23627
2018
eng
10
article
FLTD consortium
1
2021-04-30
--
--
A language-based sum score for the course and therapeutic intervention in primary progressive aphasia
Background
With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions.
Methods
We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials.
Results
Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures.
Conclusion
Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.
Alzheimer's Research & Therapy
10.1186/s13195-018-0345-3
urn:nbn:de:bvb:20-opus-236277
publish
Alzheimer's Research & Therapy (2018) 10:41. https://doi.org/10.1186/s13195-018-0345-3
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Elisa Semler
Sarah Anderl-Straub
Ingo Uttner
Janine Diehl-Schmid
Adrian Danek
Beate Einsiedler
Klaus Fassbender
Klaus Fliessbach
Hans-Jürgen Huppertz
Holger Jahn
Johannes Kornhuber
Bernhard Landwehrmeyer
Martin Lauer
Rainer Muche
Johannes Prudlo
Anja Schneider
Matthias L. Schroeter
Albert C. Ludolph
Markus Otto
eng
uncontrolled
frontotemporal dementia
eng
uncontrolled
cognitive neuropsychology in dementia
eng
uncontrolled
assessment of cognitive disorders/dementia
eng
uncontrolled
volumetric MRI
eng
uncontrolled
aphasia
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23627/s13195-018-0345-3.pdf
22050
2018
eng
6
article
1
2021-01-14
--
--
Detecting significant genotype–phenotype association rules in bipolar disorder: market research meets complex genetics
Background
Disentangling the etiology of common, complex diseases is a major challenge in genetic research. For bipolar disorder (BD), several genome-wide association studies (GWAS) have been performed. Similar to other complex disorders, major breakthroughs in explaining the high heritability of BD through GWAS have remained elusive. To overcome this dilemma, genetic research into BD, has embraced a variety of strategies such as the formation of large consortia to increase sample size and sequencing approaches. Here we advocate a complementary approach making use of already existing GWAS data: a novel data mining procedure to identify yet undetected genotype–phenotype relationships. We adapted association rule mining, a data mining technique traditionally used in retail market research, to identify frequent and characteristic genotype patterns showing strong associations to phenotype clusters. We applied this strategy to three independent GWAS datasets from 2835 phenotypically characterized patients with BD. In a discovery step, 20,882 candidate association rules were extracted.
Results
Two of these rules—one associated with eating disorder and the other with anxiety—remained significant in an independent dataset after robust correction for multiple testing. Both showed considerable effect sizes (odds ratio ~ 3.4 and 3.0, respectively) and support previously reported molecular biological findings.
Conclusion
Our approach detected novel specific genotype–phenotype relationships in BD that were missed by standard analyses like GWAS. While we developed and applied our method within the context of BD gene discovery, it may facilitate identifying highly specific genotype–phenotype relationships in subsets of genome-wide data sets of other complex phenotype with similar epidemiological properties and challenges to gene discovery efforts.
International Journal of Bipolar Disorders
10.1186/s40345-018-0132-x
urn:nbn:de:bvb:20-opus-220509
publish
International Journal of Bipolar Disorders(2018) 6:24. https://doi.org/10.1186/s40345-018-0132-x
242257
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
René Breuer
Manuel Mattheisen
Josef Frank
Bertram Krumm
Jens Treutlein
Layla Kassem
Jana Strohmaier
Stefan Herms
Thomas W. Mühleisen
Franziska Degenhardt
Sven Cichon
Markus M. Nöthen
George Karypis
John Kelsoe
Tiffany Greenwood
Caroline Nievergelt
Paul Shilling
Tatyana Shekhtman
Howard Edenberg
David Craig
Szabolcs Szelinger
John Nurnberger
Elliot Gershon
Ney Alliey-Rodriguez
Peter Zandi
Fernando Goes
Nicholas Schork
Erin Smith
Daniel Koller
Peng Zhang
Judith Badner
Wade Berrettini
Cinnamon Bloss
William Byerley
William Coryell
Tatiana Foroud
Yirin Guo
Maria Hipolito
Brendan Keating
William Lawson
Chunyu Liu
Pamela Mahon
Melvin McInnis
Sarah Murray
Evaristus Nwulia
James Potash
John Rice
William Scheftner
Sebastian Zöllner
Francis J. McMahon
Marcella Rietschel
Thomas G. Schulze
eng
uncontrolled
bipolar disorder
eng
uncontrolled
subphenotypes
eng
uncontrolled
rule discovery
eng
