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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.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
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.
Results
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.
Conclusions
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.
Yoga may pose a promising complementary therapy in the multimodal treatment of schizophrenia spectrum disorders (SSD). However, to date, no studies have qualitatively examined the patients’ experience of practising Yoga.
Objectives
This qualitative study aimed to assess the mechanisms and processes of Yoga-based group therapy (YBGT) for in-patients with SSD by exploring their subjective experiences.
Methods
Twenty-five semi-structured interviews were conducted with in-patients with SSD after they participated in a YBGT session. Interviews were transcribed, coded by two independent researchers, and analysed using an inductive thematic approach. The research team collaboratively discussed emerging categories to reduce redundancy and form meaningful themes and subthemes.
Results
The analysis revealed seven main themes. YBGT was perceived as feasible and focusing on individual adaptation, captured by the theme ‘inclusivity’. Nevertheless, participants encountered ‘challenges’; thus, physical limitations need to be considered. While practising together, participants experienced ‘interconnectedness’ and developed a ‘mindful stance’ as they accepted their limitations and adapted exercises with self-compassion. Following the flow of asanas required physical persistence, which ultimately led many participants to experience ‘confidence’ and ‘relaxation’. YBGT affected ‘symptom representation’ as heightened awareness led participants to notice impeding as well as improved symptoms.
Conclusions
YBGT seemed to have various promising effects on in-patients with SSD. Future research should examine to what extent these effects can be sustained and how the mindful approach during YBGT can be transferred to areas outside the Yoga class. Furthermore, a randomised-controlled trial could investigate the effectiveness of a manualised YBGT.
Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness.
Methods
A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects.
Results
Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF.
Conclusions
Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.
Based on evidences in molecular neuroimaging, postmortem and genetic studies, impaired serotonergic neurotransmission has been implicated with affective disorders. Moreover, a growing number of evidences showed strong interrelations within the serotonergic system suggesting a common mechanism in the modulation of receptor and transporter densities.
Objective
Here we directly investigated the regional expression of the 5-HT1A, 5-HT2A and 5-HTT using PET and the three highly selective and specific radioligands [carbonyl-11C]WAY-100635, [18F]Altanserin and [11C]DASB in healthy subjects.
Methods
A total of 55 healthy subjects (5-HT1A: 36 subjects, 18 males, age = 26.0 ± 4.9; 5-HT2A: 19 subjects, 11 males, age = 28.2 ± 5.9; 5-HTT: 8 males, age = 28.12 ± 3.6) were included in this study. Binding potential (BPND) values were quantified according to the AAL parcellation scheme.
Results
BPND values averaged over both hemispheres ranged from 0.40–6.35 for the 5-HT1A receptor; 0.01–2.01 for the 5-HT2A receptor and 0.09–2.05 for the 5-HTT, respectively. There was a specific topological pattern according to the ratio between the 5-HT1A, 5-HT2A receptors and 5-HTT (“fingerprints”).
Conclusions
Such information can be essential for detecting potential local alterations in the ratio between different binding proteins on a network level in pathological conditions.
Moreover, these data might provide further insight in area-specific effects of frequently prescribed selective serotonin re-uptake inhibitors (SSRI):
1) due to the distinct local receptor and transporter availability;
2) SSRI application alters the postsynaptic receptor expression and thus;
3) leads to a modified interaction of inhibitory and exhibitory receptors.
An outbreak of measles in the Netherlands in 2013–2014 provided an opportunity to assess the effect of MMR vaccination on severity and infectiousness of measles.
Measles is notifiable in the Netherlands. We used information on vaccination, hospitalisation, complications, and most likely source(s) of infection from cases notified during the outbreak. When a case was indicated as a likely source for at least one other notified case, we defined it as infectious. We estimated the age-adjusted effect of vaccination on severity and infectiousness with logistic regression.
Of 2676 notified cases, 2539 (94.9%) were unvaccinated, 121 (4.5%) were once-vaccinated and 16 (0.6%) were at least twice-vaccinated; 328 (12.3%) cases were reported to have complications and 172 (6.4%) cases were hospitalised. Measles in twice-vaccinated cases led less often to complications and/or hospitalisation than measles in unvaccinated cases (0% and 14.5%, respectively, aOR 0.1 (95% CI 0–0.89), P = 0.03). Of unvaccinated, once-vaccinated and twice-vaccinated cases, respectively, 194 (7.6%), seven (5.1%) and 0 (0%) were infectious. These differences were not statistically significant (P > 0.05).
