PARP10 (ARTD10) modulates mitochondrial function

KA, L

Claims data analysis on the dispensing of tricyclic antidepressants among patients with dementia in Germany

Objective: A restrictive use of tricyclic antidepressants (TCA) in patients with dementia (PwD) is recommended due to the hazard of anticholinergic side effects. We evaluated the frequency of TCA dispensing in PwD over a period of 1 year and the use of TCA before and after the incident diagnosis of dementia. Methods: This analysis was based on administrative data from a German statutory health insurance for a period of 2 years. Totally, 20,357 patients with an incident diagnosis of dementia in 2014 were included. We evaluated the dispensing of TCA in 2015. Subgroup analyses were conducted to evaluate associations between the incident diagnosis of dementia and modifications in TCA dispensing. Results: In 2015, 1,125 dementia patients (5.5%) were treated with TCA and 31% were medicated with TCA in all four quarters of 2015. Most dispensings were conducted by general practitioners (67.9%). On average, patients received 3.7 ± 2.6 dispensings per year. Amitriptyline (56.3%), doxepin (26.8%), and trimipramine (16.8%) were dispensed most often. Subgroup analyses revealed that the dispensing of TCA remained mainly unchanged following the incident diagnosis. Conclusion: A relevant number of PwD were treated with TCA. To maintain the patients' safety, an improved implementation of guidelines for the pharmaceutical treatment of PwD in healthcare institutions might be required. Since 68% of the patients suffered from depression, future studies should further evaluate the indications for TCA. Copyright © 2019 Hessmann, Zeidler, Stahmeyer, Eberhard, Vogelgsang, Abdel-Hamid, Wolff-Menzler, Wiltfang and Kis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

The Effects of Acute Tryptophan Depletion on Reactive Aggression in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and Healthy Controls

Background: The neurotransmitter serotonin (5-HT) has been linked to the underlying neurobiology of aggressive behavior, particularly with evidence from studies in animals and humans. However, the underlying neurobiology of aggression remains unclear in the context of attention-deficit/hyperactivity disorder (ADHD), a disorder known to be associated with aggression and impulsivity. We investigated the effects of acute tryptophan depletion (ATD), and the resulting diminished central nervous serotonergic neurotransmission, on reactive aggression in healthy controls and adults with ADHD. Methodology/Principal Findings: Twenty male patients with ADHD and twenty healthy male controls were subjected to ATD with an amino acid (AA) beverage that lacked tryptophan (TRP, the physiological precursor of 5-HT) and a TRPbalanced AA beverage (BAL) in a double-blind, within-subject crossover-study over two study days. We assessed reactive aggression 3.25 hours after ATD/BAL intake using a point-subtraction aggression game (PSAG) in which participants played for points against a fictitious opponent. Point subtraction was taken as a measure for reactive aggression. Lowered rates of reactive aggression were found in the ADHD group under ATD after low provocation (LP), with controls showing the opposite effect. In patients with ADHD, trait-impulsivity was negatively correlated with the ATD effect on reactive aggression after LP. Statistical power was limited due to large standard deviations observed in the data on point subtraction, which may limit the use of this particular paradigm in adults with ADHD

Dose-Dependent Onset of Regenerative Program in Neutron Irradiated Mouse Skin

Background: Tissue response to irradiation is not easily recapitulated by cell culture studies. The objective of this investigation was to characterize, the transcriptional response and the onset of regenerative processes in mouse skin irradiated with different doses of fast neutrons. Methodology/Principal Findings: To monitor general response to irradiation and individual animal to animal variation, we performed gene and protein expression analysis with both pooled and individual mouse samples. A high-throughput gene expression analysis, by DNA oligonucleotide microarray was done with three months old C57Bl/6 mice irradiated with 0.2 and 1 Gy of mono-energetic 14 MeV neutron compared to sham irradiated controls. The results on 440 irradiation modulated genes, partially validated by quantitative real time RT-PCR, showed a dose-dependent up-regulation of a subclass of keratin and keratin associated proteins, and members of the S100 family of Ca2+-binding proteins. Immunohistochemistry confirmed mRNA expression data enabled mapping of protein expression. Interestingly, proteins up-regulated in thickening epidermis: keratin 6 and S100A8 showed the most significant up-regulation and the least mouse-to-mouse variation following 0.2 Gy irradiation, in a concerted effort toward skin tissue regeneration. Conversely, mice irradiated at 1 Gy showed most evidence of apoptosis (Caspase-3 and TUNEL staining) and most 8-oxo-G accumulation at 24 h post-irradiation. Moreover, no cell proliferation accompanied 1 Gy exposure as shown by Ki67 immunohistochemistry. Conclusions/Significance: The dose-dependent differential gene expression at the tissue level following in vivo exposure to neutron radiation is reminiscent of the onset of re-epithelialization and wound healing and depends on the proportion of cells carrying multiple chromosomal lesions in the entire tissue. Thus, this study presents in vivo evidence of a skin regenerative program exerted independently from DNA repair-associated pathways

