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1.
Nat Commun ; 15(1): 2516, 2024 Mar 21.
Article En | MEDLINE | ID: mdl-38514628

ATGL is a key enzyme in intracellular lipolysis and plays an important role in metabolic and cardiovascular diseases. ATGL is tightly regulated by a known set of protein-protein interaction partners with activating or inhibiting functions in the control of lipolysis. Here, we use deep mutational protein interaction perturbation scanning and generate comprehensive profiles of single amino acid variants that affect the interactions of ATGL with its regulatory partners: CGI-58, G0S2, PLIN1, PLIN5 and CIDEC. Twenty-three ATGL amino acid variants yield a specific interaction perturbation pattern when validated in co-immunoprecipitation experiments in mammalian cells. We identify and characterize eleven highly selective ATGL switch mutations which affect the interaction of one of the five partners without affecting the others. Switch mutations thus provide distinct interaction determinants for ATGL's key regulatory proteins at an amino acid resolution. When we test triglyceride hydrolase activity in vitro and lipolysis in cells, the activity patterns of the ATGL switch variants trace to their protein interaction profile. In the context of structural data, the integration of variant binding and activity profiles provides insights into the regulation of lipolysis and the impact of mutations in human disease.


Lipase , Lipolysis , Animals , Humans , Lipolysis/genetics , Lipase/genetics , Lipase/metabolism , Cell Cycle Proteins/metabolism , Binding Sites , Amino Acids/metabolism , Mutation , Mammals/metabolism
2.
Neuropsychobiology ; 82(4): 220-233, 2023.
Article En | MEDLINE | ID: mdl-37321188

INTRODUCTION: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality. METHODS: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera. RESULTS: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI ≤8). CONCLUSION: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.


Depressive Disorder, Major , Gastrointestinal Microbiome , Mental Disorders , Sleep Wake Disorders , Humans , Gastrointestinal Microbiome/genetics , RNA, Ribosomal, 16S/genetics , Cross-Sectional Studies , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System , Mental Disorders/diagnosis , Sleep
3.
J Chem Inf Model ; 63(4): 1249-1259, 2023 02 27.
Article En | MEDLINE | ID: mdl-36799916

Glutamate carboxypeptidase II (GCPII) is a metalloprotease implicated in neurological diseases and prostate oncology. While several classes of potent GCPII-specific inhibitors exist, the development of novel active scaffolds with different pharmacological profiles remains a challenge. Virtual screening followed by in vitro testing is an effective means for the discovery of novel active compounds. Structure- and ligand-based pharmacophore models were created based on a dataset of known GCPII-selective ligands. These models were used in a virtual screening of the SPECS compound library (∼209.000 compounds). Fifty top-scoring virtual hits were further experimentally tested for their ability to inhibit GCPII enzymatic activity in vitro. Six hits were found to have moderate to high inhibitory potency with the best virtual hit, a modified xanthene, inhibiting GCPII with an IC50 value of 353 ± 24 nM. The identification of this novel inhibitory scaffold illustrates the applicability of pharmacophore-based modeling for the discovery of GCPII-specific inhibitors.


Glutamate Carboxypeptidase II , Male , Humans , Ligands
4.
Front Psychol ; 13: 858291, 2022.
Article En | MEDLINE | ID: mdl-36033064

Anger, indignation, guilt, rumination, victim compensation, and perpetrator punishment are considered primary responses associated with justice sensitivity (JS). However, injustice and high JS may predispose to further responses. We had N = 293 adults rate their JS, 17 potential responses toward 12 unjust scenarios from the victim's, observer's, beneficiary's, and perpetrator's perspectives, and several control variables. Unjust situations generally elicited many affective, cognitive, and behavioral responses. JS generally predisposed to strong affective responses toward injustice, including sadness, pity, disappointment, and helplessness. It impaired trivialization, victim-blaming, or justification, which may otherwise help cope with injustice. It predisposed to conflict solutions and victim compensation. Particularly victim and beneficiary JS had stronger effects in unjust situations from the corresponding perspective. These findings add to a better understanding of the main and interaction effects of unjust situations from different perspectives and the JS facets, differences between the JS facets, as well as the links between JS and behavior and well-being.

