Refine
Has Fulltext
- yes (31)
Is part of the Bibliography
- yes (31)
Year of publication
- 2018 (31) (remove)
Document Type
- Doctoral Thesis (17)
- Journal article (14)
Keywords
- Depression (3)
- Serotonin (3)
- ADHD (2)
- Coffin-Lowry syndrome (2)
- RSK2 (2)
- Stress (2)
- Vagus (2)
- depression (2)
- epigenetics (2)
- fNIRS (2)
- tDCS (2)
- 123I-mIBG (1)
- Adipositas (1)
- Alzheimer’s disease (1)
- Angst (1)
- Angstsensitivität (1)
- Angststörung (1)
- Animal behavior IntelliCage system (1)
- Animal model (1)
- Antidepressants (1)
- Antidepressiva (1)
- Anxiety (1)
- ApoE-Genotyp (1)
- Arzneimittelüberwachung (1)
- Assoziationsstudie (1)
- Auditory pathway (1)
- Aufmerksamkeit (1)
- Aufmerksamkeitslenkung (1)
- Aurikuläre Vagusnervstimulation (1)
- Bipolar-affektive Störung (1)
- Bipolare affektive Störung (1)
- Borderline-Persönlichkeitsstörung (1)
- Caudate nucleus (1)
- Cerebellar nuclei (1)
- DNA methylation (1)
- DNA-Methylierung (1)
- Demenz vom Alzheimer Typ (1)
- Diabetes Mellitus Typ 2 (1)
- Diabetes mellitus (1)
- Dissoziale Persönlichkeitsstörung (1)
- Drosophila model (1)
- Emotionsregulation (1)
- Entwicklung (1)
- EphA4 (1)
- Epigenetik (1)
- FEV gene (1)
- G-protein inwardly rectifying potassium channel (1)
- GIRK 2 (1)
- Gehirn (1)
- Gen Polymorphismen (1)
- HRV (1)
- Herzfrequenzvariabilität (1)
- Hurst Exponent (1)
- KCNJ6 (1)
- Kaliumkanal (1)
- Knockout (1)
- Knockout <Molekulargenetik> (1)
- Leichte kognitive Beeinträchtigung (1)
- MDD (1)
- Manisch-depressive Krankheit (1)
- Maus (1)
- Molecular biology (1)
- NIRS (1)
- NOS1 (1)
- Nebenwirkung (1)
- Neostriatum (1)
- Nerve fibers (1)
- Nucleus accumbens (1)
- Panikstörung (1)
- Pharmakoepigenetik (1)
- Pharmakotherapie (1)
- Polygener Risikoscore (1)
- Prädiabetes (1)
- Präfrontaler Kortex (1)
- Psychiatric disorders (1)
- Psychopharmakon (1)
- Q-T-Verlängerung (1)
- QTc-Verlängerung (1)
- Regulator of G protein signaling 2 (1)
- Rgs2 (1)
- Ruhebedingungen (1)
- Schizophrenie (1)
- Selbstwirksamkeit (1)
- Serotonerges System (1)
- Serotonin-Transporter-Gen (1)
- Somatosensibel evozierte Potentiale des N. vagus (1)
- Somatosensorisch evoziertes Potenzial (1)
- Spinal nerves (1)
- Stickstoffmonoxid-Synthase (1)
- TPH2 gene (1)
- Thalamic nuclei (1)
- Therapeutisches Drug Monitoring (1)
- Tiermodell (1)
- Transkutane Vagusnervstimulation (1)
- Transkutane elektrische Nervenstimulation (1)
- VFT (1)
- VSEP (1)
- Vagusevozierte Potentiale (1)
- Würzburger Adipositas Studie (1)
- Xenopus laevis oocytes (1)
- adult ADHD (1)
- adult treatment (1)
- adultes ADHS (1)
- affective disorders (1)
- affektive Störungen (1)
- amino acid analysis (1)
- antidepressant (1)
- anxiety (1)
- aphasia (1)
- assessment of cognitive disorders/dementia (1)
- association study (1)
- auricular vagusnervstimulation (1)
- behavior (1)
- behaviour (1)
- biomarker (1)
- bipolar disorder (1)
- brain stimulation (1)
- capecitabine (1)
- cardiac sympathetic nerve system (1)
- cell membranes (1)
- children (1)
- cognitive neuropsychology in dementia (1)
- crystal structure (1)
- data mining (1)
- differentiation (1)
- distraction (1)
- early-life stress (1)
- efficacy (1)
- emotion regulation (1)
- extinction (1)
- fMRI (1)
- fear conditioning (1)
- frontal cortex (1)
- frontotemporal dementia (1)
- functional near-infrared spectroscopy (1)
- funktionelle Nahinfrarotspektroskopie (1)
- gene (1)
- gene polmorphism (1)
- genotype-phenotype patterns (1)
- glucose (1)
- glucose transporter (1)
- impulse control disorders (1)
- insulin receptor (1)
- insulin-like growth factor 1 receptor (1)
- major depressive disorder (1)
- membrane potential (1)
- membrane proteins (1)
- mental disorders (1)
- mild cognitive impairment (1)
- monoamine oxidase A (1)
- mothers (1)
- mouse model (1)
- myocardial sympathetic innervation imaging (1)
- neural stem cells (1)
- neuronal dysfunction (1)
- niederfrequente Oszillationen (1)
- nucleus accumbens (1)
- oral anticancer drugs (1)
- parent training (1)
- patient-doctor-relationship (1)
- processing speed (1)
- proliferation (1)
- rodent model (1)
- rule discovery (1)
- schizophrenia (1)
- skin conduction response (1)
- streptozotocin (1)
- subphenotypes (1)
- task complexity (1)
- trail making test (1)
- transcutaneous vagusnervstimulation (1)
- vagus somatosensory evoked potentials (1)
- vagus-evoked potentials (1)
- ventromedial prefrontal cortex (1)
- volumetric MRI (1)
Institute
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (31) (remove)
Sonstige beteiligte Institutionen
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.