uncontrolled
data mining
eng
uncontrolled
genotype-phenotype patterns
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/22050/s40345-018-0132-x.pdf
22363
2019
eng
11
article
1
2021-02-10
--
--
DNA methyltransferase isoforms expression in the temporal lobe of epilepsy patients with a history of febrile seizures
Background
Temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) is a common pharmaco-resistant epilepsy referred for adult epilepsy surgery. Though associated with prolonged febrile seizures (FS) in childhood, the neurobiological basis for this relationship is not fully understood and currently no preventive or curative therapies are available. DNA methylation, an epigenetic mechanism catalyzed by DNA methyltransferases (DNMTs), potentially plays a pivotal role in epileptogenesis associated with FS. In an attempt to start exploring this notion, the present cross-sectional pilot study investigated whether global DNA methylation levels (5-mC and 5-hmC markers) and DNMT isoforms (DNMT1, DNMT3a1, and DNMT3a2) expression would be different in hippocampal and neocortical tissues between controls and TLE patients with or without a history of FS.
Results
We found that global DNA methylation levels and DNMT3a2 isoform expression were lower in the hippocampus for all TLE groups when compared to control patients, with a more significant decrease amongst the TLE groups with a history of FS. Interestingly, we showed that DNMT3a1 expression was severely diminished in the hippocampus of TLE patients with a history of FS in comparison with control and other TLE groups. In the neocortex, we found a higher expression of DNMT1 and DNMT3a1 as well as increased levels of global DNA methylation for all TLE patients compared to controls.
Conclusion
Together, the findings of this descriptive cross-sectional pilot study demonstrated brain region-specific changes in DNMT1 and DNMT3a isoform expression as well as global DNA methylation levels in human TLE with or without a history of FS. They highlighted a specific implication of DNMT3a isoforms in TLE after FS. Therefore, longitudinal studies that aim at targeting DNMT3a isoforms to evaluate the potential causal relationship between FS and TLE or treatment of FS-induced epileptogenesis seem warranted.
Clinical Epigenetics
10.1186/s13148-019-0721-2
urn:nbn:de:bvb:20-opus-223636
publish
Clinical Epigenetics (2019) 11:118. https://doi.org/10.1186/s13148-019-0721-2
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Laurence de Nijs
Kyonghwan Choe
Hellen Steinbusch
Olaf E. M. G. Schijns
Jim Dings
Daniel L. A. van den Hove
Bart P. F. Rutten
Govert Hoogland
eng
uncontrolled
febrile seizures
eng
uncontrolled
temporal lobe epilepsy
eng
uncontrolled
epigenetics
eng
uncontrolled
DNA methylation
eng
uncontrolled
DNA methyltransferases
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/22363/s13148-019-0721-2.pdf
32482
2023
eng
30381-30392
34
42
article
1
--
--
--
Valence framing induces cognitive bias
Valence framing effects refer to inconsistent choice preferences in response to positive versus negative formulation of mathematically equivalent outcomes. Here, we manipulate valence framing in a two-alternative forced choice dictator game using gains and losses as frames to investigate the cognitive mechanisms underlying valence framing. We applied a Drift-Diffusion Model (DDM) to examine whether gain (i.e., “take” money) and loss (i.e., “give” money) frames evoke a cognitive bias as previous research did not consistently reveal framing effects using reaction times and response frequency as dependent variables. DDMs allow decomposing the decision process into separate cognitive mechanisms, whereby a cognitive bias was repeatedly associated with a shift in the starting point of the model. Conducting both a laboratory (N = 62) and an online study (N = 109), female participants allocated money between themselves and another person in a prosocial or selfish way. In each study, one group was instructed to give money (give frame), the other to take money (take frame). Consistent with previous studies, no differences were found in response times and response frequencies. However, in both studies, substantial bias towards the selfish option was found in the take frame groups, captured by the starting point of the DDM. Thus, our results suggest that valence framing induces a cognitive bias in decision processing in women, even when no behavioral differences are present.
