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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 manuscript describes the institutional and clinical considerations that apply to the question of whether to mandate opioid dose reduction in patients who have received opioids long-term. It describes how a calamitous rise in addiction and overdose involving opioids has both led to a clinical recalibration by healthcare providers, and to strong incentives favoring forcible opioid reduction by policy making agencies. Neither the 2016 Guideline issued by the Centers for Disease Control and Prevention nor clinical evidence can justify or promote such policies as safe or effective.
As approximately one-third of peer-victimized children evidence heightened aggression (Schwartz, Proctor, & Chien, 2001), it is imperative to identify the circumstances under which victimization and aggression co-develop. The current study explored two potential moderators of victimization–aggression linkages: (a) attentional bias toward cues signaling threat and (b) attentional bais toward cues communicating interpersonal support. Seventy-two fifth- and sixth-grade children (34 boys; Mage = 11.67) were eye tracked while watching video clips of bullying. Each scene included a bully, a victim, a reinforcer, and a defender. Children's victimization was measured using peer, parent, and teacher reports. Aggression was measured using peer reports of overt and relational aggression and teacher reports of aggression. Victimization was associated with greater aggression at high levels of attention to the bully. Victimization was also associated with greater aggression at low attention to the defender for boys, but at high attention to the defender for girls. Attention to the victim was negatively correlated with aggression regardless of victimization history. Thus, attentional biases to social cues integral to the bullying context differentiate whether victimization is linked to aggression, necessitating future research on the development of these biases and concurrent trajectories of sociobehavioral development.
Prenatal maternal depression and a multilocus genetic profile of two susceptibility genes implicated in the stress response were examined in an interaction model predicting negative emotionality in the first 3 years. In 179 mother–infant dyads from the Maternal Adversity, Vulnerability, and Neurodevelopment cohort, prenatal depression (Center for Epidemiologic Studies Depressions Scale) was assessed at 24 to 36 weeks. The multilocus genetic profile score consisted of the number of susceptibility alleles from the serotonin transporter linked polymorphic region gene (5-HTTLPR): no long-rs25531(A) (LA: short/short, short/long-rs25531(G) [LG], or LG/LG] vs. any LA) and the dopamine receptor D4 gene (six to eight repeats vs. two to five repeats). Negative emotionality was extracted from the Infant Behaviour Questionnaire—Revised at 3 and 6 months and the Early Child Behavior Questionnaire at 18 and 36 months. Mixed and confirmatory regression analyses indicated that prenatal depression and the multilocus genetic profile interacted to predict negative emotionality from 3 to 36 months. The results were characterized by a differential susceptibility model at 3 and 6 months and by a diathesis–stress model at 36 months.
Disorganized attachment is an important early risk factor for socioemotional problems throughout childhood and into adulthood. Prevailing models of the etiology of disorganized attachment emphasize the role of highly dysfunctional parenting, to the exclusion of complex models examining the interplay of child and parental factors. Decades of research have established that extreme child birth weight may have long-term effects on developmental processes. These effects are typically negative, but this is not always the case. Recent studies have also identified the dopamine D4 receptor (DRD4) as a moderator of childrearing effects on the development of disorganized attachment. However, there are inconsistent findings concerning which variant of the polymorphism (seven-repeat long-form allele or non–seven-repeat short-form allele) is most likely to interact with caregiving in predicting disorganized versus organized attachment. In this study, we examined possible two- and three-way interactions and child DRD4 polymorphisms and birth weight and maternal caregiving at age 6 months in longitudinally predicting attachment disorganization at 36 months. Our sample is from the Maternal Adversity, Vulnerability and Neurodevelopment project, a sample of 650 mother–child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 was obtained with buccal swabs and categorized according to the presence of the putative allele seven repeat. Macroanalytic and microanalytic measures of maternal behavior were extracted from a videotaped session of 20 min of nonfeeding interaction followed by a 10-min divided attention maternal task at 6 months. Attachment was assessed at 36 months using the Strange Situation procedure, and categorized into disorganized attachment and others. The results indicated that a main effect for DRD4 and a two-way interaction of birth weight and 6-month maternal attention (frequency of maternal looking away behavior) and sensitivity predicted disorganized attachment in robust logistic regression models adjusted for social demographic covariates. Specifically, children in the midrange of birth weight were more likely to develop a disorganized attachment when exposed to less attentive maternal care. However, the association reversed with extreme birth weight (low and high). The DRD4 seven-repeat allele was associated with less disorganized attachment (protective), while non–seven-repeat children were more likely to be classified as disorganized attachment. The implications for understanding inconsistencies in the literature about which DRD4 genotype is the risk direction are also considered. Suggestions for intervention with families with infants at different levels of biological risk and caregiving risk are also discussed.
