Search

Introduction Drug-induced liver injury (DILI) is the 4th most common cause of liver damage in Western countries and can be caused by antidepressants. Methods Against the background of increasing antidepressant prescriptions and increasing use of polypharmacy, we analyzed administered antidepressants and other pharmacological substances, liver toxicity, comorbid somatic secondary diseases together with the occurrence of DILI in a patient population of 6 centers throughout Germany. Results The majority of the enrolled 329 patients received polypharmacological treatment in an inpatient setting. During antidepressant treatment 5.1% of the patients had elevated serum transaminase levels, whereby exactly and not more than 1 criterion proposed to be indicative for DILI, was fulfilled by 3 patients (0.9%). Discussion During patient characterization it becomes clear that a sensitization for relevant risk constellations causing liver injury in MDD patients is relevant to prevent further serious adverse events. [ABSTRACT FROM AUTHOR]

Coercive measures are a sensitive, much‐discussed ethical and legal issue in the psychiatric context. Hence, the identification of their predictors and ways of prevention are of utmost importance. The present study aimed to determine the impact of the social‐psychiatric services (SPS) in North Rhine Westphalia (NRW) on involuntary admissions according to the German Mental Health Act and to identify predictors for the reduction of these involuntary admissions. A dataset including details from 31 districts and 23 towns in NRW over a time period of 10 years (2005–2014) was analysed regarding the number of involuntary admissions, gender and age of admitted patients, and person/institution initiating the compulsory act. All 56 SPS in NRW were contacted for information on the number of clients/contacts, home visits, areas of responsibility and their involvement in involuntary admissions. Thirty SPS participated in the survey. We found a significant increase of involuntary admissions over time with significantly higher proportions of male patients and patients younger than 60 years in every year. Regarding the characteristics of SPS, a negative correlation between the number of clients contacting the SPS on their own initiative and low‐income households was observed. Additionally, the number of clients contacting the SPS on their own initiative was significantly higher in districts/towns associated with lower involuntary admission rates. These data suggest that patient‐based factors were of great importance in the context of involuntary admissions. Furthermore, the SPS and home treatment should be strengthened and intensified to achieve lower involuntary admission rates. [ABSTRACT FROM AUTHOR]

Background: Difficulties in emotion regulation have been related to psychological and physiological stress responses such as lower mood and lower parasympathetic activation (HF-HRV) under resting condition, but evidence on the potential link to the hypothalamic-pituitary-adrenal (HPA) axis functioning and to physiological stress responses during a stress task is still scarce. The aim of the study was to investigate stress responses in young women when confronted to a daily stressor such as exposure to thin ideals and to understand the role of correlates of self-reported trait-like emotion regulation difficulties (ERD). Methods: Heart rate variability (HRV) and salivary cortisol data were collected in a sample of 273 young women aged 18–35 with and without mental disorders during a vivid imagination of thin ideals (experimental condition) or landscapes (control condition). Changes in mood states were measured on a visual analogue scale (0–100). Correlates of trait-like ERD were self-reported using the Difficulties in Emotion Regulation Scale (DERS). Results: Participants with higher ERD showed a stronger decline in self-reported mood after vivid imagination of thin ideals compared to participants with lower ERD in the experimental condition but also a stronger increase of positive mood with increasing ERD in the control condition. ERD were not related to baseline HF-HRV or baseline salivary cortisol levels nor to any physiological response during and after the imagination of thin ideals. Discussion and conclusion: The results corroborate the role of ERD regarding the immediate psychological impact of daily stressors. Exposition to daily stressors in the laboratory results in discrepant psychological and physiological reactivity. Future studies should investigate under what conditions the complex interrelations between immediate and long-term ERD and biological activation are amenable to assessment in a laboratory setting. The additive effects of multiple exposition to stressors, such as thin ideals in daily life, also need to be addressed. [ABSTRACT FROM AUTHOR]

This study examined the consequences of media exposure to thin ideals compared to pictures of landscapes in healthy young women and women with eating and mixed mental disorders and investigated whether appearance-related cognitive factors and cognitive distortions moderate the effects. Two hundred seventy-five women in a multisite laboratory trial (174 in- or outpatients and 101 healthy women; Mage 22.87 years, SD = 3.94) were exposed to either thin ideals or to landscape pictures and guided through a vivid imagery of these pictures thereafter. Changes in body image dissatisfaction, mood, eating behavior, and physiological markers were assessed. After thin ideal exposure and even more after guided imagery, women's body image dissatisfaction increased and mood declined. The effect on mood was most pronounced in women with eating disorders, less in women with mixed disorders, and smallest in healthy controls. No effects were found on physiological measures. Higher values of appearance-related cognitive factors moderated the effect of thin ideal exposure and guided imagery on all psychological outcomes. Cognitive distortions moderated the effect of thin ideal exposure and guided imagery on mood. Findings indicate an overall susceptibility to viewing thin ideal pictures in magazines in young and especially in women with eating disorders. Though exposure in the laboratory resulted in psychological effects, it did not lead to a physiological stress response. The impact of thin ideal exposure on mood is in line with affect-regulation models in eating disorders, with appearance-related cognitive factors and cognitive distortions potentially accelerating such effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