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.
Background
The efficacy of parent-child training (PCT) regarding child symptoms may be reduced if the mother has attention-deficit/hyperactivity disorder (ADHD). The AIMAC study (ADHD in Mothers and Children) aimed to compensate for the deteriorating effect of parental psychopathology by treating the mother (Step 1) before the beginning of PCT (Step 2). This secondary analysis was particularly concerned with the additional effect of the Step 2 PCT on child symptoms after the Step 1 treatment.
Methods
The analysis included 143 mothers and children (aged 6–12 years) both diagnosed with ADHD. The study design was a two-stage, two-arm parallel group trial (Step 1 treatment group [TG]: intensive treatment of the mother including psychotherapy and pharmacotherapy; Step 1 control group [CG]: supportive counseling only for mother; Step 2 TG and CG: PCT). Single- and multi-group analyses with piecewise linear latent growth curve models were applied to test for the effects of group and phase. Child symptoms (e.g., ADHD symptoms, disruptive behavior) were rated by three informants (blinded clinician, mother, teacher).
Results
Children in the TG showed a stronger improvement of their disruptive behavior as rated by mothers than those in the CG during Step 1 (Step 1: TG vs. CG). In the CG, according to reports of the blinded clinician and the mother, the reduction of children’s disruptive behavior was stronger during Step 2 than during Step 1 (CG: Step 1 vs. Step 2). In the TG, improvement of child outcome did not differ across treatment steps (TG: Step 1 vs. Step 2).
Conclusions
Intensive treatment of the mother including pharmacotherapy and psychotherapy may have small positive effects on the child’s disruptive behavior. PCT may be a valid treatment option for children with ADHD regarding disruptive behavior, even if mothers are not intensively treated beforehand.
Trial registration
ISRCTN registry ISRCTN73911400. Registered 29 March 2007.
Epigenetic mechanisms have been proposed to mediate fear extinction in animal models. Here, MAOA methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells before and after a 2-week exposure therapy in a sample of n = 28 female patients with acrophobia as well as in n = 28 matched healthy female controls. Clinical response was measured using the Acrophobia Questionnaire and the Attitude Towards Heights Questionnaire. The functional relevance of altered MAOA methylation was investigated by luciferase-based reporter gene assays. MAOA methylation was found to be significantly decreased in patients with acrophobia compared with healthy controls. Furthermore, MAOA methylation levels were shown to significantly increase after treatment and correlate with treatment response as reflected by decreasing Acrophobia Questionnaire/Attitude Towards Heights Questionnaire scores. Functional analyses revealed decreased reporter gene activity in presence of methylated compared with unmethylated pCpGfree_MAOA reporter gene vector constructs. The present proof-of-concept psychotherapy-epigenetic study for the first time suggests functional MAOA methylation changes as a potential epigenetic correlate of treatment response in acrophobia and fosters further investigation into the notion of epigenetic mechanisms underlying fear extinction.
Neuroanatomy of the equine brain as revealed by high-field (3Tesla) magnetic-resonance-imaging
(2018)
In this study, the morphology of the horse brain (Equus caballus) is decribed in detail using high field MRI. The study includes sagittal, dorsal, and transverse T2-weighted images at 0.25 mm resolution at 3 Tesla and 3D models of the brain presenting the external morphology of the brain. Representative gallocyanin stained histological slides of the same brain are presented. The images represent a useful tool for MR image interpretation in horses and may serve as a starting point for further research aiming at in vivo analysis in this species.
In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n = 93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n = 98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.
