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Altered expression of the complement component C4A gene is a known risk factor for schizophrenia. Further, predicted brain C4A expression has also been associated with memory function highlighting that altered C4A expression in the brain may be relevant for cognitive and behavioral traits.
We obtained genetic information and performance measures on seven cognitive tasks for up to 329 773 individuals from the UK Biobank, as well as brain imaging data for a subset of 33 003 participants. Direct genotypes for variants (n = 3213) within the major histocompatibility complex region were used to impute C4 structural variation, from which predicted expression of the C4A and C4B genes in human brain tissue were predicted. We investigated if predicted brain C4A or C4B expression were associated with cognitive performance and brain imaging measures using linear regression analyses.
We identified significant negative associations between predicted C4A expression and performance on select cognitive tests, and significant associations with MRI-based cortical thickness and surface area in select regions. Finally, we observed significant inconsistent partial mediation of the effects of predicted C4A expression on cognitive performance, by specific brain structure measures.
These results demonstrate that the C4 risk locus is associated with the central endophenotypes of cognitive performance and brain morphology, even when considered independently of other genetic risk factors and in individuals without mental or neurological disorders.
Psychiatric intensive care is supposed to offer treatment and to hold patients with psychiatric illness, if they pose a threat to themselves or to others. Besides treating the underlying psychiatric diagnoses, it is also necessary to take care of severe somatic comorbidity, which is often impeded by patients’ limited ability to cooperate. Treatment often requires the administration of sedative medication and occasionally the use of medical restraints. Involuntary commitment, involuntary treatment and the usage of physical restraints is regulated by national mental health laws. Medical professionals working in the field of psychiatric intensive care must have expert knowledge in the fields of psychopharmacology and intensive care medicine. Treatment concepts should be aimed to provide optimized care for psychiatric inpatients in a potentially life-threatening phase of their illness. This article outlines current clinical practice at the psychiatric intensive care unit of the Medical University of Vienna (Austria). Furthermore, we present diagnoses, diagnostic procedures and specific treatments of a sample of 100 consecutive inpatients treated in the years 2008 and 2009 at this ward.
Recent studies suggest that the menopausal transition may constitute a period of greater risk for the development of new onset/recurrent depressive episodes. In addition, the presence of vasomotor and other menopause-related complaints may adversely affect quality of life and overall functioning. With the long-term safety of hormone therapies being questioned, non-hormonal strategies are needed for the management of symptomatic midlife women. This report is a preliminary analysis of a study investigating the effects of quetiapine extended-release (Seroquel XR) in symptomatic perimenopausal and postmenopausal women with major depressive disorder (MDD).
Peri and postmenopausal women, age 40 to 60 years, suffering from MDD and reporting menopause-related symptoms were recruited into a 2-week, placebo lead-in phase, followed by an open trial (8 weeks) with quetiapine extended-release, flexible dose, 150-300 mg/day. The primary outcome measure (i.e. changes in depressive symptoms) was assessed via Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Other measures included: Hamilton Depression Rating Scale (HAM-D), menopause-related symptoms (Greene Climacteric Scale - GCS), Clinical Global Impression (CGI-S), sleep characteristics (Pittsburgh Sleep Quality Index - PSQI) and the impact of hot flashes on daily functioning (Hot Flash-Related Daily Interference Scale (HFRDIS).
Thirty-nine women (mean age 49.3±4.3 years) were enrolled in the placebo lead-in phase. Of those, 25 were considered eligible for the 8-week trial with quetiapine extended-release. This interim analysis (LOCF) included 18 women who completed 4 to 8 weeks of treatment with quetiapine extended-release (median MADRS total scores at baseline = 28 ±6.1; median final dose of quetiapine extended-release=200 mg/day). At the end of the study, 13 out of 18 (72.2%) participants achieved remission (total MADRS scores < 10). Overall, subjects showed significant reduction in total MADRS (p< 0.001) and HAM-D scores (p< 0.001). Treatment with quetiapine extended-release improved menopause-related symptoms, as shown by a decrease in Greene Climacteric Scale total scores (p< 0.001) and sub-scores for psychological (p< 0.001), vasomotor (p=0.001), and somatic (p=0.001) complaints (Wilcoxon tests). Quetiapine extended-release did affect menopause-related sexual dysfunction (changes in CGS sexual sub-scores, p=0.06). There was a substantial reduction in overall burden associated with vasomotor symptoms, i.e., decreased HFRDIS scores (p< 0.001). Lastly, sleep efficiency, perceived sleep quality, and daily sleep disturbances improved significantly after treatment with quetiapine extended-release (p< 0.001 for all PSQI sub-scores).