The role of macrophage-inducible C-type lectin Mincie in lung innate immunity against mycobacterial infection is incompletely defined. In this study, we show that wild-type (WT) mice responded with a delayed Mincie induction on resident alveolar macrophages and newly immigrating exudate macrophages to infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG), peaking by days 14-21 posttreatment. As compared with WT mice, Mincie knockout (KO) mice exhibited decreased proinflammatory mediator responses and leukocyte recruitment upon M. bovis BCG challenge, and they demonstrated increased mycobacterial loads in pulmonary and extrapulmonary organ systems. Secondary mycobacterial infection on day 14 after primary BCG challenge led to increased cytokine gene expression in sorted alveolar macrophages of WT mice, but not Mincie KO mice, resulting in substantially reduced alveolar neutrophil recruitment and increased mycobacterial loads in the lungs of Mincie KO mice. Collectively, these data show that WT mice respond with a relatively late Mincie expression on lung sentinel cells to M. bovis BCG infection. Moreover, M. bovis BCG-induced upregulation of C-type lectin Mincie on professional phagocytes critically shapes antimycobacterial responses in both pulmonary and extrapulmonary organ systems of mice, which may be important for elucidating the role of Mincie in the control of mycobacterial dissemination in mice. [ABSTRACT FROM AUTHOR]

The growth factor GM-CSF has an important role in pulmonary surfactant metabolism and the regulation of antibacterial activities of lung sentinel cells. However, the potential of intra-alveolar GM-CSF to augment lung protective immunity against inhaled bacterial pathogens has not been defined in preclinical infection models. We hypothesized that transient overexpression of GM-CSF in the lungs of mice by adenoviral gene transfer (Ad-GM-CSF) would protect mice from subsequent lethal pneumococcal pneumonia. Our data show that intra-alveolar delivery of Ad-GM-CSF led to sustained increased pSTAT5 expression and PU.1 protein expression in alveolar macrophages during a 28-d observation period. Pulmonary Ad-GM-CSF delivery 2-4 wk prior to infection of mice with Streptococcus pneumoniae significantly reduced mortality rates relative to control vector-treated mice. This increased survival was accompanied by increased inducible NO synthase expression, antibacterial activity, and a significant reduction in caspase-3-dependent apoptosis and secondary necrosis of lung sentinel cells. Importantly, therapeutic treatment of mice with rGM-CSF improved lung protective immunity and accelerated bacterial clearance after pneumococcal challenge. We conclude that prophylactic delivery of GM-CSF triggers long-lasting immunostimulatory effects in the lung in vivo and rescues mice from lethal pneumococcal pneumonia by improving antibacterial immunity. These data support use of novel antibiotic-independent immunostimulatory therapies to protect patients against bacterial pneumonias. [ABSTRACT FROM AUTHOR]

Background: Old age bipolar disorder has been an orphan of psychiatric research for a long time despite the fact that bipolar disorder (BD)-I and II together may affect 0.5-1.0% of the elderly. It is also unclear whether aetiology, course of illness and treatment should differ in patients with a first manifestation in older age and patients suffering from a recurrence of a BD known for decades. This narrative review will summarize the current state of knowledge about the epidemiology, clinical features, and treatment of BD in the elderly., Methods: We conducted a Medline literature search from 1970 to 2021 using MeSH terms "Bipolar Disorder" × "Aged" or "Geriatric" or "Elderly". Search results were complemented by additional literature retrieved from examining cross references and by hand search in text books., Summary of Findings: Varying cut-off ages have been applied to differentiate old age from adult age BD. Within old age BD, there is a reasonable agreement of distinct entities, early and late-onset BD. They differ to some extent in clinical symptoms, course of illness, and some co-morbidities. Point prevalence of BD in older adults appears slightly lower than in working-age adults, with polarity of episodes shifting towards depression. Psychopharmacological treatment needs to take into account the special aspects of somatic gerontology and the age-related change of pharmacokinetic and pharmacodynamic characteristics. The evidence for commonly used treatments such as lithium, moodstabilizing antiepileptics, antipsychotics, and antidepressants remains sparse. Preliminary results support a role of ECT as well as psychotherapy and psychosocial interventions in old age BD., Conclusions: There is an obvious need of further research for all treatment modalities of BD in old age. The focus should be pharmacological and psychosocial approaches, as well as their combination, and the role of physical treatment modalities such as ECT.Appeared originally in Ann Gen Psychiatry 2021; 20:1 ., (Copyright © 2023 by the American Psychiatric Association.)