Our findings suggest a protective effect of vaccination on the occurrence of complications and/or hospitalisation as a result of measles and support the WHO recommendation of a two-dose MMR vaccination schedule.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Methods
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
Results
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Conclusions
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Measles is a notifiable disease, but not everyone infected seeks care, nor is every consultation reported. We estimated the completeness of reporting during a measles outbreak in The Netherlands in 2013–2014. Children below 15 years of age in a low vaccination coverage community (n = 3422) received a questionnaire to identify measles cases. Cases found in the survey were matched with the register of notifiable diseases to estimate the completeness of reporting. Second, completeness of reporting was assessed by comparing the number of susceptible individuals prior to the outbreak with the number of reported cases in the surveyed community and on a national level.
We found 307 (15%) self-identified measles cases among 2077 returned questionnaires (61%), of which 27 could be matched to a case reported to the national register; completeness of reporting was 8.8%. Based on the number of susceptible individuals and number of reported cases in the surveyed community and on national level, the completeness of reporting was estimated to be 9.1% and 8.6%, respectively. Estimating the completeness of reporting gave almost identical estimates, which lends support to the credibility and validity of both approaches. The size of the 2013–2014 outbreak approximated 31 400 measles infections.
The objective of this study was to examine temporal trends in mental health visits to the emergency department (ED) and to determine differences in length of stay (LOS) between mental health visits and visits for non-mental health conditions.
Methods
A population-based retrospective study was conducted for patients who visited the ED of an academic hospital located in Toronto, ON, between fiscal years 2012 and 2016. Trends in the number of visits and descriptive statistics were calculated for both mental health and non-mental health groups. Quantile regression was used to compare the median and 90th percentile LOS.
Results
In five years, the absolute increase in the number of mental health visits to the ED was 55.7%. The 90th percentile LOS was similar for mental and non-mental health visits that were internally transferred (10.7 hours v. 8.3 hours) but significantly higher for those who were discharged (11.4 hours v. 7.3 hours), admitted (52.6 hours v. 29.3 hours), and externally transferred (21.9 hours v. 10.0 hours). After adjusting for other variables, the 90th percentile LOS was 3.3 hours longer for mental health visits resulting in discharge (p<0.001), 24.5 hours longer for those admitted (p<0.001), and 12.7 hours longer for those externally transferred (p<0.001).
Conclusion
The number of mental health visits to the ED is linearly increasing over time, and the LOS in the ED is significantly longer for mental health visits for almost all discharge dispositions. Thus, systematic changes are needed to address the ED capacity to provide care for the growing mental health population.
Risk populations for HIV infections tend to neglect condom use, making alternative preventive approaches necessary. Accordingly, we modelled the risk of sexual HIV transmission for condom use vs. use of rapid diagnostic test (RDT) systems with subsequent exclusion of potential sexual partners with a correctly or falsely positive test from unprotected sex with and without the use of HIV pre-exposure prophylaxis (PrEP) in a bio-statistical approach. We combined a previously described model of transmission risk for HIV-exposed individuals with a newly suggested model of risk of HIV exposure for sexually active HIV-negative individuals. The model was adapted for several stages of infection and different strategies of HIV infection prevention.
HIV prevention with RDTs can reduce the transmission risk by up to 97% compared with having sex without any prevention and up to 80% compared with condom use. Nevertheless, RDT-based prevention strategies demonstrate a lack of protection in several stages of infection; in particular, RNA-based RDT systems may fail under treatment. RDT-based pre-screening of potential sex partners prior to unprotected sexual contacts substantially reduces HIV transmission risk. Combination of different prevention strategies is advisable for high-risk groups.
Interdisciplinary collaboration is a critical component of translation, dissemination, implementation, and improvement (TDII) science. Yet, little is known about effective frameworks and practices regarding interdisciplinary research in TDII.
Methods
This study drew on data collected from an expert panel during a regional symposium.
Results
Findings highlight facilitators and barriers to stimulating interdisciplinary TDII research in different domains: intrapersonal, interpersonal, organizational, power and hierarchy, physical environment, and communication and language.
Conclusions
Findings have significant implications for TDII of clinical practices.