Fresh water is vital for the function of all terrestrial ecosystems – the flora and the fauna that make up those ecosystems, and, of course, for humans. Humanity relies on water not just for drinking, but also for food production, dealing with waste, providing energy and transport, to name but a few. To meet its needs humanity harnesses water through dams, irrigation networks, and pumps and pipes that supply drinking water and remove wastes. It is estimated that humanity consumes 1000–1700 m3 of the globe's surface and groundwater resources per year; that is between 22% and 150% of the annual global supply of fresh water (Hoekstra & Wiedmann 2014). This proportion is likely to increase as the global human population increases in the next 30 years and the demands for water in developing countries catches up with that of developed countries. According to the Intergovernmental Panel on Climate Change, changes in climate will amplify existing stress on water availability and will exacerbate different forms of water pollution, with impacts on ecosystems, human health, and water system reliability in large parts of the world (Stocker et al. 2013).
For a number of years, academics have tried to understand the linkages between the water system and human needs and the impacts that anthropogenic activities have on the water system itself. In the early days, the scientific approach sat within individual domains (e.g. hydrology for the water cycle (Thompson 1999); ecology for ecological impacts of water pollution (Abel 1996)). Given the complexity of the interactions and the centrality of humans in the water environment, more recently interdisciplinary approaches have come to the fore (e.g. Ferrier & Jenkins 2010; Renaud & Kuenzer 2014). The latest of such approaches is what we define in this book as ecosystem services-based approaches. These encompass a range of ways of understanding, assessing, and managing ecosystems at which core is the notion of ecosystem services, understood as the benefits that humans obtain from ecosystems.
This comprehensive volume describes how ecosystem services-based approaches can assist in addressing major global and regional water challenges, such as climate change, biodiversity loss, and water security in the developing world, by integrating scientific knowledge from different disciplines, such as hydrological modelling, environmental economics, psychology and international law. Empirical assessments at the national, catchment and regional levels are used to critically appraise this systemic approach, and the merits and potential limitations are presented. The practicalities of this approach with regard to water resources management, nature conservation, and sustainable business practices are discussed, and the role of society in underpinning the concept of ecosystem services is explored. Presenting new insights and perspectives on how to shape future strategies, this contributory volume is a valuable reference for researchers, academics, students and policy makers, in environmental studies, hydrology, water resource management, ecology, environmental law, policy and economics, and conservation biology.
Understanding water ecosystem services requires both an elucidation of the interrelationships between hydrology, landscapes and ecology, and a contextualization of how water influences human livelihoods and wellbeing and how ecosystems themselves are affected by human activities. Ecosystem services-based approaches, as defined in this book, aim to understand these complex relationships to support more efficient and sustainable decision-making. Society needs to recognize the requirement to balance and manage the benefits derived from water resources, rather than simply managing the resource itself (United Nations Environmental Programme 2009). These benefits come from the realization of a whole range of provisioning, regulating, and cultural services provided by ecosystems. This way of interpreting water systems and water resources represents a change from traditional sectoral control policies and approaches to delivering an integrated view of natural resource management.
In this book the editors and authors took up the challenge, ten years after the publication of the Millennium Ecosystem Assessment (2005), of reflecting on what has been achieved, what lessons have been learnt, and how to improve the application of ecosystem services-based approaches for managing water ecosystems in the future. By proposing a structured definition of ecosystem services-based approaches (in Martin-Ortega et al.) and exploring the forefront of their application at the conceptual level and through a series of national and regional case studies from across the world, the authors have completed a comprehensive vision of the current knowledge and challenges of applying ecosystem services-based approaches to address water challenges.
In this concluding chapter we reflect upon the key messages that have emerged from the discussions contained in this book and on the way forward. We organize this discussion around the four parts in which the book is structured.
20.1 HOW CAN ECOSYSTEM SERVICESBASED APPROACHES HELP ADDRESS MAJOR GLOBAL CHALLENGES?
Capon et al., Febria et al., and Salman and Martinez explore how ecosystem services-based approaches have been, and can be, applied to address three of the critical global challenges that humanity currently face, namely climate change, biodiversity loss, and meeting the growing population's food and energy demands (notably in the developing world).