This is the first study examining the efficacy of Seroquel XR for the treatment of Major Depressive Disorder in a population of symptomatic peri and postmenopausal women. Treatment with Seroquel XR not only reduced depressive symptomatology but also improved vasomotor symptoms and sleep complaints. Larger randomized, placebo-controlled studies are warranted to better explore the efficacy and predictors of response with quetiapine extended-release for this specific population.
There have been a number of recent findings that elucidate the ways repeated episodes relate to cognitive impairment and poor functioning in Bipolar Disorder. While available treatments are undoubtedly helpful, many patients are still lacking improvement and adequate prophylaxis even when adherence to treatment is accomplished. New research point to neural glial cells resilience and connectivity as major contributors to the pathophysiology of the disorder. In this context, growth factors such as the brain-derived neurotrophic factor (BDNF) have been pointed out as potential targets for the development of new treatments. In the psychological domain, better assessment of the cognitive decline associated with the disorder is a major issue. Once cognitive disability is present, interventions with the potential to recover functioning have been put forward. In the biological domain, strategies aiming at reducing neural damage and with the potential to regenerate connectivity among brain cell are promising avenues for the development of new treatments. Another important development would be the incorporation of biological markers as a means to help staging the degree of severity of the disorder and guide the pharmacological treatment. These topics and their relationship to the clinical context will be discussed in this session.
Intensive care at a psychiatric intensive care unit (PICU) traditionally includes the treatment of severely ill psychiatric patients with suicidal or violent behavior .
A chart review was performed including 100 consecutive inpatients (52% females, age: 45.7 ± 17.8 years) treated at the Viennese PICU between 2008–2009.
Psychopharmacotherapy and the rate of electroconvulsive therapy (ECT) in these patients is reported here.
87% of patients were treated with antipsychotics: 44% with quetiapine (447.7 ± 421 mg), 32% with risperidone (4.3 ± 2.3 mg), 25% with olanzapine (16.9 ± 7.5 mg), 20% with haloperidol (10.5 ± 5.4 mg), 16% with aripiprazole (15 ± 8.4 mg), 6% clozapine (416.7 ± 147.2 mg) and 3% ziprasidone (120 ± 56.6 mg). 36% of patients received treatment with mood stabilizers: 15% with valproic acid, 8% with lamotrigine, 6% with lithium, 4% with pregabaline, 3% with topiramate, 2% with gabapentine and 2% with oxcarbazepine. In 49% of patients antidepressants were prescribed: in 23% selective serotonin reuptake inhibitors, in 12% selective dual acting reuptake inhibitors, in 5% tricyclic antidepressants and in 33% other antidepressants (mostly trazodone or mirtazapine). 84% of patients were treated with benzodiazepines (30.3 ± 22.4 mg diazepam equivalents), in 17% the opioid nalbuphin was applied. Intravenous psychopharmacotherapy was used in 31% of cases. 10% of patients received ECT.
Psychotropic compounds with sedative properties are frequently used at the Viennese PICU. However, the dosages for antipsychotics do not appear to be higher than on normal psychiatric wards.
Tricyclic antidepressants (TCAs) are more likely to cause cardiovascular and neurological toxicity than compared to Selective Serotonin Reuptake Inhibitors (SSRIs).
In a prospective hospital-based cohort study, we addressed the question of severity and outcome of antidepressant self-poisonings in patients who attended the Loghman-Hakim Hospital Poison Center. The severity was judged by impairment of consciousness, the outcome criteria were the requirement of inpatient treatment and endotracheal intubation as well as mortality. The aim of the study was to find out if TCA intoxications require more therapeutic efforts than SSRI intoxications.
From 28 March to 20 May 20 2006, all patients presented to the Poison Center were documented using preformatted forms by three trained nurses blinded to any study hypotheses. From 3.578 intoxications, a number of 334 patients with antidepressant or lithium self-poisoning was identified (9.3% of all poisoning cases; 233 females, 101 males; median age 24 years, min 13, max 70).
As compared to SSRI single-substance intoxications (n = 17), TCA single-substance intoxications (n = 73) were associated with (1) a significantly lower level of consciousness (p = 0.005); (2) a significantly higher admission frequency (80.8% vs. 35.3%; p < 0.001) and (3) a higher intubation frequency (13.7% vs. 0%; p = ns). SSRI multiple-substance intoxications were associated with a significantly lower level of consciousness than SSRI single-substance intoxications (p = 0.042), while there was no significant difference between TCA multiple- and single-substance intoxications.
