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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.
Grain-scale discrete element simulations of bidisperse mixtures during bedload transport are used to understand, and model, bedload transport and particle-size segregation in granular media. For an initial distribution of fine particles on top of a coarse granular bed, this paper investigates the gravity driven percolation/segregation of the fine particles down into the quasi-static part of the bed. The segregation is observed to be driven by the inertial number at the bottom of the fine particle layer, and is independent of the number of fine particles. A novel travelling wave solution for the evolving concentration distribution is constructed using the continuum particle-size segregation model of Thornton, Gray & Hogg (J. Fluid Mech., vol. 550, 2006, pp. 1–25) and Gray & Chugunov (J. Fluid Mech., vol. 569, 2006, pp. 365–398). The observed behaviour is shown to be related to a local equilibrium between the influence of the concentration and of the inertial number. The existence of the exact solution relies on the segregation flux and the diffusion coefficient having the same dependency on the inertial number. This functional dependence allows the continuum model to quantitatively reproduce the discrete simulations. These results significantly improve on our understanding of the size segregation dynamics and represent a step forward in the up-scaling process to polydisperse granular flows in the context of turbulent bedload transport.
Internet sex offending is a rather new class of criminal acts and therefore little is known about previous convictions, recidivsm and especially correlation with hands-on sexual offences. Previous studies on small samples reported an insignificant correlation between previous convictions for child pornography and later contact sex offences on the one hand and an important role of pornography as a risk factor for sexual recidivsm of convicted sexual offenders. As an increasing number of defendants accused of child pornography is assigned for forensic risk assessment, better evidence and understanding of the role and the amount of the influence of child pornography on later offending is most urgently needed.
We therefore explore these correlations by means of the complete set of all offenders convicted of illegal pornography in the Swiss federal crime registry at the time of november 2008. The analysis of 4658 criminal records reveal that 7.9% of the internet sex offenders were at the same time convicted of child abuse. The child molesters with 20.7% recidivated more frequently in general, compared to 9.8% of the offenders who were not convicted of a contact offence. Furthermore, the contact offenders with 11.4% were significant more likely to reoffend in terms of illegal pornography and sexual acts involving children with 6.0%.
We will present all recidivism rates and our conclusions at the conference.
Murder-Suicide may be defined as extreme pattern of domestic violence. Research is hampered by the fact that with the death of the perpetrator the files are usually closed and an analysis of the cases is hardly possible. Knowledge about the circumstances of murder-suicide, however, is of special interest for the forensic-psychiatric expert when the perpetrator survives and the need for forensic assessment arises. Since forensic-psychiatric assessment is always based on comparison with similar cases we compared the files of surviving perpetrators of murder-suicide with those of lethal domestic violence.
All forensic-psychiatric expertises about surviving perpetrators of homicide-suicide which occurred in the region of Basle, Switzerland, between 1987 and 2006 (n = 6) were compared with those of perpetrators of homicide in a domestic environment (n = 20) in the same period.
There were comparatively more women but less foreigners among the perpetrators of homicide -suicide, their socioeconomic level was much higher and there were more children among the victims. The most frequent psychiatric diagnosis in both groups was personality disorder, but the range in the domestic murder group, however, went from no diagnosis at all to psychosis, i. e. assumed full criminal responsibility to assumed not guilty by reason of insanity. There was no case of not guilty by reason of insanity among the homicide-suicide group.
The disparities of these two patterns of domestic violence are much greater than we expected, which underpins the need for specific forensic assessment as well as preventive actions.
Drugs which affect the level of dopamine have also an impact on the level of prolactine and hence influence the sexual conduct of patients. Hypersexuality is a well known side effect of the treatment of Parkinson's' disease, whereas hyposexuality is a side effect of the drug-treatment of schizophrenia by classical and some atypical antipsychotics. The novel antipsychotic drug Aripiprazole, however, has a partial dopaminergic effect, causes no hyperprolactinaemia and might alter the sexual conduct of some schizophrenic patients.
Three case reports of patients with iatrogenic forensic-psychiatric relevant hypersexuality.
Case 1: Comparatively young Parkinson-Patient with sexual desinhibition, frequent visits in brothels contracting debts and sexual harassment towards women after treatment with Ropinirol.
Case 2: Chronic hebephrenic patient with homoerotic paedophilia, who only started molesting boys after changing medication from Olanzapine to Aripiprazole.
Case 3: Chronic-paranoid young schizophrenic patient with no criminal record who seriously assaulted a foreign woman short time after changing from Amisulpiride to Aripiprazole.
Hypersexuality as side effect of the treatment of Parkinson's disease is well known, it might be more important an issue, if the patient is young. Hypersexuality as side effect of the treatment with partial dopaminergic drugs should be considered in the drug treatment of schizophrenic patients.
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.
Women are at higher risk than men to develop major depressive disorder (MDD), but the mechanisms underlying the higher risk for MDD in women are unknown. There is a wealth of data showing gender differences in brain morphology and function. In addition, preclinical studies have demonstrated reciprocal relationships between ovarian hormones and serotonin neurotransmission. Thus, gender differences in brain serotonin neurotransmission are potential underlying mechanisms. In the present study, we compared normalized α-[11C]methyl-L-tryptophan brain trapping constant (α-[11C]MTrp K*; ml/g/min), an index of serotonin synthesis, between men and women with MDD.
α-[11C]MTrp K* was measured in 25 medication-free individuals with MDD (13 females and 12 males) using positron emission tomography. Comparisons of normalized α-[11C]MTrp K* values between men and women were conducted at the voxel level using Statistical Parametric Mapping 2 (SPM2) analysis.
