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Recent work suggests that antihypertensive medications may be useful as repurposed treatments for mood disorders. Using large-scale linked healthcare data we investigated whether certain classes of antihypertensive, such as angiotensin antagonists (AAs) and calcium channel blockers, were associated with reduced risk of new-onset major depressive disorder (MDD) or bipolar disorder (BD).
Two cohorts of patients treated with antihypertensives were identified from Scottish prescribing (2009–2016) and hospital admission (1981–2016) records. Eligibility for cohort membership was determined by a receipt of a minimum of four prescriptions for antihypertensives within a 12-month window. One treatment cohort (n = 538 730) included patients with no previous history of mood disorder, whereas the other (n = 262 278) included those who did. Both cohorts were matched by age, sex and area deprivation to untreated comparators. Associations between antihypertensive treatment and new-onset MDD or bipolar episodes were investigated using Cox regression.
For patients without a history of mood disorder, antihypertensives were associated with increased risk of new-onset MDD. For AA monotherapy, the hazard ratio (HR) for new-onset MDD was 1.17 (95% CI 1.04–1.31). Beta blockers' association was stronger (HR 2.68; 95% CI 2.45–2.92), possibly indicating pre-existing anxiety. Some classes of antihypertensive were associated with protection against BD, particularly AAs (HR 0.46; 95% CI 0.30–0.70). For patients with a past history of mood disorders, all classes of antihypertensives were associated with increased risk of future episodes of MDD.
There was no evidence that antihypertensive medications prevented new episodes of MDD but AAs may represent a novel treatment avenue for BD.
The Early Growth and Development Study (EGDS) is a prospective adoption study of birth parents, adoptive parents and adopted children (n = 561 adoptees). The original sample has been expanded to include siblings of the EGDS adoptees who were reared by the birth mother and assessed beginning at age 7 years (n = 217 biological children), and additional siblings in both the birth and adoptive family homes, recruited when the adoptees were 8–15 years old (n = 823). The overall study aims are to examine how family, peer and contextual processes affect child and adolescent adjustment, and to examine their interplay (mediation, moderation) with genetic influences. Adoptive and birth parents were originally recruited through adoption agencies located throughout the USA following the birth of a child. Assessments are ongoing and occurred in 9 month’s intervals until the adoptees turned 3 years of age, and in 1 to 2 year intervals thereafter through age 15. Data collection includes the following primary constructs: child temperament, behavior problems, mental health, peer relations, executive functioning, school performance and health; birth and adoptive parent personality characteristics, mental health, health, context, substance use, parenting and marital relations; and the prenatal environment. Findings highlight the power of the adoption design to detect environmental influences on child development and provide evidence of complex interactions and correlations between genetic, prenatal environmental and postnatal environmental influences on a range of child outcomes. The study sample, procedures and an overview of findings are summarized and ongoing assessment activities are described.
Dishion and Patterson's work on the unique role of fathers in the coercive family process showed that fathers' coercion explained twice the variance of mothers' in predicting children's antisocial behavior and how treatment and prevention of coercion and promotion of prosocial parenting can mitigate children's problem behaviors. Using these ideas, we employed a sample of 426 divorced or separated fathers randomly assigned to Fathering Through Change (FTC), an interactive online behavioral parent training program or to a waitlist control. Participating fathers had been separated or divorced within the past 24 months with children ages 4 to 12 years. We tested an intent to treat (ITT) mediation hypothesis positing that intervention-induced changes in child problem behaviors would be mediated by changes in fathers' coercive parenting. We also tested complier average causal effects (CACE) models to estimate intervention effects, accounting for compliers and noncompliers in the treatment group and would-be compliers in the controls. Mediation was supported. ITT analyses showed the FTC obtained a small direct effect on father-reported pre–post changes in child adjustment problems (d = .20), a medium effect on pre–post changes in fathers' coercive parenting (d = .61), and a moderate indirect effect to changes in child adjustment (d = .30). Larger effects were observed in CACE analyses.