This study suggests that an overdose with SSRIs results in a more favorable clinical outcome than an overdose with TCAs.
Psychiatric disorders per se or treatment resistance can cause life-threatening conditions. More than 25 years have passed since the term “psychiatric intensive care unit” (PICU) was introduced in the United Kingdom. This system is comprised of security units for psychiatric patients with suicidal or violent behaviour, providing a locked environment with more resources regarding personnel and care. The PICU concept at the Department of Psychiatry and Psychotherapy in Vienna, Austria, represents a progress towards optimal care of patients with serious psychiatric illnesses who also have critical somatic illnesses. One third of the patients are transferred from inpatient facilities of medical departments such as internal medicine, emergency medicine, trauma surgery or anesthesiology. Our PICU is dedicated to somatically, critically ill patients who have psychiatric symptoms (e.g., agition, aggression, impulsivity, delusions, catatonia, confusion, reduced consciousness, impaired self-reliance) complicating recovery from their critical, somatic condition. Generally, the dosages for antipsychotics are not higher than those at normal psychiatric wards. Benzodiazepine dosages of about 30mg diazepam equivalents per day are frequently used. In the years 2008 and 2009, 10% of all patients at the Viennese PICU were treated with electroconvulsive therapy. Delirium requires immediate therapy of underlying intracerebral pathologies, extracerebral illnesses or toxic features. Involuntary commitment, physical restraints and urinary catheterization were applied in approximately 50% of the patients, nasogastric tube or central venous catheter in 20%. In every case, intensive care nursing, monitoring of vital functions and specific experience at the interface between psychiatry and somatic medicine are required.
Psychiatric intensive care is supposed to offer treatment and to hold patients with psychiatric illness, if they pose a threat to themselves or to others.
A chart review was performed including 100 consecutive inpatients (52% females, age: 45.7 ± 17.8 years) treated at the Viennese psychiatric intensive care unit (PICU) in the years 2008 and 2009. Clinical key features and the distribution of mental disorders (according to ICD-10) in these patients are reported here.
The mean duration of stay was 18.9 ± 14.8 days. 52% of patients were admitted involuntarily. 18% suffered from organic mental disorder (12% from delirium), 20% were diagnosed with mental disorders due to psychoactive substance use (9% alcohol dependency, 6% benzodiazepine dependency, 5% multiple drug use), 16% had a diagnosis of schizophrenia, 10% of schizoaffective disorder and 5% of transient psychotic disorder. 20% suffered from recurrent depressive disorder, 15% from bipolar affective disorder and 3% from a single depressive episode. 8% fulfilled diagnostic criteria of a neurotic, stress-related or somatoform disorder. 12% had eating disorders, 9% had personality disorders and 1% was diagnosed with mental retardation. Only 15% of patients had a first episode of psychiatric illness. 4% were admitted after an accident and 21% after a suicide attempt (45% poisoning, 25% jumping from height, 20% cutting/piercing with sharp object, 5% vehicular impact, 5% self-immolation).
All major psychiatric diagnoses can be found at the Viennese PICU, either if patients are in a life-threatening condition, or if additional somatic illnesses require intensive care management.
Prior studies to determine the economic consequences of schizophrenia have largely been undertaken in clinical settings with a small number of cases and have been unable to analyze effects across different age cohorts. The aim of this study is to investigate the burden of schizophrenia in Germany.
Costs, service utilization, and premature mortality attributable to schizophrenia were estimated for the year 2008 using a retrospective matched cohort design. Therefore, 26,977 control subjects as well as 9411 individuals with a confirmed diagnosis of schizophrenia were drawn from a sickness fund claims database. To reduce conditional bias, the non-parametric genetic matching method was employed.
The final study population comprised 8224 matched pairs. The annual cost attributable to schizophrenia was €11,304 per patient from the payers’ perspective and €20,609 from the societal perspective with substantial variations among age groups: direct medical expenses were highest among patients aged > 65 years, whereas younger individuals (< 25 years) incurred the greatest non-medical costs. The annual burden of schizophrenia from the perspective of German society ranges between €9.63 billion and €13.52 billion.
There are considerable differences in the distribution of costs and service utilization for schizophrenia. Because schizophrenia is characterized by an early age of onset and a long duration, research efforts should be targeted at particular populations to obtain the most beneficial outcomes, both clinically and economically.