Introduction: Non-trauma centers (NTC) and community hospitals commonly deliver medical care during the “golden hour” of trauma, which has significant implications on the health outcomes of patients. The Niagara Health System (NHS) and its 3 community NTC hospitals provide trauma care to over 100 patients annually during this critical period. NTCs lack standardized resources commonly found in trauma centers. Checklists and bundles have been effective in streamlining process to ensure health care providers provide the right care, at the right time and address critical points during patient care. A trauma care bundle was designed and implemented in the NHS as a means to improve trauma care and patient outcomes. Methods: A quality improvement (QI) approach was used to design, implement and evaluate a trauma care bundle at one of the NHS’s community hospitals. These interventions were adapted and modified for community trauma care purposes. We piloted the trauma care bundle using rapid cycle improvements, known as Plan-Do-Study-Act (PDSA) cycles. We assessed outcome and process measures through a chart audit of all trauma care patients in the NHS from July 2015-December 2015. A safety attitudes questionnaire (SAQ) was administered to health system staff who were involved in the pilot to assess balancing measures. Results: Improvements to the bundle and its implementation from 4 PDSA cycles resulted in increased utilization. This continuous monitoring of the bundle and ongoing, conscious efforts to improve the intervention were used to spread and scale across all 3 sites of the NHS. 30% of patients received the trauma care bundle during phase 1 of the pilot from July 1- October 31, 2015. We are presently analyzing preliminary data to understand how the trauma care bundle impacts health outcomes and process and will present a comparative analysis between patient groups. Conclusion: Trauma care bundles may foster safer and more efficient patient care in community hospitals where the golden hour of trauma often occurs. This community trauma care bundle shows promising results for streamlining the care process to ensure patients receive appropriate care during the golden hour. Spread and scale of this bundle across other community hospitals will likely yield similar improvements in patient care.
The control of Johne's disease requires the identification of Mycobacterium avium ssp. paratuberculosis (MAP)-positive herds. Boot swabs and liquid manure samples have been suggested as an easy-to-use alternative to sampling individual animals in order to diagnose subclinical Johne's disease at the herd level, but there is a need to evaluate performance of this approach in the field. Using a logistic regression model, this study aimed to calculate the threshold level of the apparent within-herd prevalence as determined by individual faecal culture, thus allowing the detection of whether a herd is MAP positive. A total of 77 boot swabs and 75 liquid manure samples were taken from 19 certified negative and 58 positive dairy herds. Faecal culture, three different polymerase chain reaction (PCR) methods and the combination of faecal culture with PCR were applied in order to detect MAP. For 50% probability of detection, a within-herd prevalence threshold of 1·5% was calculated for testing both matrices simultaneously by faecal culture and PCR, with the threshold increased to 4·0% for 90% probability of detection. The results encourage the use of boot swabs or liquid manure samples, or a combination both, for identifying MAP-positive herds and, to a certain extent, for monitoring certified Johne's disease-negative cattle herds.
The impact of haematozoan infection on host fitness has received substantial attention since Hamilton and Zuk posited that parasites are important drivers of sexual selection. However, short-term studies testing the assumption that these parasites consistently reduce host fitness in the wild have produced contradictory results. To address this complex issue, we conducted a long-term study examining the relationship between naturally occurring infection with Haemoproteus and Plasmodium, and lifetime reproductive success and survival of Mountain White-crowned Sparrows. Specifically, we tested the hypothesis that birds infected with haematozoan parasites have reduced survival (as determined by overwinter return rates) and reproductive success. Contrary to expectation, there was no relationship between Haemoproteus and Plasmodium infection and reproduction or survival in males, nor was there a relationship between Plasmodium infection and reproduction in females. Interestingly, Haemoproteus-infected females had significantly higher overwinter return rates and these females fledged more than twice as many chicks during their lifetimes as did uninfected females. We discuss the impact of parasitic infections on host fitness in light of these findings and suggest that, in the case of less virulent pathogens, investment in excessive immune defence may decrease lifetime reproduction.
Two independent prospective longitudinal studies that cumulatively spanned the age interval from 4 years to 14 years used multiwave designs to investigate developmental associations between language and behavioral adjustment (internalizing and externalizing behavior problems). Altogether 224 children, their mothers, and teachers provided data. Series of nested path analysis models were used to determine the most parsimonious and plausible paths among the three constructs over and above stability in each across age and their covariation at each age. In both studies, children with poorer language skills in early childhood had more internalizing behavior problems in later childhood and in early adolescence. These developmental paths between language and behavioral adjustment held after taking into consideration children's nonverbal intellectual functioning, maternal verbal intelligence, education, parenting knowledge, and social desirability bias, as well as family socioeconomic status, and they applied equally to girls and boys.