To advance research from Dishion and others on associations between parenting and peer problems across childhood, we used a sample of 177 sibling pairs reared apart since birth (because of adoption of one of the siblings) to examine associations between parental hostility and children's peer problems when children were ages 7 and 9.5 years (n = 329 children). We extended conventional cross-lagged parent–peer models by incorporating child inhibitory control as an additional predictor and examining genetic contributions via birth mother psychopathology. Path models indicated a cross-lagged association from parental hostility to later peer problems. When child inhibitory control was included, birth mother internalizing symptoms were associated with poorer child inhibitory control, which was associated with more parental hostility and peer problems. The cross-lagged paths from parental hostility to peer problems were no longer significant in the full model. Multigroup analyses revealed that the path from birth mother internalizing symptoms to child inhibitory control was significantly higher for birth parent–reared children, indicating the possible contribution of passive gene–environment correlation to this association. Exploratory analyses suggested that each child's unique rearing context contributed to his or her inhibitory control and peer behavior. Implications for the development of evidence-based interventions are discussed.
Type 2 diabetes (T2D) is a chronic disease that disproportionately affects Indigenous Australians. We have previously reported the localization of a novel T2D locus by linkage analysis to chromosome 2q24 in a large admixed Indigenous Australian pedigree (Busfield et al. (2002). American Journal of Human Genetics, 70, 349–357). Here we describe fine mapping of this region in this pedigree, with the identification of SNPs showing strong association with T2D: rs3845724 (diabetes p = 7 × 10−4), rs4668106 (diabetes p = 9 × 10−4) and rs529002 (plasma glucose p = 3 × 10−4). These associations were successfully replicated in an independent collection of Indigenous Australian T2D cases and controls. These SNPs all lie within the gene encoding ceramide synthase 6 (CERS6) and thus may regulate ceramide synthesis.
Objective: Post-stroke cognitive impairment is common, but mechanisms and risk factors are poorly understood. Frailty may be an important risk factor for cognitive impairment after stroke. We investigated the association between pre-stroke frailty and acute post-stoke cognition. Methods: We studied consecutively admitted acute stroke patients in a single urban teaching hospital during three recruitment waves between May 2016 and December 2017. Cognition was assessed using the Mini-Montreal Cognitive Assessment (min=0; max=12). A Frailty Index was used to generate frailty scores for each patient (min=0; max=100). Clinical and demographic information were collected, including pre-stroke cognition, delirium, and stroke-severity. We conducted univariate and multiple-linear regression analyses with covariates forced in (covariates included were: age, sex, stroke severity, stroke-type, pre-stroke cognitive impairment, delirium, previous stroke/transient ischemic attack) to investigate the association between pre-stroke frailty and post-stroke cognition. Results: Complete data were available for 154 stroke patients. Mean age was 68 years (SD=11; range=32–97); 93 (60%) were male. Median mini-Montreal Cognitive Assessment score was 8 (IQR=4–12). Mean Frailty Index score was 18 (SD=11). Pre-stroke cognitive impairment was apparent in 13/154 (8%) patients. Pre-stroke frailty was significantly associated with lower post-stroke cognition (Standardized-Beta=−0.40; p<0.001) and this association was independent of covariates (Unstandardized-Beta=−0.05; p=0.005). Additional significant variables in the multiple regression model were age (Unstandardized-Beta=−0.05; p=0.002), delirium (Unstandardized-Beta=−2.81; p<0.001), pre-stroke cognitive impairment (Unstandardized-Beta=−2.28; p=0.001), and stroke-severity (Unstandardized-Beta=−0.20; p<0.001). Conclusions: Pre-stroke frailty may be a moderator of post-stroke cognition, independent of other well-established post-stroke cognitive impairment risk factors. (JINS, 2019, 25, 501–506)
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
Population ageing and the global burden of dementia pose a major challenge for human societies and a priority for public health. Cognitive enhancement, i.e. the targeted amplification of core cognitive abilities, is raising increasing attention among researchers as an effective strategy to complement traditional therapeutic and assistive approaches, and reduce the impact of age-related cognitive disability. In this paper, we discuss the possible applicability of cognitive enhancement for public health purposes to mitigate the burden of population ageing and dementia. After discussing the promises and challenges associated with enhancing ageing citizens and people with cognitive disabilities, we argue that global societies have a moral obligation to consider the careful use of cognitive enhancement technologies as a possible strategy to improve individual and public health. In addition, we address a few primary normative issues and possible objections that could arise from the implementation of public health-oriented cognitive enhancement technologies.