We considered that completed opiate detoxification resulted in increased life expectancy and earning capacity as compared to non-completed detoxification.
The cohort study sample included pure opioid or poly-substance addicts admitted for voluntary in-patient detoxification between 1997 and 2004. Of 404 patients, 58.7% completed the detoxification program and 41.3% did not. The Austrian Social Security Institution supplied data on survival and employment records for every single day in the individual observation period between discharge and December 2007. Statistical analyses included the calculation of standardized mortality rates for the follow-up period of up to 11 years.
The standardized mortality ratios (SMRs) were between 13.5 and 17.9 during the first five years after discharge, thereafter they fell clearly with time. Mortality did not differ statistically significantly between completers and non-completers. The median employment rate was insignificantly higher in completers (12.0%) than in non-completers (5.5%). The odds for being employed were higher in pure opioid addicts than in poly-substance addicts (p = 0.003).
The assumption that completers of detoxification treatment have a better outcome than non-completers has not been confirmed. The decrease in mortality with time elapsed since detoxification is interesting. Pure opioid addicts had better employment prospects than poly-substance addicts.
Major depression and sleep disturbances are closely related and often occur concomitantly. Many of the observed changes of sleep characteristics in depression are also present in healthy aging, which led to the premise that sleep in depression resembles premature aging.
Here, we aimed at quantifying the homeostatic and circadian sleep-wake regulatory components in young women suffering from major depression disorder and healthy young and older control women during 40 hours of sustained wakefulness.
After an 8-h baseline night 9 depressed women, 8 healthy young and 8 healthy older women underwent a 40-hour sustained wakefulness protocol followed by a recovery night under constant routine conditions. Polysomnographic recordings were carried out continuously. Sleep parameters as well as the time course of EEG slow-wave activity (SWA) (EEG spectra range: 0.75-4.5 Hz), as a marker of homeostatic sleep pressure, was analyzed during the recovery night.
Young depressed women exhibited higher absolute mean SWA levels and a stronger response to sleep deprivation compared to healthy young and healthy older women, particularly in frontal brain regions. In contrast, healthy older women exhibited attenuated SWA values compared to the other two groups and an absence of the frontal predominance of mean SWA during the recovery night.
Our data clearly show that homeostatic sleep regulation as well as sleep architecture in young depressed women is not equal to premature aging. Moreover, our findings demonstrate that young depressed women live on an elevated level of homeostatic sleep pressure.
The observance of possible somatic and environmental causes is essential to improve safety and efficacy in the treatment of agitated states. Severe agitation is considered a medical emergency requiring immediate psychopharmacologic intervention.
To establish a clinically applicable consensus statement based on evidence- as well as eminence-based medicine with respect to schizophrenia and mania.
The recommendations given are based on information from psychopharmacologic treatment studies as well as logistic and practical factors intrinsic to clinical settings.
Atypical antipsychotics given orally together with Lorazepam are considered the first-line treatment of agitated states in psychotic patients. Adequate communication with the patient is considered essential for effective oral administration. A novel alternative, Loxapine 4.5 mg or 9.1 mg (approved by the EMA 2013), is administered via an inhaler and exerts its sedative effects within 10 minutes. Inhalation may carry the benefit of greater patient acceptance. In contrast, intramuscular administration of antipsychotics is typically perceived by patients to be more invasive and persuasion or coercion may be necessary in severely ill patients. On the other hand, Aripiprazole, Haloperidole, Olanzapine and Ziprasidone show clinical efficacy within 15-30 minutes in psychopharmacologic trials when administered intramuscularly (i.m.). When taking extrapyramidal symptoms, QTc-prolongation and potential for combination with benzodiazepines into account, Aripiprazole i.m. carries the highest recommendation grade. Lorazepam may be administered intravenously. Currently, no antipsychotics are approved for intravenous administration.
This project gives recommendations which consider risk-benefit ratios and patient compliance.
Although discussed controversially, coercive practices during involuntary admission are common in mental health services. The impact of physical restraints on patients has not been sufficiently studied.
To investigate the subjective perception of patients during and after physical restraint.
47 patients in a psychiatric intermediate care facility experiencing belt fixation were interviewed and filled out self-assessment forms at 4 visits.
The median duration of restraint was 99 hours. Median VAS scores indicated moderate levels of anxiety. With increasing time span from the fixation, memory regarding this event decreased and patients experienced a regain of self-control. Consistently, 50% perceived high levels of coercion at admission, PTSD could be supposed in 25% of the patients.