Selective Hyper-responsiveness of the Interferon System in Major Depressive Disorders and Depression Induced by Interferon Therapy

Though an important percentage of patients with chronic hepatitis C virus (HCV) undergoing interferon (IFN) therapy develop depressive symptoms, the role of the IFN system in the pathogenesis of depressive disorders is not well understood.50 patients with HCV infection were treated with standard combination therapy (pegylated IFN-α2a/ribavirin). IFN-induced gene expression was analyzed to identify genes which are differentially regulated in patients with or without IFN-induced depression. For validation, PBMC from 22 psychiatric patients with a severe depressive episode (SDE) and 11 controls were cultivated in vitro with pegylated IFN-α2a and gene expression was analyzed.IFN-induced depression in HCV patients was associated with selective upregulation of 15 genes, including 6 genes that were previously described to be relevant for major depressive disorders or neuronal development. In addition, increased endogenous IFN-production and selective hyper-responsiveness of these genes to IFN stimulation were observed in SDE patients.Our data suggest that selective hyper-responsiveness to exogenous (IFN therapy) or endogenous (depressive disorders) type I IFNs may lead to the development of depressive symptoms. These data could lead to the discovery of novel therapeutic approaches to treat IFN-induced and major depressive disorders

Severe supraaortal atherosclerotic disease resembling Takayasu’s Arteritis

Bernhard Kis1,2, Thomas Liebig3,4, Peter Berlit11Department of Neurology, Alfried Krupp Hospital, Essen, Germany; 2Department of Psychiatry, University of Duisburg-Essen, Essen, Germany; 3Department of Neuroradiology, Alfried Krupp Hospital, Essen, Germany; 4Department of Neuroradiology, Technical University of Munich, Munich, GermanyAbstract: We report a case of a 64 year-old man whose clinical presentation and neuroimaging findings strikingly resembled those found in Takayasu’s Arteritis which is characterized by the triad of absent radial pulses, ischemic retinopathy, and carotid sinus hyperreflexia causing syncopes. Angiographically, the patient exhibited severe atherosclerotic changes of the supraaortic large vessels. Stent-assisted angioplasty resulted in both clinical improvement and increased cerebral blood flow as measured by angiography and ultrasound.Keywords: Takayasu’s arteritis, atherosclerosis, angiography, stent, angioplast

Bacterial infections among patients with psychiatric disorders: Relation with hospital stay, age, and psychiatric diagnoses.

The prevalence of infections is supposed to be higher in older patients and to extend the length of hospital stays. This study aimed, first, to test this supposition within a large psychiatric population which we divided into four clusters of psychiatric ICD-10 diagnoses: F00-F03 (dementias), F10 (substance disorders), F20-29 (schizophrenia, schizophreniform and other non-mood psychotic disorders), F32-F33 (major depressive disorders). Second, despite the increasing evidence for the role of infections in psychiatric disorders, it is, to the best of our knowledge, largely unknown whether the rates of infections with pathogens of the four most frequent germ families differ between psychiatric diseases. Thus, in a retrospective study, the results of clinical routine examinations (pap smear, analysis of midstream urine, stool) dependent on symptoms in 8545 patients of a German psychiatric clinic were analyzed in a 12-year dataset. Results show that a longer hospital stay was associated with an increased number of microbiological tests, but led to no significant difference between positive vs. negative findings. Consistent with previous studies, patients with infections were older than patients without infections. For the F10 diagnosis cluster we found a significantly reduced (F10: Staphylococcaceae) and for the F20-29 cluster a heightened risk of infections (Staphylococcaceae, Corynebacteriaceae). Furthermore, patients belonging to the F00-F03 cluster exhibited elevated rates of infections with all four germ families. The latter can be ascribed to patients' age as we found higher age to be associated with these infections, independently of the presence of dementia. Our results suggest that different psychiatric diagnoses are associated with a heightened or lowered risk of bacterial infections and, furthermore, that clinical routine infection-screenings for elderly psychiatric patients seems to be reasonable