In this editorial, we argue that current attitudes toward terminally ill patients are generally too paternalistic, and that it is wrong to assume that patients suffering from mental health issues (including depression) cannot consent to assisted suicide.
Herbicide resistance, and in particular multiple-herbicide resistance, poses an ever-increasing threat to food security. A biotype of junglerice [Echinochloa colona (L.) Link] with resistance to four herbicides, imazamox, fenoxaprop-P-ethyl, quinclorac, and propanil, each representing a different mechanism of action, was identified in Sunflower County, MS. Dose responses were performed on the resistant biotype and a biotype sensitive to all four herbicides to determine the level of resistance. Application of a cytochrome P450 inhibitor, malathion, with the herbicides imazamox and quinclorac resulted in increased susceptibility in the resistant biotype. Differential gene expression analysis of resistant and sensitive plants revealed that 170 transcripts were upregulated in resistant plants relative to sensitive plants and 160 transcripts were upregulated in sensitive plants. In addition, 507 transcripts were only expressed in resistant plants and 562 only in sensitive plants. A subset of these transcripts were investigated further using quantitative PCR (qPCR) to compare gene expression in resistant plants with expression in additional sensitive biotypes. The qPCR analysis identified two transcripts, a kinase and a glutathione S-transferase that were significantly upregulated in resistant plants compared with the sensitive plants. A third transcript, encoding an F-box protein, was downregulated in the resistant plants relative to the sensitive plants. As no cytochrome P450s were differentially expressed between the resistant and sensitive plants, a single-nucleotide polymorphism analysis was performed, revealing several nonsynonymous point mutations of interest. These candidate genes will require further study to elucidate the resistance mechanisms present in the resistant biotype.
Maternal trauma is a complex risk factor that has been linked to adverse child outcomes, yet the mechanisms underlying this association are not well understood. This study, which included adoptive and biological families, examined the heritable and environmental mechanisms by which maternal trauma and associated depressive symptoms are linked to child internalizing and externalizing behaviors. Path analyses were used to analyze data from 541 adoptive mother–adopted child (AM–AC) dyads and 126 biological mother–biological child (BM–BC) dyads; the two family types were linked through the same biological mother. Rearing mother's trauma was associated with child internalizing and externalizing behaviors in AM–AC and BM–BC dyads, and this association was mediated by rearing mothers’ depressive symptoms, with the exception of biological child externalizing behavior, for which biological mother trauma had a direct influence only. Significant associations between maternal trauma and child behavior in dyads that share only environment (i.e., AM–AC dyads) suggest an environmental mechanism of influence for maternal trauma. Significant associations were also observed between maternal depressive symptoms and child internalizing and externalizing behavior in dyads that were only genetically related, with no shared environment (i.e., BM–AC dyads), suggesting a heritable pathway of influence via maternal depressive symptoms.
In a recent essay, Harker and coauthors stated that considering herbicide resistance as a wicked problem “without clear causes or solutions” ignores what weed scientists know about the biology and management of herbicide-resistant weeds. In this response, we argue that this misrepresents what is meant by “wicked” and that the wicked problem concept is valuable in understanding the multifaceted nature of herbicide resistance as a human-caused phenomenon.
Early callous–unemotional behaviours identify children at risk for
antisocial behaviour. Recent work suggests that the high heritability of
callous–unemotional behaviours is qualified by interactions with positive
To examine whether heritable temperament dimensions of fearlessness and
low affiliative behaviour are associated with early callous–unemotional
behaviours and whether parenting moderates these associations.
Using an adoption sample (n=561), we examined pathways
from biological mother self-reported fearlessness and affiliative
behaviour to child callous–unemotional behaviours via observed child
fearlessness and affiliative behaviour, and whether adoptive parent
observed positive parenting moderated pathways.
Biological mother fearlessness predicted child callous–unemotional
behaviours via earlier child fearlessness. Biological mother low
affiliative behaviour predicted child callous–unemotional behaviours,
although not via child affiliative behaviours. Adoptive mother positive
parenting moderated the fearlessness to callous–unemotional behaviour
Heritable fearlessness and low interpersonal affiliation traits
contribute to the development of callous–unemotional behaviours. Positive
parenting can buffer these risky pathways.