5.
J Orthop Surg Res ; 16(1): 417, 2021 Jul 01.
Article En | MEDLINE | ID: mdl-34210335

BACKGROUND: In cemented primary total knee arthroplasty (TKA), aseptic loosening remains a major cause for failure. Cementing techniques and characteristics of a chosen cement play a key role for good fixation and implant survival. A pastry bone cement was developed to facilitate the cement preparation and to rule out most of preparation-associated application errors. The pastry bone cement was compared to a conventional polymethyl methacrylate cement in a TKA setting. METHODS: Standardized implantations of total knee endoprostheses were performed in bilateral knee cadavers to investigate handling properties, variables of cement application, working time, and temperature development. Mechanical aspects and cementation quality were assessed by pull-out trials and microscopic interface analysis. RESULTS: Both cements expressed similar characteristics during preparation and application, only the curing time of the pastry cement was about 3 min longer and the temperature peak was lower. Fractures of the conventional cement specimens differed from the pastry cement specimens in the tibial part, while no differences were found in the femoral part. Penetration depth of the pastry cement was similar (tibia) or deeper (femur) compared to the conventional cement. CONCLUSIONS: The pastry cement facilitates the feasibility of cemented TKA. The pre-clinical tests indicate that the pastry bone cement fulfills the requirements for bone cement in the field of knee arthroplasty. A clinical trial is needed to further investigate the approach and ensure patient safety.


Arthroplasty, Replacement, Knee/methods , Bone Cements , Cementation/methods , Femur/surgery , Tibia/surgery , Cadaver , Feasibility Studies , Humans , Knee Joint/surgery , Knee Prosthesis , Polymethyl Methacrylate
6.
Clin Neurophysiol ; 132(1): 13-22, 2021 01.
Article En | MEDLINE | ID: mdl-33249251

OBJECTIVE: Huntington's disease (HD) is characterized by psychiatric, cognitive, and motor disturbances. The study aimed to determine electroencephalography (EEG) global state and microstate changes in HD and their relationship with cognitive and behavioral impairments. METHODS: EEGs from 20 unmedicated HD patients and 20 controls were compared using global state properties (connectivity and dimensionality) and microstate properties (EEG microstate analysis). For four microstate classes (A, B, C, D), three parameters were computed: duration, occurrence, coverage. Global- and microstate properties were compared between groups and correlated with cognitive test scores for patients. RESULTS: Global state analysis showed reduced connectivity in HD and an increasing dimensionality with increasing HD severity. Microstate analysis revealed parameter increases for classes A and B (coverage), decreases for C (occurrence) and D (coverage and occurrence). Disease severity and poorer test performances correlated with parameter increases for class A (coverage and occurrence), decreases for C (coverage and duration) and a dimensionality increase. CONCLUSIONS: Global state changes may reflect higher functional dissociation between brain areas and the complex microstate changes possibly the widespread neuronal death and corresponding functional deficits in brain regions associated with HD symptomatology. SIGNIFICANCE: Combining global- and microstate analyses can be useful for a better understanding of progressive brain deterioration in HD.


Brain Mapping , Brain/physiopathology , Electroencephalography , Huntington Disease/physiopathology , Adult , Case-Control Studies , Cognition Disorders/physiopathology , Disease Progression , Female , Humans , Huntington Disease/complications , Male , Mental Disorders/physiopathology , Severity of Illness Index
7.
J Affect Disord ; 281: 908-917, 2021 02 15.
Article En | MEDLINE | ID: mdl-33279261