Women with MDD displayed significantly higher (p< 0.005) normalized α-[11C]MTrp K* than men in the inferior frontal gyrus, anterior cingulate cortex (ACC), parahippocampal gyrus, precuneus and superior parietal lobule, and occipital lingual gyrus.
This finding suggests that depressive women have higher serotonin synthesis in multiple regions of the prefrontal cortex and limbic system involved with mood regulation. Gender differences in brain serotonin synthesis may be associated with higher risk for MDD in women because extra levels of tissue 5-HT could create non-physiological connections influencing changes in mood.
We examined the change in Swiss suicide rates since 1969, breaking down the rates according to the method used. The descriptive analyses of the main suicide methods are presented. The suicide rates reached a peak in the late 1970s/early 1980s and declined in more recent years. Firearm suicides and suicides by falls were the exception and sustained their upwards trend until the 1990s. Suicide by vehicle exhaust asphyxiation showed a rapid decline following the introduction of catalytic converters in motor vehicles. No substantial method substitution was observed. Suicide by poisoning declined in the 1990s but rose again following an increase in assisted suicide in somatically incurable patients. Suicide is too often regarded as a homogeneous phenomenon. With regard to the method they choose, suicide victims are a heterogeneous population and it is evident that different suicide methods are chosen by different people. A better understanding of the varying patterns of change over time in the different suicide methods used may lead to differentiated preventive strategies.
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.
We Are All Treaty People is a Canadian play for young audiences (ages eight to twelve) that addresses difficult knowledge, Elders’ story sharing, and contemporary and historical Indigenous–settler relations. This article discusses the contemporary and historical political context of the play and its production, the creation process and its narrative anchors. It argues that through a respectful, Indigenous-led creation process, and structural techniques, the play has the potential to offer hope and healing, and encourage relationships based on knowledge.
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.
We describe experimental approaches to real time examination of the microstructural evolution of Ti 6%Al 4%V upon cooling from above the beta transus (~995 °C) while imaging in the scanning electron microscope. Ti 6%Al 4%V is a two phase, α+β titanium alloy with high strength and corrosion resistance. The β →α transformation on cooling can give rise to different microstructures and properties through various thermal treatments. Fully lamellar microstructures, bi-modal microstructures, and equiaxed microstructures can each be obtained by accessing different cooling rates upon the final treatment above the beta temperature, each resulting in uniquely enhanced material properties.
Utilizing the capabilities of a heating/ tensile stage developed by Kammrath & Weiss Inc., are able to apply real-time imaging techniques in the scanning electron microscope to monitor the development of the microstructure. Annealing temperatures up to 1100 °C are attainable, with cooling rates ranging from 0.1 ° C per second to 3.3 °C per second. This has allowed us to directly observe the formation of lamellae at different annealing temperature/ cooling rate combinations to determine the lamellar microstructure width, separation, and colony size.
Patients with major depressive disorder (MDD) display cognitive deficits in acutely depressed and remitted states. Childhood maltreatment is associated with cognitive dysfunction in adults, but its impact on cognition and treatment related cognitive outcomes in adult MDD has received little consideration. We investigate whether, compared to patients without maltreatment and healthy participants, adult MDD patients with childhood maltreatment display greater cognitive deficits in acute depression, lower treatment-associated cognitive improvements, and lower cognitive performance in remission.
Healthy and acutely depressed MDD participants were enrolled in a multi-center MDD predictive marker discovery trial. MDD participants received 16 weeks of standardized antidepressant treatment. Maltreatment and cognition were assessed with the Childhood Experience of Care and Abuse interview and the CNS Vital Signs battery, respectively. Cognitive scores and change from baseline to week 16 were compared amongst MDD participants with (DM+, n = 93) and without maltreatment (DM−, n = 90), and healthy participants with (HM+, n = 22) and without maltreatment (HM−, n = 80). Separate analyses in MDD participants who remitted were conducted.
DM+ had lower baseline global cognition, processing speed, and memory v. HM−, with no significant baseline differences amongst DM−, HM+, and HM− groups. There were no significant between-group differences in cognitive change over 16 weeks. Post-treatment remitted DM+, but not remitted DM−, scored significantly lower than HM− in working memory and processing speed.
Childhood maltreatment was associated with cognitive deficits in depressed and remitted adults with MDD. Maltreatment may be a risk factor for more severe and persistent cognitive deficits in adult MDD.
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.
Proglacial environments are ideal for studying the development of soils through the changes of rocks exposed by glacier retreat to weathering and microbial processes. Carbon (C) and nitrogen (N) contents as well as soil pH and soil elemental compositions are thought to be dominant factors structuring the bacterial, archaeal and fungal communities in the early stages of soil ecosystem formation. However, the functional linkages between C and N contents, soil composition and microbial community structures remain poorly understood. Here, we describe a multivariate analysis of geochemical properties and associated microbial community structures between a moraine and a glaciofluvial outwash in the proglacial area of a High Arctic glacier (Longyearbreen, Svalbard). Our results reveal distinct differences in developmental stages and heterogeneity between the moraine and the glaciofluvial outwash. We observed significant relationships between C and N contents, δ13Corg and δ15N isotopic ratios, weathering and microbial abundance and community structures. We suggest that the observed differences in microbial and geochemical parameters between the moraine and the glaciofluvial outwash are primarily a result of geomorphological variations of the proglacial terrain.