Objective: Impairments in facial emotion recognition are an underlying factor of deficits in emotion regulation and interpersonal difficulties in mental disorders and are evident in eating disorders (EDs)., Methods: We used a computerized psychophysical paradigm to manipulate parametrically the quantity of signal in facial expressions of emotion (QUEST threshold seeking algorithm). This was used to measure emotion recognition in 308 adult women (anorexia nervosa [n = 61], bulimia nervosa [n = 58], healthy controls [n = 130], and mixed mental disorders [mixed, n = 59]). The M (SD) age was 22.84 (3.90) years. The aims were to establish recognition thresholds defining how much information a person needs to recognize a facial emotion expression and to identify deficits in EDs compared with healthy and clinical controls. The stimuli included six basic emotion expressions (fear, anger, disgust, happiness, sadness, surprise), plus a neutral expression., Results: Happiness was discriminated at the lowest, fear at the highest threshold by all groups. There were no differences regarding thresholds between groups, except for the mixed and the bulimia nervosa group with respect to the expression of disgust (F(3,302) = 5.97, p = .001, η = .056). Emotional clarity, ED pathology, and depressive symptoms did not predict performance (RChange ≤ .010, F(1,305) ≤ 5.74, p ≥ .079). The confusion matrix did not reveal specific biases in either group., Conclusions: Overall, within-subject effects were as expected, whereas between-subject effects were marginal and psychopathology did not influence emotion recognition. Facial emotion recognition abilities in women experiencing EDs compared with women experiencing mixed mental disorders and healthy controls were similar. Although basic facial emotion recognition processes seems to be intact, dysfunctional aspects such as misinterpretation might be important in emotion regulation problems., Clinical Trial Registration Number: DRKS-ID: DRKS00005709.

FMS-like tyrosine kinase-3 ligand (Flt3L) is a dendritic cell (DC) growth and differentiation factor with potential in antitumor therapies and antibacterial immunization strategies. However, the effect of systemic Flt3L treatment on lung-protective immunity against bacterial infection is incompletely defined. Here, we examined the impact of deficient (in Flt3L knockout [KO] mice), normal (in wild-type [WT] mice), or increased Flt3L availability (in WT mice pretreated with Flt3L for 3, 5, or 7 days) on lung DC subset profiles and lung-protective immunity against the major lung-tropic pathogen, Streptococcus pneumoniae. Although in Flt3L-deficient mice the numbers of DCs positive for CD11b (CD11b(pos) DCs) and for CD103 (CD103(pos) DCs) were diminished, lung permeability, a marker of injury, was unaltered in response to S. pneumoniae. In contrast, WT mice pretreated with Flt3L particularly responded with increased numbers of CD11b(pos) DCs and with less pronounced numbers of CD103(pos) DCs and impaired bacterial clearance and with increased lung permeability following S. pneumoniae challenge. Notably, infection of Flt3L-pretreated mice with S. pneumoniae lacking the pore-forming toxin, pneumolysin (PLY), resulted in substantially less lung CD11b(pos) DCs activation and reduced lung permeability. Collectively, this study establishes that Flt3L treatment enhances the accumulation of proinflammatory activated lung CD11b(pos) DCs which contribute to acute lung injury in response to PLY released by S. pneumoniae.

Apoptotic death of alveolar macrophages observed during lung infection with Streptococcus pneumoniae is thought to limit overwhelming lung inflammation in response to bacterial challenge. However, the underlying apoptotic death mechanism has not been defined. Here, we examined the role of the TNF superfamily member TNF-related apoptosis-inducing ligand (TRAIL) in S. pneumoniae-induced macrophage apoptosis, and investigated the potential benefit of TRAIL-based therapy during pneumococcal pneumonia in mice. Compared with WT mice, Trail(-/-) mice demonstrated significantly decreased lung bacterial clearance and survival in response to S. pneumoniae, which was accompanied by significantly reduced apoptosis and caspase 3 cleavage but rather increased necrosis in alveolar macrophages. In WT mice, neutrophils were identified as a major source of intraalveolar released TRAIL, and their depletion led to a shift from apoptosis toward necrosis as the dominant mechanism of alveolar macrophage cell death in pneumococcal pneumonia. Therapeutic application of TRAIL or agonistic anti-DR5 mAb (MD5-1) dramatically improved survival of S. pneumoniae-infected WT mice. Most importantly, neutropenic mice lacking neutrophil-derived TRAIL were protected from lethal pneumonia by MD5-1 therapy. We have identified a previously unrecognized mechanism by which neutrophil-derived TRAIL induces apoptosis of DR5-expressing macrophages, thus promoting early bacterial killing in pneumococcal pneumonia. TRAIL-based therapy in neutropenic hosts may represent a novel antibacterial treatment option.