BACKGROUND: Previous MRI studies reported deep grey matter volume increases after electroconvulsive therapy (ECT) in patients with major depressive disorder (MDD). However, the clinical correlates of these changes are still unclear. It remains debated whether such volume changes are transient, and if they correlate with affective changes over time. We here investigated if ECT induces deep grey matter volume increases in MDD-patients; and, if so, whether volume changes persist over more than 9 months and whether they are related to the clinical outcome. METHODS: We examined 16 MDD-patients with 3Tesla MRI before (baseline) and after an ECT-series and followed 12 of them up for 10-36 months. Patients' data were compared to 16 healthy controls. Affective scales were used to investigate the relationship between therapy-outcome and MRI changes. RESULTS: At baseline, MDD-patients had lower values in global brain volume, white matter and peripheral grey matter compared to healthy controls, but we observed no significant differences in deep grey matter volumes. After ECT, the differences in peripheral grey matter disappeared, and patients demonstrated significant volume increases in the right hippocampus and both thalami, followed by subsequent decreases after 10-36 months, especially in ECT-responders. Controls did not show significant changes over time. LIMITATIONS: Beside the relatively small, yet carefully characterized cohort, we address the variability in time between the third scanning session and the baseline. CONCLUSIONS: ECT-induced deep grey matter volume increases are transient. Our results suggest that the thalamus might be a key region for the understanding of the mechanisms of ECT action.


Depressive Disorder, Major , Electroconvulsive Therapy , Brain/diagnostic imaging , Depression , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/therapy , Gray Matter/diagnostic imaging , Humans , Magnetic Resonance Imaging
8.
Eur J Med Res ; 25(1): 34, 2020 Aug 18.
Article En | MEDLINE | ID: mdl-32811560

BACKGROUND: Prosthetic joint infection (PJI) is a serious complication of orthopedic implant surgery. Treatment often includes the use of an antibiotic-loaded Polymethyl methacrylate (PMMA) bone cement spacer. Several antibiotics are commonly used for the preparation of these spacers, but due to the increasing number of infections with resistant Gram-negative bacteria, there is a need for the use of carbapenem antibiotics such as meropenem and imipenem as drugs of last resort. Unfortunately, the reaction heat generated during the preparation of the bone cement can be a major problem for the stability of these antibiotics. In the present study, the stability of meropenem and imipenem was tested before and after the admixture to PMMA bone cements. METHODS: High-performance liquid chromatography with ion-pairing reversed-phase separation and spectrophotometric detection was used for analysis. Stability tests with meropenem and imipenem were performed with antibiotics in solution and solid form at different temperatures (37 °C, 45 °C, 60 °C, 90 °C) and times (30 min, 60 min, 120 min). To test the stability of both antibiotics in PMMA after exposure to the reaction heat during polymerization, three different bone cements were used to generate specimens that contained defined amounts of antibiotics. Reaction heat was measured. The form bodies were mechanically crushed and aliquots were dissolved in ethyl acetate. Samples were prepared for HPLC DAD analysis. RESULTS: Meropenem and imipenem showed the highest degradation levels after heat stressed in solution, with maximum levels of 75% and 95%, respectively. In solid form, degradation levels decreased dramatically for meropenem (5%) and imipenem (13%). Stability tests of both carbapenems in bone cement showed that they remained largely stable during PMMA polymerization, with retrieved amounts of about 70% in Palacos® R and Copal® G+V, and between 80 and 90% in Copal® spacem. CONCLUSIONS: In contrast to the results of meropenem and imipenem in solution, both antibiotics remain stable in solid form and mostly stable in the cement after PMMA polymerization. The low degradation levels of both antibiotics after exposure to temperatures > 100 °C allow the conclusion that they can potentially be used for an application in PMMA cements.