Current Psychology
1046-1310
10.1007/s12144-022-03797-2
urn:nbn:de:bvb:20-opus-324824
@articleIotzov.2022, author = Iotzov, Vassil and Weiß, Martin and Windmann, Sabine and Hein, Grit, year = 2022, title = Valence framing induces cognitive bias, issn = 1046-1310, journal = Current Psychology, doi = 10.1007/s12144-022-03797-2
md5:fffc1a7a0dd8e408e517b3d53cbb1188
2023-08-12T10:56:56+00:00
/tmp/phpnE7pE7
bibtex
64d765783167f8.61832599
Current Psychology (2023) 42:34, 30381-30392. DOI: 10.1007/s12144-022-03797-2
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Vassil Iotzov
Martin Weiß
Sabine Windmann
Grit Hein
eng
uncontrolled
valence framing
eng
uncontrolled
cognitive bias
eng
uncontrolled
decision making
eng
uncontrolled
drift-diffusion modeling
eng
uncontrolled
laboratory and online studies
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/32482/s12144-022-03797-2.pdf
32483
2022
eng
689-701
5-6
129
article
1
--
--
--
Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone
Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose–concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20–60 ng/ml) is applicable for minors. In the 64 patients (aged 11–18 years) included, a positive correlation between daily dose and the active moiety (RIS\(_{am}\)) concentration was found (r\(_s\) = 0.49, p = 0.001) with variation in dose explaining 24% (r\(_s\)\(^2\) = 0.240) of the variability in serum concentrations. While the RIS\(_{am}\) concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RIS\(_{am}\) concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RIS\(_{am}\) was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions.
Journal of Neural Transmission
10.1007/s00702-022-02485-6
urn:nbn:de:bvb:20-opus-324833
@articleTaurines.2022, author = Taurines, R. and Fekete, S. and Preuss-Wiedenhoff, A. and Warnke, A. and Wewetzer, C. and Plener, P. and Burger, R. and Gerlach, M. and Romanos, M. and Egberts, K. M., year = 2022, title = Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone, pages = 689–701, volume = 129, number = 5-6, journal = Journal of neural transmission (Vienna, Austria : 1996), doi = 10.1007/s00702-022-02485-6
md5:9d3e438a110c95c9bdcd103c4ff2d48d
2023-08-12T10:56:56+00:00
/tmp/phpnE7pE7
bibtex
64d765783167f8.61832599
Journal of Neural Transmission (2022) 129:5-6, 689-701. DOI: 10.1007/s00702-022-02485-6
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
R. Taurines
S. Fekete
A. Preuss-Wiedenhoff
A. Warnke
C. Wewetzer
P. Plener
R. Burger
M. Gerlach
M. Romanos
K. M. Egberts
eng
uncontrolled
risperidone
eng
uncontrolled
children
eng
uncontrolled
serum concentration
eng
uncontrolled
schizophrenia
eng
uncontrolled
therapeutic drug monitoring
eng
uncontrolled
pharmacovigilance
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/32483/s00702-022-02485-6.pdf
33066
2024
deu
doctoralthesis
1
2023-11-11
--
2023-10-12
Psychopharmakotherapie in Schwangerschaft und Stillzeit: Dynamik der Wirkstoffspiegel in Schwangerschaft und Stillzeit und Auswirkungen auf das Neugeborene
Psychopharmacotherapy during pregnancy and breastfeeding:
Dynamics of drug levels in pregnancy and lacation and effects on the neonate
Schwangerschaft und Stillzeit gehen mit erheblichen metabolischen Veränderungen des mütterlichen Organismus einher. Bis dato ist über die Pharmakokinetik von Psychopharmaka in dieser Zeit wenig bekannt. In unserer naturalistischen Beobachtungsstudie untersuchten wir 61 Frauen hinsichtlich der Dynamik psychotroper Medikamente innerhalb der Schwangerschaft und Stillzeit im Serum und teils in der Muttermilch. Zudem erhoben wir Eckdaten der Entwicklung der exponierten Kinder innerhalb des ersten Lebensjahres.