Despite a considerable restraint of freedom, distress related to belt-fixation seems acceptable in our sample. Patients’ disapproval concerning restraint measures seems to diminish with time, probably related to decreasing memory regarding the fixation practice.
Methane (CH4) production is a ubiquitous, apparently unavoidable side effect of fermentative fibre digestion by symbiotic microbiota in mammalian herbivores. Here, a data compilation is presented of in vivo CH4 measurements in individuals of 37 mammalian herbivore species fed forage-only diets, from the literature and from hitherto unpublished measurements. In contrast to previous claims, absolute CH4 emissions scaled linearly to DM intake, and CH4 yields (per DM or gross energy intake) did not vary significantly with body mass. CH4 physiology hence cannot be construed to represent an intrinsic ruminant or herbivore body size limitation. The dataset does not support traditional dichotomies of CH4 emission intensity between ruminants and nonruminants, or between foregut and hindgut fermenters. Several rodent hindgut fermenters and nonruminant foregut fermenters emit CH4 of a magnitude as high as ruminants of similar size, intake level, digesta retention or gut capacity. By contrast, equids, macropods (kangaroos) and rabbits produce few CH4 and have low CH4 : CO2 ratios for their size, intake level, digesta retention or gut capacity, ruling out these factors as explanation for interspecific variation. These findings lead to the conclusion that still unidentified host-specific factors other than digesta retention characteristics, or the presence of rumination or a foregut, influence CH4 production. Measurements of CH4 yield per digested fibre indicate that the amount of CH4 produced during fibre digestion varies not only across but also within species, possibly pointing towards variation in microbiota functionality. Recent findings on the genetic control of microbiome composition, including methanogens, raise the question about the benefits methanogens provide for many (but apparently not to the same extent for all) species, which possibly prevented the evolution of the hosting of low-methanogenic microbiota across mammals.
In the last decade, the exponential increase in migration studies focusing on the mobility of groups and single individuals—mostly based on aDNA and strontium isotope analyses—has provided an important extra layer of information regarding past social dynamics. The current relatively large quantity of data and their constant increase provide an opportunity to examine human mobility in unprecedented detail. In short, the course of academic dialogue is changing from producing evidence for movement to examining differences or similarities in human mobilities across temporal and geographical barriers. Moreover, the amount and type of new data are beginning to provide new kinds of information that can help us grasp why that movement first came about. We present the first potential mobility model focusing on single individuals during different life stages based on in vivo movement patterns. We draw on previous studies in recent mobility research that provide a variety of case studies to illustrate the model. We hope that this model will prove valuable for future discussions regarding human mobility by integrating the present archaeological contextual discourse with the increasing body of data being produced.
OBJECTIVES/SPECIFIC AIMS: Macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone are known to be associated with Torsade de pointes/QT prolongation (TdP/QTP). Other antibiotics may also lead to TdP/QTP, but no study has systemically compared TdP/QTP risks of different antibiotics using recent data. Therefore, the objective of this study was to evaluate the association between TdP/QTP and antibiotics in recent years using the FDA Adverse Event Report System (FAERS). METHODS/STUDY POPULATION: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP/QTP cases. We calculated the Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and TdP/QTP. An association was considered to be statistically significant when the lower limit of the 95%CI was greater than 1. RESULTS/ANTICIPATED RESULTS: A total of 2,042,801 reports (including 5,221 TdP/QTP reports) were considered, after inclusion criteria were applied. Macrolides had the greatest proportion of TdP/QTP reports, representing 2.9% of all macrolide reports. TdP/QTP RORs (95%CI) for the antibiotics were (in descending order): macrolides 11.73 (9.74-14.12), linezolid 9.39 (6.45-13.68), amikacin 8.94 (4.22-18.92), imipenem-cilastatin 5.01 (2.38-10.56), fluoroquinolones 4.67 (3.96-5.52), penicillin combinations 3.52 (2.56-4.86), cephalosporins 1.90 (1.14-3.16), metronidazole 1.49 (0.74-2.99), vancomycin 1.26 (0.70-2.28), clindamycin 0.83 (0.27-2.58), trimethoprim-sulfamethoxazole 0.82 (0.31-2.18), and amoxicillin 0.57 (0.18-1.78). DISCUSSION/SIGNIFICANCE OF IMPACT: This study confirms prior evidence for TdP-QTP risks with macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and cephalosporins. This study provides new evidence for TdP-QTP risks with amikacin. Macrolides had the highest TdP/QTP ROR among the antibiotics evaluated in this study.