Anti-Bacterial Agents/chemistry , Bone Cements/chemistry , Carbapenems/chemistry , Gram-Negative Bacteria/drug effects , Gram-Negative Bacterial Infections/drug therapy , Polymethyl Methacrylate/chemistry , Prosthesis-Related Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Arthroplasty, Replacement/standards , Austria/epidemiology , Carbapenems/pharmacology , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/microbiology , Humans , Prosthesis-Related Infections/epidemiology , Prosthesis-Related Infections/metabolism
9.
Curr Nutr Rep ; 9(3): 183, 2020 Sep.
Article En | MEDLINE | ID: mdl-32504412

The original version of this article unfortunately contained mistake. The sure name "Cyran" of the author John F Cyran (J. F. Cyran) should be corrected to read John F. Cryan (J. F. Cryan) as presented above.

10.
Curr Nutr Rep ; 9(3): 171-182, 2020 09.
Article En | MEDLINE | ID: mdl-32406013

PURPOSE OF REVIEW: Probiotics are living bacteria, which when ingested in adequate amounts, confer health benefits. Gut microbes are suggested to play a role in many psychiatric disorders and could be a potential therapeutic target. Between the gut and the brain, there is a bi-directional communication pathway called the microbiota-gut-brain axis. The purpose of this review is to examine data from recent interventional studies focusing on probiotics and the gut-brain axis for the treatment of depression, anxiety and schizophrenia. RECENT FINDINGS: Probiotics are likely to improve depression but not schizophrenia. Regarding anxiety, there is only one trial which showed an effect of a multispecies probiotic. However, determinants like the duration of treatment, dosage and interactions have not been thoroughly investigated and deserve more scientific attention. Microbiome-based therapies such as probiotics could be cautiously recommended for depression to enhance beneficial bacteria in the gut and to improve mood through the gut-brain axis.


Brain/physiology , Gastrointestinal Microbiome , Mental Disorders/prevention & control , Probiotics , Animals , Humans
11.
Clin EEG Neurosci ; 51(3): 155-166, 2020 May.
Article En | MEDLINE | ID: mdl-31845595

Bipolar disorder (BD) is a chronic illness with a relapsing and remitting time course. Relapses are manic or depressive in nature and intermitted by euthymic states. During euthymic states, patients lack the criteria for a manic or depressive diagnosis, but still suffer from impaired cognitive functioning as indicated by difficulties in executive and language-related processing. The present study investigated whether these deficits are reflected by altered intracortical activity in or functional connectivity between brain regions involved in these processes such as the prefrontal and the temporal cortices. Vigilance-controlled resting state EEG of 13 euthymic BD patients and 13 healthy age- and sex-matched controls was analyzed. Head-surface EEG was recomputed into intracortical current density values in 8 frequency bands using standardized low-resolution electromagnetic tomography. Intracortical current densities were averaged in 19 evenly distributed regions of interest (ROIs). Lagged coherences were computed between each pair of ROIs. Source activity and coherence measures between patients and controls were compared (paired t tests). Reductions in temporal cortex activity and in large-scale functional connectivity in patients compared to controls were observed. Activity reductions affected all 8 EEG frequency bands. Functional connectivity reductions affected the delta, theta, alpha-2, beta-2, and gamma band and involved but were not limited to prefrontal and temporal ROIs. The findings show reduced activation of the temporal cortex and reduced coordination between many brain regions in BD euthymia. These activation and connectivity changes may disturb the continuous frontotemporal information flow required for executive and language-related processing, which is impaired in euthymic BD patients.


Bipolar Disorder/physiopathology , Prefrontal Cortex/physiopathology , Temporal Lobe/physiopathology , Adult , Brain/physiopathology , Electroencephalography , Female , Humans , Male , Middle Aged , Neural Pathways/physiopathology , Retrospective Studies , Signal Processing, Computer-Assisted , Young Adult
12.
Fortschr Neurol Psychiatr ; 87(1): 39-45, 2019 02.
Article De | MEDLINE | ID: mdl-30049020