Bis auf Citalopram stellten wir bei allen analysierten Medikamenten Spiegelabfälle in der Schwangerschaft fest: vom ersten zum zweiten Trimenon fielen die Spiegel bei Escitalopram, Sertralin, Duloxetin, Amitriptylin, Clomipramin und Quetiapin. Während wir in der Spätschwangerschaft bei Escitalopram, Venlafaxin, Clomipramin, Mirtazapin, Aripiprazol und Quetiapin eine weitere Reduktion der Serumkonzentrationen protokollierten, blieben die Spiegel von Amitriptylin stabil, die Sertralin-Spiegel erholten sich sogar partiell. Citalopram zeigte keine Änderung der Serumspiegel. Direkt postpartal kam es bei allen Medikamenten zu einem Spiegelanstieg. Im postpartalen Verlauf zeigten die einzelnen Medikamente widersprüchliche Dynamiken. Hohe Penetrationsraten in die Muttermilch wiesen Escitalopram und Venlafaxin auf; Duloxetin, Clomipramin und Quetiapin gingen kaum bzw. nicht in die Muttermilch über. Wir fanden keine signifikanten Unterschiede zwischen in utero nicht exponierten zu exponierten Kindern bezüglich Geburtsparametern wie Schwangerschaftswoche, Körpermaße oder APGAR-Wert. Während die nicht exponierten Kinder vermehrt unter leichten Auffälligkeiten direkt postpartal litten, wiesen die exponierten Neugeborenen mehr mittelschwere Auffälligkeiten auf. Hinsichtlich der Entwicklung innerhalb des ersten Lebensjahres (gemessen an groben Entwicklungsmeilensteinen) ergaben sich keine signifikanten Unterschiede.
Im klinischen Alltag trägt das Therapeutische Drug Monitoring als indirekte Methode zur Kontrolle aller an der Metabolisierung beteiligten Faktoren enorm zur Steigerung der Sicherheit und Effektivität der individuellen Pharmakotherapie bei. Die pharmakokinetische Dynamik fällt bei manchen Medikamenten jedoch interindividuell sehr unterschiedlich aus (insbesondere bei Sertralin); hier stellt eine initiale Genotypisierung der Cytochrom-P450-Enzyme ein großes Potential dar, um bereits zu Beginn einer Schwangerschaft über die voraussichtliche pharmakokinetische Dynamik im Bilde zu sein und möglicher Unter- bzw. Überdosierung mit potentiell fruchtschädigender Wirkung vorbeugen zu können.
Pregnancy and lactation are accompanied by considerable metabolic changes in the maternal organism. To date, little is known about the pharmacokinetics of psychotropic drugs during this period. In our naturalistic observational study we investigated the pharmacokinetic dynamics of psychotropic drugs during pregnancy and lactation in serum and partly in breast milk by analyzing data from 61 women. In addition, we collected key data on the development (through reporting important milestones) of the exposed children within the first year of life.
Except for citalopram, we found decreases in the serum concentrations of all drugs investigated during pregnancy: The levels of escitalopram, sertraline, duloxetine, amitriptyline, clomipramine, and quetiapine decreased from the first to the second trimester,. While we observed further reductions in serum concentrations in late pregnancy for escitalopram, venlafaxine, clomipramine, mirtazapine, aripiprazole and quetiapine, levels of amitriptyline remained stable, sertraline levels even recovered partially. Citalopram showed no change in serum levels. Immediately postpartum, there was an increase in the serum concentrations of all drugs. In the postpartum course, the individual drugs presented contradictory dynamics. Escitalopram and venlafaxine showed high penetration rates into breast milk, whereas duloxetine, clomipramine and quetiapine hardly passed into breast milk. We found no significant differences between prenatally unexposed to exposed infants in regard to birth parameters such as gestational week, body measurements or Apgar score. While the unexposed infants showed a higher rate of mild abnormalities immediately postpartum, the exposed neonates presented more moderate abnormalities. There were no significant differences in development during the first year of life.
