and aging, a representative birth cohort (born 1930-1932), examined in 1993/1994 (VT1), 1997/1998 (VT2), and 2005/2007 (VT3). Of 500 participants at baseline, 381 survived and were examined at VT3. After exclusion of participants with lifetime prevalence of major psychiatric diseases or mild cognitive disorder due to a medical condition, 222 participants were included in the analysis. At VT3, 82 participants had MCI, 22 participants had AD, and 118 were in good health. Participants with MCI and AD at VT3 evidenced higher TC levels at VT1 than those who were healthy. Higher TC levels at baseline were associated with an increased risk for cognitive disorders at VT3 (highest vs. lowest quartile: OR 2.64, 95 % CI 1.12-6.23, p < 0.05). Over the 14 year follow-up, TC levels declined in those with MCI and AD, but remained stable in those who remained healthy. These findings were not modified by APOE genotype or use of cholesterol-lowering medications. Our findings demonstrate that higher TC levels are observed long before the clinical manifestation of MCI and AD in patients without psychiatric or somatic comorbidities and are independent of APOE genotype.
    European Archives of Psychiatry and Clinical Neuroscience 11/2013; 264(6). DOI:10.1007/s00406-013-0468-2 · 3.36 Impact Factor

Publication Stats

2k Citations
600.00 Total Impact Points

Institutions

  • 2009–2015
    • University of Leipzig
      Leipzig, Saxony, Germany
  • 2013
    • Otto-von-Guericke-Universität Magdeburg
      Magdeburg, Saxony-Anhalt, Germany
  • 1999–2012
    • Universität Heidelberg
      • • Department of Geriatric Psychiatry
      • • Section Gerontopsychiatrische Research
      Heidelburg, Baden-Württemberg, Germany
  • 2008
    • University Hospital Frankfurt
      Frankfurt, Hesse, Germany
  • 2003
    • German Cancer Research Center
      • Division of Radiology
      Heidelberg, Baden-Wuerttemberg, Germany