INTRODUCTION: Recent research has shown changes of the intestinal flora in anorexia nervosa (AN) patients. Alpha diversity (AD) represents the number of different bacterial species in the gut. Reduced AD and a leaky gut (zonulin) lead to inflammation and changes in nutrient absorption. METHODS: AD was calculated from stool samples of 18 AN patients and 20 normal weight controls (NC) after 16S ribosomal RNA sequencing. Furthermore, Zonulin as an indicator of gut barrier function and inflammation parameters were investigated. RESULTS: AN patients had significantly lower AD compared to NC (number of observed species p=0.042, Chao1 Diversity Index p=0.043). Zonulin was not significantly altered in AN patients compared to NC. There were no significant correlations of serum parameters and AD. DISCUSSION: Regardless of gut permeability, AN patients showed significantly decreased AD compared to NC. Decreased AD can have an additional negative impact on calorie intake in AN. These results contribute to a better understanding of the illness and the development of new therapeutic options.


Anorexia Nervosa/microbiology , Anorexia Nervosa/physiopathology , Gastrointestinal Microbiome , Intestinal Mucosa/microbiology , Intestinal Mucosa/physiopathology , Adolescent , Adult , Humans , Inflammation/microbiology , Inflammation/physiopathology , Permeability , Pilot Projects , Young Adult
13.
Bipolar Disord ; 21(1): 40-49, 2019 02.
Article En | MEDLINE | ID: mdl-30051546

OBJECTIVES: There is evidence that the gut microbiota plays a major role in the pathogenesis of diseases of the central nervous system through the gut-brain axis. The aim of the present study was to analyze gut microbiota composition in bipolar disorder (BD) and its relation to inflammation, serum lipids, oxidative stress, tryptophan (TRP)/kynurenine (KYN) levels, anthropometric measurements and parameters of metabolic syndrome. Further, microbial community differences of individuals with BD compared with healthy controls (HC) were explored. METHODS: In this cross-sectional study, we performed 16S rRNA gene sequencing of stool samples from 32 BD individuals and 10 HC. Laboratory parameters included inflammatory markers, serum lipids, KYN, oxidative stress and anthropometric measures. Microbial community analysis and correlation to clinical parameters was performed with QIIME, differential abundance analysis of taxa encompassed linear discriminant analysis effect size (LEfSe). RESULTS: We found a negative correlation between microbial alpha-diversity and illness duration in BD (R = -0.408, P = 0.021). Furthermore, we identified bacterial clades associated with inflammatory status, serum lipids, TRP, depressive symptoms, oxidative stress, anthropometrics and metabolic syndrome in individuals with BD. LEfSe identified the phylum Actinobacteria (LDA= 4.82, P = 0.007) and the class Coriobacteria (LDA= 4.75, P = 0.010) as significantly more abundant in BD when compared with HC, and Ruminococcaceae (LDA= 4.59, P = 0.018) and Faecalibacterium (LDA= 4.09, P = 0.039) as more abundant in HC when compared with BD. CONCLUSIONS: The present findings suggest that causes and/or consequences of BD may also lie outside the brain. Exploratory research of the gut microbiota in affective disorders like BD may identify previously unknown underlying causes, and offer new research and therapeutic approaches to mood disorders.


Bipolar Disorder/microbiology , Bipolar Disorder/psychology , Depressive Disorder/microbiology , Depressive Disorder/psychology , Gastrointestinal Microbiome , Biomarkers/blood , Bipolar Disorder/blood , Case-Control Studies , Cross-Sectional Studies , Depression/blood , Depression/microbiology , Depression/psychology , Depressive Disorder/blood , Humans , Inflammation/blood , Inpatients , Kynurenine/blood , Male , Tryptophan/blood
14.
Neuropsychobiology ; : 1-9, 2018 Sep 17.
Article En | MEDLINE | ID: mdl-30223263