Since therapeutic drug monitoring is an indirect method to control all factors involved in metabolism, it contributes greatly to the safety and effectiveness of individual pharmacotherapy in today’s clinical practice. However, the pharmacokinetic dynamics of some drugs vary considerably between individuals (especially for sertraline); here, initial genotyping of the cytochrome p450 enzymes has a great potential to increase knowledge about probable pharmacokinetic dynamics already at the beginning of a pregnancy. This tool may be able to prevent possible under- or overdosing with potentially harmful effects on the fetus on a large scale.
urn:nbn:de:bvb:20-opus-330668
10.25972/OPUS-33066
publish
true
true
Deutsches Urheberrecht mit Print on Demand
Lara van Braam
deu
swd
Pharmakokinetik
deu
swd
Psychopharmakon
deu
swd
Schwangerschaft
deu
swd
Psychische Störung
deu
uncontrolled
Psychopharmaka
deu
uncontrolled
peripartale psychische Erkrankungen
Pharmakologie, Therapeutik
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/33066/vanBraam_Lara_Dissertation.pdf
34865
2024
deu
doctoralthesis
1
2024-01-29
--
2024-01-22
Untersuchung der Expressionslevel des Gens NR3C1 bei ängstlich-depressiven Personen in Zusammenhang mit der Funktion der Hypothalamus-Hypophysen-Nebennierenrinden-Achse und Berücksichtigung von Kindheitstraumatisierungen
Investigation of the expression level of the NR3C1 gene in anxious-depressive individuals in connection with the function of the hypothalamic-pituitary-adrenal axis and consideration of childhood traumatization
Die ängstliche Depression stellt einen Subtypus der Depression dar, der noch nicht ausreichend erforscht ist und somit eine Herausforderung im klinischen Alltag darstellt. Laut der bisherigen Literatur sind genetische Unterschiede sowie Kindheitstraumatisierungen an der Pathophysiologie von Depressionen beteiligt und mitverantwortlich für die Ausprägung des Subtypus ängstliche Depression.
In dieser Untersuchung wurde erforscht, ob es unterschiedliche Genexpressionslevel des Gens NR3C1 zwischen ängstlich-depressiven und nicht-ängstlich-depressiven Personen gibt. Zusätzlich wurde geprüft, ob Kindheitstraumatisierungen einen weiteren Einfluss auf die Genexpression der beiden Subtypen der Depression haben.
Es zeigte sich, dass ängstlich-depressive Personen in Woche 1 bis 4 höhere HAM-D-Summenwerte erzielten, mit zusätzlichen Kindheitstraumatisierungen wurden die höchsten HAM-D-Werte festgestellt. Diese Gruppe hatte gehäuft Kindheitstraumata im Fragebogen angegeben, die Traumata Emotionale Misshandlung und Körperliche Vernachlässigung kamen signifikant häufiger vor.
Anhand dieser durchgeführten Studie konnten zusammengefasst werden, dass sich die Genexpressionslevel von NR3C1 zwischen den beiden Subtypen als unterschiedlich erwies. Zusätzlich scheinen die beiden Kindheitstraumata Emotionale Misshandlung und Körperliche Vernachlässigung einen weiteren Einfluss auf die Genexpression von NR3C1 zu haben.
Die unterschiedliche Genexpression von NR3C1 deutet auf verschiedene Funktionsweisen des GR zwischen den Subtypen hin. Dies könnte für die Verlaufsbeurteilung und Therapieansätze der Erkrankung von Bedeutung sein. Die häufiger vorkommenden Kindheitstraumatisierungen bei ängstlich-depressiven Personen können als ein pathophysiologischer Baustein für die Entstehung der ängstlichen Depression gesehen werden. Daher ist es umso wichtiger, das Überprüfen von erlebten Kindheitstraumata bei initialer Befragung in den klinischen Alltag mitaufzunehmen. Da auch der Depressionsschweregrad durch Kindheitstraumatisierungen in dieser Studie zunahm, ergeben sich daraus mögliche Konsequenzen für die therapeutische Planung.
