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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
This paper links banking system development to the colonial and legal history of African countries. Based on a sample of 40 African countries from 2000 to 2018, our empirical findings show a significant dependence of current financial institutions on the inherited legal origin and the colonization type. Findings also reveal that current financial legal institutions are not major determinants of banking system development, and that institutional development and governance quality are more important. A high share of government spending relative to GDP also positively affects banking system development in African countries.
Older adults exhibit heightened vulnerability for alcohol-related health impairments. Increases in the proportion of older adults within the European Union’s total population and prevalence rates of alcohol use disorders in this age group are being observed. This large scale international study was conducted to identify those older adults with an increased risk to engage in hazardous drinking behaviour.
Socio-demographic, socio-economic, personality characteristics (Big Five Inventory, BFI-10), and alcohol consumption patterns of 13,351 individuals from 12 different European countries, collected by the Survey of Health, Aging, and Retirement in Europe, were analyzed using regression models.
Age, nationality, years of education, as well as personality traits, were significantly associated with alcohol intake. For males, extraversion predicted increased alcohol intake (RR = 1.11, CI = 1.07–1.16), whereas conscientiousness (RR = 0.93, CI = 0.89–0.97), and agreeableness (RR = 0.94, CI = 0.90–0.99), were associated with a reduction. For females, openness to new experiences (RR = 1.11, CI = 1.04–1.18) predicted increased alcohol intake. Concerning excessive drinking, personality traits, nationality, and age-predicted consumption patterns for both sexes: Extraversion was identified as a risk factor for excessive drinking (OR = 1.15; CI = 1.09–1.21), whereas conscientiousness was identified as a protective factor (OR = 0.87; CI = 0.823–0.93).
Hazardous alcohol consumption in the elderly was associated with specific personality characteristics. Preventative measures, crucial in reducing deleterious health consequences, should focus on translating the knowledge of the association of certain personality traits and alcohol consumption into improved prevention and treatment.
Suicide risk in patients is markedly elevated during psychiatric inpatient care, as well as after discharge. However, it is unclear whether, and to what extent, this increased suicide risk varies between sex. Thus, the aim of this study was to analyze sex differences for suicides during and after psychiatric hospitalization in various countries.
National suicide mortality rates and inpatient-related suicide rates (three intervals: during psychiatric inpatient treatment, 1 month, and 1 year after discharge) from 12 countries for 2000–2016 were analyzed, and a logistic model was used to quantify the effect of sex.
Persons admitted to or discharged from psychiatric inpatient care exhibited significantly increased rates of suicide compared to those in the general population. Furthermore, increase of suicide risk was significantly higher for females than for males for all investigated time intervals (inpatient suicide odds ratio [OR] 1.85; suicide within 1 month after discharge—OR 1.94; suicide within 1 year after discharge—OR 2.04).
Analysis confirmed the time during and after psychiatric inpatient care to be significantly associated with an elevated risk for suicide. Further, a significant sex effect was observed, with females in this population being at a proportionally higher risk for suicide during psychiatric inpatient treatment as well as the year following discharge. Our study implicates that more effective suicide preventive measures during inpatient stay, focusing on female patients, are needed.
Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.
We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.
We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.
This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).
Pain has been qualified under four categories: nociception, perception of pain, suffering, and pain behaviors. Most of the literature on migraine has devoted attention to the first two. The aim of the present cohort study was to investigate patients with migraine enrolled at a tertiary care unit to study suffering and mental pain and identify potential risk factors for migraine.
An observational cross-sectional study was carried out on patients with chronic migraine (CM) and episodic migraine (EM), and healthy subjects (HS). The three groups were matched for age and sex. A comprehensive assessment of migraine disability, pain, psychiatric disorders, psychosomatic syndromes, depressive and anxious symptoms, euthymia, psychosocial variables, mental pain, and pain-proneness (PP) was performed.
Three hundred subjects were enrolled (100 CM, 100 EM, and 100 HS). Based on the multiple regression analyses, those presenting PP (social impairment: odds ratio [OR] = 3.59, 95% confidence interval [CI] = 1.14-11.29; depressive symptoms: OR = 3.82, 95% CI = 1.74-8.41) were more likely to be CM than HS. Those with higher levels of PP (social impairment: OR = 4.04, 95% CI = 1.60-10.22; depressive symptoms: OR = 2.02, 95% CI = 1.26-3.24) were more likely to be EM than HS. Those presenting higher levels of mental pain were more likely to be CM than EM (OR = 1.45, 95% CI = 1.02-2.07).
Migraine is an unpleasant sensory and emotional experience associated with psychosocial manifestations that might contribute to the level of suffering of the individuals. Mental pain resulted to be the variable that most differentiated patients with CM from EM.