INTRODUCTION: Individuals suffering from psychiatric disorders experience high levels of illness burden and a significantly reduced quality of life. Despite targeted psychopharmacological strategies and complementary psychotherapeutic procedures only moderate effects are obtained, and the risk of relapse is high in many patients. Worldwide, psychiatric diseases such as depression are continuously increasing, challenging the personal life of the affected as well as their families, but also whole societies by increasing disability, early retirement and hospitalization. According to current scientific knowledge psychiatric disorders are caused by a multifactorial pathogenesis, including genetics, inflammation and neurotransmitter imbalance; furthermore, also lifestyle-associated factors gain rising importance. In line with this, there is growing evidence that the gut microbiota and nutrition have an impact on the onset and course of psychiatric disorders. AIM: This narrative review highlights the important role of nutrition in psychiatric care and underlines the significance of nutritional advice in the multifactorial, biopsychosocial treatment of patients. It focuses on current dietary interventions such as the Mediterranean diet, dietary supplements and modifications of the gut microbiota with pre-, pro- and postbiotics. RESULTS: Recent studies support the connection between the quality of diet, gut microbiota and mental health through regulation of metabolic functions, anti-inflammatory and antiapoptotic properties and the support of neurogenesis. Dietary coaching to improve mental health seems to be an additional, cost-effective, practical, nonpharmacological intervention for individuals with psychiatric disorders. CONCLUSION: The use of nutritional interventions in psychiatry equips therapists with a promising tool for both the prevention and treatment of psychiatric disorders. Besides pharmacological therapy, psychotherapy and physical activity, nutritional interventions are an important pillar in the multifactorial, biopsychosocial treatment of psychiatric disease and could be used as a potential therapeutic target.

15.
Wien Klin Wochenschr ; 130(21-22): 645-652, 2018 Nov.
Article En | MEDLINE | ID: mdl-30094664

A patient's admission to an intensive care unit (ICU) has a significant impact on family members and other relatives. In order for them to be able to cope with such a stressful situation, the availability of appropriate understandable and accessible information is crucial. The information asymmetry between relatives and medical professionals may adversely affect satisfaction of relatives and their risk of subsequent anxiety, depression and stress symptoms. The aim of this study was therefore to understand which topics are most important to the relatives of ICU patients and to quantify the perceptions of medical professionals regarding the information needs of relatives. A cross-sectional survey was conducted in 2015. The survey had 42 questions, such as 'diagnosis', 'treatment', 'comfort', 'family' and 'end of life'. In total, the survey was handed out to four different groups. A total of 336 persons answered the survey (26 relatives, 28 ICU physicians, 202 ICU nurses and 80 ICU medical professionals in a closed Facebook© group [Facebook, Menlo Park, California, USA]). Relatives ranked the five most important topics as follows: 'recent events (crisis)', 'my participation', 'contamination in hospital', 'physical pain', and 'probability'. Several significant differences (p<0.001) were detected, for example for the topics fever, medication, recent events (crisis), appointments, relapse, and investigations. Even the topic with the lowest ranking (religion) had a score of 3.15 (min. 1.00, max. 5.00) among relatives. The ICU professionals appear to have divergent opinions regarding the most important topics for ICU relatives as compared to relatives themselves.


Critical Illness , Intensive Care Units , Adolescent , Adult , Aged , Aged, 80 and over , Critical Care , Cross-Sectional Studies , Family , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , Young Adult
16.
Front Behav Neurosci ; 12: 27, 2018.
Article En | MEDLINE | ID: mdl-29535615

Previous research has indicated that executive function (EF) is negatively associated with aggressive behavior in childhood. However, there is a lack of longitudinal studies that have examined the effect of deficits in EF on aggression over time and taken into account different forms and functions of aggression at the same time. Furthermore, only few studies have analyzed the role of underlying variables that may explain the association between EF and aggression. The present study examined the prospective paths between EF and different forms (physical and relational) and functions (reactive and proactive) of aggression. The habitual experience of anger was examined as a potential underlying mechanism of the link between EF and aggression, because the tendency to get angry easily has been found to be both a consequence of deficits in EF and a predictor of aggression. The study included 1,652 children (between 6 and 11 years old at the first time point), who were followed over three time points (T1, T2, and T3) covering 3 years. At T1, a latent factor of EF comprised measures of planning, rated via teacher reports, as well as inhibition, set shifting, and working-memory updating, assessed experimentally. Habitual anger experience was assessed via parent reports at T1 and T2. The forms and functions of aggression were measured via teacher reports at all three time points. Structural equation modeling revealed that EF at T1 predicted physical, relational, and reactive aggression at T3, but was unrelated to proactive aggression at T3. Furthermore, EF at T1 was indirectly linked to physical aggression at T3, mediated through habitual anger experience at T2. The results indicate that deficits in EF influence the later occurrence of aggression in middle childhood, and the tendency to get angry easily mediates this relation.