The use of functional near-infrared spectroscopy (fNIRS) in block designs provides measures of cortical activity in ecologically valid environments. However, in some cases, the use of block designs may be problematic when data are not corrected for performance in a time-restricted block. We sought to investigate the effects of task complexity and processing speed on hemodynamic responses in an fNIRS block design. To differentiate the effects of task complexity and processing speed, 20 subjects completed the trail making test (TMT) in two versions (TMT-A versus TMT-B) and three different speed levels (slow versus moderate versus fast). During TMT-A, subjects are asked to connect encircled numbers in numerically ascending order (1-2-3 ... ). In the more complex TMT-B, subjects are instructed to connect encircled numbers and letters in alternating ascending order (1-A-2-B ... ). To illustrate the obscuring effects of processing speed on task complexity, we perform two different analyses. First, we analyze the classical measures of oxygenated blood, and second, we analyze the measures corrected for the number of processed items. Our results show large effects for processing speed within the bilateral inferior frontal gyrus, left dorsolateral prefrontal cortex, and superior parietal lobule (SPL). The TMT contrast did not show significant effects with classical measures, although trends are observed for higher activation during TMT-B. When corrected for processed items, higher activity for TMT-B in comparison to TMT-A is found within the SPL. The results are discussed in light of recent research designs, and simple to use correction methods are suggested. (c) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
Fractal phenomena can be found in numerous scientific areas including neuroscience. Fractals are structures, in which the whole has the same shape as its parts. A specific structure known as pink noise (also called fractal or 1/f noise) is one key fractal manifestation, exhibits both stability and adaptability, and can be addressed via the Hurst exponent (H). FMRI studies using H on regional fMRI time courses used fractality as an important characteristic to unravel neural networks from artificial noise. In this fMRI-study, we examined 103 healthy male students at rest and while performing the 5-choice serial reaction time task. We addressed fractality in a network associated with waiting impulsivity using the adaptive fractal analysis (AFA) approach to determine H. We revealed the fractal nature of the impulsivity network. Furthermore, fractality was influenced by individual impulsivity in terms of decreasing fractality with higher impulsivity in regions of top-down control (left middle frontal gyrus) as well as reward processing (nucleus accumbens and anterior cingulate cortex). We conclude that fractality as determined via H is a promising marker to quantify deviations in network functions at an early stage and, thus, to be able to inform preventive interventions before the manifestation of a disorder.
Purpose:
The prescribing of oral chemotherapy agents has introduced the new challenge of ensuring patients’ adherence to therapy. Aspects of a close patient–doctor relationship are reported to be correlated with adherence to oral anticancer drugs, but data on capecitabine are scarce.
Patients and methods:
Sixty-four outpatients with a diagnosis of cancer and prescribed capecitabine were recruited from a German Comprehensive Cancer Center. We used the Patient–Doctor Relationship Questionnaire (PDRQ-9), the Medical Adherence Rating Scale (MARS), the Beliefs about Medicines Questionnaire (BMQ), and the Satisfaction with Information about Medicines Scale (SIMS) to assess patients’ perceptions and behavior. Medical data were extracted from the charts.
Results:
Non-adherence was reported by 20% of the 64 participants. The perceived quality of the patient–doctor relationship was high in general, but it did not emerge as a predictor of adherence in our survey (odds ratio [OR]=0.915, P=0.162, 95% CI=0.808–1.036). However, beliefs about medicine (OR=1.268, P<0.002; 95% CI=1.090–1.475) as well as satisfaction with information about medicine (OR=1.252, P<0.040, 95% CI=1.010–1.551) were predictors of adherence and the quality of the patient–doctor relationship was correlated with both variables (r=0.373, P=0.002 for SIMS sum score; r=0.263, P=0.036 for BMQ necessity/concern difference). Overall, adherence to capecitabine was high with a conviction that the therapy is necessary. However, concerns were expressed regarding the long-term effect of capecitabine use. Patients have unmet information needs regarding interactions of capecitabine with other medicines and the impairment of their intimate life.
Conclusions:
In order to ensure adherence to capecitabine, our results seem to encourage the default use of modern and perhaps more impersonal means of information brokerage (eg, email, internet). However, the contents of some of patients’ informational needs as well as the associations of patients’ beliefs and satisfaction about the information received suggest a benefit from a trustful patient–doctor relationship.
Loss of function mutations in the rsk2 gene cause Coffin-Lowry syndrome (CLS), which is associated with multiple symptoms including severe mental disabilities. Despite the characterization of ribosomal S6 kinase 2 (RSK2) as a protein kinase acting as a downstream effector of the well characterized ERK MAP-kinase signaling pathway, it turns out to be a challenging task to link RSK2 to specific neuronal processes dysregulated in case of mutation. Animal models such as mouse and Drosophila combine advanced genetic manipulation tools with in vivo imaging techniques, high-resolution connectome analysis and a variety of behavioral assays, thereby allowing for an in-depth analysis for gene functions in the nervous system. Although modeling mental disability in animal systems has limitations because of the complexity of phenotypes, the influence of genetic variation and species-specific characteristics at the neural circuit and behavioral level, some common aspects of RSK2 function in the nervous system have emerged, which will be presented. Only with this knowledge our understanding of the pathophysiology of CLS can be improved, which might open the door for development of potential intervention strategies.