The aim of this study was to evaluate a case-mix system to classify inpatients with mental disorders in Germany by means of self-report and expert-rated instruments. The use of case-mix systems enhances the transparency of performance and cost structure and can thus improve the quality of mental health care. We analysed a consecutive sample of 1677 inpatients with mental disorders from 11 hospitals using regression tree analysis. The model assigns patients to 17 groups, accounting for 17% of the variance for duration of stay. Patients with eating disorders had a longer duration of stay than patients with anxiety disorder, duration of mental illness of less than 3–5 years, lower levels of interpersonal problems and higher occupational position. The results showed that besides diagnosis, variables such as duration of illness and interpersonal problems are important for classifying inpatients with mental disorders. The results of the study should be critically reviewed regarding the empirical results of other studies and the appropriateness of case group concepts for inpatients with mental disorders.
Schizophrenia is characterized by poor social interaction contributing to poor functional outcome. Particularly nonverbal communication is disturbed. Neural correlates of impaired gesturing are currently unclear. We thus tested functional correlates of gesturing in schizophrenia patients and healthy controls.
We tested 22 patients and 25 controls with an event-related fMRI (instructed delay) paradigm to dissociate brain activation during planning and execution of meaningful (e.g. use scissors) and meaningless novel gestures. Preprocessing included realignment, coregistration, normalization and spatial smoothing. We used a two stage mixed effects model for statistical analysis. Conditions were contrasted against a linguistic control within and between groups. We correlated psychopathological characteristics with beta estimates of brain areas with between group effects.
During planning and execution of both gesture subtypes both groups activated brain areas of the ventral and dorsal stream. However patients’ activity was less prominent and more left lateralized. During planning patients showed additional activity in bilateral temporal poles, amygdala and hippocampus associated with the level of delusions. Furthermore patients had increased dorsomedial prefrontal cortex and precuneus activity when planning meaningless gestures.
During the planning of meaningless gestures we detected aberrant activation of limbic structures in patients typically implicated in delusion formation, which also correlated with current severity of delusions. Moreover, planning of meaningless gestures relied on areas relevant for strategic control and attention. These results argue for a pathologic search for meaning in neutral gestures and increased control effort during planning of meaningless gestures in schizophrenia.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Dementia represents one of the impending global health challenges, and low and middle-income countries (LMICs) are projected to greatly contribute to the rising dementia global burden. Currently, there is a lack of pharmacological treatment for dementia and therefore research efforts have focused on prevention, with the identification of early lifestyle, demographic and nutritional risk factors. In particular, diet may be an important modifiable risk factor for maintenance of cognitive health in later life. There are plausible suggestions to support the synergistic effects of certain nutrients, such as polyphenols, unsaturated fats and antioxidant vitamins, in having a beneficial role in the modulation of oxidative stress and neuro-inflammation – processes associated with cognitive decline. Therefore, the aim of this systematic review was to evaluate the current evidence on nutritional interventions for the prevention of dementia in developing economies in East Asia.
Materials and Methods
Four comprehensive medical databases were searched from inception until February 2019: MEDLINE, EMBASE, PsycINFO and Scopus. The literature search was restricted to randomised clinical trials [RCTs], conducted in adult humans [ ≥ 18 years], assessing the effect of nutritional interventions on cognitive performance, and / or incidence of mild cognitive impairment [MCI] or dementia. The outcome of interest for the meta-analysis was:  global cognitive performance and  domain specific cognitive performance. Data was pooled by random model analysis and estimates of effect size were given for each domain and sub-categorised according to the type of nutritional intervention.
Twenty-two RCTs were included, of which, sixteen studies showed significant beneficial effects in favor of the nutritional intervention based on single neuropsychological test scores and / or scores of global cognitive assessment tools. Sixteen studies had sufficient data reported for meta-analysis, and marginally significant beneficial effects were found on global cognitive performance in elderly for micro-nutrient supplementation [n = 4 studies, n = 451 participants, std mean difference: 0.41 [-0.03; 0.84], p = 0.07], and EPA / DHA supplementation [n = 4 studies, n = 373 participants, std mean difference 0.57 [-0.01; 1.14], p = 0.06].
Several promising strategies, such as B-vitamin supplementation, EPA / DHA supplementation and nutrition and lifestyle counselling interventions, seem to be able to decrease age-related cognitive decline in East Asia. Large, good quality, long term trials are needed to confirm these findings, to further evaluate the role of nutritional interventions on cognitive function and to identify if these interventions are feasible and effective to decrease dementia incidence in developing economies, like East Asia.