17.
Mol Cell Neurosci ; 88: 258-269, 2018 04.
Article En | MEDLINE | ID: mdl-29427775

The main olfactory epithelium (MOE) of an adult mouse harbors a few million mature olfactory sensory neurons (OSNs), which are traditionally defined as mature by their expression of the olfactory marker protein (OMP). Mature OSNs differentiate in situ from stem cells at the base of the MOE. The consensus view is that mature OSNs have a defined lifespan and then undergo programmed cell death, and that the adult MOE maintains homeostasis by generating new mature OSNs from stem cells. But there is also evidence for mature OSNs that are long-lived. Thus far modern genetic tools have not been applied to quantify survival of a population of OSNs that are mature at a given point in time. Here, a genetic strategy was developed to label irreversibly OMP-expressing OSNs in mice. A gene-targeted OMP-CreERT2 strain was generated in which mature OSNs express an enzymatically inactive version of the Cre recombinase. The fusion protein CreERT2 becomes transiently active when exposed to tamoxifen, and in the presence of a Cre reporter in the genome such as tdRFP, CreERT2-expressing cells become irreversibly labeled. A cohort of mice was generated with the same day of birth by in vitro fertilization and embryo transfer, and injected tamoxifen in their mothers at E18.5 of gestation. I counted RFP immunoreactive cells in the MOE and vomeronasal organ of 36 tamoxifen-exposed OMP-CreERT2 × tdRFP mice from 7 age groups: postnatal day (PD)1.5, PD3.5, PD6.5, 3 weeks, 9 weeks, 6 months, and 12 months. Approximately 7.8% of perinatally labeled cells remain at 12 months, confirming that some mature OSNs are indeed long-lived. The survival curve of the population of perinatally labeled MOE cells can be modeled with a mean half-life of 26 days for the population as a whole, excluding the long-lived cells.


Olfactory Marker Protein/genetics , Olfactory Mucosa/cytology , Olfactory Receptor Neurons/cytology , Vomeronasal Organ/growth & development , Animals , Cell Survival/physiology , Mice, Transgenic , Olfactory Bulb/growth & development , Receptors, Odorant/genetics
18.
World J Biol Psychiatry ; 19(3): 175-186, 2018 04.
Article En | MEDLINE | ID: mdl-28112047

OBJECTIVES: Venous thromboembolism (VTE) can be a life-threatening medical condition that may lead to leg swelling, respiratory distress and death. METHODS: The AMSP (Arzneimittelsicherheit in der Psychiatrie) is a continuous multicentre drug surveillance programme that assesses severe adverse drug reactions during treatment of psychiatric inpatients. We report on a total of 264,422 inpatients who were treated with antipsychotics (APs) and monitored from 1993 to 2011 in 99 psychiatric hospitals. RESULTS: During this period VTE events were reported for 89 inpatients, corresponding to an occurrence rate of 34 cases per 100,000 inpatient admissions treated with APs or 43 cases per 10,000 person-years. The occurrence of VTE was greatest in patients over the age of 65 years of age with mood disorders. The chemical class of butyrophenones (48/100,000) followed by atypical APs (36/100,000) showed the highest occurrence rate for VTE compared to thioxanthenes (23/100,000), which were less associated with VTE. If imputed alone, pipamperone (61/100,000) and risperidone (55/100,000) were most frequently associated with VTE. In general, there was no difference in occurrence rate of VTE between high- and low-potency APs. CONCLUSIONS: These results suggest that clinicians should consider AP drug exposure as a potential risk factor for VTE for patients older than 65 years. Additionally, the diagnosis of an affective disorder seems to increase the risk for VTE.