A population of junglerice from Sunflower County, MS, exhibited resistance to fenoxaprop-P-ethyl. An 11-fold difference in ED50 (the effective dose needed to reduce growth by 50%) values was observed when comparing the resistant population (249 g ae ha–1) with susceptible plants (20 g ae ha–1) collected from a different field. The resistant population was controlled by clethodim and sethoxydim at the field rate. Sequencing of the acetyl coenzyme A carboxylase, which encodes the enzyme targeted by fenoxaprop-P-ethyl, did not reveal the presence of any known resistance-conferring point mutations. An enzyme assay confirmed that the acetyl coenzyme A carboxylase in the resistant population is herbicide sensitive. Further investigations with two cytochrome P450 inhibitors, malathion and piperonyl butoxide, and a glutathione-S-transferase inhibitor, 4-chloro-7-nitrobenzofurazan, did not indicate involvement of any metabolic enzymes inhibited by these compounds. The absence of a known target-site point mutation and the sensitivity of the ACCase enzyme to herbicide show that fenoxaprop-P-ethyl resistance in this population is due to a non–target-site mechanism or mechanisms.
This work provides new insights into human responses to and perceptions of sea-level rise at a time when the landscapes of north-west Europe were radically changing. These issues are investigated through a case study focused on the Channel Islands. We report on the excavation of two sites, Canal du Squez in Jersey and Lihou (GU582) in Guernsey, and the study of museum collections across the Channel Islands. We argue that people were drawn to this area as a result of the dynamic environmental processes occurring and the opportunities these created. The evidence suggests that the area was a particular focus during the Middle Mesolithic, when Guernsey and Alderney were already islands and while Jersey was a peninsula of northern France. Insularisation does not appear to have created a barrier to occupation during either the Middle or Final Mesolithic, indicating the appearance of lifeways increasingly focused on maritime voyaging and marine resources from the second half of the 9th millennium BC onwards.
Sociologists define a wicked problem as one without clear causes or solutions, and thus difficult or impossible to solve. Herbicide resistance is the epitome of a wicked problem: the causes are convoluted by myriad biological and technological factors, and are fundamentally driven by the vagaries of human decision-making. Weed scientists for decades have conducted research and developed educational programs to prevent or mitigate evolution of herbicide resistance, yet resistance is more prevalent today than ever before. If we expect to achieve success in herbicide resistance management, different approaches will be essential. The second Herbicide Resistance Summit focused on “doing something different,” bringing in rural sociologists, agricultural economists, weed scientists, and crop consultants to discuss the decision-making process itself, community-based approaches to resistance management, economics of resistance management, potential regulatory and incentive programs, new approaches to educational programs, diversification of weed management, and a call to action for everyone involved in the decision-making process.
A segment of the debate surrounding the commercialization and use of glyphosate-resistant (GR) crops focuses on the theory that the implementation of these traits is an extension of the intensification of agriculture that will further erode the biodiversity of agricultural landscapes. A large field-scale study was initiated in 2006 in the United States on 156 different field sites with a minimum 3-yr history of GR-corn, -cotton or -soybean in the cropping system. The impact of cropping system, crop rotation, frequency of using the GR crop trait, and several categorical variables on seedbank weed population density and diversity was analyzed. The parameters of total weed population density of all species in the seedbank, species richness, Shannon's H′ and evenness were not affected by any management treatment. The similarity between the seedbank and aboveground weed community was more strongly related to location than management; previous year's crops and cropping systems were also important while GR trait rotation was not. The composition of the weed flora was more strongly related to location (geography) than any other parameter. The diversity of weed flora in agricultural sites with a history of GR crop production can be influenced by several factors relating to the specific method in which the GR trait is integrated (cropping system, crop rotation, GR trait rotation), the specific weed species, and the geographical location. Continuous GR crop, compared to fields with other cropping systems, only had greater species diversity (species richness) of some life forms, i.e., biennials, winter annuals, and prostrate weeds. Overall diversity was related to geography and not cropping system. These results justify further research to clarify the complexities of crops grown with herbicide-resistance traits to provide a more complete characterization of their culture and local adaptation to the weed seedbank.