Social reserve such as having close friends helps promoting activity engagement in old age. Activity engagement in turn contributes to the accumulation of cognitive reserve and is a key predictor for maintaining executive functioning in aging. We investigated the mediating role of leisure activity engagement in the longitudinal relation between close friends and subsequent change in executive functioning as measured through performance changes in the Trail Making Test (TMT).
Design, Setting, and Participants:
Longitudinal study with 897 older adults tested in two waves 6 years apart, analyzed using latent change score modeling.
TMT parts A and B, leisure activity engagement, and close friends.
A larger number of close friends in the first wave of data collection was related to a higher frequency of leisure activities in the first wave. A higher frequency of leisure activities in the first wave significantly predicted a smaller subsequent increase in TMT completion time from the first to the second wave (i.e. a smaller decline in executive functioning). Importantly, 41.3% of the longitudinal relation between a larger number of close friends in the first wave and a smaller subsequent increase in TMT completion time (i.e. a smaller decline in executive functioning) was mediated via a higher frequency of leisure activities in the first wave.
Social reserve such as having close friends may help promoting activity engagement in old age. By enhancing individuals’ cognitive reserve, this activity engagement may finally result in smaller subsequent decline in executive functioning in aging.
Identifying risk factors of individuals in a clinical-high-risk state for psychosis are vital to prevention and early intervention efforts. Among prodromal abnormalities, cognitive functioning has shown intermediate levels of impairment in CHR relative to first-episode psychosis and healthy controls, highlighting a potential role as a risk factor for transition to psychosis and other negative clinical outcomes. The current study used the AX-CPT, a brief 15-min computerized task, to determine whether cognitive control impairments in CHR at baseline could predict clinical status at 12-month follow-up.
Baseline AX-CPT data were obtained from 117 CHR individuals participating in two studies, the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP) and the Understanding Early Psychosis Programs (EP) and used to predict clinical status at 12-month follow-up. At 12 months, 19 individuals converted to a first episode of psychosis (CHR-C), 52 remitted (CHR-R), and 46 had persistent sub-threshold symptoms (CHR-P). Binary logistic regression and multinomial logistic regression were used to test prediction models.
Baseline AX-CPT performance (d-prime context) was less impaired in CHR-R compared to CHR-P and CHR-C patient groups. AX-CPT predictive validity was robust (0.723) for discriminating converters v. non-converters, and even greater (0.771) when predicting CHR three subgroups.
These longitudinal outcome data indicate that cognitive control deficits as measured by AX-CPT d-prime context are a strong predictor of clinical outcome in CHR individuals. The AX-CPT is brief, easily implemented and cost-effective measure that may be valuable for large-scale prediction efforts.
An early evaluation of a product along with the consideration of life phase specific actor(s) and environment(s) can help greatly to gain an understanding of the product's behaviour and interactions. Virtual Reality (VR) can help designers to examine later life situations of a product by means of use case scenarios. However, preparing a VR-scene is still a time-consuming and cumbersome task. A model based approach that uses behaviour models of SysML to describe a VR-scene can reduce the preparation efforts. Such an approach is helpful if it allows the reuse of already described VR-scenes or their contents. This paper talks about the reusability of SysML behaviour models that constitute a VR-scene. This reusability can only be achieved by the generic definition of model interfaces. Therefore, a new modelling approach is presented to facilitate the reuse of SysML behaviour models to form different use cases of a product in VR. This approach also talks about the interface definitions and the management of variants of SysML models. The presented approach is elaborated by an example model that contains variants and uses instances to build different use cases.