Anxious depression is a subtype of depression that has not yet been sufficiently researched and therefore represents a challenge in everyday clinical practice. According to previous literature, genetic differences and childhood trauma are involved in the pathophysiology of depression and are partly responsible for the development of the anxious depression subtype. This study investigated whether there are different gene expression levels of the NR3C1 gene between anxious-depressive and non-anxious-depressive individuals. In addition, it was examined whether childhood traumatization has a further influence on the gene expression of the two subtypes of depression. It was found that anxious-depressive individuals achieved higher HAM-D sum values in weeks 1 to 4, and the highest HAM-D values were found with additional childhood traumatization. This group had reported more childhood traumas in the questionnaire, and the traumas emotional abuse and physical neglect were significantly more frequent. On the basis of this study, it could be summarized that the gene expression levels of NR3C1 proved to be different between the two subtypes. In addition, the two childhood traumas of emotional abuse and physical neglect appear to have a further influence on the gene expression of NR3C1. The different gene expression of NR3C1 indicates different functioning of the GR between the subtypes. This could be important for the assessment of the course of the disease and therapeutic approaches. The more frequent childhood traumatization in anxious-depressive individuals can be seen as a pathophysiological building block for the development of anxious depression. It is therefore all the more important to include a review of experienced childhood trauma in the initial interview in everyday clinical practice. As the severity of depression also increased as a result of childhood trauma in this study, this has possible consequences for therapeutic planning.
urn:nbn:de:bvb:20-opus-348652
10.25972/OPUS-34865
publish
X 130887
Deutsches Urheberrecht mit Print on Demand
Jacqueline Larissa Helmel
deu
swd
Ängstliche Depression
deu
swd
Depression
deu
swd
Neuroendokrines System
deu
swd
Glucocorticosteroidrezeptor
deu
swd
Genexpression
deu
uncontrolled
NR3C1
deu
uncontrolled
modifizierter Dexamethason-Suppressions-Test
Krankheiten
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/34865/Helmel_Jacqueline_AengstlicheDepression.pdf
31350
2023
eng
5
13
article
1
--
2023-04-29
--
Neural responses to a working memory task in acute depressed and remitted phases in bipolar patients
(1) Cognitive impairments such as working memory (WM) deficits are amongst the most common dysfunctions characterizing bipolar disorder (BD) patients, severely contributing to functional impairment. We aimed to investigate WM performance and associated brain activation during the acute phase of BD and to observe changes in the same patients during remission. (2) Frontal brain activation was recorded using functional near-infrared spectroscopy (fNIRS) during n-back task conditions (one-back, two-back and three-back) in BD patients in their acute depressive (n = 32) and remitted (n = 15) phases as well as in healthy controls (n = 30). (3) Comparison of BD patients during their acute phase with controls showed a trend (p = 0.08) towards lower dorsolateral prefrontal cortex (dlPFC) activation. In the remitted phase, BD patients showed lower dlPFC and ventrolateral prefrontal cortex (vlPFC) activation (p = 0.02) compared to controls. No difference in dlPFC and vlPFC activation between BD patients’ phases was found. (4) Our results showed decreased working memory performance in BD patients during the working memory task in the acute phase of disease. Working memory performance improved in the remitted phase of the disease but was still particularly attenuated for the more demanding conditions.
Brain Sciences
2076-3425
10.3390/brainsci13050744
urn:nbn:de:bvb:20-opus-313509
2023-05-05T09:34:53+00:00
sword
swordwue
attachment; filename=deposit.zip
75aa059edede1da2af86b0bb5eb75254
Brain Sciences (2023) 13:5, 744. https://doi.org/10.3390/brainsci13050744
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Juliane Kopf
Stefan Glöckner
Heike Althen
Thais Cevada
Martin Schecklmann
Thomas Dresler
Sarah Kittel-Schneider
Andreas Reif
eng
uncontrolled
verbal n-back
eng
uncontrolled
fNIRS
eng
uncontrolled
prefrontal cortex
eng
uncontrolled
cognitive deficits
eng
uncontrolled
bipolar disorder
eng
uncontrolled
remitted/acute phase
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/31350/brainsci-13-00744-v2.pdf
30491
2023
eng
2
24
article
1
--
2023-01-04
--
Understanding the role of oxidative stress, neuroinflammation and abnormal myelination in excessive aggression associated with depression: recent input from mechanistic studies
Aggression and deficient cognitive control problems are widespread in psychiatric disorders, including major depressive disorder (MDD). These abnormalities are known to contribute significantly to the accompanying functional impairment and the global burden of disease. Progress in the development of targeted treatments of excessive aggression and accompanying symptoms has been limited, and there exists a major unmet need to develop more efficacious treatments for depressed patients. Due to the complex nature and the clinical heterogeneity of MDD and the lack of precise knowledge regarding its pathophysiology, effective management is challenging. Nonetheless, the aetiology and pathophysiology of MDD has been the subject of extensive research and there is a vast body of the latest literature that points to new mechanisms for this disorder. Here, we overview the key mechanisms, which include neuroinflammation, oxidative stress, insulin receptor signalling and abnormal myelination. We discuss the hypotheses that have been proposed to unify these processes, as many of these pathways are integrated for the neurobiology of MDD. We also describe the current translational approaches in modelling depression, including the recent advances in stress models of MDD, and emerging novel therapies, including novel approaches to management of excessive aggression, such as anti-diabetic drugs, antioxidant treatment and herbal compositions.