Antipsychotic Agents/adverse effects , Drug Monitoring/statistics & numerical data , Hospitals, Psychiatric/statistics & numerical data , Mental Disorders/drug therapy , Pharmacovigilance , Venous Thromboembolism/chemically induced , Adult , Aged , Female , Germany/epidemiology , Humans , Male , Mental Disorders/epidemiology , Middle Aged , Mood Disorders/drug therapy , Mood Disorders/epidemiology , Program Development , Venous Thromboembolism/epidemiology
19.
Int J Eat Disord ; 50(12): 1421-1431, 2017 Dec.
Article En | MEDLINE | ID: mdl-29131365

OBJECTIVES: Anorexia nervosa (AN) is a heterogeneous eating disorder associated with alterations of body structure and the gut microbiome. We aimed to investigate the gut microbiota composition of a large female cohort including different BMI groups and activity levels along with body composition parameters. METHOD: 106 female participants were included in this cross-sectional study: AN patients (n = 18), athletes (n = 20), normal weight (n = 26), overweight (n = 22), and obese women (n = 20). DNA was extracted from stool samples and subjected to 16S rRNA gene analysis. The software Quantitative Insights Into Microbial Ecology (QIIME) was used to analyze data. Additionally, we performed anthropometric assessments, ultrasound measurements of subcutaneous adipose tissue thickness, bioimpedance analysis, administered depression inventories, and ascertained laboratory parameters and dietary intakes. RESULTS: Alpha diversity was particularly lower in AN patients and obese participants compared to other groups, while athletes showed highest alpha diversity. Several categories significantly associated with community structure were identified: body fat parameters, serum lipids, CRP, depression scales and smoking. Comparative analysis revealed Coriobacteriaceae as the only enriched phylotype in AN compared to other entities (LDA score >3.5). DISCUSSION: This study provides further evidence of intestinal dysbiosis in AN and sheds light on characteristics of the gut microbiome in different BMI and physical activity groups. These insights point to new modulation possibilities of the gut microbiota which could improve the standard therapy of AN.


Anorexia Nervosa/microbiology , Athletes/statistics & numerical data , Body Composition/physiology , Gastrointestinal Microbiome/physiology , Obesity/microbiology , Overweight/microbiology , Adolescent , Adult , Body Weight , Cross-Sectional Studies , Female , Humans , Young Adult
20.
Fortschr Neurol Psychiatr ; 85(8): 474-478, 2017 Aug.
Article De | MEDLINE | ID: mdl-28841746

Introduction Mitochondriopathies are pathologies of cell organelles, which are essential for the formation of adenosine triphosphate (ATP), which is responsible for cellular energy stock. When mitochondrial mutations occur, symptoms arise frequently in those organs that rely on a continuous energy supply, such as the nervous system. Although psychiatric illness is increasingly prevalent in patients with mitochondrial disease, less attention has been paid to its psychiatric presentations. Case Report We describe a case of a 21-year-old woman who presented in our outpatient department with panic attacks and depression. The patient experienced major side effects after low-dose sertraline therapy. Conclusion Mitochondriopathies belong to the class of rare illnesses in psychiatry; nevertheless, they require adaptations of psychopharmacological therapy. Psychotropic drugs are potential respiratory chain inhibitors and could lead to distinct side effects.


Mitochondrial Diseases/drug therapy , Mitochondrial Diseases/psychology , Depressive Disorder/drug therapy , Depressive Disorder/etiology , Female , Humans , Mitochondrial Diseases/complications , Neuropsychological Tests , Panic Disorder/drug therapy , Panic Disorder/etiology , Personality , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/therapeutic use , Sertraline/adverse effects , Sertraline/therapeutic use , Treatment Outcome , Young Adult
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