OBJECTIVES/SPECIFIC AIMS: We developed a multilevel hierarchical statistical model which describes the association of prophylactic interventions to patient PONV risk, and provides an intuitive summary for anesthesiologists to understand how well they are adhering to PONV guidelines. METHODS/STUDY POPULATION: Accepted PONV risk factors as well as preventative interventions to reduce the PONV risk, (e.g. total intravenous anesthesia or pharmacological prophylaxis) are retrieved from the electronic medical record (EMR). Risk is regressed against interventions. Fig 1, Panel A visualizes adherence for an individual provider by plotting anesthesia cases, with PONV risk in the x-axis and the number of interventions in the y-axis. Fig 1, Panel B shows a “Jitterplot”, jittering individual cases, which would otherwise plot onto the same coordinates (Panel A). The distribution of the number of interventions in each risk category is better summarized in Fig 1 Panel C by overlaying a violin plot onto the “Jitterplot”. Finally, a fitted regression line provides a summary measure for the individual provider’s risk-adjusted utilization of PONV prophylaxis in Fig 1, Panel D. The model can control for confounders and interactions, such as patient or procedure characteristics, such as supervision by attending physicians, institutional culture, and surgical procedure. RESULTS/ANTICIPATED RESULTS: Fig. 2, Panel A demonstrates good adherence. The provider responded to increased risk with additional interventions leading to a steep regression line. Less discriminate administration of prophylaxis is shown in Fig 2, Panel B. The graphical representation of our proposed measure of individual provider performance is intuitive, allowing us to compare adherence of two distinct groups of providers (light lines) and institutional averages (dark lines) as shown in Fig 2, Panel C. Controlling for known risk factors and potential confounders renders the assessment irrepudiable. The rigorous statistical approach allows for multi-level modeling and comparative effectiveness research, realistically evaluating process changes and interventions like CDS in the hierarchical structure of contemporary healthcare delivery. DISCUSSION/SIGNIFICANCE OF IMPACT: The strength of our novel measure of individual provider performance is its generalizability to other care settings, as well as the intuitive graphical representation of risk-adjusted individual performance. However, accuracy, precision and validity, sensitivity to system perturbations (like the implementation of CDS), and acceptance among providers remain to be evaluated. Fig 1. Risk-Adjusted Utilization of Antiemetic Prophylaxis Fig 2. Comparing Performance between Provider Groups
To determine whether colonization with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) predicts the risk for subsequent infection and impacts carbapenem-consumption and outcome in intensive care unit (ICU) patients.
Prospective cohort study.
The 2 ICUs in the University Hospital Basel in Switzerland.
All patients admitted to the 2 ICUs providing mechanical ventilation and an expected ICU stay >48 hours.
Patients were routinely screened for ESBL-PE carriage by rectal swab on admission. Competing risk regression analyses were applied to calculate hazard ratios (HRs) for infection with ESBL-PE and mortality. Length of hospital stay, length of ICU stay, and duration of carbapenem exposure were compared using the Mann-Whitney U test.
Among 302 patients, 24 (8.0%) were colonized with ESBL-PE on ICU admission. Infections with ESBL-PE occurred in 4 patients, of whom 3 (75%) were identified as ESBL-PE colonized on admission. ESBL-PE colonization on admission was associated with subsequent ESBL-PE infection (hazard ratio [HR], 25.52; 95% confidence interval [CI], 2.40–271.41; P = .007) and exposure to carbapenems (HR, 2.42; 95% CI, 1.01–5.79; P = .047), whereas duration of carbapenem exposure did not differ in relation to ESBL-PE colonization (median, 7 days [IQR, 3–8 days] vs median, 6 days [IQR 3–9 days]; P = 0.983). Patients colonized with ESBL-PE were not at increased risk for death overall (HR, 1.00; 95% CI, 0.44–2.30; P = .993) or death attributable to infection (HR, 1.20; 95% CI, 0.28–5.11; P = .808).
Screening strategies for detection of ESBL-PE colonization on ICU admission may allow the identification of patients at highest risk for ESBL-PE infection and the correct allocation of empiric carbapenem treatment.
The Western diet is characterized by high meat consumption, which negatively affects the environment and human health. Transitioning toward eating more plant-based products in Western societies has been identified as a key instrument to tackle these problems. However, one potential concern is that radically reducing meat in the current diet might lead to deficiencies in nutritional intake. In this paper, we explore a scenario in which meat consumption in Sweden is reduced by 50% and replaced by domestically grown grain legumes. We quantify and discuss the implications for nutritional intake on population level, consequences for agricultural production systems and environmental performance. The reduction in meat consumption is assumed to come primarily from a decrease in imported meat. We use data representing current Swedish conditions including the Swedish dietary survey, the Swedish food composition database, Statistics Sweden and existing life cycle assessments for different food items. At population level, average daily intake of energy and most macro- and micro-nutrients would be maintained within the Nordic Nutrition Recommendations after the proposed transition (e.g., for protein, fat, zinc, vitamin B12 and total iron). The transition would also provide a considerable increase in dietary fiber and some increase in folate intake, which are currently below the recommended levels. The transition scenario would increase total area of grain legume cultivation from 2.2% (current level) to 3.2% of Swedish arable land and is considered technically feasible. The climate impact of the average Swedish diet would be reduced by 20% and the land use requirement by 23%. There would be a net surplus of approximately 21,500 ha that could be used for bioenergy production, crop production for export, nature conservation, etc. Implementation of this scenario faces challenges, such as lack of suitable varieties for varying conditions, lack of processing facilities to supply functional legume-based ingredients to food industries and low consumer awareness about the benefits of eating grain legumes. In sum, joint efforts from multiple actors are needed to stimulate a decrease in meat consumption and to increase cultivation and use of domestically grown grain legumes.