International Journal of Molecular Sciences
1422-0067
10.3390/ijms24020915
urn:nbn:de:bvb:20-opus-304917
2023-03-14T06:02:52+00:00
sword
swordwue
attachment; filename=deposit.zip
1ee99b08ad9171000075f96ddadbfacc
International Journal of Molecular Sciences (2023) 24:2, 915. https://doi.org/10.3390/ijms24020915
728018
101007642
953327
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Anna Gorlova
Evgeniy Svirin
Dmitrii Pavlov
Raymond Cespuglio
Andrey Proshin
Careen A. Schroeter
Klaus-Peter Lesch
Tatyana Strekalova
eng
uncontrolled
major depressive disorder (MDD)
eng
uncontrolled
aggression
eng
uncontrolled
neuroinflammation
eng
uncontrolled
oxidative stress
eng
uncontrolled
insulin receptor
eng
uncontrolled
myelination
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
OpenAIRE
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30491/ijms-24-00915-v2.pdf
34503
2023
deu
doctoralthesis
1
2023-11-16
--
2023-10-16
Auswirkungen von Distress auf den Transplantationsverlauf bei Patienten mit Multiplen Myelom während der autologen Stammzelltransplantation. Subanalyse von Zusammenhängen zwischen posttraumatischen Symptomen und klinischen Variablen
Impacts of distress on the transplantation course in patients with multiple myeloma during autologous stem cell transplantation. Subanalysis of correlations between post-traumatic symptoms and clinical variables
Ziel dieser Arbeit war es, den Einfluss psychosozialer Belastungsfaktoren auf den Verlauf einer Stammzelltransplantation zu untersuchen. Die primäre Fragestellung war, ob sich das Vorliegen einer posttraumatischen Belastungsstörung (PTSD) auf die Dauer der Immunrekonstitution, gemessen an der Aplasiezeit, auswirkt. Der Untersuchung liegen Daten aus der Medizinischen Klinik und Poliklinik II des Universitätsklinikums Würzburg zugrunde, die im Rahmen einer monozentrischen Querschnittsstudie erhoben wurden. An der Studie nahmen 50 Patienten mit der Diagnose eines Multiplen Myeloms teil, die am Tag ihrer ersten autologen Stammzelltransplantation befragt wurden. Anhand von Fragebögen konnten die Patienten Angaben zu ihrer individuellen psychischen Belastung machen. Für die statistische Auswertung wurden die Angaben aus dem NCCN-Distress-Thermometer und dem PCL-C ausgewertet.
The aim of this study was to investigate the influence of psychosocial stress factors on the course of stem cell transplantation. The primary research question was whether the presence of post-traumatic stress disorder (PTSD) affects the duration of immune reconstitution, measured by the aplasia period. The study is based on data from the Medical Clinic and Polyclinic II of the University Hospital Würzburg, collected as part of a monocentric cross-sectional study. Fifty patients diagnosed with multiple myeloma, who were interviewed on the day of their first autologous stem cell transplantation, participated in the study. Using questionnaires, patients provided information about their individual psychological stress. The data from the NCCN Distress Thermometer and the PCL-C were analyzed for statistical evaluation
urn:nbn:de:bvb:20-opus-345032
10.25972/OPUS-34503
publish
X 130798
Deutsches Urheberrecht
Ariane Müller-Zentis
deu
uncontrolled
Distress
deu
swd
Psychoneuroimmunologie
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Medizinische Klinik und Poliklinik II
Universität Würzburg
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/34503/Mueller-Zentis_Ariane_Dissertation-Distress.pdf